IF everyone in the world were like Dr. Anthony S. Fauci, there would be no need for Prozac. By any sensible reckoning, the man should be wilting around the edges. He has been at the center of the AIDS tornado since the epidemic began, serving as the director of the National Institute for Allergy and Infectious Diseases and the Government's Office of AIDS Research, which together oversee much of the AIDS-related research carried out around the nation.

Apart from his official credentials, he has been the most visible and quotable spokesman on every medical, epidemiological and social aspect of the disease, the de facto AIDS czar until the appointment last year of Kristine Gebbie as the czar de jure to the President.

The institute that Dr. Fauci runs at the National Institutes of Health not only controls about 40 percent of the Federal budget designated for AIDS, but also the money for studies of all the other infectious diseases afflicting the nation's citizenry, from tuberculosis to hanta virus infections. In addition, Dr. Fauci runs a laboratory on the Bethesda campus that does basic research on how the human immunodeficiency virus gradually disassembles the immune system, studies that lately have yielded insights into AIDS and buffed his luster as something more than a superbureaucrat.

Even among scientists, where work addicts are commonplace, Dr. Fauci, 53, is renowned as a truly hard worker. This is the bookend refrain for any discussion about him, an emphasis first and last on how astonishing it is that he manages to work 16 hours a day, day after day, year after year.

And he is working on a plague for which, scientific revelations about the virus notwithstanding, there have been depressingly few advances to help human patients. There is no vaccine in sight. There are no new drugs in the pipeline, and the antiviral drugs that do exist, like AZT, DDI and DDC, have been shown to be of questionable benefit in prolonging life.

The epidemic continues to spread relentlessly across the globe. It has killed 210,000 people in the United States alone and eviscerated entire subcultures, including the arts community, which gives depth and resonance to the rest of the population. It is a new disease that has turned the world old overnight.

Dr. Fauci has been bounced around by activists in the AIDS community, denounced one day, embraced as comrade and hero the next. Most recently, activists have put his pride and ego to the test by persuading Congress that the Office of AIDS Research should be removed from his jurisdiction and given a full-time director of its own, who is expected to be named any day now.

Yet Dr. Fauci looks the same as he has looked for years, a compact, meticulous, supremely confident, unflappable bullet of a man, at once compassionate and hard-driving, gentle and ferocious. The man with the natty suits, hearty handshake and resilient Brooklyn accent.

Doesn't he ever doubt himself, or his ability to make a real dent in the disease? Doesn't he ever get tired or depressed or demoralized, or just overwhelmed by it all?

"If you're asking whether I have fears, pain and anxieties, yes, of course I do," he said. "That's a natural human thing. But do you mean, have I ever let them interfere with my responsibilities, or get in the way of my work? No." Not once? Not one single lapse? "Never," he said firmly. "I have the self-discipline not to let that happen." As though to make a point about his purposefulness, he jumps up from the couch where he had been sitting in his office and strides over to his desk. Two of the walls in the large room are covered practically to the ceiling with his plaques and awards and degrees real and honorary.

"To take on what I take on, you have to be very organized and energetic," he said. "I have made enormous sacrifices in my family and personal life. But I don't want to be praised or pitied for this. I do it because this is what I want to do." Optimistic About AIDS Treatment

He is religiously organized, his day blocked out in chunks for his administrative duties, his rounds to see AIDS patients in the research hospital at the institutes, his lab meetings, his discussions with scientists in his group. He runs seven miles every lunch hour regardless of the brutality of the weather. He sets aside every Saturday evening and all day Sunday for his family, a commitment that is essential if he is to see his three young daughters while they are awake.

And perhaps his is the attitude that must prevail in the plague years: not robotic, because robots break down, but calmly obsessive and matter-of-fact. His pragmatism may be his strongest suit, the impulse that ultimately overrides what some say is his sensitivity and a tendency to take things personally. When told that Harold Varmus, the new head of the N.I.H., had described him as "running his institute with an iron fist," Dr. Fauci made a point of asking every subordinate he encountered that evening whether the description was accurate.

Most giggled nervously and said variations of, well, yes, but you're always fair. Dr. Fauci is a man of many opinions, the most essential of which are scientific ones. And it is in the scientific arena that he is most optimistic, although cautiously so. "We've been on a roller-coaster ride for years, from great enthusiasm to despair," he said. "Recently, there was a sense that the sky was falling, when it became clear that giving people AZT early in the course of the disease doesn't give significant benefit.

"But despite the feeling of a roller- coaster ride," he added, "the science will march ahead to the time when we'll have an enduring solution or a therapeutic intervention. And it all will be based on a step-by-step understanding of the immune pathogenesis" that is the hallmark of AIDS.

Dr. Fauci has lately devoted most of his attention to dissecting those steps. In widely praised work published last year, Dr. Fauci and his colleagues reported that the human immunodeficiency virus never really lies latent in the body, but rather is sequestered in the lymph nodes, where it disturbs many threads of the body's densely interwoven immune system. It overexcites some immune signaling pathways, while eluding the detection of others. And though the main target of the virus appears to be the famed helper T-cells, or CD-4 cells, which it can infiltrate and kill, the virus also ends up stimulating the response of other immune cells so inappropriately that they eventually collapse from overwork or confusion.

He proposes that one possible approach to treating infection with H.I.V. is not to focus on clearing every last viral particle from the body, but rather to figure out exactly how the immune system comes unstrung, and then replace or compensate for those signaling pathways thrown out of whack. For example, he and his colleagues have learned that AIDS patients suffer from a defect in the arousal of an immune signaling molecule called interleukin-2. In trials now under way, they are giving patients IL-2 in carefully calibrated doses designed to recapitulate the activity of a normal immune system. They have found that the patients' T-cell counts improve with the treatment, but they now must determine whether that rise in cell number translates into an improvement in symptoms of the disease; for example, whether the interleukin treatment causes Kaposi's sarcoma lesions to shrink.

Dr. Fauci and his colleagues are also studying the immune systems of 10 people who are members of a small and fortunate minority: they have been infected with H.I.V. for 12 years or longer, yet they have not progressed to showing any symptoms of AIDS. "We think the real clues to the disease are with these people," said Dr. Fauci. "What is it about them that's different? The architecture of their lymphoid tissue appears to be preserved compared to those who progress, and we're trying to see what is responsible for that preservation."

'A Consummate Politician'

Dr. Fauci's current fixation on his science is what keeps him from getting excessively rankled by recent struggles over who will have the greatest hand in shaping the course of AIDS research. The new legislation that reorganized the Office of AIDS Research was whisked through Congress last spring so easily that even the activists who had promoted the change were surprised. Under the plan, the office has been turned into a strong force within the N.I.H., one with more personnel and power than it had under Dr. Fauci's rule. Whoever is chosen as director will coordinate the entire $1.3 billion budget for AIDS research, keeping track of all AIDS-related programs and clinical trials that currently are run by 21 different institutes at the N.I.H.

