How HIV Informs COVID: Mark Smith on Crisis, Inequality, and Hope

; Abraham Verghese, MD; Mark Smith, MD, MBA

Disclosures

December 09, 2020

This transcript has been edited for clarity.

Abraham Verghese, MD: Welcome, everyone, to another episode of Medicine and the Machine with my wonderful co-host, Eric Topol. We are excited today to have an illustrious guest, Dr Mark Smith. Dr Smith has had a varied and colorful medical career. He just told me that his wife tells him he's failing retirement because he continues to be very engaged.

He holds a BA from Harvard College, an MD from the University of North Carolina, and an MBA from the Wharton School at the University of Pennsylvania. He is a board-certified internist and a member of the Institute of Medicine. I know him best for his role as the founding leader of the California Health Care Foundation, which is an incredible story in itself. Prior to that, he was the executive vice president of the Henry J. Kaiser Family Foundation. He's had a strong and long association with the University of California, San Francisco (UCSF) as a professor of clinical medicine, and he continues to see patients with HIV as well as serve on many important boards, such as the Institute for Healthcare Improvement, the Commonwealth Fund, and other entities.

I had the great pleasure of hearing you speak, Mark, recently in the heights of the Black Lives Matter awakening of our original 1619 sin. I was so taken with what you had to say. We had hoped to talk with you before the election, but I think in many ways your insights and thoughts are even more germane now, after the country has sort of come to this inflection point. So, a warm welcome to you and thank you for being on the show.

Mark Smith, MD, MBA: Thanks very much for having me. I've been a big fan of both of you for many years.

Verghese: That's very kind of you. Maybe we can start with your career. I know that in the years when I was working with HIV, you were also very much in the trenches at Johns Hopkins and then again at UCSF. Tell us how you made the transition to the California Health Care Foundation, and for the people who don't know much about it, maybe it's worth describing this incredible operation.

Smith: I first got involved in HIV when I was an intern at San Francisco General in 1983. And for your listeners who maybe weren't even born in 1983, San Francisco General was ground zero for the world HIV epidemic then. Many of the people who came out of that institution led the world in trying to figure out what this was and how to treat it, and eventually how to suppress the virus. We used to go to interns' report and speculate about what this could possibly be that had these young men coming in with these bizarre protozoal infections, toxoplasmosis, and Kaposi's sarcoma — these sarcomas that no one had ever seen. By the end of my 3 years there, I knew more about HIV than most of the doctors in the world — not because I started out to do that, but because it was the right place and time. It has continued to be part of my professional, political, and personal life ever since.

I then did a clinical scholars fellowship and general medicine fellowship at Penn and then went to Johns Hopkins and ran the AIDS clinic, the Moore Clinic, there. I was then recruited to come back to California to work at the Henry J. Kaiser Family Foundation, and in that role I helped to start up a number of the policy efforts that were important for HIV, including the first guidelines group, the AIDS Society, Ryan White, and other policy issues that affected HIV.

In 1996, when Blue Cross of California was converting from not-for-profit to for-profit status, an agreement was reached to help pay back the citizens of California for the many years in which this company had built up value as a not-for-profit entity. The agreement was that there would be one big foundation that was to be the beneficiary, the California Endowment, and one small foundation whose first job was to manage the monetization of the WellPoint stock and give 80% of the proceeds to endow the endowment. The small foundation was the California Health Care Foundation (CHCF).

There wasn't really an agreement or clarity about what was to happen to CHCF when the monetization was done, but by the time it was completed, we had turned WellPoint's stock into $2.5 billion. So the endowment got $2 billion and CHCF got $500 million. Our board decided that was enough to do something constructive, so we set out to build a philanthropic enterprise. And that's where I spent the next 17 years of my life and really the keystone, if you will, of my professional career.

Most of that time, I've continued to see patients at San Francisco General, in part because I thought I could be helpful. It's one of the few specialties of medicine in which there's not an oversupply of physicians. And because, frankly, I enjoy it and find value in it, and find my relationship with patients rewarding.

