EP. 141: PERSONALIZED MEDICINE — A THREAT TO PUBLIC HEALTH?

WITH JAMES TABERY

Dec 31

WITH JAMES TABERY, PHD

A bioethicist discusses the dark side of personalized medicine and uses personal stories and his philosophical propositions in equal measure to illustrate a more hopeful path forward.

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Episode Summary

We have featured many techno-optimists on this show — healthcare leaders who believe that precision medicine and emerging technologies promise to revolutionize and democratize medicine in the best of ways. But look under the glossy veneer of this optimism and we see a far more complex story, one that touches on questions of power, inequity and the troubling ways in which genetics can be wielded, intentionally or not, to shape society in potentially dangerous ways.

Our guest on this episode is James Tabery, PhD, a bioethicist, philosopher, and author of the book Tyranny of the Gene” Personalized Medicine and its Threat to Public Health (2024). Tabery gives us a tour of the rise of personalized and precision medicine, a field that promises to tailor treatments to our unique genetic profiles. Importantly, though, he highlights how the blind pursuit of these advances can distract us from larger public health challenges and exacerbate inequality. In our conversation, we explore the historical forces that have shaped modern genetics, ethical dilemmas involving the tension between patient autonomy and societal justice, and necessary guardrails around technological advances. This conversation will challenge your assumptions, whether you are a clinician, a patient, or simply someone fascinated by the ways science shapes our world.

James Tabery, PhD is a professor at the University of Utah, with appointments in the Department of Philosophy and the Department of Internal Medicine (Center for Health Ethics, Arts, and the Humanities). His research areas are history and philosophy of science, as well as bioethics. In particular, he examines the history and modern day implementation of genetics--how debates surrounding that science have evolved over the last century, what impact genetic results are having in the criminal justice system, what impact genetics is having in the clinical domain, and who has benefited and who has been harmed historically be genetic research. His research has been reported on in The New York Times, National Geographic, Time Magazine, and National Public Radio.
In this episode, you will hear about:
• 3:15 - How Tabery became drawn to his work in philosophy and bioethics
• 5:30 - Tabery’s view on the potential perils of the constant march of scientific progress
• 9:34 - The ways in which his father’s early experience with precision medicine shaped Tabery’s thinking on the topic
• 19:33 - Examining the promises and realities of precision medicine
• 30:12 - Navigating the inequities caused by the exorbitant cost of precision medicine
• 35:29 - The challenges doctors face when approaching “financial toxicity”
• 40:00 - Tabery’s worries about medical genetics and AI
• 49:51 - How innovation be controlled in order to better align with ethical concerns
Henry Bair: [00:00:01] Hi, I'm Henry Bair.
Tyler Johnson: [00:00:02] And I'm Tyler Johnson.
Henry Bair: [00:00:04] And you're listening to The Doctor's Art, a podcast that explores meaning in medicine. Throughout our medical training and career, we have pondered what makes medicine meaningful. Can a stronger understanding of this meaning create better doctors? How can we build healthcare institutions that nurture the doctor patient connection? What can we learn about the human condition from accompanying our patients in times of suffering?
Tyler Johnson: [00:00:27] In seeking answers to these questions, we meet with deep thinkers working across healthcare, from doctors and nurses to patients and healthcare executives those who have collected a career's worth of hard earned wisdom probing the moral heart that beats at the core of medicine. We will hear stories that are by turns heartbreaking, amusing, inspiring, challenging, and enlightening. We welcome anyone curious about why doctors do what they do. Join us as we think out loud about what illness and healing can teach us about some of life's biggest questions.
Henry Bair: [00:01:02] Hello everyone! It's been a few weeks since our last episode. As chance would have it, both Tyler and I have been dealing with particularly bad bouts of the cold recently and are finally on the mend. Naturally, this meant a delay in our releases. In hindsight, it actually is remarkable that until this point, the two of us had been able to keep pace with weekly releases over the past three years. It's thanks to you, our listeners, who keep us going. Anyway, to our current episode. If you have followed our show for some time, you will recall the many techno optimists we've spoken with healthcare leaders who believe that precision medicine and emerging technologies promise to revolutionize and democratize medicine in the best of ways. But we want to take some time now to dive under the glossy veneer of this optimism and uncover a far more complex story, one that touches on questions of power, inequity and the troubling ways in which genetics can be wielded, intentionally or not, to shape society in potentially dangerous ways. Our guest is James Tabery, a bioethicist, philosopher, and author of the book tyranny of the Gene Personalized Medicine and Its Threat to Public Health. Professor Tabery gives us a tour of the rise of personalized and precision medicine, a field that promises to tailor treatments to our unique genetic profiles. Importantly, though, he highlights how the blind pursuit of these advances can distract us from larger public health challenges and exacerbate inequality. In our conversation, we explore the historical forces that shape modern genetics ethical dilemmas involving the tension between patient autonomy and societal justice, and necessary guardrails around technological advances. We hope this conversation will challenge your assumptions whether you are a clinician. A patient, or simply someone fascinated by the ways science shapes our world. Jim, thank you for taking the time to join us and welcome to the show.
James Tabery: [00:03:14] Hey guys. Good to be with you.
Henry Bair: [00:03:15] So as I alluded earlier, we've had numerous guests over the years that have built entire careers around advancing precision medicine, including the recently appointed chair of medicine of our very own Stanford Medical School. We are eager to open up the dialog today to hear why you think all is not as great as we may believe. But first, can you tell us a little bit about what drew you to a career in the philosophy of science and bioethics?
James Tabery: [00:03:45] Sure. You know, I was always interested in the life sciences, in biology and medicine. When I went to undergraduate university at Fairfield University in Connecticut, I majored in biology and had visions of going to grad school in biology, or maybe going into medicine. By the time I got to my sophomore to my junior year, I realized that I didn't actually like sort of being in the lab or collecting data, like doing the grunt work of science. But around that same time, I'd also taken classes being offered by the philosophy department in Philosophy of science and bioethics. And what I did find attractive about science were these, you know, I think sort of bigger questions about how science works when it gets it right versus when it gets it wrong. What can we learn from the history of science? When new technologies roll out, who do they tend to help, and who can be left behind or maybe even harmed by them? And so, by getting exposed to these philosophy of science and bioethics classes, I sort of came to learn late in life that there were whole disciplines devoted to thinking about those things. And so I think it was in my junior year, I added a second major in philosophy. I didn't dare getting rid of my bio major because I thought my parents might stop paying for college, but I ended up double majoring in biology and philosophy and went to grad school for Philosophy of Science and bioethics after that, and then came out here to Utah in 2007. And the rest is history. So it was sort of, you know, I think a lot of people actually, in my field have similar trajectories. They start in the sciences. They're very passionate about the science, but they find themselves gravitating to more ethical social, philosophical issues about how the science gets done. And then turns out there's this whole discipline of people that think about that stuff.