Dr. Fauci and many other scientists had vigorously opposed the reorganization of the Office of AIDS Research, arguing, among other things, that it would emphasize a trend toward excessively targeted science at the expense of untethered basic research.

Dr. Fauci soft-pedals the degree to which his pride has been wounded, but friends and colleagues said they sensed his frustration. "It might be a relief for him to get some of the pressure off his back," said Dr. Donald Frederickson, a former director of the N.I.H. and one of Dr. Fauci's old friends. "It's enough to do to run his own institute, and his lab is now going full steam. But nobody likes to be downgraded from the position of national importance that he's had."

Those who know Dr. Fauci said there is no chance he will fade into the scenery. "His role will change, but anybody coming into the office would be a fool not to

take advantage of Tony's leadership skills," said Derek Hodel of the AIDS Action Council, a Washington-based lobbying group for AIDS organizations. "He's a consummate politician and a fine scientist, and it's clear he's going to continue to play a central role in AIDS research."

Dr. Fauci, say friends and co-workers, has always been like a child's punching bag, which can be pushed over but will always pop back up for more. For the first eight years of his directorship at the allergy and infectious diseases institute, he worked under Republican Administrations reluctant to focus their attention on AIDS. He has been the repeated target of activists furious at what they perceived to be bureaucratic indifference and timidity -- and he has also been their greatest friend.

"I call him murderer or hero, depending on the week," said Larry Kramer, a playwright, journalist and the most resilient bullhorn of all activists. "It's been such a complicated relationship." That complexity was reflected in Mr. Kramer's latest play, "The Destiny of Me," in which Dr. Fauci is portrayed, with scant attempt at disguise, as Dr. Anthony della Vida, or Dr. Life, a chipper physician-researcher who accepts descriptions of himself as "a son of a bitch of Hitler" and a "scientific fraud" from his churlish AIDS patient -- modeled after Mr. Kramer -- yet who tries with equal fortitude to keep that patient alive. Dr. Fauci attended the play's opening.

Assailed and Beloved by Activists

"I've worked with Dr. Fauci for years, and during that time we've have a combination adversarial and collaborative relationship," said Mr. Hodel. He and other activists give Dr. Fauci tremendous credit for lending his support several years ago to the idea of a parallel track, of allowing experimental drugs to be made available to AIDS patients even as the compounds are tested in clinical trials. They also appreciate that he has spoken out against mandatory H.I.V. testing of health care workers, and has opposed barring immigrants who carry the virus. They said he has been willing to listen to members of the AIDS community and to persuade grudging researchers and pharmaceutical companies that they should do the same.

Yet for every cheer there is a hiss. Some activists recall bitterly that during the Reagan and Bush Administrations Dr. Fauci defended research budgets that they thought were dreadfully inadequate. Some say he is a great scientist but a poor administrator; others insist that he is too smooth a bureaucrat to make any scientific headway. Scientists also have criticized Dr. Fauci for capitulating to the demands of activists too readily.

And through it all, Dr. Fauci accepts the criticisms, and he accepts that someone must absorb the anger and terror that AIDS has spawned, so why not somebody of strong vertebrae who was raised on the streets of Bensonhurst? "I was on a CSpan program a couple of months ago with Tony, and I attacked him for the entire hour," said Mr. Kramer. "He called me up afterwards and said he thought the program went very well. I said, 'How can you say that? I did nothing but yell at you.' He said, 'You don't realize that you can say things I can't. It doesn't mean I don't agree with you.' "

Dr. Fauci claims he does not take the intermittent blasts personally. "That's the activist mode," he said. "When there's a disagreement their tendency is to trash somebody. But I know that when Larry Kramer says the reason we're all in so much trouble is because of Tony Fauci, he's too smart to believe that. "I don't want them to change or compromise that mode," he added, "as long as they don't ask me to change my opinions."

"I'm totally obsessed by this problem," said Dr. Fauci. "I'm going to finish this job." That is why he turned down an offer to take over the entire National Institutes of Health several years ago, he said, and that is why he does not mind ceding control over the Office of AIDS Research now.

"I think Tony believes he will find a cure for AIDS," said Mr. Hodel. "I hope he's right. And I hope a lot of other people are given the opportunity to believe that as well.

After years of recommending AZT as the first-line drug for treating the virus that causes AIDS, Federal health officials are considering a change because of surprising results with other drugs.

Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, said in an interview that he planned to convene a meeting where independent experts could decide whether AZT should remain the first choice.

A large study paid for by Dr. Fauci's institute and reported this week found that AZT was less effective than another drug, didanosine, or ddI, and also less effective than combinations of AZT with either ddI or zalcitabine, known as ddC.

One part of the study showed that ddI lowered the rate of death from H.I.V. infection to 5 percent from 10 percent when compared with the use of AZT alone over 147 weeks.

The study provided the first conclusive evidence that a drug could reduce the risk of death in symptomless people who are at an intermediate stage of infection with H.I.V., Dr. Fauci said.

Two similar independent studies are due to be completed by January. One is being conducted in the United States, the other in Europe and Australia.

Dr. Fauci said he would ask the meeting of experts to review the findings of all three studies and consider whether a change in recommendations for the treatment of H.I.V. was needed.

Two AIDS experts who participated in the study that was reported this week, Dr. Paul Volberding of San Francisco General Hospital and Dr. Fred T. Valentine of New York University Medical Center, joined Dr. Fauci in calling the findings important.

David Barr, the director of treatment education at the Gay Men's Health Crisis in New York City, said that "the way ddI stands out has taken everyone by surprise."

"It suggests," Mr. Barr said, "that ddI is a better single drug to start with than AZT. But it does not answer the question whether ddI is better than nothing."

Indeed, Dr. Fauci and other experts confirmed that ddI had never been compared with a placebo in a large study, even the one now being reported, whereas AZT had proved better than a placebo in earlier studies.

Mr. Barr said the Gay Men's Health Crisis would withhold judgment on the new study's findings until completion of an independent statistical analysis. New calculations are needed, he said, because of the large amount of data involved in the study and his organization's concern that problems had arisen with statistical analyses of earlier federally sponsored studies.

One point of concern, Mr. Barr said, is the unusually large dropout rate -- 53 percent of the 2,500 people who began as subjects in the study did not complete it -- and that rate's effect on the statistical power of the study.

Federal health officials said the high dropout rate reflected adverse reactions to the drugs, disease progression and the study's demands on patients. A Federal analysis said that "the premature withdrawal rate may have diluted the power to detect differences but does not appear to have negated the results and conclusions."

The study was carried out at 52 medical centers in the United States. It involved infected patients whose immune system had been moderately impaired by H.I.V. and who had CD4 counts from 200 to 500. CD4 cells are the prime target of H.I.V., and CD4 counts are a standard measure of immune system function. The normal count is 800 to 1,200.

