Science for the Common Good

A smile comes easily to the face of Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, as he encounters visitors to his offices at the Institute. He does not, however, allow himself to be distracted from his duties for longer than it takes to nod warmly. The sense of discipline and the determination and preparedness that were instilled in him through a Jesuit course of education are apparent. He is as direct and as clear spoken in person as you've seen him on television, speaking on innumerable occasions over the past two decades about the pathology and treatment of AIDS, and more recently, delineating the public health from the national security issues precipitated by the bioterrorist events of the past year. The three office assistants who occupy his reception area have been particularly taxed in the management of Fauci's schedule since 9/11; as they pause briefly from their work to share photographs of a friend's recent wedding, Fauci is there to admonish them, semi-good–naturedly, as government employees, to return to their official duties. He has been meeting with high government officials and has been courted by the media for interviews regularly since the tragedies began. Given his high profile, it is easy to forget that Fauci is, foremost, a clinical immunobiologist and physician. His dedication to science is part of his commitment to public service, also a value instilled in him by the Jesuits. Fortunately for all of us, Fauci was pursuing this combination of interests—within the venue of bioterrorism—in his official capacity at the NIAID well before the general public had awoken to the threat.

MI: Your father was a pharmacist. What kind of influence did that have on your professional development?

AF: Well, he was a person very much interested in public service and in doing things for people. So it was much more his character that influenced me than what he did for a living.

MI: Both of your parents were the children of immigrants, right?

AF: Yes, all of my grandparents were born in Italy.

MI: And your parents both went to college, and you followed an intensive kind of academic life even as a youngster. Where did that motivation come from?

AF: You know, it was subconscious. The influential basis for the things I did—for the things that anybody does—is a combination of genetics, environment, nurturing from parents, tutors, mentors and others, but I think that the continuum of factors includes genetics—that I genetically came from people who happened to be interested in intellectual things. So I was immediately interested in those things, too. The idea about doing things less for monetary gain and more for what they really mean is something that I got from my family right from the very beginning, from both my mother and my father. There was never a driving interest in making money; the stress was always on what you could do for society. Now if it had stopped with just genetics and my home environment, then maybe that sort of motivation would have been lost. But then I trained in a parochial elementary school with the nuns, who were very strict and taught you discipline. And then I went into a training scheme with the Jesuits that included four years in high school and four years of college (Holy Cross). And their entire modus operandi was public service, intellectual pursuits, the pursuit of excellence, responsibility—those were things that were just drilled into you every single day. So I was fortunate enough to come from a family background that seeded those qualities to begin with, and then lucky for me, I was put into an environment where intellectual pursuit was the norm of the day.

MI: And then in college, what did you pursue as your major?

AF: Classics. My high school training with the Jesuits in New York City was very heavy in the classics, and then at Holy Cross, I took an unusual type of premed course. It was called AB Greek–Premed, and you studied Greek, Latin, French, thirty-two credits of philosophy, and just enough science to fill the requirements of getting into medical school.

MI: I imagine, to do all the things you do at the scale that you do them, that you’d have to remain something of a philosopher. Do you consciously practice a particular philosophy?

AF: No, I don't consciously think about it; it really is part of me. My view towards science is always very much a high-altitude perspective—the broad, big-picture look. I don't get bogged down in the minute little details. Always to ask, “What is the question I'm asking? Is it an important question? Where is this question taking me? Does the answer that I get solve the question or not?” I always focus on the big picture, and I think that my broad philosophical background is a very important part of that general orientation that I have.