The irony, of course, is that I have had to go back to being a general internist because most of my patients, if they're lucky, will die with their HIV, not of their HIV. So I've had to go back to figuring out whether to do a PSA test on a patient or if their statins are at the right dose. That's challenging even for people who do general medicine full-time, as I clearly don't do. But I continue to find it rewarding and will keep on as long as I can.

Verghese: Not only do I remember those times, but I was actually accepted to be a fellow at UCSF in '83. I wound up going to Boston University. I sometimes wonder how the trajectory of my life might have gone if I'd gone to UCSF instead, with your wonderful talent there in HIV.

Eric J. Topol, MD: That's a coincidence that brings the three of us together: I left San Francisco General/UCSF in 1982 — so I'm the old dog here — to start my fellowship. And, of course, that was the beginning of HIV/AIDS. We didn't have a name for it yet, but patients were coming in in flocks every day. I didn't realize until today, Mark, that we actually were like strangers in the night.

Smith: Both of you remember those days. I remember when, as a senior resident, we used to send interns to the airport to pick up pentamidine that the CDC had sent us, because if you had a patient with pneumocystis who had a sulfa allergy, you were using pentamidine. When I was at Hopkins, we had the blueprint for a room that was going to have negative pressure, where we could sit patients in chairs to do inhaled pentamidine. Now I have a patient who's on one pill once a day for his HIV. The two of you probably take more medicine than he does. In some ways, it's really nothing short of a miracle.

It's a marker in some ways for the growing role of pharma, which is another interesting discussion. When I was in business school, people talked about pharma and everybody would say, "Drugs are 6%, 7% of healthcare costs; it's not much." Clearly it's a lot more than that now, and it's become the centerpiece of both political and economic issues in healthcare. Nowhere is that more apparent than in the progress of HIV, from really the holocaust that it was when the three of us were all around UCSF to the more or less manageable chronic disease that it is today.

'Old Truths Laid Visibly Bare'

Verghese: I want to switch gears a bit, Mark. One of the things that stood out for me when I heard your talk, the one I referred to at the opening, is that you talked about this whole Black Lives Matter epiphany we were having as "old truths laid visibly bare." In other words, this really wasn't news unless you were totally tuned out, as most of us in the nation seem to be, until that moment; we hadn't fully embraced the pain and the suffering. Frame this issue for us of Black Lives Matter, from your wonderful perspective.

Smith: Well, first of all, thank you. It really was quite remarkable to see the outpouring of support for a reexamination and attention to racial and social justice that came from people of all ages and all ethnicities, from big cities and small towns around the country. It was the result, in part, of the culmination of many little things over the years, which at every point when you saw some horrible outrage and said, "This finally is going to wake people up." Yet one could see the same thing happening over and over again.

This spring, when these events happened in rapid succession, people had reached a boiling point. It is interesting in the wake of the election, as we again contemplate the structure of the United States Senate and the existence of this weird Electoral College, to recognize how much of American history, how much of America's economy, how much of America's political structure really does go all the way back to slavery. It goes all the way back to the protection of the rights and power of the slaveholding states, the apportionment of votes to make sure that Black people could not exercise the same political power that was commensurate with their numbers. I don't need to tell you about Reconstruction and the extraordinary lengths to which people in our lifetimes went to keep Black people in places like Mississippi, Alabama, and Georgia from voting.

I think part of what you saw was the accumulated frustration of people and the support of folks, some of whom were awakened for the first time to the complicated interlocking issues that affect Black and brown people in America. I was heartened by that response. But also I'm old enough to remember similar responses and over the very same issues. I went to the March on Washington with my father. I remember it well. And if you think about the issues that they were complaining about then, if you think about the issues that started the mass uprisings in 1968, if you think about the birth of the Black Panther Party here in Oakland, these were the same issues. They haven't gone away.

So I was really struck by both the outpouring of support and by the sense of frustration that these issues are not new ones. But they were again laid open for people to see in a way, in part because the ubiquity of cell phones and video allows people to experience and document events that in the past would have been, frankly, swept under the rug or lied about.