The participants were randomly divided into four groups, which received AZT alone, ddI alone, a combination of ddI and AZT, or a combination of ddC and AZT.

AZT was less effective than each of the three other treatments in preventing death, progression of infection to AIDS and significant drops in the CD4 count.

The three favorable treatments were similar in effectiveness and side effects, according to the preliminary findings, which will be reported in San Francisco on Monday at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The Gay Men's Health Crisis is advising callers to take their questions to doctors, Mr. Barr said, because the differences in reported benefits "are not that great that somebody should be immediately changing what they do."

"It is going to take some time to sort out this information and to figure out what it means," he said.

Although the three studies that the panel of experts will review are not identical, Dr. Fauci said, they and some earlier studies are similar enough for common threads to be detected. The European-Australian study involves 3,300 symptomless infected patients with fewer than 350 CD4 cells. The second American study involves 1,100 patients with fewer than 200 such cells.

Until the expert committee makes its recommendations early next year, Dr. Fauci said, data from the study reported this week suggest that a patient's prior experience with AZT can guide a doctor's choice.

Of the participants, 57 percent had taken AZT before entering the study, and 43 percent had not. Although all three other treatments in the study fared better than AZT alone, among participants who had never taken AZT the most significant benefit was found in those who received the combination of ddC plus AZT.

In contrast, among patients who had taken AZT before, the best results were seen in those who took either ddI alone or ddI plus AZT.

The findings should lead scientists to focus on developing improved combinations of anti-H.I.V. drugs, Dr. Fauci said.

For instance, recent studies have shown favorable results from a combination of AZT and a drug called 3TC. And with AIDS experts hailing the promise of a new class of drugs known as protease inhibitors, studies of different combinations may demonstrate substantially increased benefits, Dr. Fauci said.

London: In 1996, scientists solved a mystery surrounding certain gay men who were immune to AIDS. This year, Pfizer Inc. will sell the first drug based on that discovery.

The US and European researchers, writing in several science journals, said a small group of Caucasian gay men carry a gene mutation that provides natural protection against HIV, the virus that causes AIDS. This week, culminating an 11-year race among three drugmakers, Pfizer released successful studies of a new pill specifically designed to mimic the gene defect.

“We still remember reading those papers and thinking, ‘God, we should do something with this’," says [Giuseppe "Pino" Ciaramella (born 1968)], a scientist at Pfizer’s laboratories in the UK seacoast town of Sandwich, where the drug was created.

Regulators in Canada, Europe and the US have accelerated reviews of the drug, called maraviroc, based on clinical trials showing that, when combined with other medicines, the pill is more effective than existing therapies in treating AIDS patients. The new drug may gain regulatory approval this year and generate more than $300 million (Rs 1,322 crore) in sales by 2011 for New York-based Pfizer, the world’s largest drugmaker. It also may arm doctors with a new weapon against forms of the virus that are resistant to current treatments.

Ciaramella, 38, says he and his colleagues were spurred into action because the reports involving gay men were followed three months later by another study reinforcing the notion that some people can inherit immunity to HIV. In that research, Canadian and Kenyan investigators reported that 60 prostitutes in Nairobi didn’t become infected after being repeatedly exposed to the virus over 10 years.

As a result of the studies, scientists realized that HIV carries out its damage by first hooking onto a spike called a receptor that juts out from the surface of white blood cells, much as a key enters a lock. The scientists found that the gay men of European descent were shielded from HIV infections by inheriting a defective version of the cell receptor, called CCR5.

Pfizer scientists say this critical finding led them to believe they might be able to create a drug against the virus that worked by binding to the CCR5 receptor, thereby blocking the doorway HIV uses to infect cells.

“The whole thing was started by noticing this genetic defect," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

Other drug companies, including GlaxoSmithKline Plc, based in London, and Schering-Plough Corp. of Kenilworth, New Jersey, also began chasing after their own CCR5-blockers when the gene defect discovery was reported in 1996. Glaxo terminated its project in 2005 when its drug proved to be toxic to the livers of test patients.

Schering-Plough’s candidate suffered a setback in 2006 after five patients in one study developed cancer. The company expects to begin a larger trial of the drug later this year after an independent monitoring board ruled there wasn’t enough evidence to determine the drug caused the cancers, says spokesman Robert Consalvo.

“That’s why competition is good," says David Roblin, Pfizer’s head of clinical research and development at the Sandwich site. “It’s lucky it was us" that succeeded. Shares of Pfizer rose 8 cents to $25.04 on 1 March in New York Stock Exchange composite trading. The stock has dropped about 4.8% this year.

Maraviroc, when used in combination with other drugs, more effectively suppressed blood levels of the virus than the standard three-drug HIV therapy in current use, according to data Pfizer presented at an AIDS research meeting in Los Angeles on 27 February.

[Giuseppe "Pino" Ciaramella (born 1968)], a biochemist, had only arrived at Pfizer a few months before the 1996 studies were published. “It was one of my first projects," he says.

He and his colleagues spent five months in 1997 at the Sandwich lab, where five of the company’s current 20 top-selling medicines, including Viagra, were discovered.

After finding the chemical with the most promise, the team spent the next two years modifying it. Using robots in a laboratory outfitted to limit the risk of accidental infection, they tinkered with the drug candidate, manipulating its structure to produce more than 1,100 different versions.

By 2000, their research had led to two compounds, maraviroc and another, called UK-436488. The chemicals were structurally identical except a nitrogen bond in the center of the molecules projected outwards in one and inwards in the other.

That difference meant UK-436488 was also 1,000 times less active than maraviroc, says Tony Wood, 41, head of discovery chemistry at the lab. “You can make very small changes and lose activity altogether," he says.

That year, Wood and his colleagues synthesized a prototype drug that tightly experiments in test-tube bound to the CCR5 hook and also appeared unlikely to cause side effects.

“What really made maraviroc stand out was that it was a compound that seemed to balance all the properties we were looking for better than the others," Wood says. “It was very potent."

In the next year, Pfizer tested maraviroc in lab animals including rodents. It was first administered to people in 2001 and, after positive initial results, trials aimed at gaining regulatory approval began at 250 centres in 16 countries in 2004.

Marketing clearance this year would mean that it took about a decade for maraviroc to go from the laboratory to the market. That’s less than the average time of 14.2 years, according to research by Joseph A. DeMasi of the Tufts Center for the Study of Drug Development in Boston.

“That’s faster than most," said Annette Doherty, a Pfizer senior vice president and director of the Sandwich lab.

The US Food and Drug Administration says it will review Pfizer’s application on 24 April and may make its decision in June. The European Medicines Agency may rule on the drug later this year.

One drawback for the drug is that it only works in patients in which HIV uses CCR5 to pierce cells, estimated to be about half the people infected. The virus can use another similar receptor to enter cells of other patients. The drugmaker plans to sell maraviroc only to those patients identified in blood tests as having active CCR5 receptors, company spokesman Joel W Morris says.

