Body Of Work

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Body of Work is an exploration of health topics in the news and important matters facing science with experts from Baylor College of Medicine. Scientists, physicians and specialists from diverse disciplines discuss the impact of hot button issues on healthcare, research, community and education.

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Trevor M. Bibler, Ph.D. is a clinical bioethicist with a background in religious studies and philosophy. Dr. Bibler performs clinical ethics consultations at Houston Methodist Hospital. He teaches a variety of audiences and conducts research in clinical bioethics, religion and medicine, and philosophical ethics. His current research focuses on the ways religious worldviews—especially worldviews that include ideas related to miracles—influence clinical medicine.

See below for more of Dr. Bibler’s research:

Transcript

Welcome to Body of Work, an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair and this is part two of our interview with Clinical Bioethicist Dr. Trevor Bibler. If you haven't listened to part one yet, we suggest you go back and start there. This is also the final episode of season one of Body of Work.

Erin: We often think about the worlds of science and faith being distinctly separate. What is it about health that inevitably raises questions about faith?

Dr. Bibler: Well I think that one of when we feel quite healthy we're able to take our bodies for granted. There's a philosopher a German philosopher named Gadamer who talks about the role of medicine as kind of getting us back to this spot where we can take our bodies for granted again. And when we when we end up feeling quite sick whether it's just like a common cold where we have to miss work and are kind of stuffed up so we can't enjoy food in the way if we always have or whether we just we know a family member who had a stroke or we've been diagnosed with a terminal illness or something that's completely irreversible or we might be a candidate for a kidney transplant, all of these issues can end up making us question what it means to live in this world, what it means to die in this world. And oftentimes faith is a way of trying to understand and really reconcile what the type of suffering either we or the people we love are actually going through at this moment as especially when people get near death. Some people I think of science and faith as completely distinct. There's a philosopher and scientist who talks about faith and science as being uses this technical phrase of “non-overlapping magisterial” and what he means by that is that well, from his perspective science is about facts things you can validate based on empirical evidence based on the evidence that's right in front of our eyes and then faith and religion are more about value and science can't touch it and can't touch the other side. And I think that's a little bit too extreme of a view; I think we have enough reason to think that faith reacts to, let's stick to medicine, faith reacts to the ways in which medicine moves forward, and science also has its own set of values that are often part of what they do, even if it's so basic as, “Well, we value answering this question,” it’s still a value. In science while there are definitely objective elements to it, we're still humans who have subjective experiences, our own individual experience who are we're the ones doing the science. I think that strict view ends up not being able to really be fleshed out but I think your question is a good one because we do often think of these two areas as distinct, but it's really to my mind when we get sick that we really have to try to reconcile with both aspects of how we try to think through what's important for us and for most people, many people at least. That involves faith and religion and spirituality. We try to reconcile that with the fact that there are these incredible medical technologies that have something to say about how we can get better. It ends up being a really valuable relationship that I think we as ethicists and we in the healthcare field really need to consider because it's so complex.

Erin: Do you make a distinction between religion and spirituality?

Dr. Bibler: Yeah I think that there's a couple ways of unpacking that. In general I think many scholars, and since their scholars there's a lot of disagreement about it, but I think many of us think about spirituality as this general individual impetus towards trying to get answers to our biggest questions about what it means to be alive, and often time there's some type of an appeal to the divine, whether that's a god or many gods or something even more general, there is that type of impetus to try to wrestle with these questions and precisely get at that but that's the spiritual side of things. And then often I at least think of religion as kind of being a cultural and institutional and organizational really response to this impetus lots of people have. And so to my mind you can always have a spirituality with one person but there can't really be a religion with one person because the religious aspect of it is really about a organizational response to trying to figure out what's sacred and how we better understand what's sacred and how often we try to live in alignment with what we view to be important based on what the sacred has to say.

Erin: Why as human beings are we inclined to believe in miracles?

Dr. Bibler: Yeah well yeah that's a hard question to answer. So there are quite a few scholars, both anthropologists and scholars of religious studies and evolutionary biologists, who argue that to some degree some type of spirituality or faith is hardwired, and some actually argue that there's an evolutionary advantage to having this predilection towards seeing things as being animated. So if we can imagine putting ourselves back a couple millennia and to the polytheistic folk religions of various places across the world, there might be an evolutionary benefit to when you see that bush rustle you pay attention to it because it might be a predator or if nothing's there then maybe that was the divine trying to say something to me, or if you see a very rare bird fly by and then turns out there's a rainstorm maybe that was some type of God giving you a signal of some sort. So that there's a sense that being hardwired to believe in this can have some type of evolutionary advantage because you're ascribing meaning to natural events that might not otherwise have meaning, so you might be more likely to pay attention to these other areas of life. To the point about miracles themselves, yeah I'm not sure. I think that many people are inclined to hope for rare events that might not happen but our to our benefit. And there might be this one in a million chance that some fortuitous event would happen but then different people would ascribe whether or not that means that has to do with God or the divine or many gods they would have different answers to that portion of it, but I think that in general there is a general push towards wanting to find meaning in things and to kind of be hoping against hope that something good will happen even in the worst situations.

Erin: The hope for a miracle is a very complex idea. Does miracle mean something different to every patient?

Dr. Bibler: It certainly can mean quite a few different things. Part of part of my research is really trying to pay attention to the complexity of what this belief might mean while also recognizing that to some degree we can think of people who hope for a miracle in different ways and it can be a helpful way, especially in the clinical setting, to think through them in terms of groups. So I'll just give you a few examples that I think are especially helpful; I think some people hope for a miracle and it's in a way o, “Well my babies a miracle,” or “Every day is a miracle,” or “My healthcare workers are miracle workers,” and it’s a way of thinking about the possibility of a miracle that doesn't really have a direct effect on your medical decisions because the miracle is going to happen either way. But not everybody's like that; some people who I've met they've been very shaken by their experiences by either themselves or their loved ones and then they still hope for a miracle but they themselves actually aren't sure what they mean by miracle. It can mean many different things it can evolve over time. They're just very shaken by the illness and they view the hope for a miracle as something that they can justifiably I think latch on to. But as I very well also learned, not everybody who hopes for a miracle is shaken or thinking through things. Some people are very clear as to what the miracle is what it has to be and how we get there, primarily through lots of praying an additional time for God to work a miracle. Those people in our work we've sometimes called them integrated invocators; their sense of who they are and what's going on and the suffering that they might see, that's all integrated into a framework. Primarily when I hear healthcare professionals say they're in denial, well they're probably not in denial. They just have a very concrete idea as to what sickness is what health looks like and how we get better and that's through hoping for a miracle. Other folks sometimes use it in a more individualized spiritual way of hoping for a miracle. So they might not have a religious community to rely upon, they might be a person who at one time was part of our religious community and now rejects it, or they might think that, “Well no I've never been part of a religious community and when I go and think about these religious communities their idea of miracle doesn't quite overlap with mine, so I'm going to continue thinking about it in my own way.” And then I think what's also quite common are people who are part of a religious community and they're seeking a miracle of some sort but they're also kind of at ease with the possibility of if the miracle doesn't happen in the way that they think it should happen. So I've met folks who thought that at the beginning of their care a miracle would be if my cancer went into complete remission, and then that doesn't happen so they say, “Okay well I guess now my miracle is something else. My miracle might be that my family got to say goodbye to me, or that my family got to reconcile about this issue, or the miracle the whole time was in the life I lived before getting this sick.” So they themselves negotiate what the miracle might be while all the time they're trying to seek it, but unlike those first people I mentioned who are really shaken by it, their faith in their own faith commitments end up staying quite strong; they have it to bounce they have it to anchor how they think about things, but their idea of what a miracle might be just fluctuates over time.

Erin: Can a medical procedure or treatment be a miracle?

Dr. Bibler: Oh I definitely think that quite a few people, and especially health care professionals, they definitely view medical procedures as miracles, everything from routine medical treatments to life-sustaining treatments to very high-risk ones, they can all be viewed as miracles depending on what the health care professionals think. For example, I was once in a meeting with a cardiologist where he tried to convey to the family that it would be most appropriate to concentrate on the patient's comfort and allow him to die rather than continue to add additional life-sustaining interventions and the language that he used was “We're all out of miracles.” And with that he meant, “Well we've gone through all of these processes we've gone through all of these interventions and there's just nothing else that will get us to the point where he's going to recover, there's nothing else that can cure.” So yeah I think miracle can end up being a lot of different things, especially on the healthcare professional side.

Erin: Are there practices in place to teach clinicians how to react to patients who are hoping for a miracle?

Dr Bibler: Part of my research is precisely on that topic. My colleagues and I, we've suggested practices for clinical ethicists, for palliative care professionals, for chaplains, and now we're writing about pediatricians, trying to help trying to give them tools for precisely that. And it does really involve trying to understand patients and families where they're at and ask this radical question of, “What do you mean by a miracle?” and then listening to the answer, because in those instances that I mentioned earlier, for example, a family or a patient who whose life is completely integrated into their spiritual community and they have no question about a miracle would what that would mean, it might be a good idea to invite their spiritual authorities into the conversation, which would be very different than somebody who is completely shaken and the last thing that they want to see is anybody who has any religious affiliation; their miracle is what they think it is right? So there is there is a little bit of education out there from our group on that. But luckily over time, I just read a statistic recently that around 80% of medical schools have some type of spiritual care aspect that's in some part of their teaching in their curricula. Not every medical school that meets that 80% has a full course dedicated to it or anything like that, but there are specific actions and specific classes that are being taught across medical schools, and I believe the number is somewhere similar for nursing schools as well. There is quite a bit of education around these issues about religion and medicine, but it's primarily under this this guys this concept cultural competency. So what happens if I as a person who does or doesn't believe in God and caring for a patient from Saudi Arabia, right, or they're simply a patient who wouldn't share my faith if I have no faith or doesn't share my faith even if I do have one? And oftentimes getting at the religious aspects is part of this broader idea of cultural competency, getting a sense of other people's culture and I think that's always a good place to start but there are differences between culture and religion. There's also quite a few what are called spiritual assessment tools where it's kind of like, you know, we've done a good job of training doctors to do a clinical history, why not try to get them to do a spiritual history? And so they have a number of prompting questions about previous relationships to the divine, if you're going to your church or synagogue or mosque or your house of worship. And so there's quite a bit of education along that side as well, but for the most part it occurs in medical school and there is still most hospitals have quite a bit of support with chaplaincy services and the health care professionals I meet rely quit heavily upon Hospital chaplains to try to address those issues.

Erin: Are there certain diagnoses or situations where seeking a miracle is more common?

Dr. Bibler: I think so I think so, especially when people hear of a terminal diagnosis I think that's quite common, or generally if there's been a devastating event, like somebody has a neurologically devastating stroke and they're never expected to be able to talk with the people they love again, I found that quite a few family members then try to try to reorient their hope around a miracle because the medical professionals have said this isn't going to happen so then there's this kind of appeal to this one-in-a-million shot or to the possibility of the divine having a direct effect on your loved one. That said I have seen when I've met with patients and families it does tend to be the case that families are especially those who hope for a miracle, I think as part of just the psychological trauma that goes along with acting as a surrogate or seeing your loved one extremely sick. And it's also kind of interesting that recent studies have started to demonstrate and show that people who are part of religious communities, whether they're the big three monotheism like Judaism, Christianity, or Islam, they have a tendency to request additional life-sustaining interventions toward the end of life, additional medical care rather than less, but that that research is still kind of in its infancy, but that does seem to be where it's pointing right now is that those people from those groups do tend to request additional life-sustaining interventions rather than less interesting.

Erin: Interesting, almost like they want a little bit more time for that miracle to work out.

Dr. Bibler: Exactly yeah, that's the hypothesis that researchers have right now is that's precisely right is that; since they're people of faith and many people of faith hope for a miracle then they're waiting for God to perform that miracle. I've met many families who say, “God needs more time to perform the miracle,” and I think that's definitely part of it.

Erin: Have you witnessed any bedside miracles in your profession?

Dr. Bibler: I'm a person who doesn't really believe in miracles. I definitely have seen rare events that were beneficial to patients and families and others that were completely unexpected, but I myself don't really believe in that possibility, so I would say no if that's what we mean. But if we mean an event that was completely unexpected but was fantastic for the patient then yes I've definitely seen those.

Erin: Would you mind sharing an example of what you've seen?

Dr. Bibler: Sure sure definitely. The one that pops to mind right now is there was recently a patient for whom he was on a bunch of cardiac supports and a left ventricular assist device a right ventricular assist device and there was talk about him maybe even needing a total artificial heart when he was waiting for his heart transplant, but it turned out with a type of minimal support that they were offering that the main problem that he had just kind of went away and no one could explain it. I talked with a couple surgeons, I talked with the heart failure doctors, I did a literature search on my own, and there was just no real accounting for how the problem that he had could have been resolved with the drugs that he was on with, the interventions he was on, and in the amount of time that it took to resolve the issue. So that was that was definitely close to a miracle. It was definitely completely unexpected by everybody who was at the bedside.

Erin: On a more general note, can faith or spirituality affect your overall health?

Dr. Bibler: Yeah well there's an entire field of study called Religion and Health that precisely tries to answer that question. This has been a question that scholars have thought about. I think Émile Durkheim and his famous work about the Protestant Work Ethic in the late 19th century. He was trying to answer that question to some degree. And then Sigmund Freud after him. And it's been an area of controversy over the last 30 to 40 years or so. It's become a burgeoning field that ends up being very, it's very interesting to me. There is a lot of bad research out there on it, and the current scholars in the field recognize that. A lot of the research doesn't really meet the gold standard of good research so then it's very hard to replicate but in general there are a couple themes that have come out. One is that there does seem to be some type of association between participation in religious services and a decrease in mortality, so a little bit of that, a decrease in depression, and a decrease in suicide. There's quite a bit of other research related to heart disease and specific psychological disorders but part of the challenge of the entire field is trying to explain that mechanism right. Why is this the case? And that's what's extremely hard to actually sort out; is it the beliefs that the people have, is it the intensity of the beliefs? That's one hypothesis. Is it the fact that they're just out and about and talking to people, they're going to their synagogue, they're going to their church, are going to their mosque, they’re going to their temple? Is it because they're actually doing something? Is it because they have strong social support, like post-op care? One of the most important things after you have a big surgery is post-op support, whether it's people coming by to say a quick hello or people go to Walgreens to try to help alleviate the load of getting out in your car and so on. There's some question if that confers any type of social support, but it's just really tough to disentangle because there's the question of well if it's this social support aspect of it could feasibly somebody could really robust atheist book club offer the same type of benefits if somebody was a part of it for their entire lives? Because it is it about just getting up and getting going and keeping active? It’s a really hard issue to sort through. The field has moved a little bit away from some of the more, how should I put it, some of the more headline-grabbing areas. Like for example there were some studies done decade or two ago about the relationship between intercessory prayer so prayer where you ask God to help heal somebody quicker or make it through their surgery, and there seem to be benefits related to intercessory prayer where there happened before or after, but luckily we've gotten the field, I should say has gotten, a little away from that because there are there's so many variables that you just can't address. Like okay well what happens if the synagogue down the street has a prayer for everybody who's in the hospital right now did I just ruin the entire experiment? Well yeah, probably, because if you're talking about intercessory prayer in the way that people pray for this then. It's really hard to quantify what that means it's very different than a drug X and placebo Y; it's about the nature of prayer. So there's been quite a bit of I think justified pushback about that type of study but the types of studies where they're really trying to account for how it is that participation in services can your mortality. There's also quite a bit of research that says people who attend services more often are more likely to report being happy and having better overall well-being, but again is that divine favor, is that because they're out and about talking to the people they trust? It's really hard to disentangle.

Erin: What does the future of faith and medicine look like? Is the clinical world shifting to being more proactive and addressing patient spiritual needs?

Dr. Bibler: It seems to be. I think that healthcare professionals and hospitals and many other medical institutions are recognizing that if you really want to take this claim that you care for patients and you care about their overall well-being rather than just their bodies, if the way that many people think about their wellbeing and how they function in the world and what their life best lived would look like, then you have to start taking into account the spiritual aspects of it. Organized religion in the United States, there does tend to be a waning at this point in organized religion. There's up to 20% of people across America don't really identify as part of any specific religious group. So while 80 percent do 20 percent of the population is still a still a very significant number, is there's a question of how to incorporate people like this into medical care. I do think there's been a little bit of a push to have those who are hoping for a miracle, or just in general they value their faith, to have them be incorporated into the conversation a little bit more, because again if we're gonna say that we care about people and not just individual patients and the bodies that are in front of us then that means talking with them about what's most important to them because that's the way that they make their medical decisions, as incorporating these big idea.

Erin: Do you find it ironic that your last name is Bibler and your life's work is focused on faith?

Dr. Bibler: I don't know. When I went to Divinity School at first I was planning on doing biblical studies and at that time it was a constant, so every time I would introduce myself they would people would either roll their eyes and say that it was expected or some variation of that. So my family who has done a little bit of research to the nature of the name itself, it does seem like there's it could be the B-I-B could be like bibliography the book side of things, or more related to the imbibe like the drinking of alcoholic drinks side of things. And I don't think it's I think both could make a whole lot of sense. And I don't know where my family comes from in German Bavaria there was definitely the case that monks brewed their own beer and so on so it could be a combination of both but I have the feeling I would probably have ended up doing similar research even if my last name was Smith. So I don't know, it might have had some influence but if it did have an influence it was more subtle than I recognized.

Erin: I see

Erin: Thank you for tuning in to our inaugural season Body of Work by Baylor College of Medicine. If you enjoyed this episode be sure to subscribe, give us a five star review, and tell your friends to listen. We're available on Spotify, Apple Podcast and Stitcher, as well as at BCM.edu/podcast. There you can also find the episode notes including information about the experts featured on the show. A quick note about the medical advice and opinions stated in this podcast; each individual's health profile is unique so please see a health care professional about any questions you may have. Until next time take care.

See more of Dr. Bibler’s research:

Transcript

Erin: Welcome to Body of Work an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair, and my guest today is Clinical Bioethicist Dr. Trevor Bibler.

Erin: You are a Clinical Bioethicist. Can you tell us a bit about what that means and what goes into your day to day job?

Dr. Bibler: Yeah yeah gladly. So there are quite a few different types of medical ethicists but

I'm a Clinical Bioethicist which means that I go to Patients’ bedsides, families as well, talk with healthcare professionals and so on and my main task is really to try to identify and analyze and sometimes even hopefully resolve any type of ethical conflicts or even any types of ethical confusions that end up popping up in the course of clinical care. That's really what I do. It primarily involves talking with people. Asking questions, facilitating conversations, sometimes mediating conflict, but in general we're the ones who go by the bedside. Here in the U.S. some hospitals have clinical bioethicists who are their volunteers or are staffed such as myself. Most hospitals some have to have some way of I believe what the regulations call “resolving ethical conflicts” but most of the time that has to do primarily with implementing policy rather than actually going to the bedside. So that's most of most of my job is spending time at the bedside.

Erin: How did you get into this field?

Dr. Bibler: Well I first heard about clinical bioethics when I was a Master's of Theological Studies student at Vanderbilt Divinity School and I took a course called “Theology in Medicine” and as part of that the bioethicist who was also an MD and philosopher, Jeff Bishop, he had us round with the palliative care doctors and then also round with the Clinical Bioethicists and I really got a sense of what they were doing; I thought it was extremely interesting, I thought it was a good way of combining my analytic interests with trying to help people out and a little bit of personal skills. And the first case discussion that I actually ever sat in on was of a little boy who was about four years old and dying of liver failure and his parents were saying, “No he should not have a liver transplant because we're hoping for a miracle.” And so I was extremely interested by this and I asked the bioethicist if he asked them what they mean by miracle and he said “oh no not really I just kind of assumed I knew what they meant.” So I became very interested in that question as well and I stuck around and at Vanderbilt Divinity School and then I went to Vanderbilt’s graduate school to get my PhD in in Clinical Ethics and I spent quite a bit of time shadowing and then leading a few cases on my own at Vanderbilt University but then I came to Baylor College of Medicine and I was their inaugural clinical ethics fellow and I got lots of experience there.

Erin: So tell us a little bit about your own research.