Tyler Johnson: [00:05:30] So I think there is a something of a misconception that people who do science, that they're like, yeah, there's a thing called bioethics. And you might like call the ethics department if you have a really difficult sort of personal ethical question in the hospital, right. You're taking care of a patient. And I don't know, they have their unconscious and they have two different family members who want different things. Right? And so you need to call the ethicist to figure out which family member's wishes get to supersede the others or whatever. And so I think people all know that, but I think that the in terms of kind of the march of science through history, I think a lot of people who are in the biomedical sciences actually doing the research, you know, like, what else would you do? Of course you do the research, and of course, you want to have the most cutting edge technologies and the most, you know, exciting new therapies and whatever else. And a lot of what you and people similar to you do is to complicate some of that idea that, yes, of course, this is just a linear progression that, you know, has gone on forever and should go on forever. Can you just talk before we get to maybe your your very specific concerns, but talk about why that idea of the march of progress or the, you know, like endlessly advancing idea of technology, why is that actually more complicated or more problematic than maybe initially, it seems.
James Tabery: [00:06:55] I'll come at it sort of by way of also thinking about how it's often the case that the people actually doing the science aren't incentivized to think about those things. You know, I think a lot of people, academic clinicians, people who are doing the biomedical research, the system is set up now where, you know, people are constantly motivated to get that next grant, get that next publication out, get that next thing that keeps the machine moving forward. A lot of it moves on soft money. And so you're basically, you know, financially and career wise, dependent on keeping that moving forward. And so in my experience, what I see is it's oftentimes the practicing scientists and clinicians. It's not until they get sort of late in life, they get off the wheel, and then they can sort of reflect on what they've been doing for the last 40 years, where you see them thinking about like, okay, what? You know, why am I doing what I'm doing? Why did I do it that way? How could it have gone differently? I went all in on this particular approach, widening it, deliver what I expected it was going to deliver 20 years ago. And so, you know, I think I consider myself privileged in that my job doesn't work that way. I'm given the sort of freedom to kind of have a little bit of distance from this practice and not be as invested in it in terms of like, it has to go the way it has to go in order for me to survive.
James Tabery: [00:08:12] And I can, you know, take that kind of more bird's eye perspective on how this is unfolding. What can we draw on from history to get a better sense of what's happening right now? And I think when you do that, you do see that when it comes to some new technology or some new approach or some new way of thinking about doing medicine, it's very rarely all good and all evil. Typically what happens is this new thing, whether it's, you know, AI or a new form of genetic diagnostic or a new form of harvesting organs, right? Or just a new way of keeping people alive when their kidneys are failing, that thing goes out into the world, and that world is already pre-structured with people that have resources and people that don't have resources and people that have access and people who don't have access. And so mainly what I'm trying to be mindful of is sort of when you sort of take that thing, whatever it is, and it goes out in the world, how is it that the world is structured such that it's going to have a differential impact on different people? And so I think it would be wonderful if every new thing that came along was only good. But our world isn't structured that way to allow that. And so I think that's what creates the space and the opportunity to think about sort of like what is our existing landscape that receives these new technologies and digest them in a particular way?
Tyler Johnson: [00:09:34] I was really struck by an anecdote that you tell in the introduction to your latest book, and then sort of the way that you use that to frame a larger discussion. But so I'm going to get to that anecdote. But first, I want to frame your anecdote by telling something from my experience. So I remember very distinctly, every May or June, I go to Chicago for the annual meeting of the American Society of Clinical Oncology. Asco. And if you have not been to this, it is almost impossible to explain the circus like carnivalesque atmosphere of this place. I mean, it is at least tens if not more than 100,000 people. There is a sort of a set aside advertising floor that is just wilder than something from like a Kurt Vonnegut. I mean, it is like airplane hangar sized. They build these things somehow over the course of like they build them in like 24 hours, and then they're there for three days and then they disappear. It's like Brigadoon or something. It disappears after 24 hours. But they are enormous, like these huge things hanging from the ceiling and these telescreens that are, like, literally storeys high. I mean, it must be in the, I imagine, tens, if not hundreds of millions of dollars to set up this thing that then disappears after three days.
Henry Bair: [00:10:55] I was there earlier this year. Right. And I remember seeing these giant like, Times Square esque jumbotrons with, like, blaring, like, ads for. I thought pretty obscure new chemotherapies. And I remember thinking like, who is this for? Like, who's going to get this? But then I realized, okay, this is like, this is where all the world's oncologists are. So I guess it's reaching someone, you know?
Tyler Johnson: [00:11:15] Right. So I remember going a few years ago and hearing the presidential address. So the president that year was of Asco was a doctor who is a lung cancer oncologist. And the thrust of his message was the miracle of the advance of precision medicine within oncology, specifically within lung cancer. And the thing that I remember the most distinctly from that address was this series of slides he showed where he had pie graphs. So if you can imagine with me, let's just pretend that the pie graph just had. It was more complicated than this, but for the purposes of illustration, trying to talk through it, we'll consider it as having two colors. So the bright red part of the pie graph was the percentage of patients with lung cancer for whom there was no targeted therapy available. And the bright blue was the percent of patients for whom there was a targeted therapy available. And then what he showed is that over the course of the last about two decades, the blue part of that graph has gone from, I'm making up the numbers, but the gestalt is right. It's gone from like 5% to like 70% or something of patients with newly diagnosed metastatic lung cancer who have a targetable mutation. So to put that in words that are a little more digestible for people who are not in the cancer space, basically what that means is that we've gone from a place where about one inch 20 to a place where about 7 in 10 patients have who are diagnosed with new lung cancer, there is a therapy that is available to them that is only available to them because of a distinct genetic or molecular marker.