The cost of that test may be as high as $1,000 in the US, says Bob Huff, editorial director of New York-based Treatment Action Group, an advocacy group. Pfizer hasn’t set a price for maraviroc. Analysts estimate Pfizer will charge about $5,000 a year for the drug.

Maraviroc may be especially valuable in treating patients for whom existing drugs don’t work anymore. Doctors now estimate that as many as 65,000 people with HIV in the US are resistant to all three major classes of medications and in worsening health.

Blocking the receptor may lead to unintended effects, including the possibility that the virus may eventually find a way into cells through another receptor, say Huff and Fauci. Humans have numerous such receptors, which is why some people can function normally without a working version of CCR5.

“It’s a theoretical risk," says Fauci, “but it’s not so far-fetched either."

This is an interview with Dr. Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases), in his office at the National Institutes of Health, in Bethesda, Maryland, on March 7, 1989. The interviewer is Dr. Victoria Harden, Director of the NIH Historical Office.

Harden: Dr. Fauci, could you begin by describing the home in which you grew up, your parents, your grandparents and siblings; what you enjoyed doing as a boy, and your elementary and secondary education?

Fauci: I was born in Brooklyn, New York. My grandparents on both my mother's and father's side were born in Italy, except for my grandfather on my mother's side, who was born in Switzerland. They came to the United States at the end of the nineteenth century. Both my parents were born in New York City and went to public schools in New York City. My father, Stephen Fauci, graduated from the College of Pharmacy, Columbia University, as a pharmacist. My mother, Eugenia Fauci, went to Brooklyn College and Hunter College. They married very young, when they were eighteen years old, and went to college after they were married, while they were still growing up. I went to the neighborhood parochial schools in New York City. I was brought up in a Catholic grammar and high school environment. I went to Our Lady of Guadeloupe Grammar School in Brooklyn and to Regis High School, a Jesuit high school in Manhattan. I had the interesting experience of having to take a bus and three separate subway trains to get from my home in Brooklyn to high school in Manhattan. I believe that my childhood was a typical, very happy, and very active growing-up period in New York City during the early forties. I was born in December of 1940 in New York City and grew up as a child in the World War II and post World War II years.

My major interest was sports. I lived in a very sports-oriented neighborhood. We used to play basketball from the beginning of the basketball season to the end, baseball throughout the spring and the summer, and then basketball and football again in the winter. My sister, who is three years older than I, also went through the same sort of school system, same grammar school I went to, went to an all-girls' Catholic high school, and ultimately St. John's University in New York City. She was a teacher before she stopped to raise her family.

Harden: Who were your boyhood heroes?

Fauci: My boyhood heroes were predominantly sports figures like Joe Di Maggio, Mickey Mantle, and Duke Snyder. I was unusual in that I grew up in Brooklyn but was a New York Yankees fan. I was somewhat of a sports outcast among my friends who were all Brooklyn Dodgers fans. This was the time the Dodgers were actually located in Brooklyn as opposed to Los Angeles, where they are currently located.

Harden: How did a young man who was devoted to sports decide to become a physician?

Fauci: I don't think I can tell you the precise time when I knew that I wanted to be a physician. It was very early on. I know that in high school, when I was deciding the options I would have in college, there really was no question that I was going to be a physician. I went to Regis High School, a Jesuit high school, which had a major impact on my career even up to today. It was a highly academic, exclusive scholarship school. Students from every parochial grammar school in all the five boroughs of New York competed to receive admission, making it highly competitive, and the courses were extraordinary. They were very heavily weighted towards the classics. We took four years of Greek, four years of Latin, three years of French, ancient history, theology, etc. When I was at Regis, it seemed that the very bright people in school really had just a few options. If you wanted to go into medicine, that was fine. The other choices were law, science, engineering, or careers like that. My interest in medicine stems from my keen interest in people, in asking questions and solving problems.

Also, I think there was subliminal stimulation from my mother, who, right from the very beginning when I was born, wanted me to be a physician. She never really pressured me in any way, but I think I subtly picked up the vibrations that she wanted very much for me to be a physician. When the time came to go to college, I went to Holy Cross College, which has an extraordinarily fine reputation for premedical work. They do it in a very interesting way, at least it seemed so back in the fifties. I went to Holy Cross in 1958 and graduated in 1962. At that time, it was not unusual for premedical students to take a very strong classics course in premed. The title of my premed course was “A.B. Greek Premed,” which was a classics course very heavily weighted with philosophy–32 credits of philosophy, plus French, Greek and Latin. At the same time we took the minimal scientific courses to get us into medical school. The students did very well, getting into the best medical schools in the country but with a very strong liberal arts background. The liberal arts background is something that was very much a part of my family because virtually all of my relatives on my mother's side–her father, her brother, and her sister's children–are all artists. They are successful people who made their living through the arts, usually painting. I was always and still am very interested in art, but I am somewhat of a frustrated artist because I certainly don't have the time, and probably not the talent either, to pursue it. I still am very interested in the classics. They were a very important part of my education.

Harden: Would you evaluate the broad, liberal arts, humanistic training and your Catholic upbringing in terms of how they have influenced your performance as a physician and as a researcher? I'm thinking of things like your world view, your interaction with patients, and your approach to ethical questions.

Fauci: You can't separate very well natural abilities in a vacuum from your training, or from the combination of factors that have an influence on how you perform. But certainly, the humanistic education that I had has had a very positive influence on my ability to deal with sensitive situations with people. I credit very much the Jesuit training in precision of thought and economy of expression in solving and expressing a problem and in the presentation of a solution in a very succinct, accurate way. This has had a major, positive influence on the fact that I enjoy very much and am fairly good at being able to communicate scientific principles or principles of basic and clinical research without getting very profuse and off on tangents. This is something that was drilled into us from the very early days in high school.

Harden: Did you continue your interest in sports in college?

Fauci: My interest in it continued, but not my active participation. In high school, I played competitive sports–I played basketball at a time when you could play basketball without being 6'9“ at the shortest. I don't think I would have any chance of playing basketball if I were in high school now. I enjoyed basketball, was the captain of the team and had a very successful time in high school. Alongside it, I played baseball. These were my two major sports. When I went to college, I continued to play a modest amount of intramural sports, but due to the nature of the premedical curriculum at Holy Cross, it was very difficult to be very active in sports. I did not play competitive basketball or even baseball at the college level, since they had very good teams. I could not play as much as I wanted to because the demands of the curriculum were such that you really had to put a lot of time into your studies.

Harden: Could you talk about your experiences at Cornell University Medical College and comment on how actually becoming a doctor compared to your earlier conceptions of the profession?