Dr. Bibler: Sure gladly. My own research is primarily it really does center around the ways in which religion and spirituality, and I think faith in general, how that plays a role in medical decision making. As I mentioned that first time I heard about the patient, the little kid who was very sick and his family said “We don't need the liver, we're hoping for a miracle,” I've been very interested in this question of what people mean when they say “miracle.” To my mind it's a very complex idea and it can end up affecting people in many different ways and it can definitely play a role in the way in which they think about medical decisions that they have in front of them, both when you're a patient and when you are a health care professional and when you're a family member; it can end up having an effect on all of that. I also do quite a bit of research into what I is a clinical ethicists I'm actually doing, like what am I committed to when I'm saying “Yes this path seems like the good thing to do this seems like something that's okay to do, this seems like something that you should definitely not do,” what are my commitments as part of that? Because I think there's a lot that is really we assume a lot as Clinical Ethicists and there's been lots of about that but it's still I think quite a open question as to what we actually mean when we say that. And I've also done a little bit of research more recently into the ways in which individual healthcare professionals faith has an effect on the way in which they see medicine or the way in which they talk with patients and families to begin with. Yeah so it's those are my those are a couple areas but I am just really fascinated by this question of how in general I think how faith and medicine function in America and in the West today because it's a complex relationship.

Erin: How do you conduct research on faith in such a multicultural world

Dr. Bibler: Yeah that's that's a really really important question. One of the ways in which I do my research is to appeal to this idea of an insider versus outsider perspective. I don't really do research from an insider perspective. I'm much more interested in the ways in which people who profess a faith or profess a spirituality how they're wrestling with these types of issues. I'm extremely extremely interested in that. And the point about it being a multicultural world and that there are just so many faiths and that we in medicine try our absolute best to attend and pay attention to people of different faith backgrounds, because it's not always the case that if you are a Sunni Muslim your patients are all Sunni Muslim or if you're if you're a protestant that all your patients will be protestant. So it ends up being a little bit of, to my mind at least the research that I do ends up starting out with a pretty specific question, like I began my research on miracle language with just really concentrating on Christian faith because that's where I thought I could based on my background that's where I thought I could best understand what was going on, but then I’ve gradually expanded to other monotheistic faiths, so Judaism and Islam primarily and working with scholars who have additional experience and knowledge of those faith traditions and then just kind of expanding expanding and expanding based on the different professionals I talked with and based on their own professional responsibilities. That is something that I'm always trying to think through, is that I as an ethicist have a different set of responsibilities than the chaplain, than the doctor, than the bedside nurse, than the social worker, than the food service worker. And so when I hear this language, what am I actually what am I actually committed to? And to my mind at least taking an outsider's approach it's been extremely helpful because I'm able to try to get a sense of where they're coming from without having to identify with a specific faith tradition itself.

Erin: How do you put aside personal faith biases when doing your research, or does your faith background aid in your research and in working with other researchers and patients?

Dr. Bibler: Yeah yeah that's a that's a good question, one that I I think about myself quite often. I was raised Catholic but I don't identify as Catholic anymore. I've gotten a lot of guff from my colleagues when I say not only am I not religious but I'm not spiritual either. They don't quite believe that because of my interest in these types of things, but it is it is a fair question it's a good one because there is always I think some concern that the beliefs of the individual researcher will end up affecting either the research question or their answers to the research question. Luckily that, as an as an outsider to the faiths that I research, I don't really find myself all that concerned with whether or not I think they are right or wrong. I just don't know. My unfortunate sneaking suspicion is that everybody's wrong but me. What not really. But I have no I have no real skin in the game. Let's say so let's say I'm researching the ways in which patients from Islamic faith background use a term “miracle.” I'm not interested in saying that their theology is right or wrong or that the way in which they reason through these issues is right or wrong; what I'm most interested in is the process and how I as a healthcare professional can help them receive the best medical care possible when they use this language that might be a little bit for. Whether or not the healthcare professional is Christian or Islamic or Jewish or or any or any other world Religion, my hope is that the type of research that I do would be applicable to pediatricians independent of what confessional faith they might have, would be of interest to chaplains independent of what type of chaplain they are, because what I really and my group really try to hone in on is what we as healthcare professionals not we as individual believers what's required of us in medicine today rather than what's required of us as Christian bioethicists or Islamic chaplains or any type of permutation of that.

Erin: It's almost more a translation job.

Dr. Bibler: Translation I think is a great word for it. Yeah I'm definitely trying my best to get healthcare professionals to recognize that when religious language is used it's not the case that this is something that we can't question or that we already know the answer to or anything like that. It's trying to dig through in a in a very conscientious way about what people's individual faiths actually commits them to, because sometimes the people of these individual faiths have a very clear idea as to what their faith requires and sometimes they're just making assumptions. I hope that my research helps sort through the issue and a little bit of a way that relies more upon our professional identity than our personal confessional beliefs.

Erin: How is your job different from that of a chaplain?

Dr. Bibler: Yeah that's a you keep asking me questions that I've thought a lot about but still don't have good answers to. One of the one of the ways that I try to disentangle myself from a chaplain is that I at least if I go to the bedside and I talk with a patient or family and they bring up these religious terms these spiritual terms my job isn't to provide them with spiritual care; my job is to actually try to think through what these terms mean and how they're affecting their own medical decisions. In the same way that if I go by and talk with a patient or family and they don't use religious terms in the least it's still my job to kind of sort through what they mean. So even if they don't say miracle, what if they are hoping for something that's one in a hundred or one in a thousand, right? So even if there's not this religious language, my job is to try to get at the moral fabric and the ethical framework that underlies it. To my mind it's just often the case that, where I trained in Nashville and here in Texas, that often includes an appeal to spiritual or religious issues. So I think that my main job is to really try to unpack the way in which people decide what is good, what's valuable, and how that relates to medical care, whereas the job of the chaplain is to provide spiritual care and be the open voice and sometimes be a patient advocate for those who are undergoing spiritual crises. And I just don't have the tools or the inclination really because it's not part of who I am to try to address that, but it does end up being a challenge. And I should also mention that different ethicists and different healthcare professionals disagree with my approach. Some healthcare ethicists who I really respect say, “This is the job of the chaplain. We have absolutely no reason to even ask, ‘What do you mean by miracle?’ This is what the chaplain should be doing.” Others go to the other side of the continuum and say no not only do we need to jump in on this we actually need to negotiate these theological tenants with them and argue with them about, “Well if you're saying God has the power to perform miracles, then surely if we stop the ventilator God could still provide the miracle, so why don't we stop the ventilator?” So it's a whole big spectrum of responses and what I've tried to do is really stake out a middle position that says, “I'm not there to negotiate theology, I'm not there to offer spiritual care; I'm there to try to understand how these spiritual and religious ideas play a role in your decision-making and see if we can't map up the values that you have with a course of care that the health care professionals also think is a good idea.” That's really my job.

Erin: Wow, that's really remarkable

Dr. Bibler: Yes it's rewarding. It's tough but it's rewarding.

Erin: I can imagine. I can just imagine. I would imagine that working with surrogate decision makers of family members who have the responsibility to make health care decisions for a patient who can't speak for herself, I would imagine that that would be a particularly sensitive part of your job. Do you have a set method for unpacking that sort of a conversation?

Dr. Bibler: Mm-hmm yeah, I do have a couple practices that end up being quite helpful because there's a couple concrete steps that are involved in these types of conversations. One is I always ask if the patient ever filled out any type of advance care planning documentation, and that can end up being quite helpful. Sometimes not all that helpful but oftentimes quite helpful. And if they haven't then I've tried my best to try to get a sense of what's important to the patient, get a sense of their values, and just asking a family member what was the patient's values isn't going to get you very far. So a question that I returned to all the time and it's a question I really drill into my fellows is this question of, “What did a good day look like before our loved one got this sick?” And when you ask that question people just open up often. They'll say, “Oh yeah no they he loved to go and spend time with family, she loved to cook, we'd always get together on Wednesday nights for card games,” and you just start building a little bit of a portrait of who this person was and then I asked about well what their job was, and then I get some sense of that there's this combination of questions with that often being one I appeal to of trying to get at what was important for this person. And the reason I'm doing that isn't just my own fascination. It's, which does play a role to some degree I am very interested in what people have to say about this, but I'm able to try to help think through with the. It's more of a thinking through with than anything else. If this if this was a person who if his ideal day was having an apple for breakfast and then going for a jog and then going to work and then spend in the evening with the kids and watching TV, what happens if he can never eat an apple again? What happens if he can never go to work again or take a walk or be able to hold his kids, be able to say hello to his grandkids again, right? What happens if that's the case? And then once you get the sense and again people have different answers to this question. If we hear from family members that, “Oh yeah well no, I know he'd like to run, but really if but really if he was never able to speak with his grandkids again, I don't think he would want to live.” Or if we hear, I had a patient a couple years ago who spent his entire life on the water he was a sailor and he had just retired and he raced in boat races and so on, and he was a candidate for a left ventricular assist device which you can't get wet, and the possibility of him not spending his entire life on the water was just unfathomable, but that's different than other people. So it's these types of questions where you're able to get a get a sense of who the patient is and then think through, “Okay well if this is who they are what interventions are then available for them?” and at that point I try to I rely very heavily on the clinical care team to try to help me sort out what the most likely scenario is, what a best-case scenario is, and then speaking honestly about what a worst-case scenario would be, and then we're able to do a little bit of a mapping I suppose of these values. If they can meet what the clinical care team views to be as appropriate how can we have we actually put those together? And a lot of my job ends up trying to be again you used it earlier translate trying to translate these values and preferences into a plan of care that makes most sense for the individual patient. That's really that's really where I spend a lot of my time is it's I really do think ethics at the bedside at least it's primarily inquiry driven, where I'm there to ask questions and listen to the answers and try to add a little bit of the person into people's descriptions of the patient, and then see if the health care professionals feel comfortable offering interventions that the patient, or in this case I guess the family, views that the patient would have wanted, and when we can make that plan overlap then I think I've really done my job to help a patient get care that he or she would have wanted in this context.

Erin: Your job sounds really hard, really emotionally intense, stressful, kind of sad in fact. You know these are dire life-or-death sorts of decisions that you're helping a patient’s family make. How do you how do you decompress from a day or a week like that?

Dr. Bibler: Yeah yeah that’s a fair question. It's not it's not easy but because sometimes it just ends up being the case that you end up thinking about a patient or a family for a long time. Just as last time I was on call I talked with a patient who said that he wanted to die; that he did not want CPR, he wanted to go home and play with his dogs one more time and be allowed to die there. And I got a family meeting together with members of the family and members of the hospital team and it sounded like that was the plan. And then we left the room and then the patient's family talked with him he said, “No that's not the plan, I completely changed my mind.” It was a complete 180. And that case I still think about a lot and it's it ends up being quite hard, but one of the one of the nice things as well about clinical ethics is that I don't think there's been a week yet where I haven't made a family laugh, because when you ask this questions like “What a good day look like?” that puts people in a different headspace than “Give me an update on the clinical picture,” because then people concentrate on, “Well for the last month she was in the hospital after she had this stroke and then hasn't moved since,” but when you put people back in that other frame of mind of reflecting on who the patient was when they were really at their best then people lightened up quite a bit. And I really do think it's rare when I don't laugh with a family or a patient or make a joke or engage in some type of self-deprecating dialogue about me missing a point that they said or something. So even though it does end up being quite heavy I do think that we as Ephesus do a pretty good job of keeping some aspects of it light when we can. There's a growing dialogue about moral distress and there's been a lot of conversation about what it means for a nurse or a doctor to feel as though they can't do the right thing but there are these impediments. So there's this distress that they feel that isn't just about being overworked but it's about I can do the right thing. And there's a growing conversation about ethicists who themselves undergo moral distress because we have very often very strong opinions about what the right thing to do is, but sometimes it's just the case that we can't effectuate that either because we're uncertain or because there are institutional barriers. So I it is a very good question and one that the field itself is trying to reconcile with. Where I'm at right now I'm quite lucky because I have an appointment at Baylor College of Medicine and I do clinical ethics consultations at Houston Methodist Hospital and luckily I'm on for two weeks and then doing research and teaching for the next two weeks. So it's only 50 percent of the job and that actually ends up being quite a bit of a relief because you can go from having this type of in-depth conversation and facilitating conversations where there's disagreement and trying to minimize conflict and mediate and all that to then okay well now I'm gonna write a paper or okay now I've got to go and teach a class. So there are there are natural breaks if I was 100 percent clinical ethics I think I'd have a much tougher time with the aspect of it's just incessantly heavy.

Erin: Is there anything else that you'd like to add to you know our audience understanding the clinical bioethics?

Dr. Bibler: Well I think it's just primarily that we're there to help and that many hospitals do have clinical ethics consultant, even if you've never heard of us. I think patients and families if they're at a relatively large hospital they should ask if there's an ethics consultation service. Health care professionals should also know that at these larger institutions there are ethics consultants who can help out with these big issues at the end of life, at the beginning of life, about surrogate decision making and privacy and confidentiality and we're here to help. Sometimes we address moral distress just by being a sounding board and listening to what people have to say that can end up being quite helpful to alleviate moral distress. So whether they're patients or families or healthcare professionals when they feel as though they're really struggling with what the right thing to do is, it might be a good idea to just ask at your institution if they have clinical bioethicists and they very well might. It's a growing field and even when there aren't people who are there to staff it 24 hours a day they're often our volunteers, so we might be able to be of help. I always say err on the side of asking if there's an ethicist around rather than trying to struggle through medical decisions on your own.

Erin: Thank you for tuning in to Body of Work by Baylor College of Medicine. If you enjoyed this episode be sure to subscribe and be on the lookout for part two of our interview with Dr. Bibler. It focuses on his research into miracles. If you like the show please give us a five star review and tell your friends to listen. We're available on Spotify, Apple Podcast and Stitcher, as well as at BCM.edu/podcast. There you can also find the episode notes including information about the experts featured on the show. A quick note about the medical advice and opinions stated in this podcast; each individual's health profile is unique so please see a health care professional about any questions you may have. Until next time, take care.

Harvey Levin, Ph.D., is a professor and research scientist at Baylor College of Medicine and the Michael E. DeBakey Veterans Affairs Medical Center, where he researches the chronic effects of traumatic brain injuries.

See below for more of Dr. Levin’s research:

Transcript

Erin: Welcome to Body of Work an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair and my guest today is Dr. Harvey Levin professor of physical medicine and rehabilitation.

Erin: Although we hear the term quite often, what exactly is a concussion or, more clinically, a mild traumatic brain injury?

Dr. Levin: So, these terms concussion and mild traumatic brain injury are interchangeable. This is a sudden onset of neurological changes associated with impact to the head or impact to other regions of the body which causes sudden acceleration of the brain inside the skull which have similar effects as an impact to the head. Concussion or mild traumatic brain injury can be detected by observing the individual to lose consciousness or have impaired consciousness. The symptoms that typically arise immediately or after some delay include: headaches, dizziness, poor postural control, fatigue, and frequently confusion. However, some concussions, especially in sports, may be difficult to detect just by visually following the player. They may be quite subtle and the player may not lose any consciousness and may appear to the layperson to be functioning normally. So, there are different gradations of concussion and mild traumatic brain injury.

Erin: You hear a lot about concussions in regards to contact sports or just athletes at risk of mild traumatic brain injuries? What other events cause concussions?

Dr. Levin: It's a good question. We hear the term concussion in the news frequently in reference to athletes, but in fact in non-athletes the most common causes are motor vehicle crashes, assaults, being struck with an object, or impact of the head against a solid object. The causes depend also on the individuals age. Older people, for example, are more vulnerable to falls and in young adults and late adolescents motor vehicle crashes occur at a high rate.

Erin: So, whether it's an older person with a fall or cheerleader or a professional athlete, car crash victim, can you describe what happens in the brain in a concussion?

Dr. Levin: In a concussion, there's a tearing or stretching of these nerve fibers that connect different regions of the brain. This may be reversible or the effects may be more persistent and what those fibers do is help the brain work. Ordinarily, they help with communication among different regions of the brain. For example, communication between the prefrontal cortex which is heavily involved in our cognition decision-making computation and the parietal region which gets involved in working memory. That complex functioning that we are capable of most days depends on brain networks so if there is a disruption in communication among brain regions these relevant networks are dysfunctional and we don't perform well. Other changes in the brain that I mentioned earlier have to do with focal brain lesions such as contusions.

Erin: Is that like a bruise?

Dr. Levin: Yes, it's a bruise to the cortex of the brain. In fact, these are quite infrequent in sports related concussions but they're more common in persons who are involved in a motor vehicle crash especially in a high velocity rollover they're much more common and they contribute to the severity of the impairments that result from the injuries.

Erin: So what kind of post-concussion symptoms do patients experience? How long can that persist?

Dr. Levin: The most common symptoms are headaches, dizziness, fatigue, increased sensitivity to light or to noise. The question of how long these symptoms may persist is somewhat unsettled and controversial.

Erin: What kind of recovery is required? Are there personal factors that might affect the amount of time it would take for someone to recover from a concussion?

Dr. Levin: After a concussion, an individual is more vulnerable to suffering another concussion. Consequently, it's important to observe a period in which the individual refrains from engaging in a contact sport, or even if their hobby is boxing, they shouldn't be sparring. They should take it easy, not completely rest necessarily, but take precautions not to have another injury within a short period after having their first concussion. In the early 1990s, there were seminal reports about college football players and reporting that 90% of these players would fully recover in terms of their symptoms and being capable of returning to play in seven to ten days. We now know that there are exceptions to that timeline, particularly in adolescence. For example, high school contact sport athletes and youth contact sport athletes and also female athletes in these groups approximately 20% have not recovered in terms of their post-concussion symptoms even at 30 days after injury. So, there are subgroups that are more vulnerable. People who've had previous concussions, people who have had migraine headaches prior to their injury, and individuals who've had some emotional conditions, depression especially, are also more vulnerable to having a longer period of post-concussion symptoms. We've learned that in non-sports-related mild traumatic brain injury there's a shift toward older age. We also know that mature adults are now more often engaged in sports than they used to be and we don't know as much about the timeline for their recovery.

Erin: Say the concussed person was an athlete and continues to play an impact sport, what happens if they endure another concussion?

Dr. Levin: We're still learning about the effects of repeated concussions and I'll make the distinction between repeated concussions and repetitive head impacts. Repetitive head impacts, for example in football players, in rugby players, occur often during a typical game depending on what position the individual plays. There is emerging evidence that the effects of these repetitive impacts over the course of a season which can be hundreds of these head impact, and over successive seasons, thousands of repetitive head impacts may have cumulative effects. There are some investigators who are of the opinion that these head impacts are more deleterious than the concussions, but this is an unsettled question. In regard to repetitive concussions, there's some evidence that the effects are cumulative and also that the distribution of these concussions over time is a relevant factor. In other words, individuals who have repetitive concussions in short succession, for example separated by days or even a week or two, these might be more deleterious than someone who's had several concussions spread out over a decade. This issue is important not only for athletes but also those in the military where they may be exposed to repetitive blast-related trauma affecting the brain. In the combat theater, many of these blasts could occur in a short period of time.

Erin: Would say that to the individual, repeated head impacts would feel less dire or less distressing than a concussion?

Dr. Levin: For the persons experience, the head impacts probably less of a concern because they don't typically cause symptoms as following a concussion as I described earlier. However, we do know that there are effects which are subtle. There are a small number of recent brain imaging studies showing that over the course of a season, for example playing hockey or football, there are detectable changes in these brain white matter tracks which can be seen on a type of imaging called diffusion tensor imaging. The player may or may not have had a concussion and may or may not be aware of any changes and it's still not clear whether there are cognitive changes associated with these detectable changes on brain imaging. This is ongoing work, and it raises issues but we're just at the beginning of this area of research.

Erin: Why aren't helmets preventing mild traumatic brain injuries?

Dr. Levin: Helmets are quite important and there's some evidence they may protect against focal lesions of the brain or perhaps skull fracture, they may prevent that. I don't think it's entirely clear what the effects of helmets are on preventing this sudden stretching of these white matter tracks or these fibers this effect occurs after an impact to the head. If we think of the brain floating in cerebral spinal fluid, yes, an analogy that sometimes is made, if you have a plastic toy and a bathtub full of water. So, at the time of the sudden acceleration/deceleration, there's a swirling or rotational acceleration imparted to the brain and these nerve fibers then may tend to stretch. If this rotational acceleration is of sufficient velocity, they may tear. The effects of this rotational acceleration to the brain may not necessarily be diminished very much by wearing the helmet.

Erin: Sure, it's not keeping the head still, in one place. It's just protecting.

Dr. Levin: Yes, exactly. So, for focal impacts it does offer protection. But if the head is accelerated very quickly and suddenly decelerated as, let's say a running back running at a high speed, and suddenly there's a collision or suddenly the players thrown on the ground there is likely to be this type of acceleration/deceleration effect of the brain floating in this cerebral spinal fluid.

Erin: I understand that's it's quite an image. You had said that the age of the person had an effect on the recovery time. Why is that?