Tyler Johnson: [00:12:52] That makes us think that this particular therapy will be more helpful for them than it would be for other patients in a similar boat. So the reason that I bring this up is because, I mean, we were like three levels away from any analysis of whether that was I mean, a good thing, of course. I mean, the whole underlying paradigm was that any thinking person who saw those graphs would understand that that was unquestionably a good thing, right? Like, this was sort of in microcosm. This was the march of science, the march of technology and progress. Right. So in the introduction to your book, you tell this really interesting story about your own father, who receives this devastating diagnosis of metastatic non-small cell lung cancer and receives it in this really dramatic and terrible way, where he basically wakes up one morning paralyzed and then finds out over the course of the next weeks or whatever, that he has lung cancer that has gone to his brain and his spinal cord and whatever, and basically has pinched off the part of his spinal cord that supplies strength to his leg so he can't walk anymore. Though he had been an avid fisherman and sportsman and whatever. And then you go on to say, in the midst of this pretty bleak prognosis and and receiving this devastating diagnosis, then word comes back a couple of weeks later that he has this thing called the EGFR mutation. And then because of the presence of the EGFR mutation, he gets this medication called tarceva, which is, you know, I can tell you as an oncologist that is considered one of the quintessential examples of this is precision medicine, right? Like a devastating diagnosis, Theretofore got really yucky old fashioned chemotherapy.
Tyler Johnson: [00:14:31] And now they just take this pill and it has an effect that is virtually like magic is what many oncologists would say. As chronicled in the book by Paul Kalanithi When Breath Becomes Air. He had the same, same mutation. So you tell this whole story, and then he starts the medication and does have a response to it. And your family members are all excited and what have you. But then in the latter half of the introduction and then setting up what you're going to discuss in the book, you sort of turn the whole story on its head and say, actually, maybe this precision medicine revolution of which this is supposed to be emblematic is actually a lot more complicated and maybe is, in effect, not all it's cracked up to be. And I have to say that, as you know, Henry sort of teases me sometimes on the show because I'm sort of the to some degree a techno pessimist to his techno optimist a little bit. And I tend to be not quite as excited about a lot of the technological stuff that our guests talk about. But I have to say that as an oncologist, I had this weird sort of visceral like, well, no, actually, Tarceva really is that cool? I was sort of sure, I sort of found my role reversed. So to start off with, maybe talk us through why, even in what would seem to many to be the quintessential example of when precision medicine is working, why do you argue that it's actually more complicated?
James Tabery: [00:15:53] You know, I think it's all about what the contrast is. The way I came to this field was my father was diagnosed with lung cancer in 2011. He died in 2012. Precision medicine, targeted therapies, personalized medicine, whatever they were calling it at the time was not on my radar then. I was just sort of experiencing the loss of a parent. But I did. You know, I recalled very clearly the kind of roller coaster of being just shocked by that diagnosis, as you said, and then going and visiting and learning what was going on and the severity of it and the fact that, you know, he wasn't walking. And then this drug comes along and we're seeing signs of improvement. You know, ultimately, he dies about 13 months after that day that he couldn't get out of bed. Fast forward to about 2015. That's when precision medicine, I would say, first really got on my radar. I think it was probably when it got on a lot of people's radar. When President Barack Obama at the time mentioned this precision medicine initiative in his state of the Union address, and the fact that there was going to be this massive federal investment in it. And so, you know, for me, I'm a philosopher of science, a bioethicist. I'm interested in genetics. Here's going to be this massive new federal program. And so I wanted to start learning more about this thing and what was so exciting. And I came to it, I think, with some of the same optimism that you were just talking about earlier.
James Tabery: [00:17:04] What I found when I started moving around in that space was these references to I didn't know what imatinib was yet. I learned about that later. I didn't know what Herceptin was like. I learned that later. But I saw all this talk about Tarceva, and it was, as you were saying, sort of this, you know, this great success story that then got me thinking, well, you know, wait a second here. My father never regained the ability to walk. I can still remember distinctly sitting in the in the ICU when we got that diagnosis of lung cancer. That was all through his body immediately going online to look at, you know, what is the survivability, you know, based on on where he's at. And it's set about eight months at that time. So Tarceva probably, you know, I think by all accounts he lived longer because of that. But there's a way in which he's very representative of this space, which is this drug does not make the cancer go away. It puts it in remission. If you're lucky, it can put it in remission long enough to find another drug that maybe can then attack it with. But, you know, somebody who works in oncology, you know, when that cancer evolves and adapts to that drug, it comes back with a vengeance. And that's exactly what happened. Once the tarceva stopped working. My my dad was dead within weeks. And so on the one hand, I think if you think the contrast is, well, what did the world look like for people with lung cancer before a drug like Tarceva came along? I can see why people are excited about that, right? I mean, you know, he never had to go under that general chemo Tarceva is fairly symptom free compared to lots of other chemotherapies.
James Tabery: [00:18:32] And it did. You know, I think he clearly lived longer because of it, but that benefit came at a great cost. The drug was extremely expensive and the drugs that have come out since then, in the decades since. You know, they're even more and more expensive. And, you know, I think what really hit home for me was. Again, the drug didn't make his cancer go away. You know, he died of lung cancer. And really. What I would have liked is him for never to have got lung cancer in the first place. And so. You know, I think what I've been trying to pay more attention to is what are the things that medicine can be doing to try to prevent people from getting sick in the first place, which is largely about things in our environment, giving people access to healthier food, healthier air, healthier living spaces, so that when they get the cancer or they don't get the cancer in the first place. Because, you know, I think what happens then is you end up dealing with extremely expensive things, which typically aren't cures. They just delay a terminal illness for a period of time.
Henry Bair: [00:19:33] So correct me if I am mistaken here, but it sounds to me as if the issue isn't with precision medicine. It's not with the approach. It's not with the technology itself. It really does sound like the issue you have with it is the communication around it. Maybe the attitudes people have, the overoptimism people have around it, and maybe how it's implemented in terms of who gets it, who doesn't get it. How are the resources of the country and of the healthcare system allocated in terms of precision medicine? Does that sound right to you?
