Arthur Caplan: Medicine’s Toughest Ethical Questions

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University. We’re trying to get closely to the truth about health and healthcare. We’re excited to welcome Dr. Art Caplan today. But first we’d like to check in on current hot topics. What do you got for us this week, Harlan?

Harlan Krumholz: Well, today was kind of a big week in the biotech industry, and I’m always sort of following what’s going on now in the life science. I’m very interested. It’s just, some things are moving so fast, but it’s unusual, not unprecedented, but unusual for a company to come out of nowhere and commandeer a billion-dollar investment, not a billion-dollar valuation.

Howard Forman: Yeah, it’s phenomenal.

Harlan Krumholz: But actually a billion dollars in capital being directed towards a new company. I don’t know—

Howard Forman: Almost unheard of.

Harlan Krumholz: You hear about them?

Howard Forman: Yeah, it’s almost unheard of.

Harlan Krumholz: Yeah, I don’t even know how to pronounce the company. It’s spelled X-A-I-R-A, and what’s it about? It’s about synthetic protein. So this can be quite abstract, and it can be kind of hard to understand what the heck is this thing with the synthetic proteins. So just think about it like this. Just like an engineer can design a robot to carry out specific actions, there are scientists who can design these synthetic proteins with specific structures and functions in mind, and then they can use them to actually execute on specific actions within the body, for example, or even to build materials.

So for example, in building robots, various parts are manufactured to precise specifications, so that that robot, perhaps in a factory, can do the exact function that it’s supposed to do. In synthetic protein production, they’re taking the building blocks, the amino acids, they can be assembled in a specific order to create a protein. And here’s the important part, they’re learning how they fold on each other so they can understand the three-dimensional architecture, so that they can fit just where they’re supposed to fit, to do the underlying—for example, in biology—the biological process that they are supposed to do.

Howard Forman: Which is the hardest part, because we know the chains of amino acids, very often for decades. We don’t know why they fold a certain way or how they fold, and this is helping that.

Harlan Krumholz: So this is it, because you know you want to fit them right into a little crevice of another protein, and now you can sort of see how these things can fit together. These robots, for example, can be programmed to perform specific tasks. I’m taking this to a large-scale extension of this metaphor, but synthetic proteins can be designed to interact in specific ways with other molecules acting like tiny biological machines programmed to conduct tasks such as breaking down toxins or repairing tissues or attacking viruses like flu, which they can do. So anyway, this is why this is such an advance, is that they’re basically at very small molecular levels now, creating proteins with particular conformations, particular architectures that can perform certain functions in ways we could never do before. And that’s unlocking potentially a whole new age of therapeutics that we couldn’t have imagined before.

Howard Forman: It is fascinating.

Harlan Krumholz: Yep. Hey, let’s get onto our guest, Art Caplan.

Howard Forman: Dr. Arthur Caplan is a bioethicist who serves as the Drs. William F. and Virginia Connolly Mitty Professor of Bioethics at the Population Health Department of the NYU Grossman School of Medicine. He’s a nationally renowned expert in bioethics, appears regularly in media, and has had an immense impact on bioethics across the nation. He helped found the Division of Medical Ethics at NYU Langone, and before coming to NYU, Dr. Caplan also founded and ran the respective bioethics program at the University of Pennsylvania, which is when I first met him, and the University of Minnesota just before that. Dr. Caplan has been asked to serve on many committees for his expertise in bioethics. He has chaired the NCI—National Cancer Institute—the Biobanking Ethics Working Group, and the United Nations Advisory Committee on Human Cloning, among many other appointments and also serves on the Compassionate Use Advisory Committee as a chair.

Over the past decades, he has been named as one of the most influential people on science matters in the U.S. by several media outlets. He completed his undergraduate degree in philosophy at Brandeis University, and obtained his PhD at Columbia, and he has received seven additional honorary degrees from other prestigious institutions. And so first of all, I welcome you. I’ve been fortunate to know you since meeting you when you came to Penn around the same time I did my fellowship there, and I have followed you very closely over these years, then, and recognized how important it is for someone like you and others to illuminate very challenging topics, and we never run short of challenging topics in medicine and healthcare. And so I want to start off by just asking, you go to Brandeis, did you immediately know that you wanted to pursue a career in this path or when did you first come to want to pursue this area?