Dr. Levin: An underappreciated aspect of concussion and mild traumatic brain injury is in pre-adolescence and throughout adolescence and until at least the mid-20s. The prefrontal cortex and the underlying white matter connections between prefrontal cortex and other regions of the brain are still undergoing maturation. So, if there are repeated concussions or head impacts during this period of maturation, there is concern about what the long-term effects may be when the individual is an adult. This isn't known, but we do know a fair amount about these maturational changes because there have been major brain imaging studies of healthy children and adolescents as they age chronologically, and we suspect that there could be deleterious effects by exposure to multiple concussions and repetitive head impacts. In an older individual and here I'm talking about a person perhaps 60 years old or older, we know that there's a higher vulnerability to developing a collection of blood in the subdural compartment of the brain even from what we would consider to be relatively minor head trauma. We don't know what the long-term effects of that are, and we don't know much about what the long-term effects of concussions and repetitive head impacts may be as a person is getting into their 50s and 60s and 70s. But, we do know that from epidemiologic studies that having a history of concussion and mild traumatic brain injury is a risk for developing neurodegenerative diseases such as Alzheimer's and Parkinson's.

Erin: In recent years, we've heard a lot about aging football players and boxers having CTE. What is CTE?

Dr. Levin: Anyone that is attentive to the news has heard about chronic traumatic encephalopathy which is a pathological diagnosis, so it's not a diagnosis made clinically in a living person. It's a diagnosis made strictly on the presence of specific pathologies in the brain. So, it's made in brains that have been donated, and at this point, most of these brain donations came from families of former athletes, particularly NFL football players. In studies of these brains, the presence of chronic traumatic encephalopathy has been confirmed in large proportion of these donated brains and it's thought that this occurred as a result of being exposed to multiple concussions and repetitive head impacts over the course of their careers with athletes. However, it's unclear how much of a risk factor this is for the other thousands, millions of athletes. These athletes whose brains were donated had very extensive careers playing at the highest level of professional football, and we don't know to what extent any of this can be generalized to people that play contact sports in college, high school, or younger. We don't know what the threshold is for causing this type of pathology. Chronic traumatic encephalopathy typically begins in the depths of the frontal lobes involving white matter below the cortical surface, and it's associated with an excess of what's described as hyper-phospholated tau. Tau is found in other brains but an excessive amount is found in the brains of individuals who have CTE pathology. Initially, it's located in a very local or discrete region of the brain, but as the years pass it tends to spread to other regions such as to the temporal lobe, the parietal lobe, and it may become diffuse through the brain. As it increases, there are associated changes or degeneration of the brain that can even be seen on an imaging, but in the early stages it cannot be seen or detected by currently available brain imaging. Again, this is under investigation. With the changes in the pathology as it progresses, there have been published descriptions of the onset of changes in behavior and in cognition, but this is based on retrospective reports by family members because the pathology has been analyzed in the brains of former athletes, primarily. These individuals did not undergo any particular assessments before their death, so it's all based on retrospective reports by families who were interviewed at some point after the pathology was analyzed.

Erin: So, you're saying that CTE can only be detected with the donation of the brain of a dead athlete?

Dr. Levin: It's a pathological diagnosis.

Erin: So, there's not biomarkers or anything like that that we can see now and say oh that's a problem you know? You could have more problems as you get older...

Dr. Levin: There are biomarkers, and there are studies that have been done. For example, I mentioned the tau? There was a study of analyzing the cerebral spinal fluid of boxers in Sweden. They were Olympic level boxers, and they had analysis of their tau from undergoing spiral taps. There was some elevation and it tended to be elevated after they had finished bouts, but we don't know what the threshold is for tau. We don't know what predictions can be made by doing this measurement of tau in the spinal fluid. There are now some biomarkers that are measured using positron emission tomography which is a type of brain imaging or nuclear medicine. This work is ongoing. We still have very little data about how frequently there is an elevation of tau on the PET scanning, and we don't know yet to what extent this is predictive of changes in cognitive performance or changes in behavior. So, most of the information on cognitive problems and behavior at this point is based on this retrospective interview information that was obtained from the next-of-kin of those whose brains have been analyzed pathologically.

Erin: Can we attribute any particular diseases or conditions to CTE?

Dr. Levin: CTE is a disease. It's a neurological degenerative disease, but what has been reported is that there is a co-occurrence in a sub-group of these brains with evidence for Parkinson's disease and possibly Alzheimer's.

Erin: What steps are being taken to prevent CTE or multiple mild traumatic brain injuries?

Dr. Levin: There have been changes in the clinical management. This is particularly the case in sports in which there are health providers which can be physicians, there are athletic trainers, neuropsychologist who perform various standard tests on players after they've had a concussion. These tests are often done preseason, so there's a baseline while the player is healthy. So, these tests include a checklist for the symptoms such as headaches and dizziness and cognitive performance, reaction time, attention, memory. This kind of assessment is done, and before the player can return to play she or he has to have resolution of these symptoms. Their postural control or balance has to be returned to normal, and their cognitive performance has to return to normal. So, they're monitored by the health provider, and when they're thought to have been clinically recovered, they're cleared to return to play. This is very common now in school systems, high schools, in collegiate sports, and professional sports. The concussions are managed. I don't know that there's as much reporting about how they're managed as there is at the college level in regard to mild traumatic brain injury versus non-sports related. I think there's a lot of work to be done and here. I'm referring to individuals who are brought to the emergency department. The rate of clinical follow-up of these individuals is fairly low, and in my view there's a lack of standard protocols compared to what we see have been developed in the care of athletes. Now of course in the individuals who are cared for in emergency departments, these individuals are not returning to practice and to games where they're going to be exposed more head impacts. So, it's much different, but that's not to say that closer follow-up, especially of individuals at high risk for persistent post-concussion symptoms. I think a case could be made that these subgroups should be followed up, and they may need some follow-up care.

Erin: Do you think that parents should discourage their children from engaging in contact sport? Is it something where there's enough known about traumatic brain injuries to caution young people against contact sports all together?

Dr. Levin: This is a difficult question which I think many families are confronting. I think, taking football as an example, I think the quality of the training by the coaches is extremely important. One aspect of this is that, from what I've read, the quality of the training and oversight of student athletes tends to be much higher at the level of collegiate sports then for example junior high school or high school. It's not to say anything disparaging, and I would surmise that there are major differences across the schools. Some schools have higher quality programs than others but I do think that it should be thought through very carefully, and the player and the family should be aware of the risks. I think it's important for the player if she or he is hit and is experiencing the symptoms that we've discussed that they should come forward and mention this to their coach, and not try to be tough about it. Because in the past, and unfortunately, even at present, there's a tendency for some players to feel very loyal to their team, and they want to make a contribution. They may feel macho. They may be reluctant to come forward and say that they were hit, that they have headache, that they're dizzy. We know now there is a vulnerability after having a concussion. So, this individual has to have some rest, not for a real long time – maybe a couple of days, but they should definitely not be in play. They need to go through the concussion management that we talked about and gradually return to exercising and training with the team, then returning to game. But, they have to go through this concussion management. If they don't, based on the evidence that we have seen, this is increasing their risk of persistent effects that may only be detected later when they're adults.

Erin: Can you tell us a little bit about your research areas?

Dr. Levin: My research areas include concussion and sports concussion. Recently, with colleagues at Baylor and University of Texas Medical School in Houston, we completed a study of high school athletes who had sustained concussions. They were primarily football player, and we tested the hypothesis that players who had a concussion and were thought to clinically recover within 30 days and were cleared by their health providers to return to football would still have aberrant or dysfunctional brain imaging findings on advanced brain imaging. So, our hypothesis was that the brain was not recovered in these individuals even though they were clinically returned to return to play. We had a control group of similar athletes, similar demographic features, but they had an orthopedic injury – no involvement of the head. Sure enough, we found that there was evidence on the functional MRI that their brain networks were still dysfunctional. We also found on diffusion tensor imaging that these white matter tracks were not recovered to what would be normal for their age. So, we are planning a follow-up project to that look at related questions. For example, comparing male and female athletes in their recovery of brain function and structure as well as their clinical recovery.

Erin: With all that you know about traumatic brain injury, you bicycle in the Texas Medical Center. Do you ever think about the fact that you could injure your own brain?

Dr. Levin: It probably crosses my mind several times a week, and I try to be careful. I have to balance that against my enjoyment, exercise, and I have an excellent parking space free of charge. So, there are benefits but I have to be careful.

Erin: Thank you for tuning in to Body of Work by Baylor College of Medicine. If you enjoyed this episode, be sure to subscribe and be on the lookout for our next episode. If you like the show, please give us a five-star review and tell your friends to listen. We're available on Spotify, Apple Podcasts and Stitcher as well as at BCM.edu/podcast. There you can also find the episode notes including information about the experts featured on the show. A quick note about the medical advice and opinions stated in this podcast. Each individual's health profile is unique, so please see a health professional about any questions you may have. Until next time, take care.

Malcolm Brenner, M.D., Ph.D., is a professor of molecular and human genetics, pediatrics and medicine and Founding Director of the Center for Cell and Gene Therapy at Baylor College of Medicine. He is also a member of the Dan L Duncan Comprehensive Cancer Center.

See more of Dr. Brenner’s research:

Transcript

[Music]

Erin: Welcome to Body of Work, an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair, and my guest today is professor of genetics, medicine, and pediatrics, Dr. Malcolm Brenner.

Before we get into defining immunotherapy, can you explain the relationship between cancer and the immune system?

Dr. Brenner: Well, that's a very controversial question, and it's one that people have changed their minds about many times over the past years. Originally, people observed that individuals who had chronic irritation, like chimney sweeps, developed cancer at the sight of the inflammation. So there was an association made between the inflammatory response and cancer. Then subsequently, immunologists said that the immune system was able to act as a kind of surveillance mechanism, go around the body looking for cancerous cells. Cells that had abnormalities on their surface, or in their behavior, and picking out and destroying these cells, also called an immune surveillance. But for a long time that that theory was debunked, really. No very few, people came to believe it. But gradually, more and more immunology showed that cancer and the immune system could be very closely related, particularly with the discovery, for example, of virus-associated cancers. And as there was greater success I suppose in identifying the cellular mechanisms and the molecular mechanisms underlying cancer, and underlying the function of the immune system, investigators began to discover ways in which those two things could be connected, and show that the immune system did indeed have an important part to play potentially in the control and even the origin of cancer.

Erin: So how does immunotherapy work?

Dr. Brenner: The immunotherapy essentially is a way of targeting cancer. So most of the research on cancer therapy over the past few years has been into developing targeting mechanisms, whether that small molecules, or better radiation, or better surgery. And the immune system is a superb targeting system, it's what it's designed to do. And it has two major elements that can target cells and potentially recognize, discriminate, between normal and malignant cells. And one of those involves the production of soluble factors, like antibodies. And the other involves the direct activity of various different cell types that can recognize abnormalities on the cancer cell surface, and attack the cells that have those abnormalities.

Erin: How long has immunotherapy been used as a cancer treatment?

Dr. Brenner: Most people generally accept that the first true immunotherapy was well over a hundred years ago. It was William Coley, Memorial Hospital as that was, and he developed the so-called Coley's vaccine which was a mixture of different bacteria, and he'd inject the bacteria into patients with cancer. And there was no doubt that, a significant doubt, of the significant proportion of them had tumor responses, and some of them appear even to have been cured. It’s difficult to know exactly what cancers they had because of record-keeping at the time, but certainly there were responses. The problem was that it was a mixture of bacteria, lots of different bacteria. It was very difficult to get the same mixture every time, and the patients had to be injected on a regular basis. And one of the things that they had to have was quite a severe fever in order to see the response. So the patients fell ill for a considerable period of time, and gradually this group fell out of favor and was replaced by chemotherapy and by radiation, although it sort of made occasional comebacks. But after that time really, people developed approaches that were more readily reproducible, such as monoclonal antibodies, and more recently cell based therapies, in which we can predict with much greater accuracy how well and when they're going to work.

Erin: So what is monoclonal antibody?

Dr. Brenner: Monoclonal antibodies were first discovered where I did my Ph.D. in fact, in Cambridge. And they are antibodies that can be made with in almost unlimited quantities, from a single, originally from a single cell, which has made to multiply and produce these antibodies. A very defined specificity and very defined behavior, so you know exactly what they're recognizing, exactly how they're going to recognize it, and how much quantity you can produce from them. In other words, it's the exact opposite of what we talked about earlier. This Coley’s toxin which was a huge mix of different things that nobody could ever exactly replicate. So these are very specific very defined unlimited quantity antibodies and we can, therefore, work with them to show how best to administer them, and to make them as safe and effective as possible.

Erin: And what is the antibody action in the cell?

Dr. Brenner: The antibody recognizes structures on the surface of the cell. It binds to those structures, and then can either attract in other components of the immune system to kill that cell, or it can itself contain a poison that is taken up by the cell. A targeted drug in other words that it's taken up by the cell and specifically kills the cell to which it binds. And they can do both of those things it can have a drug attached to it and attract the immune system.

Erin: So what's the difference between immunotherapy and chemotherapy?

Dr. Brenner: Well immunotherapy is based essentially on the immune system, which is endogenous, it's within ourselves. Whereas chemotherapy is based on agents that come from outside ourselves, and capable of producing changes, potentially in all cell types, but which are targeted to particular molecular lesions or behavioral characteristics of the cancer. The immune system essentially recognizes structures on the cell surface, either external structures or internal structures, that have been taken out of the cell and pushed onto the cell surface, recognizes those patterns, if you like, as foreign and attacks the cells that bear them.

Erin: So are there any cancers for which immunotherapy has proven significantly more effective than earlier chemotherapy radiation surgery ways of treating them?

Dr. Brenner: I think there's no doubt that immunotherapy, for some cancers, can produce responses, and its long-term responses, where radiation and chemotherapy have failed. Examples include Hodgkin's disease, acute lymphoblastic leukemia, some lung cancers, and so on melanoma, but whether they can replace the other therapies is another question. At the moment these immunotherapies are very rarely frontline therapies. They’re mostly brought in as reserve therapies, but the other therapies have failed. Now if they can be brought into the frontline and shown to produce better, superior responses, superior survival, then yes they'll be better. But at the moment we can only say they can work even where other therapies have failed. that sort of sounds like a strange distinction, but I think it's an important one.

Erin: So when in treatment is immunotherapy generally introduced? Is it only after failure of the chemotherapy or radiation gradual?

Dr. Brenner: At the moment that's it's mostly a second, third, or fourth, or in one case in a series we've been doing 17th line of therapy.

Erin: 17th, wow.

Dr. Brenner: Yeah 17^th line, it’s been successful at that level. So as we get more know more about it and how successful it is and where it works, gradually it will be taken further back into being part of primary therapy. And that has already happened with monoclonal antibodies, which have been around a lot longer. For example there's a monoclonal antibody to malignancies of one cell type B cells lymphoma, in which the antibody is used as a part of the frontline therapy. But it's also combined with more conventional chemotherapy and/or radiation so it's not a complete replacement, it's an add-on. So I think that's what will be the pattern. We'll see these immunotherapies coming earlier and earlier in treatment, becoming a component of that early treatment, and gradually as we learn how to combine them, the different components the cell-based ones, the antibody-based ones, all the other ones, we’ll see it becoming more widely used.

Erin: Because of the memory of the immune system, is immunotherapy a more long-term solution to preventing recurring cancer?

Dr. Brenner: So one of the big advantages of cell-based therapy, not so much the antibody therapies, but of cell-based therapies is that many of the immune system cells have what you might call stemness. In other words they can be present essentially for patient’s life. Some of the very first patients we treated with cell-based therapies 30 years ago still got those same cells circulating. We can detect the genetic modifications we made to them to track them we can still see them 30 years later and they're still potentially protecting the patients from their cancer. So yeah in principle one cell one time could cure a patient for life.

Erin: Remarkable

Dr. Brenner: Yes, but its potential at the moment.

Erin: Are there different types of immunotherapy treatments better suited for treating different kinds of cancers? Does it depend on the patient are you still in a sort of mix-and-match combination?

Dr. Brenner: Yes, so for the moment the cell-based therapies have been probably most successful for blood cancers. Although, other some other cancers like melanoma, or cancer of the skin, and certain other ones have responded to cell therapies. Antibody therapies have been effective for some solid tumors or example HER-2 antibody very widely used as part of the treatment of breast cancer again, in combination with more conventional chemotherapy, and, or radiotherapy. And so I would say that for the moment immunotherapy has a most dominant place in the blood malignant sis lymphoma and leukemia, while antibodies have a broader place in the treatment I saw the tumors, but I think those will converge.

Erin: A friend of mine is preparing to have a bone marrow transplant. Is that a type of immunotherapy, or is that a different thing altogether?

Dr. Brenner: When bone marrow transplant was first mooted, and first implemented, the idea was that the patients would have very high dose chemotherapy and radiotherapy that would cure their cancer. But it was realized that at the same time that higher dose of drugs and radiation would destroy their normal bone marrow. So the idea originally was that the bone marrow would simply transplant, would simply be a rescue from the damaging consequences of the treatment. But as time went by, people realize that that wasn't the main mechanism by which benefit was produced. Instead it was what was called a graft versus leukemia, or graft versus cancer effect, where the incoming immune system from the donor recognized the cancerous cells, along with some of the normal cells in the recipient, as being foreign and rejected, killed them, eliminating the cancer. So the bone marrow transform probably works by combination of mechanisms by reducing the burden of tumor, and then by eliminating those that are left behind.

Erin: Chemotherapy is known to have some side effects hair lost, exhaustion. Are there adverse reactions associated with immunotherapy as well?

Dr. Brenner: I think every effective drug has adverse effects. With immunotherapy, they depend on the type of immunotherapy being used, and also what's being targeted, and what component of the body is being targeted. And some of the effects are due to damage to normal organs that are also attacked by the immune system, or by the treatment used. and some of the effects are due to the immune system itself getting overexcited when it's introduced into this environment kill tumor cells, and releasing products that cause inflammation, and so-called cytokine release syndromes, and brain toxicities, and various other complications that are slowly being overcome and resolved. But in general it's a very powerful system, and these off-target effects, and the effects of the immune system itself can be very devastating, and have to be controlled.

Erin: Could immunotherapy lead to some kind of an autoimmune disease in a patient?

Dr. Brenner: One of the big dangers of having an immune system that's been activated or over-activated is that it won't confine itself to attacking the malignant target. That it will start recognizing your normal tissues as being part of the disease and will produced this so-called graft versus host disease, in which it attacks normal components of the body and damages them. And after bone-marrow transplant, that was for many years a very feared complication. It damaged the skin, the gut, and the liver, sometimes the fatal consequences. Certainly we've been able to control that more, and we have many more tools to control it now, but it is still a risk, absolutely.

Erin: How affordable and available is immunotherapy at this point?

Dr. Brenner: One of the big problems with immunotherapy, certainly cell based immunotherapy, is the very high cost. Every drug has high cost of development because of the various rules and regulations that you have to go through. But once the development is over, then the drugs can be manufactured extremely cheaply, for a few fractions of a cent per dose. Well that's not what's charged to the patient of course, but that's the actual per item cost. The problem with cell therapies in particular is that they are very continued to be very expensive, and complicated to manufacture. Those sort of handcrafted or artisanal products rather than something you buy and that's mass-produced. It’s a three-star Michelin restaurant on McDonald's so to speak. The issue also is that they are given in a different way. Very few chemotherapy drugs are curative, and they have to be given over a long period. The hope with cell therapies, in particular, is that one dose one time is curative, as we mentioned earlier. And that means that the initial cost can be quite eye watering, and so more and more people are trying to work out ways of breaking down the cost over a period of time, so that you have a few like a reverse annuity. The longer you live, the more you pay, or that you only pay if the drug actually works. There’s various advantages and disadvantages to that and other models, but for the moment it's not that huge a problem because most these cell based therapies are confined two relatively uncommon diseases. But as they get to apply to much more common diseases, than these issues of cost and availability are going to become quite troubling.

Erin: What other diseases could be, or are currently being treated with immunotherapy besides cancer?

Dr. Brenner: There's a lot of interest in using monoclonal antibodies to do the opposite of what they're doing in in cancer therapy. In other words, using them to lock immune attack and to minimize the immune response. So for autoimmune diseases and for inflammatory diseases, like Crohn's disease and other inflammatory bowel diseases, monoclonal antibodies and rheumatoid arthritis, monoclonal antibodies are proving extremely useful. And I think almost certainly, the same will be true once we can invert the findings we have for cancer with the cell therapies that we'll be able to develop cells that can inhibit these autoimmune attacks, and prevent inflammatory disorders, and autoimmune disease. And that, of course, opens up a much wider spectrum of disorders because there are probably many diseases, degenerative diseases, that have a significant component of information and an immune response within them, and being able to deal with those will be very important. All the more reason to get the costs down.