MI: I found it something of a surprise to learn that your first big splash in research was in the area of pharmacology. I'm thinking of your work with cyclophosphamide…

AF: …Right, and the glucocorticoids. There are really several stages to my career, I guess. The first stage was the pharmacology component where I looked at cyclophosphamide. The second phase was the fundamental regulation of the human immune system. And the phase I'm in now is using that knowledge to understand the pathogenesis of HIV disease, so I'm doing fundamentally all HIV, but it was a natural transition. My training was a classic internal medicine training. I passed my Boards in internal medicine, in infectious diseases, and in allergy and immunology. Then I came to the NIH on a dual fellowship in infectious diseases and in immunology. When I started off here, I was trying to determine the effect of glucocorticoids, as well as immunosuppressive agents like cyclophosphamide, on the immune system. I was one of the few people at that time—it's very common, now—who was actually studying the fundamental basics of the regulation of the human immune system. That early work resulted in the first demonstration in humans that glucocorticoids, instead of lysing normal cells, as was thought for animal systems, actually led to the redistribution of circulating lymphocytes into different body compartments, so that when the lymphocyte count dropped, it wasn't because you were destroying cells—it was because you were redistributing them to different compartments, including the bone marrow. That work was actually very novel, because it wasn't appreciated what the effects of glucocorticoids were on the human immune system.

What I did with cyclophosphamide was to show that an agent that had formerly been used almost exclusively at high concentrations to kill tumors could actually be used, in low doses, for people who had autoimmune and inflammatory diseases. Cyclophosphamide had been used solely in people with malignant diseases, like leukemias and lymphomas. We then looked to treat diseases, such as Wegener's granulomatosis, polyarteritis nodosa, and lymphomatoid granulomatosis, which were invariably fatal at the time. The step we took, which was considered rather bold at the time, was to design a regimen to suppress aberrant immune responses without depressing the normal immune system. It turned out to be a resounding success, because we actually developed the long-term remission (if not cure) of diseases that had previously been, fundamentally, fatal. And that, I think, was the thing that brought me to the public eye. That's when people really started to notice the importance of the research.

MI: Was that your first experience in clinical trials?

AF: Well, my interactions in clinical trials began with the very first day that I got here, because in addition to my fundamental basic research, I was taking care of patients on the ward from my first day, so my clinical investigations ran parallel with my basic investigations. It was all bench-to-bedside, bedside-to-bench.

MI: You now function in more than just two arenas. Without using a title, how do you describe yourself professionally?

AF: Well, it's tough, you know, to describe, because I do several things. I'm certainly an administrator—at a multibillion-dollar institute, the National Institute of Allergy and Infectious Diseases—but I think that above all I'm a scientist. I'm a person trained in science in its very basic form, and there is a very strong clinical flavor to what I do. Fundamentally, all of the functions that I carry out are geared towards particular questions that have to do with human disease.

MI: Do you still maintain clinical duties?

AF: Oh yes. I make rounds twice a week on the ward.

MI: Why?

AF: Because that is an extraordinarily important part of my identity in being a physician. I could not stop. It would be impossible for me to stop seeing patients. Totally impossible. It has to do with a contribution to society, but it also has to do with what my identity is. I look on myself as a physician. I really like administration and I think I do it quite well, but I look at myself fundamentally as a physician. You know in those questionnaires that ask, “Please rank what you think you are.” Clearly, a physician is number one.

MI: Why is that number one?

AF: That's what I want to be number one. I feel that the qualities of a physician transcend a whole bunch of other disciplines, and it gives you the chance to execute your science, interact with people, have public service, be a human being. Sometimes when you get bogged down in paper and administrative things, you feel like a computer as opposed to a human, but you never forget you're a human when you're dealing with other people.

MI: And immunobiology is still where you would set yourself.

AF: Absolutely.

MI: Because I was thinking about pharmacology in the context of AIDS, which is still fraught with pharmacological and toxicological problems. Do you see any special intersection between immunobiology and pharmacology or toxicology?

AF: Well, if you're fundamentally looking at an aberrant immune system, that's immunobiology; if you're looking at bioterrorism, then, fundamentally, the microbe is your concern. But whatever the matrix study is, if you're talking about interventions, pharmacology almost invariably comes in, because it's part of a multidisciplinary approach to the understanding and intervention of pathogenic processes. So in some respects, sooner or later, all of us have to invoke pharmacological interventions. It just so happens, in my studies, that I came to it as an immunologist and as an infectious diseases person, but the questions that I was asking were intimately connected with pharmacology because I was using therapeutic interventions with drugs in the context of the immunology.