Arthur Caplan: Well, when I was at Brandeis, this area didn’t exist. So there was no bioethics. It wasn’t really a field like about, I think 70% of people at Brandeis when I was there coming out in the class of ‘71—I was a pre-med too, by the way, for inside baseball, my roommate was Fred Alt, the famous immunologist at Boston Children’s, who drove me crazy during my entire time at Brandeis because he didn’t appear to study, and I was killing myself and he was flying through everything with a little effort. Anyway. But I was there at a time when the campus was roiled with ethical controversy, Vietnam War, certainly civil rights, women’s rights, gay rights, all being discussed on the campus, widely, all over the place, strikes taking place a little bit like the environment we’re seeing with the war in Gaza and reactions and responses. So I was caught up in those issues, and it led me to take a couple of philosophy courses, and the long and short of it is philosophy at that time was not interested in answering any ethical quandaries. It was trying to figure out, could there be ethics? So we call that meta-ethics, and that’s nice, but it wasn’t what I was there for.

It was sort of saying, “Well, over the past two thousand years we haven’t agreed on the right theory. When we do, then you can tell people what they ought to do.” And I said, “It can’t be right. We’re not going to wait for the ultimate theory.” But I did trot off, and I’ll make this shorter, to Columbia Med School, and while there I observed a couple of things. One, we were letting newborns die who had spina bifida and Down syndrome when parents said they didn’t want to care for them, and there were series of reports about this. It wasn’t a secret. It was in New England Journal. Yale had a sequence published at that time as well in addition to Columbia, and so were people in England, in Lancet, as well. Big fights about, in vitro fertilization wasn’t ethical. Could you make babies outside the body in dishes? Big battles about what to do about kidney dialysis.

We had four machines in an acute unit, and many, many more people who wanted access, some of whom couldn’t necessarily pay. What was that all about? So I went to our dean of students, and I said, “When do we talk about these things?” And you and Harlan will laugh at this. He said, “Well, when you have those ethics issues, you discuss them with your attending.” Now I’m talking about let’s say 1972, if I had brought these things up with my attending, I would’ve been assigned to clean out the closets. It would not have flown. They were not going to listen to that.

So I thought, well, maybe I’ll go take a philosophy course in ethics. Long story short, I thought there is some way to put these two things together. The ethics and the medicine, these issues are omnipresent. So I think it was getting a dose of it on rotations. And by the way, sorry to go on about this, but last little bit of the story, I did not finish medical school. So I did through year three and then got my PhD in philosophy and spent the next fifty years explaining to my mother why I hadn’t finished medical school.

Howard Forman: You’re certainly not the first, so—

Arthur Caplan: [Laughs]

Harlan Krumholz: Well, I would say you’ve more than matched most people who did finish medical school in terms of your contributions. I think about, they say it was sort of getting started…. there was kind of this golden moment of bioethics. I mean, Al Jonsen sort of sets the stage early on, and then there’s the Belmont Report that comes out, and the National Commission for the Protection of Human Subjects of Biomedical and Behavior Research, for people who listening, was a group that convened and put together a foundational document. The important thing about this document, for me, was how it laid out a rubric to think about these problems.

It didn’t solve problems; it laid out a rubric and talked about respect for persons or beneficence, justice. Of course you’re steeped in this, but I’m just saying this for people listening, that it was, sort of laid it out. It’s what I think is lacking today is bringing people together and prioritizing how we should be thinking about the very many things that are coming down the pipe. Now, whether that is A.I. in medicine or whether it’s about... we’re talking today or in the segment before this about David Baker in the University of Washington. He’s developing new proteins, synthetic proteins, and he and George Church, I’ve been talking recently about, well, how are we going to prevent and what are the ethics around this? Because it could fall into the wrong hands of people, cause a whole lot of mischief and worse.