Erin: So what's next for immunotherapy?

Dr. Brenner: I think the main increase in interest now is in applying these to a broader range of cell therapies, and antibodies to a broad range of solid malignancies, solid tumors rather than the blood cancers. And the second big push, I would say at the moment, is to make these products off the shelf. So instead of having to make an individual product for each individual patient-

Erin: Artisanally?

Dr. Brenner: Artisanally, exactly, you can have a bulk product, freeze it down, and then use them when you need it. You take it out of the freezer and inject it immediately into the patient. And there are huge resources going into this, in part because it's much easier to scale, and in part also because then become this prohibitive.

Erin: Could you talk a bit about your own research?

Dr. Brenner: Yes, so we're interested in really in moving cell therapies into additional blood cancers, and we're treating now t-cell malignancies with some very promising results, and a disease called Hodgkin's lymphoma, again with very promising results, and these are some of the patients who really have failed every other therapy, multiple different types of therapy. We’re also pushing to treat solid tumors more effectively, and the way that we're trying to do that is to make use of the immune system's ability to recognize virus infections. That’s really, probably, what its primary purpose is. So what we do is we take a virus, and we modify it so that will only grow within malignant cells. And we inject that virus into the malignant cells, and we put within that virus, a kind of reverse Trojan horse. So a kind of signal that attracts the immune system into the tumor, and helps remove virus infected cells. But at the same time, because the virus doesn't get into every tumor cell, we recruit in a whole range of different immune cells that can recognize other abnormalities on the tumor, even if they're not infected by viruses, and start to attack them and destroy them. And we can do this very successfully in animal models, and we are a launching now, or in the middle of launching, a clinical study of this within the next six months. The danger of it, of course, will be that we do too much as we were discussing earlier, and start to get autoimmunity. But we're hoping, and certainly the animal models suggest, that there's a gap between enough immune activity to kill cancer, and so much immune activity that you get autoimmunity. So we want to identify and exploit that sweet spot.

Erin: Are there any particular solid cancer solid tumors that you're focusing on right now?

Dr. Brenner: Well we're going to start with head and neck, cancers of the cervix, and cancers also of the lung.

Erin: So at least some of those are ones that do have a viral component to them?

Dr. Brenner: And some of those do, you're right. Some of are already got potentially viral tumors, some of them have papillomavirus in them. So we hope that that will help us along, give us a double dose of virus as it were.

Erin: It's really exciting. I am sure that all the people who have cancer, had a family with cancer, are following these remarkable accomplishments, and steps forward and immunotherapy with a lot of interest.

Dr. Brenner: Yes it's been a long time. I've been one of the few people who's lasted the course, really. I started doing immunotherapy of cancer in about early 1980s. And it's been a long road. I remember when we were always confined to the very last session, of the very last day, at any meeting on cancer therapy, and now, of course, we sort of front-and-center. I think it is going to be continued to be a long road, but we are at least somewhere along it, and we are beginning to see some very nice results.

[Music]

Erin: Thank you for tuning in to Body of Work, by Baylor College of Medicine. If you enjoyed this episode, be sure to subscribe and be on the lookout for our next episode. If you like the show, please give us a five star review and tell your friends to listen. We're available on Spotify, Apple podcast, and Stitcher, as well as at BCM dot edu slash podcast. There you can also find the episode notes, including information about the experts featured on the show.

A quick note about the medical advice and opinions stated in this podcast, each individual's health profile is unique, so please see a health professional about any questions you may have. Until next time, take care.

Sharmila Anandasabapathy, M.D., is a professor of medicine in gastroenterology and director of Baylor Global Health at Baylor College of Medicine. She is also a member of the Dan L Duncan Comprehensive Cancer Center. An advanced gastrointestinal endoscopist by training, Dr. Anandasabapathy’s research focuses on developing new technologies for the diagnosis of early gastrointestinal cancer.

Learn more about Baylor Global Health.

See below for more of Dr. Anandasabapathy’s research:

Transcript

[Music]

Erin: Welcome to Body of Work, an exploration of health topics in the news and important issues facing science, with experts from Baylor College of Medicine. I'm Erin Blair, and my guest today is the director of Baylor Global Health Dr. Sharmila Anandasabapathy.

So what diseases are of the most global concern?

Dr. Anandasabapathy: So, the diseases that are of the most concern worldwide, right now, are what we call non-communicable diseases. So cardiovascular disease, heart disease, stroke, cancer, followed closely by neurodegenerative diseases. These are Alzheimer's, and other related dementias, diabetes. This doesn't mean that infectious diseases, or the communicable diseases, are not important. We still have tuberculosis, aids, and malaria, particularly in low-income countries, but they're rapidly being overtaken worldwide by these non-communicable diseases and diseases of our lifestyle, basically in the aging population. Now, unfortunately, countries within sub-Saharan Africa see a dual burden of disease, so they're still seeing high rates of HIV, and malaria, and of course we know there's an Ebola epidemic recently, but the leading cause of death worldwide over the next two decades will actually be cancer, and stage by stage mortality rates are higher in low-income countries, so this is really the big disease to be concerned about globally.

Erin: Why should we think about health on a global scale?

Dr. Anandasabapathy: So, today, we are truly one world, and I don't mean this as a platitude. It's not kumbaya, you know around the campfire, but literally from a healthcare perspective, we are one world, and this is directly a result of industrialization and globalization. We are deeply interconnected worldwide, so think of it food, especially with fast food going into these remote regions, is on a global scale. The internet, which has an effect on lifestyle and habits worldwide, and of course air travel right. The net result is that diseases that affect us, affect others, particularly our lifestyle-related diseases, diabetes, heart disease, lung cancer, and diseases that affect others affect us, and we often are surprised by this, but if you recall the 2014 Ebola epidemic came to Dallas. So, I think we should be concerned about other parts of the world, and we should be interested in diseases of other areas.

Erin: Can we use global health strategies to overcome some of America's homegrown challenges?

Dr. Anandasabapathy: Oh, absolutely, and we found that this happens often unexpectedly. I love to tell my students, you know, that necessity is the mother of invention right, and what this means is that when you have a lot, there's less need to be creative when you have little or nothing you are forced to innovate. So this is why many low-income countries are leapfrogging ahead in health care innovation, both in terms of technologies, physical technologies, such as mobile technologies both for diagnosis, and providing care, and their approaches. So they don't rely on traditional models, where a patient comes in to a hospital to see a doctor, but they're looking at more innovative methods of delivery into the community, often leveraging software for remote consultation, or even apps, where patients and families can directly manage their care and of course the big driver and this is cost. It almost always is right; in the US, we spend about $9,000 a year per person or more on health care. In sub-Saharan Africa, this is closer to $200 per patient. Austerity forces transformative approaches, and I'm not saying it's good to be under-resourced, rather that we could all be more cost-conscious and creative.

Erin: Why do you think so many global health solutions are developed in the form of technology?

Dr. Anandasabapathy: Well, if we've learned anything this past century, you never bet against technology right, but I do believe that this is both need and market-driven. We have an aging population, an increased onset of chronic disease, as we talked about, and we're lucky actually that there's a lot of ingenious tools and technologies that are emerging, often at a lower price point. I do think the challenge never really is technology. Technology advances, technology is continually innovated; it's often the implementation. So how do you get doctors, nurses, healthcare workers, the medical establishment to accept new tools and approaches and then utilize them safely, consistently, effectively? They're often, you know, several P's, if we use the letter P in terms of thinking about technology innovation, one is the person, you know who is using the technology, the provider, we need to think about who that is. Is it a community health worker, is it a nurse, is it a physician, so we have to target the technology to that person. And then who is the technology being used for in the patient, what is the language the literacy level, their cultural understanding, and or bias their acceptance of the technology, and then of course the place, where is it being used, and what are the challenges, their power supply, water, infrastructure. These are all things that lead to either the success or failure of a technology

Erin: What are some of the new innovations coming out of Baylor Global Health?

Dr. Anandasabapathy: So you must have heard about the smart pod?

Erin: Oh, yes.

Dr. Anandasabapathy: Everyone's talking about the smartphone. Well the smart pod is a great example of a technology that was developed for West Africa during the 2014 Ebola epidemic, but then as we learned, has tremendous applications in the US as well, and the smart pot itself is an 8 by 20 shipping container that expands within about five minutes, with four people, into a four hundred square-foot clinic. And we have deployed a clinic to Monrovia Liberia, where it's being used in Ebola patients and subsequently, we built two laboratories a biosafety level two lab, and a biosafety level three lab, as well as a pharmacy and those, are in the field in West Africa as well, and this was a really interesting challenge in term of understanding the landscape in West Africa. For one, we started out with a standard steel shipping container, and then we realized that the roads there couldn't handle the weight of the steel, and because bleach was being used for Eboli, would corrode. So we had to switch to an aluminum structure that was lighter weight. In addition, we thought we were helping the healthcare workers by providing air conditioning and all of these you know kind of first world advantages, and then we turned out the patients didn't like that, so he had to redesign it, so the doors were apart to allow cross ventilation. The idea of privacy in that culture; not only was it less of an issue; the patients wanted to be able to see their family members. So we had to think about where we were replacing windows to allow visual access at least. And lastly, we had to provide support for the doctors, nurses, and healthcare workers that were using the unit's by providing software and apps using figures and graphics, rather than language for guiding them on the procedures. And so this was a really important case example for us on developing a technology for one part of the world. It worked in Africa, which was great, and in when hurricane Harvey hit Houston, we realized that there may be a need for these types of technologies in the United States. So now we're looking at applying that model for healthcare here in Houston, which is really exciting.

Erin: What about telemedicine? I would think that would be a useful application in a remote location?

Dr. Anandasabapathy: So, one of the greatest advantages of being in Houston, I think, is being close to the Johnson Space Center in NASA, and they actually helped us, their engineers helped us with the volumetric modeling for our units that went to Africa. We took a cue from them in terms of remote medical management to support healthcare workers in the field. So we've been looking both at what we call tell a guidance, using augmented reality to guide a physician or healthcare worker through a procedure, or a laboratory procedure, in a hands-free fashion. So you can see the guidance on the augmented reality glasses, and then perform the procedure hands-free, and then we are also working with them on the development of apps for assistance in the field in real-time and training. And some of these can either be used on a cell phone or using virtual reality glasses if you need a more immersive experience.

Erin: It seems like NASA would have a lot of commonality with a lot of the problems that you see in under-resourced parts of the world.

Dr. Anandasabapathy: Well, they have to work in the most austere inhospitable under-resourced environment known to mankind, right? So ya know it's been a unique opportunity to have them close by

Erin: How does computer-assisted diagnosis work?

Dr. Anandasabapathy: So, this gets to the concept of autonomous medicine. When we have to practice medicine in an area that has no support, so either the remotest part of Africa or you know for NASA, Mars right. So we've used this actually for gastrointestinal cancer screening. I'm a gastroenterologist, and if you think about how cancer screening is done in the United States, it'll give you a sense of all of the things that can go wrong when you do this in a more austere environment. So what do I do when I look for esophageal cancer in a patient? I have to insert a scope in a patient that's asleep. I have to image the esophagus, and I've had to have you know over a decade of clinical training to learn what abnormal looks like. When I see tissue that is abnormal, I have to take a biopsy, and my technician needs to know how to assist with it and remove that biopsy. That biopsy has to get processed in a laboratory, sent to a pathologist, the pathologist has to provide a diagnosis, get back to the doctor, the doctor has to get back to the patient with a diagnosis, and the patient has to come back and if it requires treatment. So let's change that paradigm, let's talk about a portable tablet-based endoscope that perhaps, provides the diagnosis. Well, what if your scope was attached to a tablet computer, and the scope was portable and battery-operated, perhaps smaller, perhaps it could be inserted easily by a non-gastroenterologist. Perhaps even a non-physician in a patient that didn't need to be asleep, and what if the scope was powered by and connected to a tablet computer, or even a cell phone, and that tablet computer or cell phone could not only obtain the images but store the images and analyze the images, using software algorithms, effectively a computer-assisted diagnosis. And then what if you didn't need to take that piece of tissue because the computer was providing you the diagnosis, so you could basically obtain, in real-time, in the field, an optical biopsy and then treat the patient immediately if they needed it, or tell them that they were cancer-free at the time. So what have we done by changing this paradigm? We've reduced the cost, we've increased the impact, we potentially improved outcomes from loss of follow-up, and this can really provide a transformative effect on medical care. In the areas of the world that we worked in which include Africa northern China South and Central America, we've found that over 25% of patients who we do endoscopy on, once they go home often to remote or rural areas, they don't return for follow-up and this is a huge problem with cancer care, because if you find something and you can't treat it, you can imagine the devastating effect of this. So currently we've been doing clinical trials in the areas that I've mentioned working with Dr. Rebecca Richards-Kortum and her engineers at Rice, and we've enrolled over 1,000 patients worldwide looking at this tablet-based a portable endoscopic approach.

Erin: Have you been involved with maternal and child health initiatives as well?

Dr. Anandasabapathy: Yeah, this is something that's really important to us because one of the leading causes of mortality and women worldwide, particularly in low-income countries is childbirth, and it really shouldn't be a cause of death in this day. And so we're looking actually at the approach we mentioned which addresses both the infrastructure by provision of our off-grid pods for labor, and delivery, and the performance of C-section. Then also providing training via apps virtual reality and augmented reality guidance to nurse midwives and physicians in the field.

Erin: How do physicians and their health care workers in the field respond to a sort of a virtual reality training session?

Dr. Anandasabapathy: That's a great question. You would think they would be deeply skeptical, some are, but I find the skeptics are actually more in the United States. What we've actually found, and we've actually done some studies looking at acceptance of these types of technologies, what we found is really surprising. In areas of the world, such as sub-Saharan Africa and most recently we're working in Liberia where our pods are. We found that the healthcare workers were very responsive to anything that used cell phones. Our augmented reality, with the use of cell phones, and it's simply because cell phones are so pervasive and people are fairly comfortable with mobile technologies, and when you have nothing else, it can be a lifeline for many people. So we were actually surprised on how accepting the providers are in those settings.

Erin: Well, and as you say the technology is just leapfrogged there, you didn't go through the period of landlines. They just went directly to the cell phones.

Dr. Anandasabapathy: That's exactly right.

Erin: When we think of global health, we think of lack of basic resources like electricity, Wi-Fi, and water, how do you mitigate those issues when developing technologies?

Dr. Anandasabapathy: Yeah, so I mentioned that I often think about the letter P, and when we talk about the success of a technology, and so that really gets to the issue of P for place right. So think about the environment you're working in. If there's no power grid, you need to think about solar or hybrid generators, battery backup, and if there's no water supply, you have to think about using the existing water that you have, if it's from river, lake, or a stream, or rainwater, and using filtration systems. And we can't do all of this at Baylor global, so it brings us to another P which is partnerships. So we partner with others in this space, and there are a lot of groups that are coming up with really innovative batteries, which can increase capacity for storage of electricity, and also innovative water filtration systems, so that you can have an autonomous water supply in these settings.

Erin: In medical technology development, what separates a cool idea from an innovation that is sustainable and effective?

Dr. Anandasabapathy: So, what separates a cool idea from an innovation that's sustainable and effective is really how it's implemented and scaled right. So cool ideas abound, but sometimes that cool idea may not be acceptable in that culture. It may not work in that environment, and it may not have a plan for scale-up and dissemination, which includes financing, delivery mechanism, supply chain, and lastly, education is so critical. If we can't train health care workers on how to use the technology safely, effectively, then your technology is not useful. And Baylor in medical school and I believe this is where we can make the biggest difference, in terms of educating the healthcare workforce globally, and you partner that capability with engineers with business schools, who can assist with financing and delivery mechanisms, and I think it's a very powerful combination and so the most impactful approach is not incremental, it's transformative. It understands the people in the setting where it's being used, whether it's the provider or the patient. It understands the environment and the limitation, and it has the ability to be spread, get used around the world scaled up and able to access different areas.

Erin: I understand that it's a common practice for hospitals to donate their slightly older technology to the developing world are there any issues with that?

Dr. Anandasabapathy: I think this is one of the biggest issues that exists in global health. Donations abound, and I think it's wonderful that people are generous, but when we think specifically about donations of equipment or technology, we really have to make sure they're appropriate for that environment and one of the things that has always saddened me, when we work in many of these settings, are these equipment graveyards. Where you'll see a three Tesla MRI scanner, that was donated by a government that is basically sitting in the basement of a hospital, or outside in a courtyard broken and not functioning. And this is because either the power requirements were not appropriate for that area. There was nobody there to repair it, or it required so much support and maintenance that that was not feasible in that setting. So I think we need to think very hard about what types of technologies that we're putting in an area who the user is and what the capability is for both for maintenance, and then repair.

Erin: What's next for global health?

Dr. Anandasabapathy: That's my favorite question. So after Hurricane Harvey, we realized as a program, that global can be local, and there may be need for some of these approaches in the United States, especially after catastrophic natural disasters, such as the hurricane. And then you remember Star Trek right, space the final frontier. So the next few decades, I believe that global health will be galactic health. The next place we will be screening or treating cancer may be outside of Earth's orbit, and I, for one, would love to perform the next portable tablet endoscopy on Mars.

Erin: That would be cool.

[Music]

If you like the show, please give us a five-star review and tell your friends to listen. We're available on Spotify, Apple podcast, and Stitcher, as well as at BCM dot edu slash podcast. There you can find the episode notes, including information about the experts featured on the show. A quick note about the medical advice and opinions stated in this podcast, each individual's health profile is unique, so please see a health care professional about any questions you may have. Until next time, take care.

Peter Jay Hotez, M.D., Ph.D., is the founding dean for the National School of Tropical Medicine at Baylor College of Medicine. He is also a professor in the departments of pediatrics and molecular virology & microbiology. He is a health policy scholar in Baylor’s Center for Medical Ethics and Health Policy and co-director of the Texas Children’s Hospital Center for Vaccine Development.

Learn more about the National School of Tropical Medicine at Baylor College of Medicine.

For links referenced in this episode:

Transcript

[Intro Music]

Let's just get right down to brass tacks. How do vaccines for infectious diseases work?

Dr. Hotez: Well, vaccines work by stimulating the immune system to produce either antibodies or immune cells in order to fight infection. So let me give you an example: the polio vaccine. The polio vaccine is made by either working with the actual poliovirus that's either inactivated or killed using various substances or passage several times through cells in the laboratory in order to weaken it. So that when an individual gets the polio vaccine, they're getting a weakened version of the virus or a killed version of the virus that stimulates an immune response, but it protects you against getting real polio as you go about your day to day activities. Same with the measles virus vaccine. So the measles virus is one of the great killers of children globally. At one time, 2.6 million children died every year of measles. The virus was weakened in the laboratory, and then you administer that weakened virus, so you don't actually get measles, but it protects you from getting measles in the future. Then there are other vaccines that work, either they're developed through genetic engineering, like some of the vaccines we're developing. Our recombinant protein vaccines done through engineering, so it codes a part of the organism. So the bottom line is vaccines are either the entire organism that's weakened or killed or a part of the organism that then stimulate an immune response and prevent you from getting infected.

Erin: How do vaccines work on a community level?

Dr. Hotez: Well, what happens is if you vaccinate large populations at the same time, you can actually interrupt transmission of the disease. So for instance, with the measles vaccine, and today we combine the measles vaccine with the mumps vaccine and the rubella vaccine, that's why we call it MMR. That MMR vaccine, if given to more than 90 or 95 percent of the population, will actually stop the possibility of any transmission of real measles virus circulating in the community. Sometimes we refer to this as herd immunity and it's very effective it also means though that if you want to stop these diseases from returning, you know we eliminated measles in the year 2000, if you want to stop it from returning, we have to have 90 to 95 percent of the local population vaccinated, and that's why measles now is come back in 2019. We've had more than a thousand measles cases in America. It's because we have large pockets in the United States now where significant numbers of kids are not getting their MMR vaccine, and that leaves an opening for the real measles virus to come back.

Erin: So we don't have the whole herd protected?

Dr. Hotez: That's right, so nationally we're still doing pretty well, but in places such as Brooklyn, New York, or in Portland, Oregon, or even some cities here in Texas, such as Austin, and Plano Texas, we have significant pockets where there's measles, either has come back, or there's a high likelihood it will come back.

Erin: How has the advent of vaccines changed healthcare in America?