MI: To pursue your experience in science administration and AIDS: In the early 80s, when science funding was very tight, there were some researchers who complained that AIDS was going to suck up all the funding in bioscience. Did you experience this kind of backlash—was this resentment something that touched you?

AF: Well, yes, but that's a very simplistic approach that doesn't appreciate the real flavor of what was going on. In order to jumpstart a field—we're experiencing the same thing now with bioterrorism—you have to have opportunities, for both established as well as young investigators, to change directions in order to address a very important and compelling public health question. In the mid 80s and early 90s, and even up to today, that question was and is HIV/AIDS. Now, if handled correctly, you will build up a cohort of investigators to take up leadership roles in new fields. True, early investment may not be as efficient as investment in a field that has traditionally had high-quality investigators; the curve of balance between investment and return, however, must be allowed to reach a point so that, after a few years, you have a cohort of investigators who are highly qualified. The AIDS field has become as competitive, if not more competitive, than any other field. But in the early years, when you're throwing a lot of money in, you're expecting that the efficiency of the utilization of those resources, until you've built up a base of knowledge and a base of investigators, is not going to be as good. And so that was viewed back in those early days as, “Oh, if you want to get funded, just do some AIDS work and you’ll get funded.” Yeah, that's right, because there was a lot more AIDS money than there were investigators. Now it's a very, very, highly competitive field.

MI: I asked about the backlash with respect to funding of science and AIDS, because, just as you mention, I assume that counterbioterrorism is going to be an important driver of bioscience for a while. What do you foresee there?

AF: I foresee that there will be the same sort of extraordinary acceleration of effort, accomplishment, interest, and infrastructure. The discipline is going to explode in very, very important ways. And yes, there will be resentment among scientists as to why bioterrorism is getting so well funded, in the same way that there was some resentment—not a lot—but there was some resentment with HIV/AIDs in the early 80s. I fully anticipate that, but what you're dealing with in bioterrorisim is not only a public health issue, but also a national security issue. And I think people are going to be tempered in their criticism about that, because when they really sit down and think about it, it's related to their health, the health of their families, and the health of their nation.

MI: So now you sit at the edge of national security and science—where the two intersect. Did you ever think that you’d be at this point? Or did the political aspects and the politicization of AIDS already place you at this intersection of science and government policy?

AF: Certainly. I mean, AIDS was the first step to it. Now nothing surprises me, because I've been doing it for such a long period of time. But when I first got into medicine, I thought I was just going to practice in an academic setting, see patients, not do a lot of bench research—not do any administration—but just see patients, because I was a very good clinician and I liked it. And then as things evolved, I got involved into continuing my science, but also doing important administrative things.

MI: You've said that counterbioterrorism has been an important aspect of research at the NIAID even before September 11, 2001. But when those events were occurring—before the first case of Anthrax was described in Florida—did the thought occur to you that with terrorism, next would come bioterrorism?

AF: As soon as there was the tragedy at the World Trade Center, I was absolutely certain that there was going to be bioterrorism. There was no question in my mind.

MI: Why did you know to expect it at the heels of the World Trade Center tragedy?

AF: Well, just the facts, because it was clear that countries that were accessible to bioterrorists were making weapons of mass destruction. Now that the Soviet Union has dissolved, the researchers who left the Soviet Union program have admitted that they were engaged in such activities even after the 1972 bioweapons convention treaty. It is very clear from our inspectors that Iraq has weapons of mass destruction, and it is likely that other rogue nations may have them.

MI: I'm wondering what kind of information flux you as a government official experienced in implementing counterbioterrorist activities.

AF: It was much more my responsibility as a government official. I mean, I'm in charge of a 4 billion-dollar institute that's charged with infectious diseases and emerging microbes. There are several ways that microbes emerge. They emerge naturally, like an epidemic of flu, or through drug resistance, like tuberculosis and malaria, or they emerge and re-emerge deliberately, like bioterrorism. So to me, it was all part of the responsibilities that I had. I had to lead the Institute in that direction because it was important for public health.

MI: You also deal a lot with the media. Immediately after 9/11—but before the first Anthrax case—we heard on television news shows about weaponized, aerosolized Anthrax for mass destruction. And then the first case came, from all places, through the mail! What were you thinking at the time?