Fauci: This might be interpreted by some as being paradoxical, but I absolutely loved medical school. It certainly was demanding, but it was one of the most exciting experiences of my life. The exponential curve of knowledge accrual in medical school was so great that it completely overshadowed the fatigue and the stress factors and the other problems that are so commonly seen in medical school. Certainly, medical school training was very stressful, but unquestionably it ranked as one of the happiest periods of my life, because I was learning so much. The later years in medical school and in health care training and what had been my previous idealistic views about medicine did fit together. There really was the opportunity to apply a very basic scientific framework of knowledge to something that is very human, very personal, with all of the sensitivities associated with dealing with human beings. Here I had the advantage of the humanistic training that I had received earlier on in high school and in college. This is a nice dichotomy of medical school, and that's why I think that there is no question that I was meant to be a physician and a physician-scientist. I can't imagine in my wildest dreams doing anything else that would make me as happy as this makes me. I enjoy the polarity. There are strict scientific principles that have to be adhered to in medicine. At the same time a humanistic touch is needed in dealing with people. They have to be combined. You have to combine social aspects, ethical aspects, personal aspects with cold, clean science. It is the art of the physician to put them together in the care of a patient, in the development of a protocol for a disease, the diagnosis or treatment of a problem. This combination exists in every aspect of patient-involvement.

Harden: Who influenced you the most during medical school, especially in your decision to go into immunology?

Fauci: The people who influenced me most in medical school are different from those who influenced my decision to go into immunology. Taking medical school first: My heroes were the strict clinicians of the New York Hospital/Cornell Medical Center. They were and still are in so many respects the real heroes. My teachers, whom I saw on the wards as a student and during my internship and residency, were people whose entire lives were devoted to clinical medicine. They reached such levels of expertise in patient care, diagnosis, and the delivery of patient care that they were really super stars. I tried to emulate them and make myself as good a clinician as I possibly could be. They provided a great inspiration. I think that it is very important for a young medical student to have a role model. There were several of them around at the time.

The reasons I went into immunology and research in general were due to an unusual situation. I left Cornell and went into my internship and residency in 1966. That was at the exponential phase of the Vietnam War, and every single physician went into military service. I can remember very clearly when we were gathered in the auditorium at Cornell early in our fourth year of medical school. Unlike today, we had only two women in the class and seventy-nine men. The recruiter from the Armed Forces came there and said, “Believe it or not, when you graduate from medical school at the end of the year, except for the two women, everyone in this room is going to be either in the Army, the Air Force, the Navy or the Public Health Service. So, you're going to have to take your choice. Sign up and give your preferences.” I had heard about the NIH and the opportunity there. At the time, the NIH was just blossoming, and everyone who had any role in academic medicine spent some time at the NIH. So I put down Public Health Service as my first choice, and then the Navy. Essentially, I came down to the NIH because I didn't have any choice. I was very lucky because I knew that it was a phenomenal scientific opportunity.

When I was trying to decide what laboratory to go to, some of my advisers at Cornell suggested very strongly that I pursue the field of immunology, since I had developed an interest in immunology in medical school. I had done some projects during the summer and had worked for a period with Dr. Marvin Schlesinger, who was the chief of gastroenterology division of the Department of Medicine. I also had worked with [Dr.] Graham Jeffries and [Dr.] Walter Rubin. The project I did as a student turned out to be a successful project. I was lucky, since that doesn't usually happen when you have a student project. Because of this research, I applied for the National Institute of Allergy and Infectious Diseases. It so happened that Dr. Schlesinger knew Dr. Sheldon Wolff at the NIH, and I came down to the NIH for an interview. I was interviewed by Dr. Wolff, and I immediately fell in love with the man. He was just my kind of person–intellectually and personally. I was accepted by Dr. Wolff right off. At the end of my residency, I came down to the NIH to work in the National Institute of Allergy and Infectious Diseases with Dr. Wolff. Over the years, even after he left the NIH, he emerged as the major mentor–personal and scientific–in my life. There have been a number of other individuals whom I have come into contact with who have had a major influence on me, but I think that Dr. Wolff clearly stands out as the person who made the greatest impact on my career.

Harden: Could you talk about the research you did with Dr. Wolff in his laboratory in this period?

Fauci: When I came down to what was the Laboratory of Clinical Investigation, of which Dr. Wolff was the laboratory chief as well as being the clinical director of the National Institute of Allergy and Infectious Diseases, I wanted to work on cellular immunology. But, interestingly enough, as popular as cellular immunology is now, there really were not very many cellular immunologists at the time, and certainly not in the Laboratory of Clinical Investigation. I went to work with Dr. John Johnson, who now practices rheumatology in Nashville, Tennessee. John was an immunochemist at the time, but he allowed me to work on problems in cellular immunology. I had to go around to different groups in different laboratories to learn the fundamentals of cellular immunology under the auspices of the Laboratory of Clinical Investigation. It was a great experience and a testimony to the flexibility of people like Dr. Wolff and Dr. Johnson, who allowed me to work in that field even though it wasn't their field of expertise. Dr. Wolff was mainly working on the pathogenesis of fever. I told him I didn't want to work on that, although it was a very interesting topic. I wanted to learn some basic cellular immunology with the ultimate aim of going into what has been my theme for the past twenty-one years–human immunobiology and the regulation of the human immune system. I was then, and still am, extremely interested in clinical medicine, and I have been successful in being able to mix and meld together the very fundamental, basic concepts of immunology with clinical medicine. It was Dr. Wolff who encouraged me. I worked on some projects looking at the regulation of the immune system in animals, with rabbit and guinea pig models. I learned from Dr. Baruj Benacerraf, who was down the hall in the Laboratory of Immunology; from [Dr.] David Katz, who worked with him; and from [Dr.] Carl Pierce and a few others. There were in the laboratory working with Dr. Johnson two people who have gone on to be very successful and prominent immunologists–[Dr.] Alexander Lawton, who is now at Vanderbilt [University] and chairman of pediatrics, and [Dr.] Herbert Reynolds, who is now chief of medicine at the Hershey Medical Center of the Pennsylvania State University. They were just Fellows with me at the time, and we taught each other immunology. However, though I liked it very much, my main desire was to get back to the New York Hospital/Cornell Medical Center and to be a clinician. That's what I really wanted to do. I liked the scientific environment, but my real love was taking care of patients.

Harden: Why did you go back to Cornell for another year, and what made you decide to come back to the NIH and pursue your career here rather than going on into a private practice or into academic medicine?