Dr. Hotez: Well, it's made us less fearful of deadly infectious diseases. So for instance, if you were a parent in the United States in the late 1940s, early 1950s, we had terrible polio epidemics in our cities every summer because the poliovirus thrives most in the summer, so that parents lived in fear that their children would become paralyzed or even die from polio. And now parents no longer have to live with that fear. So our modern vaccines really came online, beginning in the late 50s, and going into the 60s, 70s, and 80s, and 90s, and now we have several vaccines so that parents no longer have to worry about their children dying of these diseases. I'll give you a very personal example when I was a pediatric house officer, a resident in Boston, I was on the children's service of the Massachusetts General Hospital. We were admitting a child every couple of weeks with a devastating infection called H flu meningitis, haemophilus influenza type B meningitis. It has the word influenza in it because back in 1918 when during the flu pandemic people erroneously thought that bacteria was the cause of flu. It wasn't, but the name stuck instead it causes a terrible form of meningitis and, I would as a pediatric resident, I would admit a child every two weeks to my service with that devastating disease, and some children actually perished, they died. Others were permanently injured with neurologic injury, like deafness. It was really devastating and took a big emotional toll, not only on the families but also the house staff as well. And that was in the late 1980s, but then the new vaccine came online, the H flu vaccine called the HIB vaccine, H I B, and as a consequence of that, the disease disappeared from the United States so that by the time I was a young assistant professor of pediatrics in the Yale University School of Medicine, the disease was no longer around. So I would teach the next generation of house staff pediatric residents about HIB disease purely for historic interests, just like the old timers would talk to me at Mass General about diphtheria and tetanus, I could tell them the same tales about HIB disease, that that's the power of the vaccine.

Erin: It's remarkable. Has that same sort of effect been seen on a global level?

Dr. Hotez: Absolutely, so the big push really started in the year 2000 when new organizations were created, including the Bill and Melinda Gates Foundation, and their big first tranche of money, 750 million dollars, went towards forming what's known as GAVI, the Global Alliance for Vaccines and Immunization. And the idea was we could do better vaccinating the world's children against diseases like HIB, and measles, and diphtheria, and polio, and at the same time introduced two new vaccines for rotavirus infection and pneumococcal pneumonia and meningitis. And we've made great strides, great progress, so now what we've seen is at that time in 2000, roughly half a million kids were dying every year of measles. For the first time in 2017, it decreased below a hundred thousand. So still, a lot of kids dying but you know eighty-ninety percent reductions and deaths from diseases like measles and HIB and pertussis which is whooping cough, so that's of tremendous excitement.

Erin: You founded the National School of Tropical Medicine at Baylor College of Medicine. What constitutes a neglected tropical disease?

Dr. Hotez: So the term neglected tropical diseases, or NTD's, is a term that we help shape, coin, and shape the framework for in the early 2000s, and it had to do with the fact that there was a lot of excitement because of GAVI for childhood infections as well as some other diseases like HIV/AIDS, and malaria, but there was a whole group of other infectious diseases that literally got named "other diseases" as part of the U.N. Millennium Development Goals and having something called "other diseases" was a non-starter. Nobody was going to get very excited, so a group of us who worked on chronic and debilitating parasitic diseases like hook worm infection, and schistosomiasis, and leishmaniosis, and Chagas disease got together and went about and did a branding exercise called the neglected tropical diseases and we came down, a group of us came down from Washington D.C. to Houston to Baylor College of Medicine to form a whole school around these poverty related diseases. And it's called the National School of Tropical Medicine, which is pioneering innovations for these diseases with a big focus on developing vaccines. Because these are poverty related diseases - they only occur among the world's poorest people, you can't make money on these vaccines, so there was no point in trying to create a company around it. So we're doing it in the nonprofit sector, funded by external grants, and now we've advanced several vaccines into clinical trials for neglected tropical diseases, where we're quite excited about that.

Erin: Are there neglected tropical diseases in the United States?

Dr. Hotez: Yeah, absolutely. We first looked at this framework of neglected tropical diseases. The focus was very much Africa, Asia and the poorest parts of Latin America, but then by moving to Houston in Texas, we started looking around and found a depth and breadth of poverty here that we never knew existed. And one of the things that I've learned over the years, wherever there's extreme poverty, you find neglected tropical diseases. We began to look with our faculty, and what we have found is impressive. We have found the transmission of Chagas disease, which is a parasitic infection of the heart. We found viruses transmitted by mosquito, as everyone knows about West Nile virus infection, but we have dengue fever transmission in Texas, as well as even some Zika transmission in 2016 and 2017. We have typhus, which is serious, and Rickettsia L infection transmitted by fleas, we have parasitic worm infection - so the point being we made the case that Texas is actually a disease endemic country because we have the confluence of a number of factors that help neglected tropical diseases emerge everywhere, so we have the confluence of extreme poverty and low-quality housing and lack of access to good, clean water, or sanitary services, but also climate change is affecting our state together with human migrations and of aggressive urbanization, and all of those are creating the perfect storm to allow neglected tropical diseases to form. So we've actually now have taken on one of these here in Texas for a vaccine. So we're developing now a vaccine for Chagas disease. This is a done a partnership with my long-term collaborator Maria Elena Bottazzi, who’s also a professor of the National School of Tropical Medicine and the associate dean of our school.

Erin: What happens when a new outbreak comes on the scene - an Ebola virus, Zika?

Dr. Hotez: Well you know, what happens when a new pathogen is introduced to a community is, in many cases they've never experienced disease with that pathogen before, so there is what's said to be immunologically naïve, they have no antibodies or other immune defenses against those organisms ,and they can spread through a community very quickly. We saw this with Zika in 2016 in the Western Hemisphere, where Zika affected large segments of the population in Brazil and then it moved up into Venezuela and Colombia, into Central America, and then into the Caribbean so that island of Puerto Rico got hit very hard with Zika virus infection and it caused a not only debilitating illness, but also birth defects as well. And so we saw lots of babies born with congenital Zika syndrome which includes small head microcephaly, and it's a very devastating condition. So there was a lot of worry that South Texas and South Florida were vulnerable because of that confluence of the things we're talking about, poverty and climate change and human migrations, and sure enough, we did have some Zika transmission in South Texas. Not as bad as we had feared, but we'll see, Zika still could come back.

Erin: How are new vaccines for new diseases developed?

Dr. Hotez: Well we go through quite a lengthy process, and one of the unique features about our vaccine center at the National School of Tropical Medicine, and it's done as a partnership with Texas Children's Hospital - we call it the Texas Children's Center for Vaccine Development - is we’ll often take a vaccine all the way from discovery through scale-up process development and manufacture. We then to shepherd the vaccine along for what's called toxicology testing and moving it into the clinic by filing an Investigational New Drug application with the Food and Drug Administration an IND, and then getting permission to move into clinical trials and we'll take it through clinical trials as well. So it's a unique facility especially for an academic health center, not many academic health centers have the ability to translate, and that's the term that's often used now, to translate a molecule or a vaccine all the way from discovery into clinical development, so we're very excited about that.

Erin: How is vaccine science adapting and innovating for the future?

Dr. Hotez: Well, there's a few things that have to happen. One of the problems are the timelines are long, right? So, for instance, the hookworm vaccine that is now in clinical trials in Africa and Latin America, I started working on that vaccine as an M.D./Ph.D. student in 1980s, so these are biblical time frames right, and it could be 30 years. The schistosomiasis vaccine was a little faster, we started working that in the early 2000s. So there's a need for innovation to streamline the development, but it's not easy because remember how vaccines work, we're often immunizing well individuals to prevent them from getting these infections, so the safety bar has to be very high and pristine. And so these vaccines have to go through a lot of safety testing, first in preclinical laboratory animal models, and then the slowly graded clinical trials phase 1, phase 2 phase 3. That's why I'm often aghast when I hear the anti-vaccine lobby claim that vaccines are not adequately safety tested. These products are the most extensively safety tested pharmaceuticals on the planet, often taking decades of clinical testing, but we're trying to now look at some cutting-edge biotechnologies and apply them to our neglected disease pathogens for purposes of vaccine development, and a lot of that work is going on here at Baylor College of Medicine - things like single-cell RNA sequencing, or systems biology, or gene editing. And so we're trying to apply all those technologies to our vaccines, but we also need innovation, and how we do clinical testing to maybe do more things in parallel, so we don't have this decade, several decades, of clinical testing we could streamline that down a few years.

Erin: Why are outbreaks of nearly eradicated diseases taking place in 2019?

Dr. Hotez: So, isn't it terrible? We've seen now the return of measles in 2019, and we know why. This is happening because there's been decline, local declines, in vaccine coverage in many counties in the U.S. So measles is often the first one to come back, because it's most highly transmissible of the viruses that we know about. It has what's called a reproductive number of 12 to 18. That means if a single individual has measles, on average 12 to 18 other people will get it, particularly infants under the age of 12 months, not yet old enough to get vaccinated. And that happens because the virus lingers in the atmosphere and lives on surfaces. So it's very easy to acquire measles, and now measles is back in the United States. We eliminated it in 2000, and we're going on 20 years and now we've had more than a thousand cases, so that's very discouraging, and it's happened number one due to declines in local vaccine coverage, and that in turn has happened because of the rise of a very aggressive, well organized, and well-funded anti-vaccine movement that we now have here in the United States, that's convinced parents that vaccines cause autism and other things which is absolutely not true. But what the anti-vaccine lobby has done is to create an impressive, in a bad sense, misinformation campaign. So we have this tragic situation now in the state of Texas where there's over sixty thousand kids not getting their vaccines, and so it's only a matter of time before we, our state, suffers from measles outbreak just like we've seen in New York State this year, and in Washington State earlier this year.

Erin: Your most recent book "Vaccines did not Cause Rachel's Autism," draws on your personal life and your connection to current misconceptions about vaccines. Can you tell us more about that?

Dr. Hotez: Sure, and I wrote the book in part because of what I saw happening in Texas with this dramatic rise and the number of kids not getting their vaccines. I'm a vaccine scientist and pediatrician, but I'm also, along with my wife, a parent of four adult children including Rachel, who is 26 years old and has autism and number of intellectual disabilities. And because the anti-vaccine lobby centers their misinformation around the phony claim that vaccines cause autism, I felt that I was perfectly positioned to stand up to this and wrote the book. Vaccines Did Not Cause Rachel's Autism came out late last year, published by Johns Hopkins University Press, and what it does is it goes into some detail explaining the evidence showing there's absolutely no link between vaccines and autism, but also explaining what autism is, and how we have identified more than 99 genes involved in early fetal brain development that are linked to autism. And one of the things that we were able to do here at Baylor College of Medicine with the excellent Genetics department here, is do whole exome sequencing, and Rachel and my wife and I, we were able to identify one of those genes. So it's very powerful technology. The point being, these processes that result in autism are happening in early fetal brain development, well before kids ever see vaccines. So the book really explains the evidence not only that vaccines don't cause autism, but the lack of plausibility because of the fact that autism is already underway in pregnancy well before kids are ever vaccinated.

Erin: Why do you think there is such distrust between the scientific community and the lay population when it comes to vaccines?

Dr. Hotez: Well you know, we've got a situation that, part of the reason why the anti-vaccine movement is allowed to gain ascendancy is because they're running unopposed. The scientific community has been mostly invisible or silent. That's the reason why I wrote the book, and one of the things I realized, both working on the book and being out there in the public defending vaccines, is that we don't hear from our scientists. That the scientific community is very focused on writing and speaking for each other and focusing on grants, and papers, and laboratory meetings, that we no longer see public engagement as a worthwhile activity or we don't even know how to start engaging the public. And I don't have a lot of evidence to support it but there are some interesting studies like that one done by the Research America policy group think tank in Washington that finds that 81% of Americans cannot name a living scientist. And so essentially, the American public has really no idea of what we do, and what our activities are like, and I'll partly blame our profession on that. We're too inward looking, and we don't see public engagement as a vital activity. So I've been writing and speaking about the importance of building in science communication into Ph.D. training, building health communication into medical training both at the doctoral level and the postdoctoral residency level. We've got to figure out how to turn this around and get the scientific community out there and engage so that people recognize scientists and so scientists again become a household term.

Erin: Almost having to reclaim your authority, redevelop confidence in the public.

Dr. Hotez: That absolutely right because right now, the public has no role models to identify. When was the last time you saw a scientist on cable news, or you know really profiled in the media? I mean, I think Baylor College of Medicine does a pretty good job getting our scientists out there, but we don't have the bandwidth needed to really match the bandwidth of this very aggressive, well-oiled, anti-vaccine lobby, and its 500 websites all amplified on social media and e-commerce platforms.

Erin: What questions should people ask their healthcare providers when it comes to vaccines?

Dr. Hotez: Well, I think it's important to remember that you have an expert in your community. That expert’s called your pediatrician. Pediatricians spend a lot of their training learning about vaccines, how to administer vaccines, how to use vaccines, how to schedule vaccines, and so take advantage of having a pediatrician in your community and have that conversation with them. There's certainly other sources of vaccine information. The CDC website, the Centers for Disease Control website, has got some good information, but the problem is it's a little hard to mine. It's a very dense website. I think that's one of the other lessons that we're seeing from this aggressive rise of the anti-vaccine movement, that we don't have easy to deliver information for parents. That's one of the reasons that I also in the book, in the epilogue of the book, I list the major phony assertions of the anti-vaccine lobby and talking points to provide the quick-time the information needed to counter the misinformation.

We seem to be losing the battle against this anti-vaccine lobby, and I think we've now got to take steps to counter it, and I have a few ideas of what I think we need to do. I think, for instance in states like Texas, we have to close vaccine loopholes. Right now if you're a parent, you can opt your kid out of getting vaccinated for reasons of personal or philosophical belief. I'd like to shut that down. I'd like to make vaccines compulsory if you want to send your child to public school. In the past, your child had to be vaccinated, I'd like to bring that back, here as well as in the 18 other states that allow non-medical exemptions for reasons of personal or philosophical belief. This was done in California. California allowed vaccine exemptions, they had a horrific measles epidemic in 2014-2015, the California Legislature said we're not going to do this anymore and they shut down the non-medical vaccine exemptions. We need to do the same in Texas, as well as a number of other states in the U.S. But that's not going to win hearts and minds, so we're going to have to figure out, one how to rebuild a system of robust vaccine advocacy in this country, but at the same time we have to dismantle a lot of the misinformation. So it'll take time, but I think it's doable. I think we can bring us back to the old normal. So the new normal is our parents aren't vaccinating their kids, we've got to flip that around, go back to the future as they say, and make vaccinations the new normal again.

[Music]

Erin: Thank you for tuning into Body of Work by Baylor College of Medicine. If you enjoyed this episode, be sure to subscribe, and be on the lookout for our next episode, where we'll talk with Dr. Sharmila Anandasabapathy about how technology is changing global health.

If you like the show, please give us a five-star review and tell your friends to listen. We're available on Spotify, Apple Podcast, and Stitcher, as well as at bcm.edu/podcast. There, you can find the episode notes, including information about the experts featured on the show. A quick note about the medical advice and opinions stated in this podcast: each individual's health profile is unique, so please see a health care professional about any questions you may have. Until next time, take care.

Todd Rosengart, M.D., is professor and chair of the department of surgery and a professor of molecular and cellular biology at Baylor College of Medicine. He is also a professor of heart and vascular disease at the Texas Heart Institute and current president of the national Society of Surgical Chairs.

See more information on the Michael E. DeBakey Department of Surgery at Baylor College of Medicine.

See below for more of Dr. Rosengart’s research:

Transcript

[Music]

Erin: Welcome to Body of Work, an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair, and my guest today is cardiovascular surgeon and surgical chair, Dr. Todd Rosengart.

How is the age demographic of physicians changing?

Dr. Rosengart: Well, it's an important issue at the age demographic is actually going to create a significant burden on the healthcare delivery in the United States. A number of, an increasing number of surgeons and physicians overall, are reaching the age where they're going to be functioning as physicians who are 60 years and older. The number right now is about 25,000, and that is going to at least quadruple and then in the next decade.

Erin: So, what does it look like in previous decades?

Dr. Rosengart: The number of surgeons who are retiring at a reasonably early age had been significantly higher than now. The number surgeons were looking to continue working into their 70s, 60s and 70s, is beginning to increase. There are a lot of different reasons for that, some very good. The functionality of physicians and surgeons who are older continues to improve. Some of it is, quite frankly, financial. That concerns about their ability to retire.

Erin: Do you have a sense of what the current average age of a retiring surgeon is?

Dr. Rosengart: I don't, that number is not really available. However, what's very interesting is surgeons, in particular, there has been a survey on this, usually do not have a good sense of when they should retire based upon their cognitive skills, even their clinical competency. So what would be desirable is to give them good feedback about whether or not it's time to start switching into activities that take them out of the operating room, and into other very important roles, be it teaching, research, mentoring, administrative support, or the like.

Erin: What will it look like in the future? Do you see physician surgeons practicing even longer?

Dr. Rosengart: I do. I think there is a significant shortfall in the physician workforce. There’s an estimate that there will be a gap of at least a hundred thousand physicians in the coming decades. So clearly that is going to put a lot of strain on the physician manpower, or physician human power, ability, or availability. So, there's going to be an increasing need and push to have surgeons and physicians who are 60s, or even 70s, continuing to practice.

Erin: What aspects of aging, in particular, would directly affect a surgeon's ability to operate?

Dr. Rosengart: Well, on the positive side, as we get older, hopefully, we've all gained a lot of experience and learned from that experience. So the older surgeon, or physician, for that matter, tends to do better on the basis of their experience. That’s obviously not a surprise. On the other hand, there's very clear data that beginning, really in the late 40s, early 50s, there becomes a significant decline in cognitive function and overall capabilities, again not necessarily a surprise. That can be as much as 20% when you perform standardized cognitive testing on physicians. Interestingly, in general, physicians and surgeons tend to do better than the general public. Perhaps not a surprise, and that does negate or counterbalance some of this change in cognitive function. Experience plays an important part the expression “older and wiser” exists for a reason. The importance of what we really need to do is figure out where those different factors balance out. The Society Surgical Chairs feels that that is on the basis of competency and cognitive testing, beginning at an appropriate age so we can make sure that the right, capable, and competent physicians and surgeons continue to practice, but conversely that we make sure those who may not be balanced in terms of that experience versus cognitive abilities are kept abreast of and are properly transitioned into non clinical or non-operative roles.

Erin: Has any research shown that older surgeons have poorer outcomes than younger ones?

Dr. Rosengart: Yes, that's a great question. It actually, there is research that cuts both ways. They’re clearly studies that would suggest overall, surgeons who are older do not do as well on things like incorporation of current guidelines, medical knowledge, even some outcomes. On the other hand, there are studies that show just the opposite that they do better than younger, less-experienced surgeons. So I think the takeaway from that is you can't generalize in any, in one way or the other, about clearly there's an age cutoff and in terms of who may or may not be credentialed or continued to a practice. But it's important on the other hand on an individualized basis to make sure we're keeping an active eye out, and alert out, to make sure that when there is a change in capability that we pick up on this. At the end of the day, the most important thing is to make sure our patients are well taken care of.

Erin: Can years of experience and judgment compensate for a modest physical and cognitive decline?

Dr. Rosengart: I think absolutely so, and there's no metric to measure that a priori, or prospectively, and again another reason why making sure that we test physicians, so we don't second-guess that that issue is going to, I think, be very, very, important, especially going back to your first question, “is the percentage of physicians and surgeons who are older and continuing to practice in the workforce increases proportionate to the total number of physicians.”

Erin: So, you're a surgical chair at Baylor, what's that mean to a layperson?

Dr. Rosengart: Sure, I guess the framework for that is at any institution, a college, a university, or the like, typically there are different departments in a regular University. That might be the Department of History, the Department of English, and usually, the leader of that department and the particular faculty of that department is called a chair. In the old days, we used to say, chairmen. Thankfully those days are behind us, now we just say chair.

In a medical school, those departments and chairs become a little bit more specific, of course, for the practice of medicine. So you have chairs of medicine who take care of the medical specialties, like gastroenterology or the like. Then you have a chair of surgery which obviously takes care as oversight of the faculty involved in surgeries. That could be general surgeons, cardiac surgeons, vascular surgeons of the like. So at Baylor, I'm the Chair of Surgery, the Michael E. DeBakey Department of Surgery, of about a hundred and seventy faculty members in our department. Then we also have oversight, in our case, of about a hundred and twenty resident trainees, and of course, the education and medical students who will rotate through our services and practices.

Erin: Does that translate into a national role for you as well?

Dr. Rosengart: Yeah, so back in about 1965 interestingly, the chairs, the surgery chairs all said it would be useful to compare notes and so the Society of surgical chairs, which I’m president of for this year, was formed. And it was really just an opportunity to get together, compare notes, look at opportunities to improve the profession. About two or three years ago we asked the question, “How do you deal with the challenge of a senior surgeon who may or may not feel like he or she is ready to retire and you as a surgeon chair feels that they might be?” So that was sort of an exploratory session and interestingly, everyone who's involved in this peer group session, they thought it was a very significant problem. Almost all of us had different war stories to share and compare. All of us felt that not enough was being done to deal with that.