James Tabery: [00:20:07] Yeah, that's absolutely right, Henry. You know, as I was sort of familiarizing myself with this precision medicine space, the three claims that I kept seeing over and over again was what we're seeing in cancer and also rare diseases is going to spread out across healthcare. You know, there's going to be a tarceva for bipolar disorder. There's going to be a tarceva for diabetes. There's going to be a tarceva for take your pick two, that it's going to drive down the costs of healthcare, because now we're not doing this sort of scattershot. Just throw everything at patients until you find something that works. You know, your genome sort of tells you to go this route instead of that route. And three, it was going to combat unjust health disparities that if we could sort of get all this genetic information from really diverse populations, we'll be able to ensure that this revolution reaches out across the board and everybody benefits. And that's going to sort of get rid of inequities that we think are wrong. You know, my concern about about it is on those particular things. I think there's plenty of evidence to think that actually, it doesn't deliver on those things that cancers and rare diseases are the places that it's got some purchase.
James Tabery: [00:21:07] And we should be very skeptical of thinking that we're going to see things like tarceva for diabetes or heart disease or any number of mental illnesses that it hasn't been driving down the cost of health care. In fact, it's been driving them up and that it's risk exacerbating health disparities rather than making them go away. And so you described it as a communication issue. Henry I think that's right. I mean, if if this was sort of explained, as you know, we've got these new genetic tools and there are certain medical conditions for which we've long known that there is a genetic basis for what's going on here. Whether we're talking about cystic fibrosis or sickle cell disease or various cancers. And now, look, we've got the technologies that have come along where we can harness these new genetic interventions to do something about these things that we've long known to be genetic. I wouldn't have a problem with that. It's the sort of optimistic overreach of thinking, and this is going to just spread everywhere, and it's going to drive down costs and everybody's going to benefit. And I think even when this was rolling out in the early 2000, there was reason to be skeptical of that sort of optimism.
Tyler Johnson: [00:22:17] To that point, there are, I would say, some what I perceive to be related phenomena kind of epiphenomena surrounding this whole issue that concern me. One is the problem of the receding horizon, right? Which when you couple that with the very deeply vested incentives that researchers have to try to make progress, right? Like, no matter how much progress you make and then it actually hasn't resulted in any sort of writ large benefit for humanity, you can ad infinitum say, oh, well, it's just because we haven't we just haven't made enough progress. But when we make more progress, then then it'll do this thing that we've always been wanting it to do, right. That's one issue. And then the other issue, which you have alluded to some specific examples of this, but I often think of a quote from Wendell Berry who says that in regard to sort of technological innovation in general, we all know very well how to add, but we have culturally forgotten how to subtract. In other words, it's easy enough to say, oh, but look at all of the benefits of this thing or that thing, whatever the technological innovation is. But there's this sort of almost inherent blindness, this almost inability to really grapple with what are the problems that come with that innovation, to the point that there's almost a cultural inability to perceive the complexity of so-called progress, right? I mean, even the name progress implies that it is this sort of linear upswing forever. Right? And I think that that greatly oversimplifies what are almost always yes, there are benefits for particular patients and particular scenarios. But then there are also significant drawbacks, both personal and societal, that we often just sort of kind of put in our tunnel glasses and don't even acknowledge that those are there.
James Tabery: [00:24:13] Yeah. Yeah. I mean, the case that I think of that illustrates that point are all the excitement these days about polygenic risk scores. So these are, you know, data where you get sort of whole genome information or genome wide association study information spits out all this information about SNPs spread across the genome. And then you can take that and look at particular patients and say, you know, based on not a particular gene in your genome, but this sort of distribution of SNPs across your genome, you're at elevated risk of this or relative decreased risk of that. And there's just so much excitement in the medical genetics community these days about these polygenic risk scores sort of being the thing that now everybody is going to have that sort of no matter who you are, what your family history, we can spit out a polygenic risk score for you when it comes to cardiovascular disease or diabetes or obesity, you name it. But you have to rewind. You know, polygenic risk scores were a direct response to the mid to late first part of the first decade of the 21st century, where we were doing all these genome wide association studies, and the vision was, we're going to go out there and find the genes for all these things.
James Tabery: [00:25:24] We'll find the diabetes gene, we'll find the cardiovascular disease genes, we'll find the schizophrenia genes, we'll find the bipolar disease genes. And they didn't find them. I mean, what they found instead was, you know, for any of these traits, there were just hundreds or thousands of places in the genome that were associated with the trait, and that obviously made it really difficult then to do things like say, okay, this is how we're going to intervene to stop that, or you've got this gene so you're at risk or decreased risk. And, you know, there was this period of sort of 2007 to 2009 where the medical genetics community was doing a lot of hand-wringing over what was called the missing heritability problem. They were sort of, what are we going to do? We're not finding the genes. And the polygenic risk score was essentially a kind of a workaround. It's like, well, we're not finding the genes, but maybe we can just sort of like squish all this risk information together into one score.
Tyler Johnson: [00:26:10] Which is sort of all the genes.
James Tabery: [00:26:12] Yes, exactly. So that's exactly what it is. And so it was the very thing they didn't want to do and didn't anticipate having to do, but then had to do because the human genome was just so complicated. But all that history, you know, even though it was only like 15 years ago, has essentially been forgotten. And now it's just these polygenic risk scores are the next best thing. We got to be super excited. We're going to get them from everybody. We're going to get them back to people. They're going to improve clinical care. We're going to be able to make predictions. We're going to be able to stratify patients based on their polygenic risk scores. And it's just the latest version of that receding horizon where now this is the thing that we're supposed to go all in on, because the genome wide association studies didn't turn up what they thought were going to get turned up. Well.
Tyler Johnson: [00:26:51] And it's so funny too, because this I mean, this particular company has recently sort of completely fallen apart, at least in part because of mismanagement. But for a while, all the rage around here anyway was 23 and me or things like that, right? Where you could have your genetic code read out for, you know, however, not very much money actually. And then they would send you this big fat packet with all of these polygenic risk scores and whatever. Yeah, but the thing that's so funny about most of those, yes, it is true that every once in a while, a company like that might identify something like a BRCA mutation, which that is a, you know, that's a real deal thing, that we can have a whole discussion, although even that is really complicated what to do with that information. And I think you can argue that they don't do a very good job of prepping their patients for what to do with such a weighty thing, but if you put that aside for a moment, most of what happens instead is like, oh, you have this thing that puts you at like a 15% higher risk of, you know, eventually developing cardiovascular. And they and we to some degree want to act like that's some big helpful. But like so then really what you're going to do like 15% more exercise or eat 15% fewer donuts or like yeah, I mean, I'm not even sure like what that's supposed to mean, even if as an internist, right. If some patient brings that to me and says, well, here's my report. Now what? I mean, my answer would be the same as if they had never had it done, which is eat your vegetables and go running. Like.