Fauci: I was at that very critical period in my second year as a Fellow in a three-year program having to make up my mind about what I was going to do “for the rest of my life.” Just about at that time things started to click in the laboratory. I was making some interesting observations, writing some papers that were turning out to be good papers. Virtually simultaneously, [Dr.] Alexander Bearn, who was the chairman of the Department of Medicine at Cornell at the time, asked me if I wanted to come back at the end of my third year to be chief resident in medicine. At the same time, Dr. Wolff offered me a job, which was one of those offers that you can't refuse. It was the position of senior investigator in the Laboratory of Clinical Investigation. I told him I wanted to go back and have another year in clinical medicine and make myself as excellent a clinician as I possibly could. His response was, “Fine, go back to New York; take a year as chief resident, and then come back; the laboratory will be waiting for you when you get back.” I made the decision, but when you make decisions like that, you're not really sure why you made them. I think it was a combination of the personality of Dr. Wolff, with whom I was developing a very strong friendship, and the fact that as the months were going by, my immunology research was becoming more successful. I didn't feel that I was giving up anything because I was going back to New York to cement my clinical training. I decided that I would do it. I would go back to New York and come back to NIH after a year to my own laboratory, in which I would have total independence. I think it is important to emphasize that quality of Dr. Wolff that has been responsible for the development of so many successful investigators over the years. It is important to recognize what he did with me as with many others. He could recognize early on in someone's career a person who had potential, who would succeed. Before that person did anything to make any kind of reputation, Dr. Wolff would give that person unqualified support. That was exactly what he did for me. Nobody knew who I was; nobody cared to know who I was. But Dr. Wolff said, “Here's your laboratory. You can have a technician. You can have a Fellow if you can attract a Fellow. So go ahead.” I said, “Fine, that's great.” I went to New York, came back to the NIH and started my own human immunobiology group. I was one of the few people at the time anywhere who was devoted exclusively to human immunobiology. There was [Dr.] Max Cooper in Alabama and Tom [Dr. Thomas] Waldmann at the NIH. Bob [Dr. Robert] Good and a few others were exclusively human. There were many excellent and great immunologists around who did either totally animal work or a combination of animal and human, but there were very few who were doing exclusively human immunobiology. That's when I started my work on immunoregulation of the human immune response, which I have continued throughout the past couple of decades. I am still working on it right now in 1989.

Harden: Your medical student years and just after marked the period of time when cellular immunology began to flower. Would you comment on what factors made immunology such a fruitful field?

Fauci: It was a combination of the emergence of technologies and the awareness of the extraordinary implications, if not tentacles, that the immune system had in controlling so many aspects of the human organism. For example, technology provided the ability to identify different types of cells and their subsets. There was the realization of the almost infinite possibilities of a repertoire of B-cells to recognize different antigens. The development of monoclonal antibodies and the ability to clone cells led to a virtual explosion in the delineation of the immune system, its structure and its function.

At the same time, scientists became aware that there were many immunologically mediated diseases. Diseases that were total mysteries years ago became understood as immune-mediated: lupus, rheumatoid arthritis, the connective tissue diseases, the organ-specific autoimmune diseases, and transplantation rejection are a few examples. This was also occurring during the emergence of molecular biology within the field of immunology. If you look at immunology, it has from the very beginning been inextricably linked to infectious diseases. Teleologically, what is the immune system for? The immune system protects you against invaders from without–microorganisms–as well as, in some cases, the emergence of certain tumors from within.

What was not realized until that period of explosive interest is that the immune system is an organ system just like any other system. It is an organ system like the cardiovascular system, the neurological system and the endocrine system. Initially, it was understood to be a response that the body had, but now, the immune system is viewed as a true organ system. It has structural components: there are lymphocytes; there are organs, such as the spleen; the blood is a lymphoid organ. The reticuloendothelial system, the bone marrow, the thymus and the lymph nodes are all parts of the immune system. This organ system has a way of communicating by a variety of soluble factors which we call cytokines. Knowledge about this has just emerged over the past decade. There are a large number of different molecules that have very specific functions, such as one cell's ability to talk to another cell. All of this started to emerge as the technology was developed that allowed the precise identification of the components of the immune system and their function.

Harden: Cell sorters, for example, were essential to this.

Fauci: Absolutely.

Harden: Some of the basic research in other fields, the work on protein chemistry and protein structure, for example, also facilitated the advances in immunological knowledge, I believe. It appears to be one of those “payoffs.”

Fauci: Absolutely. I think immunology, certainly is one of the major examples of something that we stress very often. Basic, fundamental undifferentiated research will inevitably, sooner or later, emerge into something that is very important; but very likely you would not have predicted that it would relate to this particular arena. You're working in one direction and then all of a sudden you find something else that you don't understand now, but ten years from now it solves problems in another direction. Immunology and basic research on the immune system really provide a classic example of this.

Harden: The 1956 research by [Bruce] Glick, [Timothy S.] Chang, and [R. George] Jaap on the bursa of Fabricius and antibody production in poultry seemed so far outside the mainstream of human immunology, if I remember correctly, that it could only be published in the journal, Poultry Science. Later, it turned out to be very important. Could you talk about your own work on Wegener's granulomatosis and some of the other problems to which you applied your knowledge?

Fauci: My research career at the NIH emerged in two parallel tracks. One was the very fundamental dissection of how the human immune system is regulated. The other parallel track was an examination of immune-mediated diseases and how one can classify and treat them. The work on the regulation of human immune system is what led me into AIDS research. What we performed in the late sixties and early seventies were probably “breakthrough” studies on the development of cures for formerly fatal diseases such as Wegener's granulomatosis and polyarteritis nodosa. Things emerged from those interesting quirks of science, things that you never would have predicted. Dr. Wolff, even before I came to the NIH, had been very interested in immunosuppression, such as some of the cytotoxic agents. His major interest was fever. This is really very interesting, a story that I tell the Fellows when they come. It is the classic example of how science is so beautiful because it is so unpredictable. Dr. Wolff had collected over the years–he had been at NIH for at least five or more years before I got there–a group of patients with prolonged fevers of unknown origin, not just five or six weeks, but a year long at least. He had a heterogeneous group of people which numbered literally in the hundreds. He had been collecting them for a few years because he wanted to study the pathogenesis of fever. Some of them had granulomatous hepatitis, a disease that had never before been described and that he described. Some of them had juvenile rheumatoid arthritis; some of them had connective tissue diseases; some of them had hematologic diseases; and others had immune-mediated vasculitic diseases. They were a very interesting group of patients–interesting because the diseases were interesting but also because most of them would die from their diseases–particularly those with Wegener's granulomatosis.

At that time, I came as a Fellow and I wanted to stay involved in some clinical work while I was doing basic research in the laboratory. This is essentially what I'm doing now–doing clinical work while I'm doing very fundamental cellular and molecular work in the laboratory. I asked him, “Could I start collecting these Wegener's and vasculitic patients and put them on a set protocol, and look at these cytotoxic agents, particularly cyclophosphamide”? I was interested in this because the agent had been used successfully in one or two patients in a manner that was not very well organized since it was given to a patient as a last resort. Dr. Wolff, as usual, was extremely accommodating, and said, “Fine. I'll support you on that. Let's do it. We'll do it together and I'll help you out.”