Erin: Why is this topic challenging?

Dr. Rosengart: There's a lot of reasons. They're very sensitive, and one reason why we wanted to tackle this as the group of surgery chairs is to avoid those sensitivities. In particular, if there are no general guidelines, then all of these interactions seem very ad-hoc. Potentially a personal, potentially a retaliatory in some way, and certainly arbitrary. So what we want to do is proactively engage physicians as they get older in a long-term process so that the expectations are clear, there's a clear runway ahead of each of us, and so that we understand our expectations.

Fascinatingly, if you look at the airline industry, where there is a mandatory retirement age, which is fairly young, it's at 65, I'm almost 60, so that's very young to me. It appears from what we've read and what we've heard, that the airline pilots actually do very well with that mandatory age. Mostly because they know it's coming. It's well done, it's well known, it's out there, and they have years and years to prepare in advance, so that when that date comes, again there's not that one-off where it's uncertain what their future is going to be. So the key on all this to avoid it being sensitive, is to plan well ahead, even mid-career, so that what comes after you transition out of the operating room, or the clinic, as well communicating in advance and there's a plan in place be it financial, practice patterns, or even the cultural and psychological elements of not tagging your self-worth, self-value, self-perception to being in the operating room, or at the bedside, but being able to understand that you can contribute in a valuable and significant way in other important activities. When you think about it, the experienced physician has so much to offer to students to residents, to trainees, in terms of that accrued knowledge, information, experience that you mentioned. There would be a shame to waste that talent contributed to a younger generation, but we want to make sure it feels valuable to that physician as they transition as well.

Erin: So, what were some of the recommendations of your survey?

Dr. Rosengart: Our survey first all showed that the Society of Surgical Chairs really was very, very, supportive of early career counseling, mentoring, career planning, retirement planning, and then thinking about ways to transition. So those ways are again fairly obvious is an important role, an opportunity for physicians and surgeons to be involved in mentoring trainees and students, be involved in peer review and administrative leadership roles, teaching education, even research roles than other hospital, or medical school, or other institutional roles in an administrative support basis. The other part is it's also okay to retire.

Erin: Do you think the surgeon lifestyle makes it difficult to retire?

Dr. Rosengart: Oh, absolutely. The surgeon, I think, in general. Every surgeon I know views their value, their worth, and even their raison d'être, so to speak, based upon their being in the operating room, doing what they love, being able to take care of patients to the point where I would actually think that surgeons in particular almost feel guilty if they're not, and not lose their value of self-worth, if they're not doing those things. So I think we need to educate our colleagues that there are valuable and important ways to contribute that go beyond being in the operating room.

Erin: Why do you think that these surgeons resist suggestions to slow down as they get older?

Dr. Rosengart: Again I think it's how we place self-worth and value on that activity that's in the operating room. If some of that is financial, we pay surgeons to operate. We don't necessarily pay surgeons to be mentors and leaders. And so it's important that we recalibrate that in a way that surgeons and physicians, in general, can contribute in a way that they feel that is valued and supported, that goes beyond the operating room, again, expanding to physicians in general, taking care of patients at the clinic or in the bedside as well.

Erin: What does the current transition process look like?

Dr. Rosengart: Basically, there is none, and that's the problem. This often becomes an emergency when there's a bad clinical outcome. All of a sudden that physician is under review, this was not telegraphed in advance. One day everything is fine, in the next, there is a catastrophe. So that, of course, is about the worst way you can possibly do this, and again one reason why we think this is important and excited about this initiative, we're actually going to try to collaborate with the American College of Surgeons on this effort, because there is no process. It has been a very sensitive issue, there's always concerns about age discrimination, even though legally there's a clear precedent that when it comes to patient safety, these measures are very appropriate. But we need to put something together, so in an organized, proactive way spanning years, if not decades, again so that this does not become an ad hoc, catastrophic moment where emotions are high, and the ability to plan in advance is least applicable.

Erin: What do you think of a mandatory retirement age?

Dr. Rosengart: I think mandatory retirement age, and this is supported by not only outside studies but by our Society of Surgical Chairs, a survey as well, does not make sense, and I think that's a very, very, important point. We clearly know that there's a lot of heterogeneity between how one 65 year old might function versus another. One, in fact, it may be very appropriate to consider retirement either voluntary or even supported by a review process. Other 65-year-olds are well within their capabilities to go on for a significant number of years, and that's again why we advocate for an individualized, competency, and cognitive, as well as a physical testing regimen so we can certify and make sure that physicians as they get older, continued to be credentialed and appropriate for continuing their practices. This will probably move forward working with individual hospitals to create credentialing, or reappointment criteria that likely would, it would involve things like cognitive testing, peer review, and even outside testing counseling if necessary.

Erin: Rather like getting your driver's license.

Dr. Rosengart: Yes, exactly. Why should it not be much different than that? That's exactly right, it's a great comparison. If we need to get tested to get our driver’s license, I certainly think to get tested to fly an airplane, run a nuclear reactor, or take care of patients should be taken with equal seriousness and care, and perhaps it's inappropriate that we're not already doing so

Erin: At what age could late career practitioner policies start?

Dr. Rosengart: Well, that depends both on how early you want to go into creating a baseline for measurement, clearly beginning at age sixty to sixty-five, that cognitive performance levels begin to change significantly. By the age of seventy, there's again, about a 20% decrease in cognitive function compared to baseline. So in our view, at a minimum, you want to capture that beginning of change, so again age sixty to sixty-five, but ideally you'd even be do cognitive testing at an even earlier age, perhaps as early as 40 or 50, to again to establish that baseline. The other part that's interesting is you can do exercises to improve your cognitive function. That may be something as simple as playing backgammon, or cribbage, or something like that. Then other tricks that you can learn memory games memory tricks memory exercises to again, help yourself if there is a cognitive decline. So you avoid even checklist for that matter, to avoid deficits that translate into a adverse clinical outcome.

Erin: So you talk about evaluations, both cognitive and physical, sort of getting a sense of where an older physician is. What would evaluations of older physicians look like?

Dr. Rosengart: Yes, so there's two components. One is a simple cognitive test, one test, for example, is called micro cog. It’s a very basic, it's about a 15 or 20-minute test. it's memory function, simple arithmetic, sylloge and the like. Then there's also which we've talked about a bit as the psychomotor function, so peg games, drawing, simple drawing exercises, and the like. Again, these are fairly standardized. They've been well established, not particularly complicated, so a hospital for example in an HR department could easily execute deliver these tests in a well-documented way, so there could be comparison to your own baseline which is perhaps most important, as well as a population norm.

Erin: Do you think these kinds of transition strategies could be used in other areas of healthcare careers or other industries even?

Dr. Rosengart: Yes, so mostly we are learning from other industries in this the medical profession is late to the game, so to speak. And there are a lot of lessons, for example from nuclear power industry, or the military. We mentioned the aviation industry and the FAA, so we probably can teach others, but we first need to be taught how to do this ourselves and implement our own strategies, which again I think is with the aging physician population, is going to be important. I do think this is something that we want to be ahead of. There are now stories actually, coincidentally, there is a story in The New York Times recently, a fairly high-profile event where a surgeon who was involved in an institution with bad programmatic outcomes was a senior physician, and there was some question about whether or not that that age-related deterioration and outcomes was perhaps a contributor to these issues. So again I think the more we're ahead of the curve on this, and maybe even a little late for that to be ahead of this curve, the better we'll be in a better service we can provide to our patients in the population in general.

Erin: Do you think it would be fair to have different standards for different kinds of medical practice?

Dr. Rosengart: Yeah, that's a great question. I don't know the answer to that. I certainly, something like surgery where there is a motor function a technical ability is going to be appropriate for surgeons, as opposed to a cognitive field, like internal medicine or Rheumatology so to speak where the obvious those technical skills may not be relevant at all. So I do think different specialties will need different assessments of actual ability to deliver a clinical care. That makes a lot of sense.

Erin: How have your colleagues responded to this survey?

Dr. Rosengart: So the fascinating part is, as far as I can tell, everyone has embraced this as an important area. I've even gotten some calls from 65-year-olds who have thought about this, and said, “boy this is important work and glad you're doing it, and am I okay?” Not so much the last part, but yeah it's actually been very encouraging when we first took this on about a year ago. We’re quite apprehensive about the politics and the atmospherics of it. But it's been very heavily supported embraced and championed actually by every colleague that we've encountered so far. So encouraging good start, sure not completely won't be smooth sailing all the way through.

Erin: It almost sounds as though you spoke what others had privately been thinking kind of brought it into the light.

Dr. Rosengart: I think that's true, I think that's true. And again ego that speaks well both for the opportunity to accomplish this. And again I think the ethos of a physician and the medical community at large that they are trying to do the right thing, and appreciate what would be fair and reasonable support and continuing to provide good care for our patients.

Erin: Thank you for tuning in to Body of Work, by Baylor College of Medicine. If you enjoyed this episode, be sure to subscribe and be on the lookout for our next episode where we'll discuss outbreaks with vaccine expert Dr. Peter Hotez. If you like the show, please give us a five-star review and tell your friends to listen. We're available on Spotify, Apple podcast, and Stitcher, as well as at BCM dot edu slash podcast. There you can also find the episode notes, including information about the experts featured on the show.

A quick note about the medical advice and opinions stated in this podcast, each individual's health profile is unique, so please see a healthcare professional about any questions you may have. Until next time, take care.

Thomas Kosten, M.D., is a professor of psychiatry, neuroscience, pharmacology, immunology and rheumatology and director of the Division of Alcohol and Addiction Psychiatry at Baylor College of Medicine. His professional interests include developing medications and vaccines for addictions and pharmacology.

See more about Baylor College of Medicine’s Department of Psychiatry and Behavioral Sciences.

See below for some of the research studies mentioned in the episode:

Transcript

[Music]

Erin: Welcome to Body of Work, an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I'm Erin Blair, and my guest today is psychiatrist and addiction expert Dr. Thomas Kosten.

For the last several years, America has been embroiled in an opioid crisis. Why are opioids so addictive?

Dr. Kosten: Why are opioids so addictive is probably a bit of a misunderstanding in the sense that a very large portion of the population gets opioids one time or another in their life, for various kinds of pain or surgery that they get. Yet, the percentage of people who become dependent, and who abuse opioids, it's actually rather small. It's about 2% of the population or less. So if you look at that sense, you would say they're not very addictive in the least. However, if you do like them, you like them a lot. And they don't have their sustained effect unless you use them at higher and higher dosages over time. Particularly that euphoric effect, but even the analgesic effect does develop tolerance, and as you get more and more tolerant, and take more and more of the drug, the withdrawal syndrome that will occur when you stop the drug is more and more severe.

Erin: What is involved with withdrawal?

Dr. Kosten: Opioid withdrawal is unlike alcohol withdrawal, or some other types of withdrawal, which can have an actual mortality associated with them. But, it is very unpleasant. It's like having a very bad case of the flu, lasts anywhere of seven to ten days, and then the acute syndrome is over. But, there is a protracted period of withdrawal that can last as long as six months, where people don't sleep well, where they feel uneasy, where they're certainly having a lot of craving to use the drug again. And it is that sustained period that often leads to relapse. Even when someone has a successful medical withdrawal, or detoxification, as it's often called.

Erin: What does the progression look like once someone is addicted? What are the effects of long term use?

Dr. Kosten: When people begin using opiates that occurs in different contexts. The most common one in the recent epidemic has been people being treated for chronic pain of various sorts. These are usually benign pains, meaning that it's low back pain, it’s headaches, it's peripheral neuropathies, it's sometimes things that seem a little odd, like being treated for gastrointestinal symptoms, when mostly opiates would make them worse. But a lot of different pains, and they are treated for months, or years with the opiates and they then become quite tolerant and dependent on them. Now for most people, they will eventually, if their doctor wants to do that, and often should do that, discontinue the opiates, they do not go on to become abusers. But, there's a percentage of them that do and that percentage is quite variable, so that in some primary care clinics and that are high-end ones, that the rates can be as low as only three or four percent of the patients that become opiate dependent and abusers of the drug. In other settings, such as in AIDS clinics, where people often have variety of pains that are reduced by the AIDS, or the medications are being treated, the rates of going on to develop opiate abuse and dependence are as high as 50%. So the setting varies a great deal. Then, there are also adolescents who will begin by using opiates that they usually snort, and that they'll just use them on weekends, and they use them to get high. As they keep doing that, they will usually move on to more frequent use and typically you have to be using the opiates daily in order to get to the point that you'll get tolerance and dependence. So, those adolescents can, in fact, become like the chronic pain patient where they are in fact quite dependent on the opiate. And when they discontinue its use, will get fairly sick. That’s the usual course that leads to people becoming, what we usually think of as addicts, that is they have to get the opiate, or they don't feel normal.

Erin: What's the difference between an opioid that's prescribed by a doctor, like OxyContin, and opioids that are obtained illegally, like heroin?

Dr. Kosten: They are fundamentally very similar drugs. Heroin is a version of morphine that has been modified chemically so that it gets into the brain faster than morphine does. So that makes it more euphoria-producing, more addictive you might say, in that way. What is on the street now increasingly are what's called pharmaceutical opioids which may, in fact, be made by a reputable manufacturer and get diverted. Or they can be made in factories that are located in various parts of the world, China and Mexico being two of the largest. They are usually made by growing poppies, and then taking those poppies and extracting the morphine from them. Then the morphine can be converted into a wide range of other drugs.

Erin: If this is just an addiction problem, why are so many people dying in this current epidemic? We’re not just hearing about increased use, but about deaths?

Dr. Kosten: One of the unfortunate characteristics of opiates is that overdose from opiates will suppress your respiration. And suppressing your respiration, if it's sustained, leads to death. And so just taking an overdose of an opiate can, in fact, kill you. And one of the ways that that happens is that when people buy opiates on the street, they don't know exactly what they're getting. They don't know the potency of it. They don't know how much they should take to just get a high, as opposed to how much they should take if they want to avoid dying from it. And because of that, they're titrating it in a way that is fairly dangerous. Now if that titration is occurring when you're smoking opiates, it's relatively easy to do. You, once you stop getting high you just put the cigarette out. On the other hand, if you're injecting, that injection is usually got a fixed amount of drug in it, and the method of doing it is to push the whole bolus in all at once so that bolus may, in fact, contain a lethal amount of it. The other way that lethal amounts are increasingly occurring is that fentanyl is anywhere from a thousand to ten thousand times more potent, depending upon what type of fentanyl it is, than are the usual opiates that are taken. So when people are buying heroin, the heroin often has fentanyl in it now, or a fentanyl derivative. And so while they may think that they're taking the usual amount that they're tolerant to and that they would get a from, they may, in fact, be taking a thousand times that dose, which would certainly be lethal to them.

Erin: How potent is fentanyl compared to OxyContin?

Dr. Kosten: Fentanyl is much more potent. In some of the formulations of it, it's merely a hundred times more potent than OxyContin on a milligram per milligram basis. Other formulations such as carfentanil can be 10,000 times more potent. Carfentanil is, of course, the one that's now been made illegal for any use, except for sedating elephants.

Erin: And is fentanyl a substance that you have to smoke or inject?

Dr. Kosten: You can certainly get fentanyl through a variety of means. You can smoke it, you can snort it, you can eat it, but unfortunately you also absorb it through your skin. And the absorption through your skin is one of the ways that it has been nearly fatal with the criminal justice people who have been cleaning up after opiate overdoses that have occurred in a person. And if they're not wearing gloves, and they touch surfaces where the drug has been, even though they might not be able to see it, they will absorb it through their skin and it will lead to an overdose. So those overdoses usually are recognized right on the spot, and they get the EMT people in there, and revive them. Usually, with large dosages of naloxone or Narcan, but it is quite a potent drug and absorbed through every way you could imagine.

Erin: Since fentanyl is so potent, is it ever used to mix in with any other kinds of street drugs?

Dr. Kosten: Certainly, that is one of the problems particularly in Texas, where the heroine often is a black tar heroin, and fentanyl is a white powder. So that black tar and white powder makes it fairly obvious that something's been mixed in with the heroin, which may not be a good thing. So the white China heroin, which it's often called, is what it's usually mixed with. However, in Texas, the fentanyl has been mixed increasingly with cocaine and with methamphetamine. With methamphetamine, some of the low-grade versions of methamphetamine, so that they're not actually 100% methamphetamine. But maybe as little as 20 to 30 percent methamphetamine. Or 20 to 30 percent cocaine, if it's cocaine shipment. Putting in a very small amount of fentanyl into that gives the user the experience as if they're taking a drug that's very potent, and they're not very good at telling opiates from stimulants. The problem with that is that when they then are treated for an overdose, either in the emergency rooms or by the EMT people, they will have cocaine or methamphetamine around, or the people around them they say that's what we were using. And if the medical professional, or EMT, is not very careful, and by very careful I mean looking at the pupils of the person who just had the overdose, they may mistreat them. That is, if you have a stimulant overdose, you have very broad pupils, and you can hardly see the colored part of your eye. On the other hand, an overdose with opiates gives you pinpoint pupils. So in that sense the distinction is very easy to make, unless you don't look for it. And if you don't look for it, and you treat the stimulant overdose, there's a very limited amount of time between when you take fentanyl and you overdose, and you can, in fact, revive them. That is if they don't breathe for several minutes, they'll be dead, and so even if you gave them naloxone at that point, or Narcan, it would not reverse the fentanyl overdose because the patient I s dead already. So, there is a very high importance in making the correct diagnosis as soon as possible, and when it is a mixture of a stimulant with fentanyl, it can be quite confusing as to what exactly you're treating, and you have to get to the treatment of the opiate first, and quickly.

Erin: Who is to blame for our current addiction epidemic?

Dr. Kosten: Depends who you want to talk to and who you want to read about, but certainly the New York Times has quoted more than once how the general public blames the doctors who have prescribed chronic opiates as much as they blame the people who take the chronic opiates and then go on to abuse them. There was certainly a period in the beginning of what would be 2000 through 2006 or 2007 where there were a number of manufacturers of opiates that were encouraging doctors to treat every patient who has pain with opiates, and treat them with escalating dosages as need be. Some of those manufacturers have in fact now faced federal lawsuits for that, and they're increasingly facing lawsuits yet again, because they didn't discontinue some of those practices. And that led to fairly massive overprescribing of opiates for people who had these chronic low-grade pain syndromes that, the data are now very clear, opiates make those syndromes worse rather than better. The way they make them worse is with the withdrawal and dependence that occurs, but they also induce a condition called hyperalgesia, where small pains get greatly magnified. And so it's not advantageous to use opiates chronically, and that was an advertising ploy that worked in such a way to sell a lot more opiates, but did not benefit the patients who got them.

Erin: What are some possible long solutions? is it greater regulation of pharmaceuticals? Is it education? Is there a cure?

Dr. Kosten: Well certainly regulation and greater education are very helpful in this particular case. I think regulation of the marketing that the pharmaceutical companies can do, since an unfortunate part of continuing medical education is that it comes from the drug company representatives as much as it comes from people attending continuing medical education. Hopefully, that trend is changing. Then, there is the other mandatory education that's increasingly being required for recertification, either in specialty boards or to just get your medical license renewed. And that I think are good advantages so that the doctors who are prescribing these medications prescribed less of them. And that approach has had a very significant effect, it’s certainly true in Texas, where the amount of opiates that are prescribed have gone down considerably. And the number of opiate prescriptions that are given for more than three months have also declined quite a bit. Finally, within that same kind of regulatory framework is the dose of opiates that people are given, that there are recommendations from both the CDC and from HHS, that have specified a highest level dose which is considerably less than what the pain medications were given out before as opiates. So those have been regulatory things that have been quite helpful. I think the lawsuits against the companies have certainly motivated people to not want to take so many opiates, and have had an effect on the pharmaceutical company's practices in terms of how they advertise their wares and push this forward with doctors or hospitals. One of the interesting things was that a fifth vital sign was invented by the hospital accrediting board, which was pain, and the way that that went is that patients are supposed to be relatively pain-free as a good mark for the hospital, and if you had patients who were complaining about pain that was a mark against hospitals further accreditation. That was not a good idea, and led to a fair amount of over-prescribing of opiates and led to, I think, part of the current epidemic that we have.

Erin: What are the other four vital signs?

Dr. Kosten: More usual things, such as your blood pressure, your pulse, your respiration, your temperature. Things that really are vital. If they stopped functioning you stopped functioning. But with pain management, in general, you're not looking for stopping all the pain, what you're looking for is improvement in function. And 80% of what your baseline function is, is usually thought of as cure.

