Dr. Arturo Casadevall shares insight into his childhood, what motivated him to go into biomedical research, the impact of the AIDS epidemic, and the lessons learned that he imparts to younger scientists.

 

Robert Bonomo, MD: Welcome to our first premier interview with distinguished members of our discipline it is a real pleasure today to bring to this forum professor Arturo Casadevall. Dr. Casadevall is currently the Bloomberg Distinguished University Professor at Johns Hopkins University and he is also the chair of the Department of Molecular Biology and Immunology at Johns Hopkins University. Arturo is also known for his leadership as the editor-in-chief and founding editor of mBio, and, currently, he is the Deputy Editor of The Journal of Clinical Investigation.

A review of Dr. Arturo Casadevall’s CV reveals accomplishment in many disciplines both in molecular and microbiology and fungal immunology and bacterial genetics and also in vaccine development.

Arturo has also distinguished himself as being our conscience in medicine. He has called out many issues that have occurred in terms of biodefense, biohazards, the areas of research integrity and also in the area of education.

Arturo served many leadership roles in the American Society for Microbiology and he has also served in many roles in our profession of infectious diseases.

So it is what great pleasure we invite Arturo here today.

Why don’t you tell us Arturo what your childhood was like.

Arturo Casadevall, MD, PhD: First thank you Robert and thank you Michael for the honor to be interviewed.

I was born and grew up the first 11years of my life in Cuba. It was such a difficult experience because my family was not happy with the government and eventually even though they supported the government, the revolution initially, by the late 60s they thought they had to leave, so we then left the country; essentially the family split up and reunited in New York, and that's where I spent most of my adult life.

RB: What were some of the influences that motivated you as a child to enter the field of medicine and biomedical research

AC: A very strong influence in my life was my grandfather who was a surgeon. He was a very large presence in the first eight years of my life. In Cuba, we lived together as an extended family but I didn't know anything about research until I got to college.

And, first of all, we had the typical immigrant experience. I grew up in Elmhurst, New York and the only place I could afford was the city university, which was free at the time.  We couldn’t afford anything frankly. And, when I was in college, tuition was minimal by today's standards but I had to get a job. In college I heard that there was such a thing as a research elective. First of all, when I got to college, I spoke English very poorly and by that time I decided that the only way out of my situation was education, so when I went to college I realized that I could get good grades if I did things in math, science, so I took primarily STEM courses.

And then I heard that there was something called a research elective I decided to go for an investigative career. I was a chemistry major and began to apply to graduate programs in chemistry and I was accepted. And then sometime around the end of my junior year, my father, who was a very very influential person in my life, basically said to me, “So what are you going to do?” And I said, “I'm going to be a researcher.”

And he looked at me. He wasn't quite sure he knew about the existence of those jobs, so he knew another Cuban who knew about employment. This person advised my dad that I should go to medical school. So, my father confronted me in the kitchen and said to me, “You're going to medical school.” And I said, “But you know, I'm not I don't have a plan to go to medical school.”

He said, “You're going to medical school. We’re going through a lot in this country. I want you to go to medical school. I want you to get a degree.”

So, in that summer, I didn't have my pre-med courses done, so I began to study for the MCAT on my own, basically completing the courses, and you know, dad told me to go to medical school, I'm going to medical school.

But I figured out that there were some things called MD/PhD programs, and they seemed to have the ability to do research too, so I began to apply to them. The people at Queen's College said to me, the pre-med said to me, “Look you're wasting your time. They will never take anybody from the city university.” And, I was the first one they took. And the interesting thing was when I told my dad about this I said, “Dad, I got into an MD/PhD program.” He said, “You're going to get a medical degree?”

I said, “Yes. But I got better news for you. They're going to pay tuition and they gave me a stipend.”

And he said, “What do you mean? What kind of racket is that? You mean they pay you to go to school?”

Michael Lederman, MD: Was this always what you wanted to do, or if you didn't go to medicine or go into biomedical research, what kind of career do you think you'd have had as your other choice?

AC: In college I had decided that I wanted a scientific career, so had I been left on my own devices, I may have ended up just going to graduate school. But with the encouragement of my dad, I was pushed into medicine and then I found the opportunity to be able to do both.

I love research. When I walked into the lab, the bug bit me. You know this idea that you are at the edge of knowledge and then you go to work and you find out new things that were not known before. My God, that was so attractive.

RB: You got your PhD thesis in what area, and then you decided to do your residency training at Bellview, correct?

AC: I was always very attracted to the physical sciences, so I did my PhD with biophysical chemistry. I looked at light scattering and things like that, but what happened was — remember I was already in medical school and AIDS was discovered in my second year. I then went to the wards around 1983 and 84.