Henry Bair: [00:28:16] Yeah, I actually I have had patients like bring in their 23 And me scores. You know, it's like oh I'm at like a 10% higher risk of dementia. What should I do about this? I'm like, I don't really know. You know, like normal stuff like I would recommend to everyone.
Tyler Johnson: [00:28:29] But you should definitely be 10% more worried about it. That's the one thing you should for sure do.
James Tabery: [00:28:34] Yeah, there was a really nice article that came out in Bloomberg in the spring by a reporter named Kristen Brown, where she basically did a deep dive into 23 and me and used it as a kind of lens to look at what's happened with the genomics industry, basically for like the last 20 years. She does a nice job of showing how the the roller coaster ride of 23 Andme is in some sense indicative of what the genomics community itself has faced. You know, if you go back to the beginning of 23 me in 2007, there's just all this excitement that, you know, we're coming out of the Human Genome Project. Now we're doing these genome wide association studies. We're going to find the genes. What makes Tyler and Henry and Jim different are our genomes. And once we get our individual reports back, we're going to be able to, you know, sort of figure out what drugs work for us and don't and what I should be doing and what you should be doing and who's at risk and who isn't. And people flock to it, right? I mean, it was an enormous, enormous The success. Oprah is giving them away, right? I mean, people are going to spit parties. And it was all wrapped up in these excitement about the thought that the genome really is what's sort of driving a lot of these health outcomes. And so now we've got the the tools that are relatively inexpensive price to find out what's lurking inside me that's going to reveal that information. Right. And today 23 Andme is a penny stock. Right. And I think it's not just the mismanagement. I think it is showing that the genome just didn't deliver on the promise. Right. That it turns out when we got all that information, there wasn't a whole lot to tell people in terms of actionable information. You can tell them, you know, you probably don't like the taste of cilantro, or you've got this kind of earwax, but like, that's not what you need when you're, you know, trying to figure out how to make better health decisions.
Henry Bair: [00:30:12] So your point is well taken. But, you know, I want to go back to talking about therapies. And I want to use like concrete language, a concrete situation. So, you know, when it comes to considerations of cost, which, you know, a lot of your concerns are resource allocation. This is a judicious use of resources, right? I think when it comes to costs of pharmaceutical development or cost of treatment, I think generally doctors don't think about it. And when they do, I feel like the culture of medical training almost takes pride in not thinking about those things. It's expensive, but the price of living longer. The price of a life is is priceless, right? We're not going to put a dollar amount on it. It doesn't matter how expensive it is, we're going to pursue it until we get a good result. And I sort of have like a personal stake in this, if you will. So my brother has spinal muscular atrophy, which is a rare genetic disorder. He's tried a few of these really fascinating, very high tech, advanced genetic zolgensma Nusinersen. Yeah, exactly. So he's been on Nusinersen and he's currently on Risdiplam. And these are medications that directly modify the genetic mutation that contributes to the production of nonfunctional proteins that control his motor neurons. It's like $400,000 a year, and he's able to go through some kind of grant or foundation, or because he's a part of a clinical trial. So there's a lot of government funding into that. And I think when it comes to like orphan drugs like that, we see it as a noble thing to not think about the cost. Right. It's almost as if it's so expensive, but we're going to do it anyway. And that is the right thing to do, and we're proud of it. Right. And I'm wondering just in response to that, what do you say.
James Tabery: [00:31:51] On that sort of case? I think we just need to be honest about the costs and then sort of, you know, have an open conversation about what we're willing to invest in. Who. Right. So I think SMA is a great example because those things like Zolgensma and Nusinersen, they've been around for quite a while now. And I think, you know, they were sort of I think if you think of imatinib and tarceva being the drugs that are sort of getting people really excited about cancer's, the treatments for SMA that follow are the ones that initially get people really excited about gene therapies for rare diseases. The initial argument for those just astronomical prices. Zolgensma is in the millions of dollars. Nusinersen is about $1 million a year is. Well, yes, these are expensive, right? But these are one off cures. You had people that had a fatal disease that who, if they, you know, lived 20 years ago, would have died or you would have invested hundreds of thousands or even millions of dollars in them over the course of their life to try to keep them alive. But now we've got these new genetic interventions that are almost sort of like a magic wand that makes the thing go away. What we've got now is lots of data that suggests that that's just not the case. I have a PhD student here who recently defended her dissertation in Pharmacoeconomics, where she got all this insurance data about people with SMA getting access to therapies.
James Tabery: [00:33:15] And what you find are in many cases, they're not on one drug. They've tried zolgensma and it didn't work. And then they tried nusinersen and it doesn't work. And then if that doesn't work, they go to a third. And so it's not this magic wand that sort of makes it go away. And also in many cases, they're still getting traditional therapies on top of that. And so I think the point is somebody who is born with SMA or lives with a period of time with SMA and then gets the drug, has already experienced a significant amount of development such that that disease is already sort of a part of their phenotype to a certain extent. And it's rare, even in the world of medical genetics success stories, that there's something that truly is like this wand that makes it just simply go away. And so, you know, I think the question becomes, what does it look like to fairly give kids with SMA access to these drugs? Is this the kind of thing where the government should be subsidizing this? You know, I've heard medical geneticists. I just wish the government would subsidize all treatments for all genetic conditions. Okay, that sounds nice, but I think at the end of the day, kids with genetic diseases I don't think are any their lives are not more or less valuable than kids with diseases that aren't derived from genetics things.