Erin: So why don't you tell us a little about your own research into addiction?

Dr. Kosten: Yeah, I've certainly been involved with the treatment of opiate dependence for quite a long time. Initially, when I was a medical student was working with methadone when that just first came out. Obviously dates me a little bit. And then, later on, did the initial studies with buprenorphine as a maintenance agent here in the United States when I was back at Yale and did the initial studies, for naltrexone as a maintenance agent. And then most recently have been interested in vaccines for treating opiate dependence, in particular for treating fentanyl. The reason is that the fentanyl derivatives are not blocked by buprenorphine, naltrexone, or methadone. so that even if you're in treatment with those drugs, you could still overdose with fentanyl. You could also get high from the fentanyl, and that can be a significant problem with the overdoses because the fentanyl is increasingly mixed in with all the other drugs of abuse.

Erin: How would a doctor and a patient use a vaccine, like a fentanyl blocker?

Dr. Kosten: The vaccines are made in such a way that you have to give usually two or three boosters after the initial vaccination, and that occurs over about a two-month period. And then you develop sufficient antibody levels to block the fentanyl. Those antibodies will remain relatively high for two to three months, and then over the normal course of time, those antibody levels drop. Unfortunately, just using fentanyl during that time will not increase the level of the antibody, so it's not like an infectious disease where every time you get infected, that stimulates the b-cells to make more antibody. You have to give the vaccine itself to stimulate that production because it is the coupling of the drug of abuse to the carrier protein that produces the antibodies. So one would need to get a booster vaccination about every, probably three months. And we did some of that work with the cocaine vaccine and found that it worked very effectively, that a single booster would push the levels of antibody back up to what were in the therapeutic range. So the expectation would be perhaps every three months, you would need a vaccination for as long as the drug of abuse is an issue. And in general what we found if people can stop using the drugs of abuse, whatever it happens to be, for about a two-year period, and at the same time engage in some various types of behavioral therapies, that they can then, you know, get on with their life and not be burdened with abusing those drugs anymore. So that would be the ideal. We could of course though conceivably vaccinate you every three months for the rest of your life.

Erin: Do you see the vaccines being used preventatively with people who are not addicted? Or would they only be for people who are already addicts?

Dr. Kosten: All of these vaccines, they’re really designed for people who have a problem. Could you use it in a preventative way? Well, many vaccines are in fact used that way, but we don't have good enough predictors who this is going to be a problem for. And to just use a small example, there was a book that I wrote with the National Academy of Sciences about 15 years ago now, about the ethical issues of if we started vaccinating people. And with nicotine, if you vaccinated say all the teenagers against nicotine so they wouldn't smoke cigarettes, it's not clear that they would stop smoking cigarettes. They may, in fact, want to smoke enough cigarettes to override your vaccine, your blocker. And what would effectively be doing is teenagers capable of sticking, you know, 10 cigarettes in their mouth all at the same time lighting them up. and they would get, you know, some effect from the nicotine at that point. But, the amount of carcinogens they would be getting would be ten times more than what is in one cigarette. So, that would be an unintended consequence that's not at all positive.

Erin: How does the current epidemic affect the future of healthcare?

Dr. Kosten: Well, I'm hoping that it leads to more educated doctors who will use opiates more sensibly, and understand something more about what the effects are, considering opiates are probably our second or third most commonly prescribed medication and the amount of medical school education that's devoted to their use, abuse and complications is vanishingly small. So that first we’ll provide more education to students as they go through medical school, and anybody else you might prescribe opiates. And then beyond that, the continuing medical education will be importantly used by all doctors and required so that they'll learn more and more about these medications, the opiate-related medications. The other is that there's still hopes for finding opiate-like compounds that would be analgesics, but would not produce the same level of tolerance and dependence, and that's a hope that has been worked on, for oh, about a hundred and fifty years at least, so one can't get overly optimistic.

Erin: Are we seeing a bigger government response to this current epidemic because of who it affects?

Dr. Kosten: Well certainly I think the political response to opiates as a problem is very much driven by who has the problem. And so, if there's a greater proportion of the voting population that is affected by opiates, either directly themselves or through their children, or relatives, then you can expect a much bigger political response to it. When opiates were a problem through the 80s, 90s, and were often more of a problem within inner cities, and areas where people didn't vote, in areas where a number of the people sometimes were in fact illegal aliens - although ironically, illegal aliens are some of the lowest rates of addiction problems - when it was confined there, then you didn't see a lot of motivation for politicians to do much. On the other hand once the voting population, the middle-class America, the out in the suburbs, or even wealthy families begin to see this as a problem that's happening in their families and people close to them, then you get political action. Now you might ask, well, “How effective is that political action?” And I think that that's been quite variable. And the current political action seems to be kind of muted in comparison to what it's been with other administrations in terms of doing something. The HEAL Initiative is a very big initiative for doing something about opiates, and has very ambitious goals. For example, the latest HEAL Initiative, which I'm involved as one of their senior scientists, is to reduce opiate overdoses by 40 percent in the next four years. Now that's a tall old order to do that, and we're doing it in four states around the country. So, we'll be looking at Ohio, Kentucky, Massachusetts, and New York. But those are the places where you have some of the highest rates of fentanyl overdoses, so that is part of the rationale. Whereas on the west coast and across the south there's less of a fentanyl overdose issue for opiates. As I said, in Texas, there’s quite a fentanyl overdose issue with stimulants, which is the next thing that's coming. So I think that, yeah, who gets affected and who votes, that makes all the difference.

Erin: Addiction has been called the American disease. Why is that?

Dr. Kosten: It's an interesting expression that I think was coined by David Musto quite a number of years ago when he wrote his book about The American Disease. And it got that name because America has always been in the vanguard of abusing drugs during, at least, the 19th and 20th centuries, and of course going into the 21^st. While there was much abuse of drugs before that that were in many parts of the world, America seems to be the leader, and has been the one that has also been the most forward going, I suppose you'd think, in terms of legislation, but also thinking about how you might develop new treatments for it, because of the National Institute of Health which had a subinstitute for alcohol, and another one for drugs of abuse.

Erin: Is this current issue part of a larger story?

Dr. Kosten: Well, the current epidemic that's happening with opioids can certainly be seen in that cyclic boom-and-bust where opiates have come back three times. The initial time was during the Civil War when the hypodermic needle was invented, and people were then injecting opiates. There then was another one that came at the turn of the century, that is the 19th to the 20th century. And then there was the one that came through in the 1970s during the Vietnam War era. And now there's the one that we're facing now, which has been highlighted by fentanyl and some of these synthetic drugs. So, with the opioids, there is a constant in and out, up and down.

Erin: Are we doomed to keep repeating this cycle of abuse, and addiction, and potential solutions, and then another cycle of the same?

Dr. Kosten: Well the creativity of the human mind in coming up with things that are potentially abusable and lead to a chemical high, and as some people have said, you know better living through chemistry, is almost endless. I think that the way it seems to go is, it's a little bit longer than generational, so it's a little bit longer than 20 years, but over that period of time if we've had an opiate epidemic, 20 or 25 years after it ends, you will see then another one because people don't seem to remember or translate things or transmit them across the generations. And the stimulant epidemics have pretty much looked like that - about every 25 years we have another stimulant epidemic.

Erin: Because see I'm 50, and I've seen over the years these cycles, and it is, 20-25 years. Yeah, I hadn't thought of it that way, but it's every generation.

Dr. Kosten: Well, David Musto deserves credit for it, he wrote the book. That's the way he thought of it. It's sad that we have no memory.

Erin: Or that we just don't transmit it down the generations.

Dr. Kosten: Yes, yeah exactly. The news cycle I guess is just way too short for that to happen. And so I don't think that my field will ever be put out of business, and that there'll always be some other new development in what people can abuse, and perhaps maybe even put them to therapeutic use. As you’re probably aware of the hallucinogens such as MDMA and psilocybin are now being tested in FDA approval studies for the treatment of post-traumatic stress disorder and the treatment of depression. Clever ideas doesn't mean that those clever ideas can't be turned into something abusable, or that something abusable can't be turned back into something that becomes a clever idea again.

[Music]

Erin: Thank you for tuning in to Body of Work, by Baylor College of Medicine. If you enjoyed this episode, you'll want to subscribe and be on the lookout for our next episode where we'll talk to Dr. Todd Rosengard about the aging physician population.

If you like the show, please give us a five-star review and tell your friends to listen. We're available on Spotify, Apple podcast, and Stitcher, as well as bcm.edu/podcast. There you can find the episode notes including information about the experts featured on the show.

A quick note about the medical advice and opinions stated in this podcast, each individual's health profile is unique, so please see a health care professional about any questions you may have. Until next time, take care.

Amy McGuire, J.D., Ph.D., is a professor of biomedical ethics and director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine. Her professional interests include ethical and policy issues raised by emerging technologies, research ethics, informed consent and confidentiality.

See more information on Baylor College of Medicine’s clinical genetic testing program.

See below for some of the research studies mentioned in the episode:

Transcript

[Music]

Erin: Welcome to Body of Work, an exploration of health topics in the news and important issues facing science with experts from Baylor College of Medicine. I’m Erin Blair, and this is part two of our interview with bioethicist Dr. Amy McGuire. If you haven’t listened to part one, we suggest you go back and start there.

It seems the popularity of at home genetic testing has skyrocketed in the last few years. Is that because the cost has come down? Will there be some unforeseen consequences of this trend?

Dr. McGuire: So the cost has certainly come down tremendously, and it's continuing to come down. So the cost now of some of the direct-to-consumer genetic tests are like $99, under $100. But it's important for customers to know that many of these companies - and I'll talk mostly about 23andme because I think they're the ones that have been really transparent about this - they're not making their money off of selling $99 tests. That's not how they're making money as a company. And 23andme recently did a huge three hundred-million-dollar deal with GlaxoSmithKline because they now have from their customer base one of the largest databases of DNA data. And when you sign up for their services and use their tests you are agreeing to allow your data to be used for research purposes. And it's not tied to your name, it's not tied to your account, but it's being aggregated and used for research purposes. So they're able to sell access to their database, their very large database, to companies like GlaxoSmithKline in order to do research using their customer’s data, and that's their business model really.

Erin: And what can GlaxoSmithKline discover? What benefit do they have from having this big population of data?

Dr. McGuire: Lots of things. I mean, what has been a challenge for us in this whole era of genomic medicine, is that the one of the biggest bottlenecks is not having enough access to patient information and patient data. We're in the world of big data now where everybody's trying to amass large amounts of data on individuals so we can better understand particular genetic variants and their association with disease. We can develop drugs that are more targeted to individuals based on their genetic makeup. So this is big business, and everybody's trying to get in on this game. And there's been some countries internationally that have tried to create population databases with their whole population in it, like Iceland and the UK bio bank. The United States is starting to try to do that through our “All of Us” research project, which is funded through the National Institutes of Health, and the goal of that is to get medical genomic and other types of wearable information on a million people. We also have an effort through the Veterans Association to collect information on a million veterans, and so you see these large-scale efforts to collect data for research purposes. 23andme still has one of the largest databases, just because they have such a such a huge number of customers.

Erin: There's also been a lot of talk in the news about using DNA from these online banks to solve some cold-case files. How much should a person consider that aspect in deciding whether or not to do an at-home genetic test?

Dr. McGuire: So the first big case that was solved using this technique was the Golden State Killer case. So the Golden State Killer was somebody who ravaged the coast of California for two decades committing over 50 rapes and over a dozen murders. And the police could never identify who the suspect was but knew it was the same person committing all of these crimes. That was in the 1970s and 1980s, and it's been a cold case ever since. They had DNA from the crime scenes, and the way that law enforcement typically tries to identify suspects based on DNA is that they use their national forensic database, which is the CODIS database. So this is a database that typically includes DNA from anybody in any state who has been convicted of a crime, and in some states it's also people who have been accused of crimes. But it certainly doesn't include everybody, and the technology that they use for the DNA analysis is fairly limited so that you're really looking for a direct match for the most part in that database.

Now what's happened over the last several years is that a tremendous number of people have gotten very interested in genetic genealogy. You submit a sample like a cheek swab, the company analyzes it, and it tells you what part of the world your ancestors might have come from. And then they want to make your data available to all of their other customers for the purpose of familial matching. So you'll go into your profile and it'll say here you are and you have in our database three second cousins, one first cousin, and an aunt, and it'll tell you who you're related to, many of them you may not know. And so some of these databases are larger than others and some companies have said, well regardless of where you do your genetic genealogy, you can upload all your information to our database and we'll have sort of a master database of all these companies. And then you can connect to all these other people who - I used ancestry you use 23andme, but we are related and I might want to connect with you, so I can use one of these other sort of super databases. So one of those companies is called GEDmatch. Those data are necessarily public, and they're connected to you because the whole purpose of it is to connect you to people.

So law enforcement picked up on this and said, hey wait a minute, maybe our suspect in some of these crimes are distantly related to people in these databases. So what they did in the Golden State Killer case, and they've done in subsequent cases since then, is they took the crime scene DNA, they sent it to a lab for processing, and they got all the DNA data from the crime scene sample, and they uploaded it to GEDmatch and said, “Here I am, John Doe, connect me to anybody I might be related to.” And they got connected to somebody who was a partial match, I think it was a second or third degree-cousin was what the match was. And then they went and they did an extensive family tree and a lot of investigation, and they said what's the family tree of this particular person who we matched to and is there anyone in that family tree who could have potentially been a suspect in these crimes? They identified Joseph D'Angelo as one of the second or third degree-cousins of the person who was in the database, and they followed him around. He seemed like he could have been a suspect, he was in the right place at the right time when those crimes were committed. They followed him around, he discarded a tissue one day into the garbage, they picked it up, they analyzed it for his DNA, and they matched it to the crime scene DNA and it was a perfect hit. Remarkable, right? So they were able to identify somebody who's committed a crime more than 20 years ago, has never been a suspect, they never would have thought of him as a suspect, and they've used this technique.

So this has sort of created a whirlwind within the direct-to-consumer genetic testing company space because the companies have all responded very differently about this. So I think there's a lot of different approaches to this now, and everybody's trying to figure out what the right thing to do is, and we're still in a space where we don't have consensus.

I'll just say one more thing that I think is interesting. So shortly after the Golden State Killer case hit the media, we did a survey of about 1,500 people in the United States and we said “What do you think of this? Do you think this is a good idea?” Now it might have been a little bit biased because the Golden State Killer case had just been solved and I think people were very enthusiastic about the idea of identifying that particular that suspect. But what was really interesting to me is that about in the 80s to 90 percent of the people that we surveyed felt that they were totally comfortable with law enforcement using these databases for the purposes of solving really violent crimes like murder and rape, for identifying missing persons and for crimes against children. And only about 40-something percent were comfortable across the board with them using this information for less violent crimes, more petty crimes so things like drug possession, immigration, things that you think might become a sensitive use of this information. So that gives a little bit more nuance into how we ought to be thinking about this from a policy perspective, I think.

Erin: Why do you think that users are putting affordability and curiosity above privacy and confidentiality with these tests?

Dr. McGuire: So I think everybody is different in sort of their appetite for privacy risks and in terms of their desire for information. So I think it's a very personal decision and it's like any other decision that we make in any other sphere of our lives where it's a trade-off. People make trade-offs whether consciously or subconsciously, they're trading off what they see as the risks and the benefits of what they're doing. So the example that I like to give is that I know that I am risking my privacy every time I shop online using my credit card. And if you were to ask me in the hypothetical, is that risk to your privacy really worth the benefit that you get from the convenience of using Amazon as opposed to driving five minutes to Target a couple times a week, I would say probably not. And yet I do it all the time. I use Amazon, I put my credit card in there, I give them all my information and I make that trade-off because in that moment the trade-off is worth it to me. I don't want to get out of bed and go to Target.

Those are the same sorts of trade-offs that people are making when they decide when they decide to get genetic testing or they decide to do direct-to-consumer genetic testing. Some people care a lot about their privacy, and they're not going to ever have these tests because they're worried that somebody might get access to their information. Other people don't care very much about their privacy, and they're really curious about who am I, and where did I come from, and what does my future look like, and can I get all of the information that I want about the circumstances of my life? So they're going to get this test. And other people just don't think that the privacy risks are that great.

So I think there is certainly a risk that if somebody gets your genetic information and they want to do something harmful with it they can, but we don't have a whole lot of documented cases of people actually using other people's genetic information in ways that are particularly discriminatory. Now that may just be because they haven't been documented because we certainly hear anecdotal cases of people feeling like they've been harmed based on their genetic information or family history information. But I think the jury's still out on what exactly are the risks in terms of people's privacy and what happens if somebody does actually get your information.

Erin: So I could assume that perhaps people would be afraid that they would not be employable if they had some high degree of risk for a cancer or something that would be medically expensive for an employer to take on. Is that the kind of concern that hypothetically is out there in the in the privacy tradeoff?

Dr. McGuire: Yes, I think most people when you talk to them and they they're worried about their privacy they're concerned about employment and insurance. Those are kind of the two big ticket things that come up. We actually do have a federal law, the Genetic Information

Nondiscrimination Act, that went into effect in 2008. And that protects people from being discriminated against in most employment situations, at least with employers who have over 50 employees and health insurance circumstances where they can't use predictive risk information based on your genetics to make discriminatory decisions about hiring, firing, coverage, reimbursement things like that. In health insurance, we also have some additional protections under the Affordable Care Act where even if you have symptoms of a disease they can't make discriminatory decisions because they can't base those decisions on pre-existing conditions any longer, so we have some protections there.

The areas where we don't have any protections are things like life insurance, long term care, disability - those types of industries still very much use risk assessment to make coverage decisions, and part of their risk assessment is going to be what is your family history? Do you have any genetic predispositions to things? That's kind of how they do business, so I think that's probably the area of most concern for people. And people who are getting these kinds of tests really need to understand that if they're subsequently going to apply for life insurance and they're asked whether they have had any genetic tests or they have any genetic predispositions to disease and they do have that information and don't disclose it, that that could interfere with their ability to collect on insurance should they need it in the future. And so having that information does put them a little bit at risk with regard to those types of things.

Erin: If I choose not to get involved in having my genetic testing done on myself, am I safe? Am I free from my privacy being violated, my personal information being accessed by law enforcement or someone else? If I haven't spit into the tube am I safe?

Dr. McGuire: So the whole premise behind this is familial matching, and that's what makes DNA so powerful in some ways, is that it doesn't just give you information about yourself, it gives you some information about all of your relatives. So the answer is no. Most of the people who have been identified as suspects in crimes did not individually participate in ancestry testing. They are not genetic genealogists, they did not do direct-to-consumer genetic testing, they don't even know anyone in their family maybe who has done direct-to-consumer genetic testing or genetic genealogy. It could be their third degree relative who they don't even know they're related to and they've never met, they you know have no relationship with who's in that database.

There was a really interesting study that came out in Science recently where the investigators looked at, just based on how many people currently engage in these genetic genealogy types of activities, how many people in the United States could be identified based on the information that are in those databases. One thing to note is that those databases tend to be biased more towards people of European descent, and this is a good and a bad thing. On the one hand, there's not a lot of racial diversity, there's not a lot of ethnic diversity. This is a good thing when you're talking about law enforcement access to these databases in some ways because one of the major criticisms of that forensic database that they typically use, the CODIS database, is that it reflects the racial biases that are inherent in our criminal justice system. So the argument has been that the majority of people that are in that database are African-American men, they're ethnic minorities, racial minorities, and so those people in those populations are more likely to be identified because they're the ones who you have access to. This sort of equalizes that because now we've got these huge databases of largely white men and women. And in the study that was done, my colleagues found that currently based on what information is in those databases, 60% of Americans of European descent could be identified by familial matching to those databases. And they suspect that with the industry growing at the rate that it's going that within a few years, everybody of European descent in the United States would be able to be identified through familial matching using those databases. So we're all sort of at risk of potential identification.

Erin: I have an ancestry account, and every major holiday they say, “Hey we've got a special on this at home test that you could you could give everybody in your family one, and then just think how much more data you'd have about your family tree! We could fill in all the little gaps!” How much of the marketing of these kits is purely for the entertainment value?

Dr. McGuire: I think a lot of people certainly find entertainment value in this, and I think the ancestry thing is a big sort of hook for that because a lot of people see that as low-risk, just kind of a matter of curiosity, and again this sort of innate drive to connect with people even if we never knew who they were. But even with the ancestry thing, I would say you have to be aware of what you're going get.