How are you thinking? How are we going to galvanize our society to realize we need to prioritize ethics, not to provide the solutions necessary, but to give us the tools to start having the kind of conversations that are necessary so we can grapple with the power that’s coming to us in so many different areas of medicine that I think we’re ill prepared to think about implications for humanity, honestly.

Arthur Caplan: Yeah. So let me answer that by going backwards and endorsing what you said, Harlan. Bioethics got its props because it contributed in very important ways. It laid out a framework, the Belmont Report, for thinking about human experimentation. I mean that was the response to the Tuskegee Study, where African American men were denied a known cure to penicillin and lied to in a study to see the effects of syphilis, and basically bioethics stepped up to the plate and said, “Look, here’s the principles you have to follow when you’re doing research on subjects.” A major, major contribution that has stood the test of time. While I could cite a long list of people that are not enamored of IRBs [institutional review boards], they have done their work, not that the system doesn’t need reform and all the rest of it, but it did, as you say, lay out the principles. They soon fell into the hands of lawyers and bureaucrats—that’s a different problem.

Bioethics contributed mightily to telling the truth, on the therapy side, when I got to that med school, nobody was told the truth about dire diagnoses in 1971, you just weren’t. Then they thought it was dangerous to tell the patient, establish patient rights, establish privacy, and a third contribution was to step in and let people understand what death was. We really came up with an agreement that this is brain death as well as cardiac death. It allowed people to shut off machines, allowed the field of organ transplant to move forward. So these are major things, they take time, they’re not done overnight, but they really were great.

Now I’m going to tell you what I think was the major failure that I’ve just lived through, and that’s COVID. And so in COVID, we have an ethic that says autonomy is the first principle that many espouse, that individualism must be respected, that personal choice should drive all behavior during the pandemic. Many of my science friends believed that what went wrong in COVID was misinformation. We just had bad facts. A lot of people promoting nonsense. Even the president, I think. We’re speaking at a time, it’s the anniversary of his famous “take bleach” pronouncement. But I don’t believe that that is the story. It’s part of the story. The other part of the story is we have seen the rise of a dangerous pernicious ethic, we say in the philosophy business, ethical egoism, many of our heroes or Silicon Valley people who say, “Just looking out for myself, Ayn Rand is my heroine in terms of thinking about moral behavior.” By the way, Ayn Rand wouldn’t get out of my sophomore ethics class, but be that as it may. And what I’m getting at is this. To fight a pandemic, you need to have concern for others. You have to decide to sacrifice even in the interest of protecting the vulnerable, restricting your freedom, or sometimes facing certain risks that one encounters. You need, in other words, without eating up all our time, a community-based ethic, one in which justice is the first priority, not autonomy, one in which the world becomes part of your community, not just whether I get to go to the restaurant or the bowling alley when I want to.

Bioethics has a lot of work to do to lay out that framework into the future. I also think it’s important for A.I. in similar sorts of ways that things should be put to the test of access. How are we sharing benefits out? What’s the priority to lay in benefits of A.I.? Maybe it’s wonderful for Elon Musk to attach us to a tether in his Neuralink experiment, but I don’t think that’s the top A.I. project that ought to be pursued in terms of what’s best for the largest population of the world. But I’ll sum this up in a different direction. In fighting hard to kill paternalism in medicine, my era, we pushed autonomy super hard. Patients get to choose. Doctors have to work with the patient, we must view them as partners, and that will debunk, corrode away paternalism on the part of a male hierarchy from a earlier time. It worked, but it went too far. Now we have to supplement that by reminding people that appropriate healthcare ethics and public health ethics is not just the pursuit of individual choice.