James Tabery: [00:34:26] Right? So it's like, why are we going to go all in on subsidizing these treatments for those kids just because their disease is of that form, but not handle these other things that are products of different etiologies? If we're not going to subsidize everything, then how do you give people access to it fairly? I mean, if you look in the asthma world, it is heartbreaking. You see families trying to crowdsource money, to get money to save their kids, traveling to different countries where they think they'll have a better chance of getting it. I think there are genuine issues of fairness where once you're in the system and doctors are already invested in you, they're more likely to try a second or even a third drug on you, even though those are extremely expensive and there's lots of patients who aren't getting access to the first one. So, you know, this is fundamentally a question of justice. And we just need to sort of be honest with ourselves and the patients about how this works and what it's going to do and what it's not going to do, and then, you know, ultimately make, you know, hard decisions about what we do. And we've got these extremely expensive treatments that not everybody can get access to.
Tyler Johnson: [00:35:29] Yeah. You know, to Henry's question and to your answer, I'm really struck. So you mentioned very early in the course of the program the term financial toxicity. And that has become a little bit in fairness to the oncology community. That's become a little bit of a buzzword recently. Right. So there are some mostly younger researchers who are starting to really take that seriously and are starting to try to integrate that into the way that we think about care models and whatnot. But I mentioned that mostly because it stands in such contradistinction to historical norms. What I mean by that is that, you know, oncology is unusual, I think, because while there are examples like SMA that have these truly astronomical price tags, and while yes, there are things like, you know, if you're in cardiology and you're talking about getting like a ventricular assist device or if you're, you know, in heart failure, liver failure, you're going to get a transplant or something like, we can look at those things. But the thing that's unusual about oncology is that for most diseases, there is this sort of litany of potential available therapies. And in most cases, the assumption is as long as the patient is well enough, if there is any even reasonably small but still reasonably small percentage chance that a thing will work, you will try the thing. Right? Right. But the thing that is so striking to me about this is that, I mean, I'm a board certified medical oncologist who trained at some of the most fantastic training programs around.
Tyler Johnson: [00:37:01] I think it is literally true that in my four years of medical school, my three years of residency, and my three years of fellowship, I think it is literally the case that not one single time did I have anyone talk to me about even a way to think about how to measure financial impacts of anything that I would ever do, ever. Right. And in fact, to Henry's point, if anything, there is often a sort of a an unstated but very strongly felt intuition that even broaching the subject of the cost of a therapy is sort of unethical or almost unseemly. Right? Like, you could never do that, even though, as you point out, what is actually happening by not addressing it, it's not like the financial toxicity goes away or doesn't exist. What largely happens is that the people for whom it's really a problem sort of self-select. They kind of weed themselves out, and then we're left with the people who are privileged, who can get access to the therapies because they're the ones who are able to get access. Right. So it's it's like it's a convenient way of pretending that that dimension of care is not a dimension, when in fact all it's probably doing is just exacerbating sort of preexisting echelons of who gets what kind of care.
James Tabery: [00:38:25] Yeah. And I mean, the other complication in all this, I think, is even if a physician wanted to have that conversation, and even if they were dealing with a patient who was really keen on getting that information, it's very difficult when a patient walks through your door and you're talking about a course of treatment to predict in any sort of reliable way what the cost of that is going to be in terms of it hitting their pocket. Right? I mean, I've tried having it, you know, uh, well, we're thinking about doing this and. Okay, what's it going to cost me? Oh, well, I have no idea what it's going to cost you. It depends on your insurance and the premiums and then this and then that. And then, of course, if they deny it, you could try, you know, sort of appealing it. It was just like, there's no way that can be predicted based on, on your situation. You just have to roll the dice and then see. And then if you want to try to, you know, haggle over it later, you can. And so I think that's just, you know, that's a problem with our current health care payment system, where there is just so much between what a clinician wants to offer a patient and what finally, you know, is on that bill that they get maybe three months later, that it makes it very difficult to try to anticipate that financial toxicity. You could have two patients who, on the face of it, look like they're clinically identical, coming into your office in one day, and you're making the same recommendation because you think it's what's in their best medical outcome. And yet, three months down the road, somebody is in basically medical bankruptcy and the other person never sees a bill.
Tyler Johnson: [00:39:53] So I remember very distinctly we had on the show, I don't know, six months ago or something, the is it chief medical officer for Microsoft? Henry is that am I getting the title right?
Henry Bair: [00:40:04] He was the chief scientific officer, Doctor Eric Horvitz.
Tyler Johnson: [00:40:07] We were talking with him in particular about the advent of AI and sort of what AI is going to mean for medicine. And the thing that was so striking to me is that I tried multiple times to because, as I mentioned earlier, I'm, I think a little less optimistic than a lot of our guests are about the likely impact, in particular, that AI is going to have in medicine. I recognize that it may. It's possible, but I think I'm less confident that it's assured than a lot of our guests have been. And so I tried to point out multiple reasons that I was concerned about the effect that AI is going to have on medicine. And, Henry, tell me if I'm mischaracterizing this. I don't want to mischaracterize, but I would say that the answer, in effect was, look, yes, we recognize that there are potential problems, but just as we've always done, we'll manage the problems, right. We'll we'll sort of respond in a way such that the net effect. I'm very confident, he said, that the net effect will be good. I'm optimistic. And I guess one of the things that strikes me the most about your book and some of your wider discussion. I mean, the title of the book, just to be clear, is is it the tyranny of the gene or the tyranny of the gene? Right. And that's a really strong title, right? That's not just a sort of well, there are some aspects here that I'm a little bit worried about. Like that seems to communicate that you have some pretty big picture overriding concerns. And so I'm hoping you can tell us a little bit about what are some of those bigger picture, pretty ominous concerns that you have. And what would you say to people who, in effect, just say, well, you know, if stuff comes up, we'll manage it. We'll just figure it out.
James Tabery: [00:41:42] Okay? Yeah. I mean, I'll give you maybe 2 or 3 examples of what the kind of big picture worries about medical genetics are. There is a big push now to go into communities of color and get diverse DNA, all under the marketing language of this is going to combat health disparities. That really worries me. You know, so you've now got there's obviously, you know, a history of well earned distrust of the medical industry when it comes to communities of color. There's now this full on push by the medical genetics community to say we learn from that. We're now fighting the good fight. You concerned about health disparities? We're concerned about health disparities to give us your DNA, and we're going to help you deal with those problems. And there are decades and decades of high quality social science research about the causes of health disparities. And no matter how much DNA you get, it's not going to solve those problems. And so I worry the medical genetics community is basically sort of setting itself up for another big debacle, when it's sort of that promise just doesn't deliver. I do think when you're thinking about precision medicine, if the precision medicine when it took shape as this, you know, vision of delivering the right treatment to the right patient at the right time, it was always set up in contrast with this character of traditional medicine, which was one size fits all medicine, sort of like no matter who comes through the door, you treat them the same. And the big vision of genomics was, oh, we now realize just how faulty that was.