AF: Well, we don't know what the motivations here were in the deliberate spread of Anthrax by mail. It may turn out to be a home-grown nut who did it to bring attention to the question of bioterrorism, but accidentally the material fell out of the envelope and killed the postal workers and others. Such a person could have been trying to do something that wasn't going to kill a lot of people, but rather just to make a big stink. Or it could have been a terrorist, with connections to terrorist organizations, who deliberately wanted to emphasize the terror over the bio. You know, bioterrorism is two things: It's a biological impact, and the terror that results from it. The disruption that Anthrax brought to our society was enormous compared to what the biological damage was: eighteen people infected and five dead. That's unfortunate, obviously, and tragic for the people who died, but just look at the effects: It shut down the postal system, it shut down the Senate. It cost hundreds of millions, if not billions, of dollars in expenses for cleanup. It was a major disruptor.

MI: But no one had thought about it coming by mail, had they?

AF: No, it was not what we think about as an efficient way of delivering it. Everyone was thinking about an aerosol in the air vent of a metro or the air vent of a building—and that still could happen. But nobody really could have imagined that it was going to come by mail.

MI: So you wouldn't have viewed the discussions that took place between September 11 and the first case in Florida as media hype?

AF: No, I don't think it was media hype. It was reality. We had just undergone the most devastating attack in the history of the United States—worse than Pearl Harbor—on September 11, and then all of a sudden we get an Anthrax occurrence. No, I don't think that was media hype at all.

MI: When one hears about “traces” of Anthrax spores, in the office next to Senator Daschle's and such, do we know to what extent that there are background traces of Anthrax spores naturally?

AF: No, I've been asking for somebody to do that study for quite a while. It is unlikely that there is a detectable background level, but there may be parts of the country in which you have a background of spores—for example, in places where animals have died that were infected, so that little bits of spores exist in trace amounts. But it is unlikely that anything that you would find in the Hart Building is a natural contaminant. I can't say for 100% sure, but it's almost certain that it's from the residual spores that were carried by mail.

MI: You say you see things from high up—the broad perspective—but you always appear to have these amazing amounts of details when you answer questions, always on the spot. How do you manage that?

AF: I live my work. I put so much time and so much energy and passion into it, that it's second nature. I deal with these questions, I'm intensively interested in them, and I try to keep an open mind. So when you hear me at these different forums and somebody asks a question, and I have the answer at the tip of my finger, it's because I deal with it all the time. I'm constantly reading, I'm constantly talking to people, I'm constantly interacting, and I get involved with difficult decisions.

MI: You said that initially you thought you might go into teaching at a university hospital setting. But now you've taken on the role of public educator in the media. Do you enjoy it and the celebrity that goes with it? Is it fun or is it a distraction?

AF: Well, the education part of it I like because that's part of what I like to do and I know I'm good at it. I think it's an important service; I think that in many respects it's as important as the science that we do. Because the media really is the outlet, the source, from which the public gains most of their information. And in the reporting of important events like these, you really have to make sure the facts are straight. And that's the reason why I take great care in being very explicitly clear about what I say. And in order to be explicitly clear, it's got to be clear in your own mind. The easiest way to be unclear is to not really have it clear in your own mind. So I try to analyze and clarify things and then express them through the media in a way that hopefully will get reported in an accurate way.

MI: You say “hopefully” educate the people. I guess I wonder why you're not more cynical—especially with some of the politics around AIDS and the personal attacks that you've experienced—and you've also publicly addressed the government's duty to disclose the truth of potential bioterrorist threats, as opposed to preventing panic. Those are all lines that you have to walk across. So why aren't you cynical?

AF: You can't be cynical—because to me, that's giving up. Sure, I don't have unrealistic expectations that when I say something, everyone who is listening is really going to get it. I mean, I've heard people come over to me—and I speak very clearly—after I've been trying to explain something, who ask a question that tells me that they didn't hear a thing I said. And that to me is frustrating. But if you're cynical, then what's left? There's no substance to your message if you're cynical about it.

• © American Society for Pharmacology and Experimental Theraputics 2002