To make a long story short, we started a protocol that gave cyclophosphamide in low doses. Previously it had been developed as an anticancer drug and was given predominantly to individuals with leukemia in very high doses that would wipe out the bone marrow. We figured from animal studies, particularly those performed by investigators such as Bob [Dr. Robert] Schwartz and others in Boston, that low doses of a cytotoxic agent could suppress the immune system without wiping out the bone marrow. We then did something that was very unorthodox. We gave low doses of this cytotoxic agent, equivalent to the amount that in animals suppressed immunological function but didn't cause very severe toxic side effects like neutropenia.

The disease that we targeted at first was Wegener's granulomatosis. The cytotoxic agent completely shut off the disease, so much so that we've now treated over the years hundreds of patients with Wegener's granulomatosis, and the disease is essentially curable. We now have a 93% remission rate, whereas when I came to the NIH in 1966, 100% of the patients died. We have fine-tuned the regimen now, writing and informing physicians that if the dose is maintained at a level that keeps the white count above a certain level, then there will be very little trouble with secondary infection. If the patient is simultaneously treated with alternate-day prednisone as opposed to daily prednisone, which has toxic side-effects, infection will be largely avoided. So, the combination of alternate-day prednisone with daily low-dose cyclophosphamide essentially was responsible for essentially curing Wegener's granulomatosis, or at least putting it into prolonged remission.

Once it became clear from the first several patients that it worked with Wegener's, we then tried it with similar diseases–polyarteritis nodosa, cerebral vasculitis, lymphomatoid granulomatosis and Takayasu's arteritis. We had a series of seven or eight diseases that formerly were completely fatal but now people were coming to the hospital, and four to six weeks later, they were walking out and going back to their jobs. It was a heady and exciting period of time–both clinically and in research. At the same time we were looking at regulation of the human immune system at the very basic level, which emerged in the 1970s from cellular phenomenological research to work at the molecular level.

Harden: It must have been very gratifying to achieve such results.

Fauci: It was gratifying not only because I could do some good but because I actually saved the lives of some people. That is the epitome of what you want to do in medicine. I've always wanted to be involved with diseases that were very, very serious. I would rather be involved with patients who have fatal diseases than those with diseases that are just an annoyance. That just happened to be my bent. I wanted to be where the action was. So there it was, we had a disease that was formerly fatal and we made a major impact on it. The other thing that was so gratifying about that experience was that we were able to do something that people said you can't do–you can't do clinical medicine at the same time that you do very basic research. That is absolutely incorrect, if you organize your time correctly. If you ask the right questions, get the right training, you can do work that is very, very basic in its approach and yet has important clinical consequences.

Harden: In our next interview I want to examine how you as a clinical immunologist responded to the first cases of AIDS that you saw. But, before we stop today, I want to pose a hypothetical question. If AIDS had struck in 1955, before we knew about T-cells and other aspects of the immune system, how do you think the medical community would have responded to it?

Fauci: I think it would have been much more frightening than it is now, and it is frightening now. I think we would not have had a clue as to how to combat this disease from a basic scientific standpoint. I think we would have realized just on epidemiological grounds that it was an infectious agent of some sort that was sexually transmitted and transmitted by blood. But about pathogenic mechanisms, we wouldn't have had a clue. We wouldn't have known how even to go about thinking about the virus, much less clone it and develop drugs against it. So within the framework of the catastrophe of AIDS, we're lucky in the sense that it came at a time when retrovirology, molecular biology, molecular immunology, and immune system studies were at that stage where we could very quickly identify the agent, how it works, the pathogenic mechanisms, its effect on the immune system, etc. If it had happened in 1955, we would have been in very serious trouble.

Harden: Thank you, Dr. Fauci. I look forward to the next interview.

President Ausiello, members and guests of the association: I am very proud to have the honor to introduce this year’s George M. Kober medalist, my good friend Anthony S. Fauci, MD.

George Martin Kober lived from 1850 to 1931 and was very active in the Association of American Physicians (AAP), serving as secretary from 1909 to 1917. From “. . . all accounts [he] . . . had great strength of character, loyalty both to persons and principles, together with humility and humanity of high degree” (1). This year’s medalist has all these qualities.

Anthony Stephen Fauci — Tony — was born on Christmas Eve, 1940. Headlines in the New York Times on that cool and cloudy winter day proclaimed “Churchill Bids Italy Oust Mussolini; Greeks Take Another Coastal Town; Germans Rain Bombs on Manchester.” One article touted “Turkey and Fixins in Home only $6.40.”

Roots

Tony Fauci’s family came from Italy. His maternal grandparents grew up in Naples. His maternal grandfather, Giovanni Abys, was an artist who painted landscapes and portraits, designed labels for commercial products such as cans of olive oil, and did illustrations for Italian magazines. Tony’s maternal grandmother, Raffaela Trematerra, was a seamstress.

Tony’s paternal grandparents were from Sciacca, Sicily. His grandfather, Antonino Fauci, was from a family who ran a hot springs spa. In Sciacca, he met and married Tony’s paternal grandmother, Coligera Guardino.

Both sets of grandparents immigrated to New York City via Ellis Island at the turn of the twentieth century and initially settled in lower Manhattan’s Little Italy, where Tony’s mom, Eugenia Abys, and dad, Stephen Fauci, were born. Later, both families moved independently of each other to the Bensonhurst section of Brooklyn. Eugenia and Stephen met in eighth grade, attended high school together, and were married one year after graduation. Tony’s dad attended Columbia University and became a pharmacist while his mom attended Hunter College. They had two children, first a daughter, Denise, and then a son, Anthony Stephen, who was born in Brooklyn Hospital.

The Faucis ran a neighborhood pharmacy at 13th Avenue and 83rd Street and lived in an apartment above . The whole family helped out in the business — his dad working in the back of the pharmacy while his mother and sister operated the register. Tony delivered prescriptions from the time he was old enough to ride a bike. He was raised in a Catholic tradition, receiving his first communion at age 7 and confirmation at age 12. Strong family relationships were an important part of Tony’s upbringing.

Education

Tony was tops in his class at Our Lady of Guadalupe elementary school. He always excelled academically, but he was not a nerd. In the 1950s Bensonhurst was a working-class Brooklyn neighborhood for Italians and Jews. You just didn’t talk about your academic achievements. Tony became streetwise, which later would serve him well. He was a strong athlete, playing basketball from fall to spring and baseball from spring to fall at Dyker Heights Park. Tony rooted for the New York Yankees, and his early heroes included Joe DiMaggio and Mickey Mantle. This made him something of an outcast among his friends, who were Brooklyn Dodger fans.

In 1958, he entered Regis High School, a free school on the Upper East Side of Manhattan, with a special mission of educating sons of Catholic immigrants in the Jesuit tradition. The Jesuit philosophy, “To be men for others,” was an important principle that ran through Tony’s education. His high school training emphasized languages and the classics. He took four years of Latin, three of Greek, and two of French. His teachers drilled into him two ideals — precision of thought and economy of expression, qualities he is known for today and instills in the people who work with him.