James Tabery: [00:43:14] The problem with that right treatment for the right patient at the right time is the way it works, is we're talking about this earlier, like it carves up patient populations into smaller and smaller units, which then necessarily drives up how much it's going to cost to provide treatments to that patient population. So whatever you say about one size fits all, it tends to be relatively cheap. And it oftentimes has an enormous public health impact. Right. Think about like the vaccines for Covid, those were one size fits all and they were tremendously effective. And so, you know, when we switch to this kind of veneration of moving away from one size fits all and trying to do right for the right, for the right, I worry that we are chasing a goal that is just necessarily going to drive up costs in a way that's going to be unsustainable. And unsustainable doesn't mean 15 years down the line there aren't going to be any more drugs. It's unsustainable means 15 years down the line, fewer and fewer people have access to the actual drugs that they need because of the way that the costs have evolved. Move over to AI. I absolutely agree with you. It is now the new thing for which there is just enormous excitement. What you didn't say, but I think is also worth getting on the table, is there's also people that think AI, you know, like we're just a few months out from the Terminator scenario where we're all being killed by the machines that made us, as in most cases, I think it's, you know, it's going to be somewhere in between there.
James Tabery: [00:44:40] There are lots of things that we need to be protecting against. Ai works off the data that you feed it. If you're feeding it a bunch of biased data about, you know, where you should go deploy your police force or where you know who you should be privileging for medical treatments in your hospital. It's going to give you recommendations that reinforce those biases. And that's something that we need to be mindful of. But, you know, we are entering the world of big data. And it's and I think AI does have the power to potentially be really useful at trying to pick up on patterns that lend themselves to interventions that might have quality health outcomes. That could be about, you know, predicting how much blood to have on hand when somebody is going in for a surgery because you don't want to waste the blood, but you also don't want to not have enough there if they need it. There's a researcher here at the University of Utah and hematology who's trying to use these sort of programs to do that kind of prediction. I think that's great. And it's just we should see it as that. It's a tool. It's a tool like any other tool. And it's not about it sort of being amazing or evil. It's about how do we appropriately harness it to deliver the results that we want it to deliver.
Henry Bair: [00:45:52] So I want to pick up on your concerns about the financial implications, economic implications of this move towards precision medicine, personalized medicine. I think it's from a sociological from an economic population level. It absolutely makes sense. But I think there's there's always this tension, right. With the the population, what's best for the population versus what's best for the individual. I have to imagine that most people, if they were in the patient's chair, why wouldn't you want. Something that was tailored to you that we know will probably work better for you than. Something that's just one size fits. All right? Like part of me just. I want to probe a little. Bit more on that. Right. Because I do have these conversations with with patients. Right. Especially since. You know, I'm an ophthalmologist and there are so many inherited eye diseases. Sure. And there are a lot. Of genetic therapies for eye diseases. And I've definitely had had patients come and say, you know. I know right now there's nothing, but is there anything in the pipeline that you're aware of? That could work for my mutation. Right. So I think that's totally valid and it's a logical thing. To want what works best for you, how do you recommend that we address that discrepancy, that tension there?
James Tabery: [00:47:01] Yeah, I think you're absolutely right. Look, if I get diagnosed with lung cancer tomorrow, I am going. To want to get genetic testing as soon as possible. If my kid is diagnosed with SMA, you better believe I'm going to be wrangling to get access to zolgensma, you know? And so like, I certainly agree with you that it's reasonable and appropriate for both. I think patients to want access to that and in turn for clinicians to try to give their patients access to that. What I would say, though, is that availability of zolgensma or a particular test for an eye degenerative disease or a particular cancer is at the tail end of years of investment in some sort of treatment for that thing. Right. Private companies were involved. Probably federal grants were at the beginning of it that then spun off to private companies. You had venture capitalists. I mean, it's sort of like there was lots and lots of money invested in bringing that thing to life. What I think is more not at the patient and clinician level, but as a society, we need to just ask questions about, you know, where do we want to invest our resources so as to maximize health across the population. When you look at the United States, compared to other developed countries, you know, we just have awful infant mortality, maternal mortality, life expectancy, chronic disease. And that's in large part because we don't invest in the kind of social safety net that gives people access to preventative medicine very easily, access to treatments earlier, just access to an environment that allows for healthier living.
James Tabery: [00:48:37] Typically, the way it works in the United States is you just wait till you're sick and then roll the dice, hoping that your insurance, if you have it, is going to cover the thing that might be out there to treat you. For some people, that can work pretty well. But I think, you know, in general, when you when you look at us across the population, it's not doing very well. You know, when we compare ourselves to other countries where we think we should have life expectancies that they have, look how much we're investing in this, or we shouldn't be having infant mortality at this rate. Look how much we're investing in this. It requires rethinking how, as a society, we are distributing resources and where we are focusing our attention. Are they in sort of in social safety nets? Are they in biomedical research? Are they about public health? Are they about clinical care? That's where I think the conversation, you know, my argument would be we should be focusing more on public health, preventative treatment, social safety net work. But we live in the world we live. And again, if my kid has asthma, I'm going to try to get him access to Zolgensma because that is the reality that we live in. We are on a massive ship that is very hard to turn, and to the extent that you're still on this ship, when something comes along in your personal life or you're a clinician dealing with a patient, I think you've got to just sort of work to give them the best shot that they've got.
Tyler Johnson: [00:49:51] So I want to ask one final question that I feel like is really important, that I confess that I often am really at a loss as to how to answer this, but it feels really foundationally important. So, you know, I mentioned near the beginning of the program that quote from Wendell Berry about that. We're really good at adding up the positives, but almost incapable of recognizing the negatives. Or as he says, we've forgotten how to subtract. The thing that I wonder is this. So again, if we think about cancer, for example, right, there are many things that we know that people could do to reduce their risk of cancer. And in fairness, there have been some public health success stories. Right? The most obvious one is the decline in smoking rates in the United States and many other places over the course of the 20th and early 21st century. Right. And, and we have seen a decrease in the, you know, the risk of lung cancer concomitantly with that decreased risk of smoking. So I want to recognize that. But nonetheless, there are many things in terms of the amount of alcohol that people drink, the kinds of food that they eat, the amount of exercise they get, how much they weigh, like there are many other places where there are much further downstream interventions.