Howard Forman: Let me ask you a question related to this a little bit more to the current moment, and that is that a lot of people look at the pharmaceutical industry and pricing around drugs and costs of drugs, and if you let the pharmaceutical industry take their position, it would generally be something like this. It’s the trolley problem to them. And that by charging people an awful lot right now and maybe even restricting access now to a small number of people, we’re going to save many more people in the long run. It’s almost like a temporal trolley problem. And I wonder, how do we illuminate this topic for people in a sufficient manner to have an honest conversation about that? Because it is not a simple one.

Arthur Caplan: Well, I’m going to make three points, and I hate making them to you two because part of what I’m going to say I probably have learned from you two, but first, you must commit to fair pricing, and fair pricing is not gouging in a monopoly. I’ve created at least one son who spends his time in antitrust lawsuits against the pharma industry. I know all their games: greening up patents, coming up with long-release medicine. I mean, there is an ethos of profit first in pharmaceuticals that I’m going to argue is inappropriate and wrong. The ethos should be healthcare benefit with generous ideas about access, consistent with profit, but not profiteering day and night—

Howard Forman: Right.

Arthur Caplan: ... which is what goes on behind the scenes. So that’s just an inappropriate ethos. Secondly, when somebody tells me it’s going to be great now to charge two million dollars for this drug, but ultimately someday it’ll cost $2,000.

Let’s be empirical. When did that happen? I see it happen with my televisions that I bought, they came down in price. My computer, that’s come down in price. But if you have a monopoly and if you extend your patents and canoodle around kinds of gaming and tricks, the price never comes down. And it’s also known that in thinking about pricing, and I’ve sat through a couple of discussions. I was there when, for example, Viagra was a drug brought forward by Pfizer. I learned a lot about how drug companies behave. They didn’t price it according to what the research cost was of the drug. They priced it according to what they could get. And again, that’s capitalism raw, but it’s just not going to work ever in the healthcare setting. I’m looking today, we have all the injectables for helping to battle obesity and overweight. The price seems to be $1,000 a month, and then you’ve got a physician visit or two in there.

So let’s say, conservatively, it’s fifteen hundred bucks. Let’s say conservatively 40% of America is overweight, we’ll treat 100 million people. So we’re going to wind up spending $1.5 trillion to inject ourselves with these drugs. And where did that price come from? Well, I think it came from being able to charge what you want. People say to me, “Oh, calm down. The price will come down.” Really? What forces are going to drive that price down?

Howard Forman: Exactly.

Arthur Caplan: Competition? They eyeball each other and they know what they’re charging just for those injectables. Nope, there’s been competition. Nothing’s come down. So I think you need a different ethos. I mean, this market model capitalism will generously, ultimately share out the benefits from a top-down point of view. It’s just false. It doesn’t work.

Howard Forman: Let me ask you a tough question. You’re welcome not to answer if you don’t want to, but you’ve been in this field for five decades now. Are there any topics in particular that you can think of where you have dramatically changed your opinion over that time?

Arthur Caplan: Yes. And further, if that hasn’t happened over fifty years, if you’re an ethicist, you’re an idiot.

Howard Forman: I agree, but I wouldn’t have said that to you, because I love you.

Arthur Caplan: Well, I believe it. I’ll give you three very quickly. I was an initial critic of Oregon’s medical assistance and dying legislation back in three decades ago now, and I worried that it would be abused. It was pretty simple. I’ll put it in a way that you’ll both understand easily. It might be nice to have a right to healthcare before you had a right to be killed by the doctor. So what’s going to happen to the disabled? Are people going to rush you off to die because you’re using up the tuition money and so on? Well, it turns out the safeguards that were put in work—it’s empirically demonstrable. There haven’t been abuses, there haven’t been slippery slopes, there haven’t been coercion. And I was wrong. And I am now a vocal supporter of, let’s call it the Oregon style, which is very restrictive of medical assistance and dying.