Verghese: One thing you said that moved me was — and I think it was directed at everybody listening — assume that you have a problem. Assume that we are all complicit until we are proven not complicit. And it's inconceivable that we don't have a problem. I think a lot of us sitting in ivory towers like to imagine that we are beyond all this. But I think there's a lot of important soul-searching that the movement made us all engage in and recognize that even when we think we're doing well, we're not doing well.

Smith: It's really true. It's been quite extraordinary, the outpouring of documented injustice and inequality in almost every part of medicine that you can imagine over the past 4 or 5 months. Any place you look, you will see the consequence of systemic injustice that affects people's educational opportunities, wealth, and economic progress that then gets reflected in their health status, and disproportionate and inequitable treatment within the healthcare system itself.

One of the interesting things that's happening now, as people are paying — appropriately — more attention to social determinants of health, is that people who are well-meaning are quick to look outside the healthcare system for the explanations of inequity and quick to point to things like farmers' markets, transportation, and food deserts. They are a little slower to look at how people may be treated differently where pain control is concerned in the emergency room or, looking at their own quality measures, hospital readmission or even things as general as net promoter scores, and looking at those things by race, by gender, and by language.

I think there are a lot of glass houses within the healthcare system. There are, to be sure, social determinants about which we all ought to be concerned. But there are also lots of issues within the healthcare system itself. And almost every place we look, we will find things we can work on to make things better. It's not about pointing fingers and castigating people and beating on chests. It's about assuming that we have a problem, looking for the dimensions of those problems, and then, as opposed to admiring those problems, getting to work to figure out how we can make progress.

Overcoming Structural Inequities

Topol: To tie in Black Lives Matter with the pandemic, Mark, I wonder if you can comment on the idea that because our health system has no recognition that it's a human right to have healthcare, we were exposed bare to have disproportionate hurt to people of color.

To say the data are incredibly sobering doesn't say enough about how that has occurred. Can you connect the dots for us on that?

Smith: From the early days of the pandemic, it was really clear that Black people were being disproportionately hospitalized and disproportionately dying.

The first rather facile explanation of this, particularly in the lay press, was, "Well, they have so many preexisting conditions. They have comorbidities." Now the first problem with that is that no one ever said, "Gee, why is that the case?" So that's number one.

But second, it became clear that that wasn't exactly all the answer. As one began to see, for instance, a dramatically disproportionate impact on Latinos and Latinas in California — where some of these historical disproportionalities of obesity and hypertension and diabetes don't exist — it became clear that a lot of people's risk was not so much medical risk but social risk. Where did you work? How did you get to work? How dense were your households? What opportunities did you have to work from home as opposed to having to go in and be an essential worker?

The pandemic has exposed at least three things. One, it is true that for many populations, including the African American population, preexisting conditions and comorbidities that are rooted in the social determinants put you at greater risk. Second, for many populations that are distinguished both by race and by economic or social position in society — such as the kind of work you do, the density of your household, your ability to work from home, your ability to travel in a way that doesn't have you next to 50 other people — it puts you at special risk for infection and, therefore, for illness. And the third thing is, it's now clear that if you go to a well-resourced institution, you have a better chance of doing well than if you go to a poorly resourced institution.

We're now beginning to hear anecdotes and, in fact, see some data about people who were turned away and told, "Go back home. It's just a cough. It's just a cold." It wasn't just a cough and a cold.

If you think about the institutions that were more or less likely to have early access to some of the antivirals and steroids that we now recognize as being effective, the ones that were likely to have early access to PPE and to ventilators, there are real differences.

So there's a complicated set of circumstances, some of which have to do with people's medical conditions, some of which have to do with people's social risks for a communicable disease, and some of which have to do with people's access to healthcare, both their insurance status and the nature of the institutions that take care of them and how those resources are disproportionately allocated. And it's interesting to note that the federal efforts to provide resources to hospitals tended to go to hospitals that had more Medicare reimbursement, but those often turned out not to be the hospitals hardest hit by the pandemic. So, once again, it's not like someone sat there and said, "Oh, let's screw these hospitals." It just happens in the normal course of doing things the way we normally do them. These inequities are built structurally into the system.