Tyler Johnson: [00:50:57] But what happens is that, in my mind, the development of precision medicines for oncology is in effect a unidirectional ratchet system. Right. Where there's just because of the ingrained incentives for both for researchers to get whether it's promoted at their company or whether it's getting tenure at their university or whatever it is. Right. And because people, as you said, understandably appropriately, it's exactly what I would do are so desperate for therapies once they get cancer, it's like the ratchet only goes in one direction, right? And especially because there's so much money to be made for private investors and pharmacology companies and whatever. The same thing happens with AI, right? I mean, it's a different set of circumstances, but because there is so much money to be made in AI, right? If you look at the what's the company that makes the chips that's had its stock go up like a zillion times in the last three years?
Henry Bair: [00:51:51] Nvidia.
Speaker4: [00:51:52] Nvidia. Yes. So if you look at Nvidia stock right. That's the emblematic example that the amount of money made there is almost incomprehensible because they're writing that AI wave. So the question that I want to ask is this. When there are so many fixed incentives and when the system is set up to incentivize that kind of iteration and innovation basically infinitely, who or what is supposed to act like a brake or who or what is in a position where they can say, hey, AI, tech bros, let's slow down a little bit. Maybe we shouldn't just go sort of careening off the cliff and hope the parachute is there once we're midair. Right. Like who in the United States, which is driving many of these innovation cycles? Like, who can do that or what would that even look like? Yeah.
James Tabery: [00:52:45] Well, I think the short answer is it's extremely difficult. And that's you mentioned the sort of controversial title of tyranny of the Gene before. In part, that's what I'm trying to capture. Like there are all these forces sort of forcing us to sort of just keep riding this train that's going faster and faster and faster, and it's not obvious how to get off. I do think, though, you can look to places where there are examples of, you know, efforts to try to slow it down or redirect it in some way. And it's not going to be any single one, but I think it's worth just sort of showing that, oh no, some things can be done. So, you know, it took a lot of political will, but it built into the Inflation Reduction Act. Was that effort to cap prices and allow the government to negotiate with drug dealers for just a handful of the most expensive drugs. I mean, we are the only developed country that doesn't do that or didn't do it up until recently, because there is just this sort of in the United States, this the sense of private industry and capitalism being sacrosanct that you like to intervene on it would be evil. And efforts to do that, just to sort of say, hey, there might be like some threshold that we think you've made billions and billions of dollars.
James Tabery: [00:53:56] That's probably enough. So we're going to cap this to make sure that more people get access to it. I think that's a big win, right? And the fact that there was so much pushback from it, from the drug companies, I think is a sign that it was a big win. You can also see, you know, different pockets of ways of thinking about doing this research differently. So there's a group called the Native Biodata Consortium, which is a collection of indigenous biomedical researchers who are very focused on data sovereignty and data control. So basically, you know, rather than letting any old private company or even the federal government get their hands on indigenous data and use it for whatever they want, trying to make sure that it's the tribal communities who have control over it, who leverage it, who decide how it's going to be used. That's a very different way of thinking, sort of like, well, if you want to develop a drug, you know, this is how you do it, you get the grant and then you spin off the company and then you get some investors, and then you charge a buttload of money, and then you get your boat, you name your boat after the drug.
James Tabery: [00:54:49] Right. Like that's sort of the trajectory that I think a lot of people just take for granted. And I don't think we have to take it for granted. There are different ways that you can imagine picking winners and losers when it comes to drug development might not just be sort of the free market gets to decide. You could have a sort of award system where you try to incentivize researchers through prestige and say, okay, you don't get to go private with this, but you get sort of like the equivalent of a Nobel Prize, and the name of the drug is going to have your name on it when it goes out there. But, you know, these are different ways of thinking about how the world has to work. And so I think something that clinicians and your listeners can do is not just take the world as it's given as a given. Think about, you know, are there different ways to do this? You don't have to be the one who solves the whole thing. But can you have a conversation differently? Can you pursue an investment opportunity differently? I think that is where you sort of have the opportunity to think about, you know, going about it in a way that doesn't just keep us accelerating on the train.
Tyler Johnson: [00:55:50] You know, normally when we have medical doctors on the show, we'll ask them sort of at the end, what's your one kind of takeaway for, you know, people who are younger who are practicing one thing they could learn. And I think actually, that's a lovely idea for us to end on that, that a way to think about how to make something of this whole discussion that we've had is that if you are playing some role in the biomedical innovation community, trying to step back, look at the bigger picture and think about, yes, but like, what is all of this writ large doing? Like, what direction is this moving in? And, you know, I may not be able to fix everything, but is there a thing that I can do to influence this in a way that is more thoughtfully about improving the world and not just by default, about improving people's pocketbooks, which is generally sort of the, you know, the motor that that fires most of what happens. I think that's a really sort of actionable and beautiful way to think about what one person might do.
James Tabery: [00:56:51] Great. And double major in philosophy, that would be the other thing.
Tyler Johnson: [00:56:54] And double major in philosophy that too that. Gym. We so appreciate having had you on the program. It's been a really fascinating discussion. We appreciate the good work you're doing and we wish you all the very best.
James Tabery: [00:57:05] My pleasure. Thanks, guys.
Henry Bair: [00:57:10] Thank you for joining our conversation on this week's episode of The Doctor's Art. You can find program notes and transcripts of all episodes at the Doctor's Art.com. If you enjoyed the episode, please subscribe, rate, and review our show, available for free on Spotify, Apple Podcasts, or wherever you get your podcasts.
Tyler Johnson: [00:57:29] We also encourage you to share the podcast with any friends or colleagues who you think might enjoy the program. And if you know of a doctor, patient, or anyone working in healthcare who would love to explore meaning in medicine with us on the show, feel free to leave a suggestion in the comments.
Henry Bair: [00:57:43] I'm Henry Bair
Tyler Johnson: [00:57:44] and I'm Tyler Johnson. We hope you can join us next time. Until then, be well.