So I have a really interesting story, I'm actually very close to my second cousins. My grandmother on my father's side had two sisters, and the three sisters were very very close to each other their whole lives, so as a consequence all the second cousins are very close to each other. And not that long ago my one of my second cousins came down to Houston for a conference and said, do you want to have brunch. And we got together for brunch and he said did you hear about our family scandal? I said, what's our family scandal? We're a pretty boring family. So we sit down to lunch, and he had spent the previous three months doing this intensive investigative work because he took an Ancestry.com test and it connected him to several of our other known relatives who were second cousins. And then there was a second cousin who popped up who nobody knew who this person was. So he reached out to this person and he said how could we possibly be related? I know all of my second cousins. And this person said I have no idea, I am super confused. My dad is Hispanic and my mom is I think Irish Catholic from Ireland, and I did this test and I'm 50% Ashkenazi Jewish and related to all you people. She says I have no idea what's going on here.

Well she ended up being related to somebody else, they ended up contacting all these people, they had this huge investigation that the two of them did together. And it turns out that they figured out that there were two generations of infidelity that happened that led to her being born. And her biological father is not actually her biological father. And her parents are still alive and they're still married, they’ve been married for 50 years, and it created a lot of family drama. You know, she didn't want to tell them but there was this whole family secret. And needless to say also her biological father, who they figured out who that was, had no idea that he had a daughter and had no idea that his biological father was not the person who he thought his father was.

So it was a really complicated story and you hear that all the time. And so you can imagine that it can be upsetting, sometimes even more upsetting than getting health risk information, to find out family information like that. So I do think if you’re going to give this as a gift, people need to understand what they're giving and what it might reveal and make sure that the other person is on board with it. If you're giving something as a gift that includes health information and I think there's another layer of understanding in terms of what they're going to do, and you always should give the kit and not just surprise them by taking their saliva somehow because that would that would be problematic.

Erin: Grabbing the Kleenex out of the trash?

Dr. McGuire: Well you do have to actually submit quite a large sample of your saliva, so it requires extensive spitting into a tube so that might be difficult to collect without somebody's knowledge surreptitiously.

But the other angle on that is that a lot of people are doing this for their children who’re under 18 years of age. And the companies will say in their Terms of Service you have to be over 18 to do this, but they don't know who's submitting the sample. And I think that can be somewhat problematic because you know as we've talked about not everybody wants the same information. And so if you have a child and they haven't had the opportunity to make their own decision about whether they want this information, we probably want to give them the opportunity to reach the age of maturity so that they can make their own decision about this.

[Music]

Erin: Thank you for tuning in to Body of Work by Baylor College of Medicine. If you enjoyed this episode, you’ll want to subscribe and be on the lookout for our next episode, where we’ll talk to addiction expert Dr. Thomas Kosten about American’s opioid crisis.

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Until next time, take care.

See more information on Baylor College of Medicine’s clinical genetic testing program.

See below for some of the research studies mentioned in the episode:

Transcript

[Music]

So we're talking about the proliferation of at-home genetic testing and the ethical implications of swabbing your cheek or otherwise providing a sample, sending it off in the mail, and getting back information about yourself. What could go wrong with that? When do you remember these at home kits first being marketed?

Dr. McGuire: In 2007, 23andme, which is one of the biggest companies that offers these direct-to-consumer genetic testing kits, hit the markets. It got a lot of publicity because 23andme was founded by the wife of one of the founders of Google so it had quite a bit of large financial backing to it. I remember reading about that in 2007 and being really fascinated by this movement. I think I wrote the for my first paper thinking about some of the issues related to this it was published

in 2008. That year we did a survey of individuals to say what do you think of this? Do you think this is a good idea? What are you concerned about? That was published in 2009. Those first early years we were kind of looking at this with a lot of curiosity thinking, along with everybody else in our field, is this a good thing? is this a bad thing? how is this going to turn out? what are people going to think of this?

Erin: Traditionally, a genetic test has been a clinical environment?

Dr. McGuire: Yeah, so traditionally when you have a concern about a particular condition that might run in your family, the method of getting testing is to go to your doctor and they'll typically refer you to a genetic counselor. They'll talk about sort of what your specific risks might be with and without genetic testing. When they do the genetic testing in a health care environment, they're really putting the results into context of everything else. One thing that we really need to understand is that genetics is, for the most part, with the exception of some really significant Mendelian disorders where if you have a gene you're going to get a disorder... and a clear example of that is something like Huntington's disease. People who are at risk of Huntington's disease if they have an affected parent. For example, they have a 50% chance of inheriting the gene themselves, and if they inherit it then they know that they're going to get Huntington's disease. There aren't very many diseases or disorders like that. Most of the things we test for from a genetic perspective are really complex, and you need to understand the results in the context of your family history, of your current symptoms, of sort of what your environmental exposures are, etc. When you get those tests done with a licensed health care professional, typically a genetic counselor or geneticists, will spend a lot of time doing a family history with you and looking at sort of how the results might fit into your bigger picture. On the other hand, when you do it through a direct-to-consumer genetic testing service, they're not looking at the whole picture. They're just giving you the genetic results back, and then it's your job to try to figure out what that means for you as an individual.

Erin: How specific are these results? How detailed is the report back to the consumer?

Dr. McGuire: Well, it depends on the company. We're talking about these as if they're one size fits all. There are a lot of different companies who offer a lot of different services. Some of the companies that are out there are not actually focused on health-related information. They're more focused on things like genetic genealogy where they want to try to map you to what parts of the world did your ancestors come from, and they can link you to people who you might be related to. There are other companies out there who might provide interpretive services, and then there's companies like 23andme, which again is one of the biggest companies that's out there, that kind of does a little bit of everything. They'll provide ancestry information. They provide information for what a lot of people refer to as "recreational genetics", so things like do you have a gene that's been associated with having a lot of ear wax or baldness. Usually curiosities that aren't really health-related in any real sense of the word. Then, they're also offering personal health information. The types of personal health information that a company like 23andme offers is risk information about very complex and common diseases like: are you at increased risk of heart disease or diabetes, or things that we see very frequently in the population based just on your genetics. Of course, we know that regardless of what your genetics says about those types of disorders a lot of it has to do with your lifestyle, your environment, your diet, and your exercise. They'll also provide information that is a little bit more predictive. Things like BRCA mutations which have been shown to be fairly highly relevant to your risk of getting breast and ovarian cancer. It depends on the company in terms of what report you get back but typically it's done online. You get information about your risk level and some of the companies have sort of color-coded schemes where they say you're at high risk, medium risk or low risk based on the findings that they have.

Erin: How could someone misinterpret these results?

Dr. McGuire: I think there's a couple ways that these results can be misinterpreted. The first is that there's the potential that somebody could not understand the significance of genetic information and how it fits into the bigger picture. They could get a report back that says based on their genetics they're at increased risk over the general population for heart disease later in their life. They could interpret that to mean I'm going get heart disease and get really upset about that. If we educate people well, I think we can minimize the risk of that because the fact of the matter is that's not what the report is actually telling you. I think most of the companies do a pretty good job of educating their customers that that's not what the results mean. Another way that people can misinterpret the results is that they don't understand what's actually being tested for. Let's take 23andme that's testing for the BRCA mutation. There are thousands of mutations in the BRCA gene that have been shown to be associated with increased risk of breast or ovarian cancer. They test for the three most common variants in the BRCA gene. They miss ninety percent of the variants. So, somebody could get a result, and it could be negative on their test. They could assume that they're not at risk but they're not accounting for the fact that they could have one of those other 90 percent of variants. So, they could neglect to follow up with more increased screening, especially if they have a family history of breast or ovarian cancer. There's also the possibility of false positives. Most of the companies are pretty good at giving you analytic validity, so there actually aren't a whole lot of false positives. But, what a lot of people end up doing is, if the company isn't testing for a certain variance, they'll send their genetic information to a third-party interpreter. There have been a lot of reports of third-party interpreters interpreting that information incorrectly.

Erin: Can you see any benefits to at-home genetic testing?

Dr. McGuire: Absolutely. I think a lot of people are very, very curious and we all constantly want to seek information out about ourselves. I don't think that's a bad thing. I think that's actually a good thing. We're very curious about: Who am I? I think that's sort of the fundamental existential question we all have. Who am I? What makes me, me? Those sorts of questions. So, I do think that there's benefits in that regard, just from a curiosity perspective for many of the things that people are looking at. I think there's also a benefit to the extent that many of these companies do ancestry testing and things like that. People also want connection they want to know not only: Who am I? but Who are my people? That's just a function of being human. You hear really interesting stories of people who get connected to a relative that they didn't know existed, or a part of their family from a whole different part of the world that they that they never knew, or adoptees who find their biological parents. You hear good and bad stories about that, but certainly people who are interested in that information find it useful. I have a colleague who knew for forever that his father was an anonymous sperm donor, and he donated sperm to put himself through medical school, and he's now gone on these direct-to-consumer genetic testing websites and has identified two half-siblings and connected with them, has a great relationship with them. Those two half siblings did not know that they were the product of sperm donation, but they feel really fortunate to now have this sort of new, extended family. You hear stories like that and I think that can be really beneficial to individuals. I also think from a health perspective there is the possibility that those who may not know that they're an increased risk for certain disorders could find out that information and it could encourage them to either make changes in their life, or to go see a physician, or to follow up on something. We do hear cases of that as well.

Erin: Have you had genetic testing done?

Dr. McGuire: I have not used a direct-to-consumer genetic testing company, not because I'm opposed to it, but I just haven't done it. I did get offered several years ago by one of my colleagues. doing a research study and was doing not the same kind of genetic testing that the companies are currently doing which is what we call snip arrays. They're looking at the single changes in your genome over thousands of sites in your genome, but they're not looking at the whole thing. I'm not reading the whole book. So this was a particular study where they were reading the whole book. They were doing a whole genome sequencing. My colleague asked me if I would be interested in participating in the study, and I would get back the results of that. It was really interesting because I'm a big proponent of research. I decided at the moment: you can take my blood and you can use it for your research but I'm not so sure yet if I want the results back. I'll tell you a little bit about why I felt that way. At the time, this was about five years ago, I hadn't really thought through the implications of this, but I have a family history of neurodegenerative diseases. My mother has Parkinson's disease, and my grandfather had Alzheimer's disease. So, I wanted to think a little bit about what I want to know if I had a genetic predisposition to either one of those diseases. I thought like I would go back to my office and I kind of do what you know people in my position, bioethicists and lawyers, do we make lists of the pros and cons, and we make a very rational decision. It turned out to be a five-year journey of thinking very carefully about who I am and what it means to be me. It was sort of an existential journey of coming to terms with what would this information mean for me. It was really interesting to me that I went through that because I know probably as well as anybody else that intellectually I know that nothing that they could tell me from my whole genome sequence would tell me whether I was going to get Parkinson's disease or Alzheimer's disease. We don't have a gene that tells us you're going to get this particular disorder for Parkinson's or Alzheimer's. I knew that really well, and yet I was still very concerned that whatever the results were, they would change how I felt about myself. It would change the things that I expected of myself. It might change my relationship to my kids and how they felt their obligations were to me later in life or things like that. So, I spent a long time thinking about that and I didn't get my results back for many years. I did recently get them back. The reason I got them back is because I decided that I wanted to have my mother have her genome sequence because they didn't really know what they were looking for in me unless they knew what she had. So, both my mother and father had their genome sequenced. Once they got their results back, which they shared with me, I felt comfortable kind of going and saying: "okay, now we know what we're looking for if we're looking for anything and I'm comfortable sort of putting that information into context for me individually". I had also gotten to the point where I really felt like I could take that information in and not only understand it intellectually and understand it emotionally what that information was telling me.

Erin: You worked with the genetic counselor through all of this?

Dr. McGuire: I worked with a geneticist, yes.

Erin: If you had gone through Ancestry.com or 23andme, how much of your journey would have been different?

Dr. McGuire: I certainly couldn't have done the test and then spent the time thinking about whether I wanted the results, in the same way. In some ways, it's not that dissimilar. I've actually had a 23andme kit that somebody bought me, which is another interesting story sitting in my house for three years, as I've gone through this journey thinking about do I want to send this in? and what do I want to find out? I haven't sent it in, but it doesn't mean I will never send it in but that was part of it. You have to make that decision before you actually go and have the test done. I will say that I think 23andme does have a couple of findings like risk of Alzheimer's disease that we think might be particularly sensitive for people. If they may not want to know, there's an extra sort of click-through when you go online to get your results and you have to click and agree to see those results. They can mask those if you decide you don't want them. You could later go back and look at them if you would like to.

Erin: If you go to see a genetic counselor versus getting your results online from your at-home test, what kind of a qualitative difference do you have in the information and the kind of understanding you have of what your results mean?

Dr. McGuire: When you get a clinical genetic test, typically you have quite a bit of counseling around what those results might mean for you in the context of your life and your family history and your current situation. When you do a direct-to-consumer genetic test, typically, you get the results on a computer screen and the burden is on you to go consult with somebody who can he can help you figure out what that means. Now, I think some of the companies are thinking about ways in which they can offer genetic counseling services more remotely to their customers and can provide sort of referrals and things like that. Hopefully we'll move more in that direction. For the most part the burden is more on the consumer to take the information if they have a positive result to go get it validated clinically, If they have a finding that they're confused about to go seek out the expertise that can help them understand it.

Erin: What about a clinical genetic test? Is that experience usually captured in a moment? Say they're helping you make a decision about whether to have children or not because of some condition that is in your family. Is it pinpointed on that condition or is it an ongoing relationship with the patient afterwards?

Dr. McGuire: It's typically a one-time test. There's a lot of discussion right now in the profession and in the field about what we ought to be doing about reinterpretation. The science is moving very quickly. Our understanding of genetics and different variants and what they mean for health and disease is advancing very quickly. So, every year there's sort of new variants that are coming up that we say: now we understand that either this variant is significant for disease or we thought it was significant for disease but now we have enough evidence that we know that it's really not significant for disease. It is important for people to get updated information. The challenge with that is that it puts a very large burden on the laboratory to continually update everybody's interpretive information, and there isn't really a way to pay for that. So, it's not something that you can submit to insurance for reimbursement to reinterpret this to see if there's any new information. There's also a challenge losing contact with patients. So, we might get new information about them, but we have no way of communicating it to them. This has been a really big challenge for the field, and I think we're still trying to figure out how to do that. There certainly is a recognition that we do need to be updating information regularly because of just the pace of scientific discovery in this space.

Erin: That does raise the question of: do these at home tests have any updating system where they go back to their customers and say: hey since we did your screening we've learned this, that or the other that might affect your results or how you think about your health going forward?

Dr. McGuire: That's a really good question. I'm actually not a hundred percent sure of the answer, but I don't think that they update your particular results. What people can do is they can sort of download all of their information from most of these companies, and there's this whole industry out there now of "third-party interpreters" where you can upload your results to them and over time they can reinterpret your results as often as you want. Now, again, there have been some issues with the validity of those findings. There have been cases that have been in the media talking about people who have gotten results back from those third-party interpreters that have ended up being false positives or things that have caused them quite a lot of anxiety, or concern that they've later gone to the medical establishment tried to get confirmed and it didn't confirm. So, I would be a little bit wary and careful about what service you're using and how much weight you put on those findings unless you go and get a second opinion.

Erin: Do you have any sense of how frequently people go back to their health care providers with the information they've gotten and say what does this mean? How can you fix me? Is doing the test at home still leading back to a conversation with your doctor about your health?

Dr. McGuire: That's a very interesting question. Most physicians don't have anything to really say on the basis of these results. So if it's a particularly concerning finding, they may want to redo the test in a clinical environment, validate it, and make sure that it's correct. Most of the findings, like I said, that people are getting are increased risk of common and complex disorders. So the clinicians advice would be something like: eat better, exercise more, be healthy. So, we don't know how much it has actually impacted healthcare. We've actually found that people who get sequencing done, get genetic testing done, don't typically follow up with a lot of very expensive tests and procedures. Either one of two things is happening there. One is that the information that they're getting isn't telling them much that is actionable, something that they can actually do something about. The other possibility is that physicians are doing their job which is that they're sort of acting as the gatekeepers and saying: no, you'd actually clinically don't need that test or that's not indicated at this point in time. This is what we should be doing. We want that. We want it to target the right treatment to the right people. So, if you get genetic test results, we want you to follow up with the appropriate follow-up care, treatment, screening, or whatever you need. We don't want you to over treat because of some concern that that may be underlying and not relevant to you at the time.

Erin: Is there any evidence that people who take it home tests are making any changes in their lifestyle, their habits, as a result of what they learned about their health?

Dr. McGuire: There certainly are anecdotal cases out there. So I think Francis Collins one time got up and for a number large group and said I had my direct-to-consumer genetic testing done and I went you know I was motivated by the results to go on a diet and lose whatever 40 pounds or whatever. So people think: yeah that's great we should be doing more of that! We've actually done some research looking more systematically at how people are responding to genetic testing information, whether through a direct-to-consumer company or not. We have one study focused on that and other studies that are focused more on getting this information in a healthcare setting and the sad news is that it's really hard to change people's behaviors. We find that generally there might be a little spike in people eating a little better and doing a little more exercise for a couple months or a couple weeks, and then they go back to their regular behaviors. We hope that it would change people. We hope that anything would change people. We know that you don't to get a genetic test to know that you should eat well and you should exercise and you should take care of yourself. If you're not doing that, maybe this is the thing that puts you over the edge and motivates you to start that diet or to start doing your daily exercise. The evidence shows that it actually doesn't do that in a significant way for the majority of people over the long haul. So, we need to look at that and say how can we better motivate people to be engaging in these behaviors.

Erin: What about psychological effects of learning more than you bargained for?

Dr. McGuire: So the major concern that we've had is that people are going to get horribly depressed and anxious by getting this information. We've now had a series of studies that have looked at people's psychological response after getting genetic testing and uniformly they show that people don't get clinically depressed or anxious. We actually are very adaptable as a human species. We are really bad at predicting how we're going to feel about things. We really are. We will say: "oh my god I would feel horrible if I got this information." -- There's been tons of human psychology studies done on this -- "My life would be miserable I would never be happy again". But, we're extremely adaptable. So what we find is that most people who get this information, including what you might think of is particularly troubling information like increased risk of Alzheimer's disease for example, don't usually get clinically depressed or anxious. Now, the data on something like Huntington's disease might be slightly different. I don't know that data quite as well, but that's kind of a special case. For most of these other risk alleles that we're looking at, people don't get incredibly anxious or depressed.

But do they have others like me who might have more subtle psychological responses to this? Like the kind I was worried about with myself. Do they think differently about themselves? Do they treat themselves differently? We don't really know. We're doing a study right now looking at babies who are getting their genetic testing done, not in a direct-to-consumer setting but in a clinical setting, and we're looking at whether getting their genetic information impacts the way that their parents interact with them, how parents treat them, how parents interact with each other, those sorts of things. We're still sort of analyzing the data, but it looks like there actually is a little bit of an effect on how vulnerable you think your child is when you get risk information about them. So do you bring them to the doctor more often? Do you worry that they're going to get sick more often? Does that have an impact on them or on their psychological development long-term? I don't think we know that yet, and I think that's worth continuing to watch and to study and to be sensitive to.

It's complicated. If there was an easy answer or there was one issue I think we might have solved it but there's new things keep coming up. I think you know part of part of our challenge is to try to get ahead of the game and not to be alarmist about it. But, to try to think about where is the science going? Where is the industry going? A lot of the work that I do is really trying to bring together industry stakeholders, scientific stakeholders, consumer stakeholders, patient stakeholders, government stakeholders. Get everybody in the same room to talk about these things. I think one of the challenges is that you know I as a scientist don't know what you know the heads of these companies are thinking what their business model is, where they want to see this going in ten years and what they see as the major challenges. Similarly, they don't know where the science is going and what we might be capable of or what we see as the challenges. So, there's a lot of opportunity there for increased dialogue across disciplines.

Erin: What should people keep in mind before taking at home tests? What kinds of questions should they ask themselves before ordering an at-home genetic test?

Dr. McGuire: Before ordering at at-home genetic test, I think people need to think about: Do I want this information? What information might I get back? Do I really understand what this information is going to mean for me? Everyone hates to read the fine print right. None of us do it. Yet, I really think these companies have relied on their Terms of Service to lay out what are their privacy policies are, who's going to get access to your information, and how are they going to be able to use it. So people really need to read the Terms of Service because all the companies are different and their terms are different. You need to kind of go in eyes wide open and know what you're signing up for.

[Music]

Erin: Thank you for tuning in to Body of Work by Baylor College of Medicine. If you enjoyed this episode, be sure to listen to part 2 of our interview with Dr. McGuire. It focuses on privacy and the use of genetic information in forensics.

A quick note about the medical advice and opinions stated in this podcast: each individual’s health profile is unique, so please see a healthcare professional about any questions you may have.

Until next time, take care.

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