A Combination That Could Work

Verghese: I think it's fair to say that we are living in a time when there is incredible suspicion of science. That's a phenomenon that is understandable, I think, when it comes to research studies in the Black community because of historic things, like Tuskegee, that really made one wary. But it's interesting how masks became so politicized and how even when we have good public health interventions, we're dealing with a society that's really split over that issue. It's become a political issue.

We have seen the vote for a new administration, yet we are left with a very divided nation. How do you see things unfolding in terms of the Black Lives Matter movement, in terms of health equity and moving forward from here? How do we heal this nation? How do we heal the body of this nation, which remains horribly divided?

Smith: I don't know that I have any special expertise or insight on that one. As I say, I try to be an optimist. I am optimistic in part because I have seen so many efforts throughout society to try to get a handle on everything ranging from police reform to building Black wealth to addressing social determinants and inequities in health. And I regard these as efforts by people of goodwill and am hopeful that they will continue. At the same time, it's worth pointing out that there have been times in our past when people have made efforts, and we see where we are now.

I'm hopeful that a new administration that respects and supports science and does not, for political purposes, undermine and discredit science can help bring the country together around public health measures necessary to control the pandemic.

It's unfortunate that controlling the pandemic and supporting the economy have been posed as opposite impulses — that you choose one or another. It's really clear that you can't hope for economic improvement until the pandemic is controlled. There seems to be good news on the horizon in terms of vaccine. So that is hopeful. There has been good news over the past several months in terms of physicians getting increasingly comfortable treating the disease. It's clear that as we've learned how to take care of patients — not just drugs, but knowledge about prone vs supine position and when to intubate, and monitoring people's oxygenation — our capacity to get them through the worst of the pandemic has improved. There are clearly people who are surviving now who would not have survived in April or May.

Nevertheless, you've seen the numbers of hospitalizations. We're by no means through this. And as the saying goes, winter is coming. I read a column by Aaron Carroll that I thought was quite good. The fact that there seems to be good news in the way of vaccines should redouble our efforts to use nonpharmaceutical public health measures, in part because there's light at the end of the tunnel. You're not asking people to sacrifice indefinitely with no idea when that sacrifice is over. If we can redouble our efforts and if there's more clarity, more consistency of messaging, more setting a good example by the leadership of the country, I'm hopeful that we can get through this next phase with minimal loss of life that should not have happened over the past several months.

Verghese: I've been itching to ask my co-host, Eric, who is really on top of everything science related to COVID — I think many of us turn to his Twitter feed to find the latest. Eric, what is your take on the Pfizer vaccine and where we stand?

Topol: I think Mark really hits the point. We need to be redoubling our efforts right now because we are looking at the worst surge of the whole pandemic in the US.

Already we've picked up in hospitalizations, and we're going to see that keep going up and along with the fatalities. We're only now weeks away from the beginning of the vaccination phase, a highly effective vaccination, one that exceeded all expectations to get to 90%, without significant safety issues. That high efficacy rate will reduce the number of people in the population that need to be vaccinated, as well as hasten the time when the virus will have a tougher time finding new hosts. There's such exciting news and it's coming at the worst time of the pandemic, as Mark touched on. So he's right. We should be aggressively taking control and using simple public health measures, including masks, distancing, avoidance of crowds, and ventilation — all the things that we know but are not doing right now.

The other thing, though, is that we need help from the government. We have no leadership and we're also in this gridlock state. And this affects what Mark is talking about, too, in that we're not getting aid to the people; these essential workers and so many others are deeply affected and we have no support financially for them. We're at a standstill.

This is not helping matters at all. Mark, how do we get out of the gridlock? How do we start to turn this thing? Because we're not that far away from light. You can almost know that we're going to see light by mid-year in 2021 or the latter part of that year. But we have to be patient. We're not doing the things that we should be doing.