I was a strong opponent of face transplants when they first appeared. Too expensive, nobody had done animal studies that I could find in the literature, and it’s aesthetic. And from an ethics point of view, you’re going to risk somebody’s life by giving them dangerous drugs and dangerous surgery so they look better is a different equation than I got to stick a liver in you because you’re going to be dead in the next three months if we don’t do that. That equation I get. Well, a lot of my transplant surgeon friends, not a few from Yale I might add, but others I know, I’ve been in the community a long time and they will trustingly talk to me. They said, “You’re wrong. And go meet some of these patients who need face transplants.” Which I did. I collected some evidence. It’s not a huge group of people, but I probably interviewed seven or eight.

And first of all, if you need a face transplant, you need it for functional reasons. You can’t swallow, you can’t make tears, you can’t breathe, you can’t sleep. It’s not “aesthetics.” I mean it is, but it’s way more than that. Just equating it as some kind of beauty operation is wrong. Secondly, they didn’t have to do the animal experiments because they were only using techniques they’d already pioneered on partial cosmetic replacement for injury burn and so on. There wasn’t anything particularly new that was coming in there that was wrong. Anyway, after those interviews and listening to the explanations, I am now a supporter of research, and I don’t think it’s quite therapeutic yet, but research on face transplants, if we can drive the cost down and that’s a separate huge dilemma. That’s probably enough examples. But yeah, I absolutely... Well, you want one more? I’ll give you this quick one.

Howard Forman: Give us one more.

Arthur Caplan: When I first broke into this realm, not knowing about Al Jonsen or anything, to tell you the truth, initially; they were out there, but I didn’t know it. At Columbia, I was meeting families who, as I said earlier, were saying, “Let your child die. They have hydrocephalus. Their brain is flattened down to a size of a Kleenex. There’s no point in treating them.” The parents would say, “Okay.” And they would be allowed to die. Later, I began to meet parents who had rejected that advice and their kids had done pretty well. The Down syndrome classic example of the young man who’s now working as a bag boy and the grocery store is very happy, and the spina bifida person whose brain was mushed but somehow came back and is now an accountant. I don’t wish that on the world, but here they are and they have a job.

And I had to rethink this. It was like the people who were giving me the evidence were seeing the worst-outcome cases. The people who had the better-outcome cases just went home and raised their kid, but we didn’t see them because we had a skew. We got the people who were not working out as well with their newborn. So it was a lesson to me. It’s great when someone heroically saves somebody in the hospital—what’s it look like a month or two or three out when they go home?

Howard Forman: So what a pleasure to have you on. Amazing to have you. I—

Harlan Krumholz: A national treasure, really. You’re great.

Howard Forman: And you were sort of the godfather of a field that continues to grow by leaps and bounds, honestly, and we don’t have enough. So thank you for all that you have done.

Harlan Krumholz: And your willingness to come out publicly to go on a show like this and so many others as educated people around the world, really.

Howard Forman: Thank you.

Arthur Caplan: Well, thank you very much. Much appreciated, and thanks for the great conversation and all the work you guys do. I’m a very big fan, big fan.

Harlan Krumholz: Thank you. Howie, let’s get to the next stage. That was great talking with Art, but as you know, I always love hearing what’s on your mind. So what’s on your mind this week?

Howard Forman: Well, as it turns out, April 25th, which is the day that we release our podcast this week, is World Malaria Day. In the grand scheme of things, malaria requires our utmost attention. It is the third or fourth highest cause of infectious disease, death in the world after tuberculosis, COVID, and HIV/AIDS. Two hundred and forty-nine million cases throughout the world, heavily concentrated in Africa, with 600,000 deaths, of which nearly 80% occur in children the age of five or below. The disease is caused by a parasite and spread through mosquito bites. Direct human-to-human transmission does not occur, but it does spread from human-to-human through the vector, a specific mosquito, right? So I want to emphasize why, because I think sometimes numbers are hard to comprehend, the enormity of these numbers. Almost every minute, a child the age of five or under dies of malaria in the world—every minute. Just while we’re doing this podcast, 35 children will have died of malaria.