You can imagine that this was the biggest thing that was happening, and I was enormously influenced by the tremendous suffering that I saw. And I then decided to go into infectious disease, because this enormous calamity was happening. We didn't know what was causing it, we did not know whether this was going to be contained, we did not know how the disease spread, so once I graduated from medical school, I did a full residency in medicine and then a full fellowship in infectious disease.

ML: With the AIDS epidemic raging, what was it like?

AC: First of all, many of the patients were my age, many younger. There was the majority of people who got admitted simply did not survive. It was a searing experience. There was nothing you could do for them. You could treat the infectious complications, you could treat their pneumocystis, you could treat their cryptococcal meningitis, the toxoplasmosis, but I was very struck by, before the end of my residency, ACT became available, and to me, that was the hope that came with that.

Think about it: We had a disease that came out of nowhere, began to kill people that appeared to be healthy, there was nothing you could do and then science, within a few years, delivers drugs, and these drugs only get better, such that by the 1990s people no longer die of AIDS if they're taking the drugs together with the protease inhibitors.

This had an enormous influence on my thinking, and in my optimism into what can be done, because I see the power of science, and I see that when it is applied the solutions emerge.

RB: Your early career as an independent investigator, what were some of the formative experiences or lessons you learned as a young investigator?

AC: One important lesson was that it was okay to take risks, and that risks were really important. So, for example, there was no one in Einstein working with cryptococcus, so by just working with cryptococcus — I didn't know it at the time, but I had created a research program on an organism, and once I began publishing, I became valuable in terms of being recruited internally when I finished my fellowship. But the most important lesson and one that I carry to this day is to succeed in any of this you have to persist and you have to be determined.

When I finished my fellowship, I could not get funded. I applied — dozens of applications. And eventually the grants came in, but that is a lesson and that's what I tell everybody, that you know these jobs are hard. They have tremendous rewards with them and that's why we continue to do that but success is just the ability to stick to it.

RB: Some of your work, in addition to the basic sciences, involves an analysis of integrity and honesty in medical research. How did you develop this interest in this area and how have you seen our field change as a result of your observations and insights?

AC: In 2005 I was asked to be one of the editors of Infection and Immunity and then a few years after that Ferric Fang became the editor-in-chief. When you're an editor, you see the process of science from behind the scenes, and I really became very upset at people rejecting work, calling it descriptive. Because it seemed to me that there was a problem. After all, all of we know about the cosmos is descriptive, all you know about anthropology is descriptive, all you know about evolution is descriptive.

It just seemed to me that something was wrong someplace, and I remember writing to Ferric and saying, “I'm tired of all these reviews putting down papers calling it descriptive and talking about this mechanistic. I don't think they have any idea what they're talking about.”

And then Ferric and I began to exchange emails and began to write essays, and I think we have published 60 or 70 essays on this. I think the first one was Descriptive Science and Mechanistic Science. So, what I began to realize was that, if the experts in the field weretrashing work by calling it descriptive, when you could argue that all science is descriptive — even if you find a new mechanism you're still describing it — that there were really intellectual problems in the way people were thinking.

RB: You said in one of your lectures that I attended that you wanted to bring back the “philosophy into PhD,” please explain what you mean.

AC: Some scientists, when they call the work descriptive, want you to go into cause, they want you to do work to establish causality, others are saying that they want you to go deeper, but they can't even often enunciate what their criticism is, so they call it descriptive. And, to me, what that shows is insufficient training in some of the fundamentals of science and philosophy: How do we know what we know?

ML: You have been a successful editor, a successful researcher, a successful author, and a leader in terms of how people in our field think about science. How would you describe a paper that is a really good paper, because some papers are not that interesting. A word that you could use that is maybe not the same as descriptive could be superficial, not thoughtful. What does it take to be a good publication that you think should have a home in a good journal?

AC: The single most important papers change the way I think, but I don't ever put down science. I don't ever put down new work. Look you still have to go out there and do a lot of the analysis that people call descriptive. You need to know what's there. That may not change your views or your thinking, but you're still adding to the human knowledge base. Don't denigrate it. On the other hand, an occasional paper, whether it is descriptive — you know describing a new thing, a new phenomenon — or whether it is mechanistic, establishing causality in ways you weren't thinking about. You read it and you walk away thinking differently. Those papers to me are in a different category.

But I don't put down work that is well done, that falls into more of the regular work, because humanity can use any information that it can get and some of these are pieces for a much larger puzzle.

What I would say is we need to encourage good work. Sometimes, if you're just following good work that appears to be boring, it can lead you to a great discovery.

ML: True enough. Likely to be true. That should be enough then?

AC: Yes. And we need to do more to confirm work. I think confirmatory is very important. Oh, you know, “it was done already.”  For God’s sake, do it again. Let's see if you get the same result. That's really important.