Smith: Right. So, Abraham, you asked how we got to this place. I think part of how we got to this place was the leadership; the president, the people around him, the people who take their cues from him, and people who are scared of him have politicized this.

But I do want to say something about why that skepticism, that denial, has taken hold. The three of us live in wonk world. The three of us can work from home. The three of us don't have economics that are dependent on our being able to go out every day or having people come in to our establishment.

I really feel for people who are dependent on such interactions. Imagine someone who's worked his way up from being a dishwasher to opening a restaurant, borrowed money, mortgaged his house, found a partner, bought furniture, signed a lease planning to open his restaurant on April 1st, and then wham! His life goes down the tubes. I imagine the people who've built businesses that they see crumbling before them while the landlords are demanding the rent and they've got no way to pay.

So, believe me — I understand the fertile ground. I understand how tempting it must be to say, "This whole thing is just a hoax. This whole thing just has to go away," because the consequences fall on deaf ears in the professional class. I think it's important for those of us who sometimes get a little high and mighty about "how could people be so stupid as to not wear masks," or to believe that we're rounding the corner, or to believe it's no worse than the flu. I get it. I get why there is fertile ground for this misleading set of distortions and denial that came from the top but found fertile ground. That is part of why, as Eric said, linking immediate assistance to help people get through to the light at the end of the tunnel is part of what you need to do to get people to adopt these measures.

If you're telling people, "You know you're stupid, you're dumb, and just suck it up forever," that's a different approach than saying, "Here's the science. Here's kind of the timeline that we think we need to get this thing under control. And here's the help that you need to get to that point." That, I think, is the combination that could work. And I'm hopeful that the new leadership of the country can put all of those things together; that's why I have some hope and optimism.

Bring in the Celebrities

Verghese: If you were advising President-elect Biden, what sort of measures would you recommend in terms of tangible public health steps? You mentioned economic assistance, but more broadly speaking, what would you recommend? At one point in your talk that I referred to earlier, I heard you talk about defunding healthcare rather than defunding the police because the healthcare system is so broken. What would you recommend if you had a blank slate to begin with?

Smith: I said at the time and I'll say it again: "Defund the police" is a horrible term, in part because it's not what's really meant. I think the people who first started using it meant it to mean reimagined policing.

And I will say the same thing about defunding healthcare. I'm not talking about firing people and laying them off and cutting their salaries. But, as both of you know well, we waste so much money in healthcare. So much money is misdirected. If we could root out the waste and improve the quality, we could not only improve the accessibility of healthcare but use that money on other things that our patients dearly need, like better policing and better education and better food and transportation. So I, like the two of you, have been a lifelong advocate for making healthcare more affordable and rooting out the waste. I think there's lots to be done there. Immediately, a combination of clear and consistent messages on the science of public health, along with economic assistance to get people through to the other side, is important.

And I'll add two more things for the public health infrastructure and our public health leaders who have taken a real beating in the past year. There's been a constant attack on them. I think the institutions like the FDA and the CDC have suffered in their professional reputations. Their staff have suffered by being demonized and criticized. There are some scores of local health officers who have resigned because they've been criticized and they've had death threats, and people have seen them as the enemy rather than the virus. So there are two other things that are really important in these next several months. One is to begin to rebuild the public health infrastructure that has been so starved of funds, not just in this administration but over several administrations, frankly. And the other is a special effort to build confidence in the vaccine among groups who, as you say, Abraham, have reason not to be confident in it.

The irony, of course, is that there's a group of anti-vaxxer science deniers who tend to be, though not entirely, associated with conservative politics. That group preexisted current events. Now among progressive people — given the way that Mr Trump has politicized the notion of the vaccine and everything about this — there is another group of people who are skeptical of vaccines from the opposite political direction. And obviously, African Americans have a long history that makes them tend to be skeptical. So imagine Operation Warp Speed, which is a military endeavor, and you now have people who are well-meaning saying, "We're going to prioritize getting this vaccine to people who are most at risk, like people of color."