The number of deaths in children under five is five times the number of cancer deaths among all children 18 and under. It’s just an enormously larger number. And unlike so many cancers, nearly all of these deaths are immediately preventable. Mosquito nets, mosquito repellent, protective clothing, window screens are highly effective in reducing the risk of getting bitten and getting infected. Use of indoor insecticides adds to this. Travelers can use chemoprophylaxis before, during, and after travel to reduce their risk of disease. And in the last two years, there are now two vaccines available with 75% to 80% effectiveness at preventing symptoms. And then there’s treatment for cases that are identified and confirmed. These treatments can substantially reduce symptomatic risks from the infection, including the risk of death. So still, children, pregnant mothers and HIV/AIDS patients are at the highest risk of this deadly disease.

So few things that I think you all should know. One, even with effective treatment and effective insecticides, we have a risk of resistance developing. So we need to constantly innovate, and we also have to make sure we don’t overuse both our treatments or our insecticides. Our best strategies involve eradication from a single region and then to move beyond that region. We reported on this about Cabo Verde earlier this year, but this is easier said than done. And even if it’s eradicated in a region, it can reenter if we’re not vigilant.

So it’s a great example of where the field of public health with holistic and population-level application of multiple tools can and has had enormous impact. We need ongoing surveillance in all of these active regions, and we need to be testing early if we want to treat early enough to save a life. And worth pointing out, that the U.S. is the absolute largest funder of malaria treatment and prevention and research and development in the world, and not far behind the U.S. as a government is the Gates Foundation. Our economic progress has translated into reduced deaths, perhaps as many as 10 million over the last two decades from this one disease. And one last point: climate change can change the geographic reach of malaria. Eradication doesn’t just help our neighbors; it might help our grandchildren.

Harlan Krumholz: Yeah, it’s a great topic, Howie, and thanks for bringing that up on World Malaria Day, just so we can direct attention to it. In our world, unfortunately, a lot of the investment, we talked about investment earlier about synthetic proteins, we’ll see where they’re directed, but sometimes things are prioritized that are going to make profit over how many lives are actually going to save worldwide. And many of the diseases that are most important worldwide have a paucity, a pittance of an investment compared to other areas because of reimbursement or prioritizing what’s in the United States because of the way our healthcare system will pay for things versus if you thought in a more global view where that would actually give you the most return in terms of lives saved.

Howard Forman: And look, Harlan, I’m embarrassed to say that I’ve read applications from students for 25 years, maybe more, and I’ve seen students write about malaria nets. I’ve seen students write about malaria efforts; until I sat down and did a little bit of research for just this segment I knew way too little, and part of me wants people to realize that for like two dollars, you can give somebody a malaria net that theoretically will save their life.

Harlan Krumholz: We need to really bring into bright focus where these ROIs are, the returns on investment, and what it can kind of derive for global health and that we all benefit when we can improve the health of people worldwide.

Howard Forman: Thank you so much.

Harlan Krumholz: That was great.

Howard Forman: You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman. So how did we do? To give us your feedback or to keep the conversation going. Email us at health.veritas@yale.edu, or follow us on any social media, LinkedIn, Threads, Twitter, and so on.

Harlan Krumholz: We very much want to hear your feedback. Any questions you may have or any suggestions you may have for us. You can also rate us on a podcastapp. We always read the reviews and it helps others find us.

Howard Forman: And if you have questions about the MBA for Executives program at the Yale School of Management, reach out via email for more information or check out our website at som.yale.edu/emba. And again, exciting news to share with our listeners. We will do a live podcast at the Yale Innovation Summit on May 30th. Links in the show notes today. Come to the Innovation Summit, see us interview some of the greatest health and technology innovators.

Harlan Krumholz: Health & Veritas is produced by the Yale School of Management and the Yale School of Public Health. Thanks to our researchers, Ines Gilles and Sophia Stumpf, amazing undergrads, give us support and it’s such a pleasure to work with them, and our producer, Miranda Shafer, who somehow makes us sound good every week.

Howard Forman: True. Thanks. Yep, absolutely.

Harlan Krumholz: Talk to you soon, Howie.

Howard Forman: Thanks, Harlan. Talk to you soon.