RB: The topic of gender clearly has influence in authorship and you've actually even addressed this in one of your papers, gender and authorship, and there's also the issue of gender inequities and funding in the field.  You've thought a lot about this. Can you share it with us?

AC: I guess the provocative idea that we have is that scientists are really good at discriminating good science from bad science, but they are terrible when it comes to ranking good science. And the current system of funding requires scientists to rank things. And the problem arises that when you sit there and you rank stuff, “Well you know I like this field more than another;” “Well you know, the figures are nicer.”

These are not the issues that should go into deciding funding — and that's by the way where gender bias comes in and ethnic bias comes in. People say, “How can it be?” Well, you know they've been ranked by people in the field, they know about this. The data are that women and underrepresented minorities don't do as well in this system.

We published a few years ago with Ferric that, in fact, scientists cannot discriminate in the critical 20 percent range. So, you have a situation in which they can't discriminate, you ask them to do something they can't do, and you have data that the current system hurts women and minorities.

So, what I would say is: make two piles and then take the pile that is acceptable science and put it through a lottery. The current system is already a lottery, in that who gets your grant, what the order it is that it gets reviewed in the morning or it got reviewed in the afternoon, who or what other one got reviewed before.

This is not the way we should be funding science, but the lottery has one major advantage. The problem is today we have a lottery, but it's not random. At least if you have a lottery that has randomness, everyone who's in the in the lottery has the same chance.

RB: You've dealt with the HIV. It clearly had a personal impact on you and influenced how you did research. Now you find yourself in the middle of the COVID-19 pandemic, and you have not shied away from this. You have actually gone in full force into the COVID-19 pandemic and have been extremely instrumental in shaping our thinking, shaping some clinical trials and shaping how we look at the data from trials that have been both positive and even some trials that have failed.

How were you able to pivot?

AC: Know the history of your field. So, I trained in antibodies, and one of the things I did very early on is I read a lot about antibody therapies which were the mainstay of therapy up to 1940 when penicillin and sulfonamides triple-listed, so I knew that knowledge. In fact, I had written papers back on these issues, and I knew that antibody could be used for therapy, and I also knew that if you were going to use it, you better use it early. The evidence are in pneumococcal pneumonia. It doesn't work after three days of symptoms in meningococcal meningitis. flexion shows it doesn't work up to three days incentive.

So what happened was that about a year ago, when it was clear as an ID person, I knew this was not containable. that you began to look at the politicians and the health authorities talking: they're talking about vaccines, antivirals and monopolies. No one is talking about plasma. Plasma needs no development. All you need are recovered people. So the question is, “How do you get the word out?”

Well I wrote an op-ed, and I spent the entire month of last February trying to get it published. And, like everything in life — just like getting into an MD/PhD program — everything is serendipity.

I sent it to the Wall Street Journal on the day that the market tanked: February 27th. If you read the op-ed back then, it basically says it works best if you use it early and, unfortunately, we have spent a year in which the entire field had to be re-educated. The first use of convalescent plasma —  a lot of it was for salvage. Look this is a disease this is an antiviral, this is a disease in which you have a viral phase in which you can neutralize the virus with plasma and then you have what gets you into the hospital is inflammation; what kills you is inflammation in the lungs. Antibody is not going to reverse an inflammatory process in the lung. So it's been a struggle in a way both trying to educate people or trying to get it to be used right.

But it has probably, to me, has been one of the most — I believe — one of the most important things that we have done. I have done.

RB: What is the most important advice you can give young scientists embarking on an investigative career? You've been really successful. If you had to tell somebody “You need to do this.” How would you do it?

AC: What I tell all the people who ask me that is become a generalist. In other words, you're already a specialist, you're already going through PhD training, you're already specialized in infectious disease. Broaden yourself. You can do that on your own.

The most important thing to do is exercise your curiosity. Curiosity is like going to the gym. If you basically feed it, it drives itself. And they say, “Well how am I going to do that? I don't have any time.” I said, “Every single day, try to learn a small fact about something else. And what happens is, if you learn one bit every day of the year, by the end of the year you have 365 new bits and you begin to make connections, and science is a lot more fun, you begin to see patterns. But you got to go outside your field. Don't become somebody that says, “That's not my field; I don't have an opinion.” You're a scientist. You should be a generalist, you should be ready to take on the world, on new problems.

RB: Your last comment just before this one, I was going to quote you and say “I'm preparing a lecture on something I know nothing about, and that uncomfortable feeling makes me grow.”

AC: Because you have to explain it to others, in areas that you don't know, you're going to process the information differently. I think we should be more in our uncomfortable zone.

RB: We've had a great afternoon

AC: You asked me some very nice questions. Thank you for all the nice things you said.