Now we have the US military coming, saying, "Hey, people of color, you're going to be the first ones to get this new vaccine we have." You can see where that is headed. From my standpoint, it's really important to make sure, first, that we recruit enough people of color into these trials so that it can be honestly said, "We have experience and know that this works not just in an elite population that was in the trials, but that people of color have been well represented in the trials." And second, I think it will be important to work hard to get people who have credibility in Black and brown and Native American communities — not only people in the health field, but celebrities and others who have credibility, to make sure that folks understand that this is not some sort of plot.

I think I would trust an FDA in the Biden administration. If they say it's safe and effective and if I can see that data, then I would trust that. I'd be willing to go say, "You can trust this." But I think we need people who have far more credibility among common, ordinary people to be able to get that message out. I'm very concerned about the combined legacy of 100 years of history and the past year in particular, leading to a vaccine acceptance problem that will not only put those communities at risk but, frankly, will put everybody at risk. As Eric said, the more people who get the vaccine, the safer the entire population is.

Trying to Understand Another's View

Topol: I want to go back for a moment about the outpouring on the streets of America. During these past 4 years, we've seen it three major times that I can recall. First, it was right after the Trump inauguration with the Women's March; and then it was with Black Lives Matter, which went on for many weeks, if not months; and then the Saturday after the election was called. That is kind of different from, as you really astutely pointed out, the Electoral College and the fact that we don't have the true democracy, we have a republic; we have not the majority rule talking here. How do we harness that energy? It's so electrifying to see people come out on the streets like that everywhere, every scene for three great causes or expressions, if you will. Can we continue to see that sort of outpouring of support coming together to fight these things?

But we have so much to work on here and we have so many people who want this to happen, to get things on track.

Does that give you some hope that we can harness that energy?

Smith: It does give me hope. But people in the streets can't set things in motion. The way things get institutionalized and sustained is through permanent power. The March on Washington was about a number of aims, some of which were achieved, some of which weren't. But the ones that were achieved, particularly having to do with voting rights, were concretized in the Voting Rights Act. It is no accident, the attack on voting rights, which began 6 or 7 years ago and has proceeded through various levels of voter suppression, intimidation, demonization, attempts to delegitimize it with modern-day poll taxes and identification.

It is no accident that that's been the focus, because in the end, one can only achieve these ends through instruments of power, legislation, and an institutionalization. And so, yes, on the one hand, I'm optimistic.

I will say this, Eric. This was a very closely divided election and it's worth remembering that. It's part of why I said what I said about COVID deniers and trying to understand how that could be. When I hear, for instance, "How could people possibly believe that?" Well, 48% of people — having seen the past 4 years, having seen what President Trump said and did — said, "Yeah, I want more of that." That was disappointing to me.

At the same time, it should cause everyone, people who are listening to this and the Biden administration, to try to understand what it is about the disconnect from the way we see the world to the way they see the world that could have them, after all we've seen and heard, still say, "Yeah, I want more of that."

I'm not smart enough to know all of what that is. But there's no question that the kind of establishment of both the Republican and Democratic Parties was taken by surprise 4 years ago — and, frankly, was taken by surprise again a few weeks ago — at the alienation that large numbers of people have from what was being said by them. I think we've got to take a deep breath and ask how to move forward in trying to understand what that was. I gave you a little example when it comes to COVID deniers, and there are similar ways of trying to understand what's happening out in the country in other areas of life. That, I think, is the task.

Topol: You're so right about that issue, but how much of that was part of the infodemic — the deliberate misinformation, disinformation — that was used to sway people to not believe that COVID was real, or that people were getting very different messages about what was really happening?

Smith: There's no question that social media plays a role. There's no question that the fracturing and the kind of alternative universes of where people get their "news" plays a role. But I think it's important for us to ask why it takes hold. Why is there such fertile ground for this belief? What is it that would allow people to believe things that seem so far from credibility to me and you? So I'm not going to blame it all on Facebook or Fox News or whatever, because they're going to do what they do. The question is, why is it that people are drawn to that?

From HIV to COVID-19

Verghese: Since we began talking about HIV, it's really interesting to contrast how profoundly different the science was this time around in terms of its speed and the rapidity with which we found the agent and the receptors and the genes and so on. Just tremendous.

And here we are with a vaccine in less than a year since the onset of COVID-19 in this country.

But one thing that hasn't changed, if you read old chronicles of the plague — from Camus' La Peste, to the Decameron to Defoe — in a way, every bit of social disorder that we are witnessing also played out in their times. You could argue that this is very much a human trait and we need to bring the best of our science to these issues in a way that I don't think we've done. We've just assumed that science will win and the truth will be heard. I think we need to give a lot more effort to the business of helping communicate truth, helping change behavior. That battle is far from over.

Smith: You're right. And, of course, there's no one more skilled and, rightly honored, than you in writing about the human part of this. It is a remarkable story of biomedical progress. Once again, our social science lags significantly behind our biomedical science. And while I hope that Eric is right about this vaccine, just a note of caution: It's still early days. Thirty thousand people is not a lot of people if you're talking about giving an agent to essentially everybody in the world. There are lots of examples of things that look good in the first 100,000 people and it's not until you got to a million or two that you realized what was going on. This takes two shots; there is a cold chain. That means that you're not going to be able to get it at your local drugstore. So we're early and we don't know about robustness in time.

Having said that, even in the most optimistic of cases, you're exactly right. In part, what we've learned about virology in the past year, prompted by our work on HIV and the remarkable progress in genetics and genomics, allowed really astounding biomedical progress here. And we find ourselves once again confounded by the behavioral and social science challenges of being able to put that biomedical progress to effectiveness.

Topol: I would agree with all of your points about the vaccine, Mark. The main thing I take away from it is that this virus has a flashing neon sign that it's vaccine vulnerable, the spike protein being the target of virtually all of these vaccines that are in phase 3 and pretty far along. We're going to get there eventually.

Your point about durability is also important. Maybe it's just 6 months or a year, but it's something. We have a lot more to see on that, no question about it.

Smith: The other interesting thing is that some of these novel platforms suggest that maybe the next time this happens, as it surely will, it doesn't even take a year. You can just swap out a large slice of the mRNA and you're good to go. There is a lot to be excited about.

Topol: Exactly. It gives you a platform.

The other thing that you touched on, which I think about and I know Abraham does as well, is that it was only a few years ago, essentially, that it was acknowledged that social determinants of health and socioeconomic class was a risk factor for health.

It took all this time for this classic Lancet paper to finally get published for people to realize that it's just as big as smoking, diabetes. So your point about the biomedical progress and the dissociation of our understanding, acknowledgment of social determinants of health, it's just so startling. I recently looked back at that Lancet paper and thought, it took us until 2017 to make this realization? This gap of the science, sequencing, and all this great immunologic stuff, but we don't understand the social science and its equivalency superseding the things that we spend all our time on.

Smith: I never did make it through my MPH, so I'm not going to put myself out as a public health expert. But my public health friends would probably argue with you a little bit and say it may have taken that long for The Lancet to recognize this, but Rudolf Virchow recognized it 100 years ago. In some ways, it's kind of that the two paths got separated, and for a variety of reasons we've now recognized how separate they've become. There's now been recognition in the medical world of how right Virchow was 150 years ago.

Topol: There you go. Perfect.

Verghese: You said early on that you wanted to mention something about pharma. Let's talk about pharma, because it has played an amazing role in our response to this particular virus. And I want to follow up on that thought.

Smith: Again, as an AIDS doc, I can't help but be struck by the degree to which pharma has completely transformed that disease. Now, part of the reason that I'm still seeing patients, to be candid, is because I'm an AIDS doc. If my clinical interest had been hypertension, I'm not sure I'd still be strapping on my boots. There's not an awful lot new in hypertension in the past 30 years. There just isn't. So HIV is a part of this amazing success story.

But I think, and Eric again knows more about this than anybody in the world, we're on the verge of truly remarkable contributions by pharma. We're talking about curing sickle cell anemia. We're talking about curing multiple myeloma — things that would have been unthinkable. And transforming our understanding of how certain diseases are managed. So it's interesting to think about the degree to which many of the things that have been scourges of healthcare and have been fatal things — HIV as the leading edge of that, but other things, too, for which we had only really very marginally effective treatments — how close we are to really dramatic breakthroughs. Now, of course, people have been promising dramatic breakthroughs for 20 or 30 years, but I think we're actually beginning to see some of them now.

It's worth contemplating how that changes our understanding of the role of different medical specialties, how it changes our understanding of insurance. If we are willing to spend $100,000 a year on the maintenance of someone with sickle cell anemia but don't want to spend $300,000 to cure them of sickle cell, that's a challenge. It challenges us with the whole issue of pharma and its costs. And its influence is one that I think is increasingly, on the one hand, tremendously exciting and optimistic — HIV has been an example of that — but also is going to strain all of our systems for training and deploying people for financing care, for building big buildings with lots of expensive beds in them, and everything else.

Verghese: Mark, you've had such a unique perspective in American medicine, and what I admire most is that you're out there seeing patients in your clinic and are still very much on the front lines. Many of our listeners are on the front lines, many of them disproportionately exposed to risk for COVID.

I'm very sensitive to the fact that 25% of American physicians are actually foreign medical graduates who had to make their way through a very stratified, layered system. And they're disproportionately exposed in the inner cities to HIV. I wonder whether you have any parting words or thoughts for our young hospitalists, young listeners, who are at the start of their careers, as we wind this down. Any thoughts about the sweep of your career?

Smith: Well, I think that they deserve our thanks and our support.

One of the interesting things about this epidemic is how it has exposed the economic vulnerability of our fee-for-service system, because if you have a practice that depends on volume and volume goes to the floor, all of a sudden you have no income. I feel immensely for people who are struggling not only with the personal and family implications of their exposure, but also the economic implications that they, just like people with restaurants and beauty parlors and barber shops, have been challenged with. I remember back to the days when we were taking care of patients whose infectious potential to us was far less than what people sometimes face now. My colleagues who lived through those days, and you, Abraham, among them, deserve our thanks, as do the people who are on the front lines taking care of people now. I'm not at that level of volume or exposure. But it must be enormously frustrating and, frankly, angering to have people masked up, gowned up all the time, and then have folks out in the community tell them, "This is all made up. It's nothing worse than the flu."

It breaks my heart to see people going in and out of institutions, with refrigerated trucks for morgues parked outside, and have someone who has the gall to say, "They're just making up these numbers to make more money." They deserve our thanks. They deserve our support. I think they, like other people who've been economically affected by this pandemic, deserve support to get through to the other end. But I think they deserve our gratitude as well, because Lord knows where we'd be if it weren't for people who are willing to strap their boots on every day and go take care of people, in the finest traditions of our profession.

Verghese: My thoughts are very much with my colleagues in El Paso, Texas, where I spent 11 years. They are facing a horrendous volume problem. It's something that other cities hopefully can avoid. But at this rate, probably a few more cities are going to experience the same level of burden.

Mark, it's been such a pleasure to have you. I'll let Eric close this down, but I want to say thank you for joining us. It's just been tremendous to share our thoughts.

Topol: I'd like to talk for a few more hours. Mark, you are such a light. You articulate it all so well. Your patients are lucky, no less everybody you touch. And we are lucky to have you today. You have an important message for everyone to hear, not just in the medical community. So thank you for joining us. And we'll look forward to connecting with you again in the future because we have a lot more to talk about.

Smith: Thank you for having me.

Eric J. Topol, MD, is one of the top 10 most cited researchers in medicine and frequently writes about technology in healthcare, including in his latest book, Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again.

Abraham Verghese, MD, is a critically acclaimed best-selling author and a physician with an international reputation for his focus on healing in an era when technology often overwhelms the human side of medicine.

Mark Smith, MD, MBA, was the founding president and chief executive officer of the California Health Care Foundation. He continues to see patients as a clinical professor at the University of California, San Francisco.

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