He continued to pursue his interest in athletics and captained the basketball team. Due to short stature, his career as a basketball player ended early.

At Regis High, it was an accepted fact that if you wanted to become a doctor you went to the College of the Holy Cross. Tony graduated Regis High School among the top in his class and in 1958 entered Holy Cross in Worcester, Massachusetts, where the strong Jesuit influence continued. His undergraduate work mixed classics and philosophy with pre-med courses. This broad academic background groomed the future Dr. Fauci for his destiny as an outstanding physician, scientist, educator, humanitarian, and public health leader.

During college summers, Tony worked on construction crews. Before his final year at Holy Cross he labored on a crew building a new library at Cornell Medical College at 69th Street and York Avenue. At the medical school’s centennial celebration in April 1998 he recalled, “On lunch break when the crew were eating their hero sandwiches and making catcalls to nurses . . . I snuck into the auditorium to take a peek. I got goose bumps as I entered, looked around the empty room and imagined what it would be like to attend this extraordinary institution. After a few minutes at the doorway, a guard came and politely told me to leave since my dirty boots were soiling the floor. I looked at him and said proudly that I would be attending this institution a year from now. He laughed and said, ‘Right kid, and next year I am going to be Police Commissioner’” (2).

In 1962 Tony Fauci did enter Cornell Medical College. He liked Cornell. Each day offered an opportunity to learn something new. He graduated in 1966, first in his class, and pursued house staff training in internal medicine at the New York Hospital.

NIH science

In 1966, during the Vietnam War, he was called to serve. He left New York City for the National Institutes of Health (NIH) to join what was affectionately called the “Yellow Berets” (3). He served his military obligation in the Public Health Service at NIH. He was a Clinical Associate in the program of Sheldon M. Wolff, MD, the Chief of the Laboratory of Clinical Investigation and Clinical Director of the National Institute of Allergy and Infectious Diseases (NIAID) (Figure ​(Figure4).4). It was during his fellowship at NIH that he completed his training in infectious diseases and in allergy/immunology and began his long, close clinical research partnership and friendship with Wolff.

From 1970 to 1971 he left the NIH to serve as Chief Resident at the New York Hospital Cornell Medical Center. His reputation as Chief Resident was legendary. Many of his house staff and medical students at Cornell became his personal friends, and Tony later recruited several of them to important positions at NIH.

Tony Fauci returned to NIH in July 1971 as a Senior Investigator in the Laboratory of Clinical Investigation and rapidly passed his clinical board examinations in internal medicine, infectious diseases, and allergy/immunology, with top scores. He then began his extensive and uninterrupted career in public service, serving continuously in the government.

I first met Tony in July 1972. He had the lab across the hall from where I worked as a clinical associate. I remember that day well. The two-module lab he entered was a dirty mess with missing equipment. He was quite rattled by what he saw, and I offered to help him clean it up. We have been friends ever since.

That small lab was where Tony’s career as a clinical investigator really flourished. He rapidly assembled a strong team focusing on immune regulation. His early studies included demonstrating the therapeutic effect of cyclophosphamide on Wegener’s granulomatosis and other vasculitides (4, 5). In 1980, Tony Fauci was made Chief of the new Laboratory of Immunoregulation. A 1985 Stanford University Arthritis Center Survey of the American Rheumatism Association ranked Dr. Fauci’s work on the treatment of polyarteritis nodosa and Wegener’s granulomatosis among the most important advances in patient management in rheumatology over the previous 20 years (6). And Dr. Fauci was not even a rheumatologist!

A transforming year for the field of infectious diseases — 1981 — had extraordinary impact on global health and Tony Fauci’s career. I remember well when the first cases of gay men with unusual opportunistic infections were reported that summer (7, 8). Tony came up to me in the corridor, quite animated, saying how he believed this new disease had the potential to explode into a worldwide catastrophe. He quickly decided to shift the focus of his laboratory to study what would soon be called the Acquired Immunodeficiency Syndrome, or AIDS, a term he helped coin. And that was the beginning of his now historic studies on the pathophysiology of AIDS.

Tony Fauci’s laboratory made major observations delineating a model of HIV pathogenesis, and his group’s publications in the mid-1980s clearly established what is now considered to be the hallmark functional defect of CD4+ T cells in HIV-infected individuals, a defect in responsiveness to recall antigens. His 1988 publication in Science on the pathogenesis of HIV (9) was the most cited paper in medicine in 1989 (10). His group’s publications in the early 1990s provided the scientific rationale for the early and aggressive suppression of HIV replication with combination antiretroviral agents. His Nature paper in 1993 (11) was the most cited paper in AIDS research from 1993 to 1995 (12). Subsequent papers, considered by many as classics in the field, delineated the link between host-virus interactions and potential targets for therapy (13) and the complex network of host factors involved in the regulation of HIV expression (14). Based on these and subsequent publications, a 2003 Institute for Scientific Information study indicated that for the 20-year period from 1983 to 2002, Tony Fauci was the thirteenth most cited scientist among the 2.5 to 3 million authors in all disciplines (15). From 1996 to 2006, he was the tenth most cited HIV/AIDS researcher in the world. Currently Tony has over 1,100 publications.

In addition to all these scientific accomplishments, Tony is first and foremost an outstanding physician and teacher of clinical medicine. His clinical rounds are legendary. I say are because he still conducts them regularly. He is demanding of his staff but always gives back by sharing his wealth of clinical knowledge, constantly educating those around him. Every patient would love to have Dr. Fauci as their doctor. Every medical student and house officer would love to have Tony Fauci as their attending.

Over the years, 108 fellows joined Dr. Fauci’s laboratory and have become members of his academic family. Many have become outstanding clinical investigators in their own right, and 7 have become members of the AAP.

Tony Fauci’s accomplishments as a scientist and a clinician have brought him remarkable professional recognition. Since 1978 he has held 33 visiting professorships, given 490 major named lectureships, and received 31 honorary degrees and 124 awards and honors. He has served on 41 editorial boards, and for the past 25 years he has been on the editorial board of Harrison’s Principles of Internal Medicine. He has been elected to the most prestigious societies in the United States and abroad. He has been a very active member of several societies, serving as President of the American Federation for Clinical Research and as a Council Member of the Institute of Medicine. In addition, for a 12-year period he held offices in this association, serving as Recorder, Councilor, Vice President, and President.

Administration

In 1984, NIH Director James B. Wyngaarden, MD, appointed Tony Fauci to be the fifth Director of NIAID. It was a perfect example of the right person being appointed to the right position at the right time. Under his direction, the funding for NIAID increased from about $320 million in 1984 to about $4.6 billion today. The size of NIAID relative to the other NIH institutes has grown from sixth to the second largest. But much more importantly, Tony has led the institute and the country through the incredible series of events his predecessor, NIAID Director Richard Krause, MD, described in his book, The Restless Tide: The Persistent Challenge of the Microbial World (16).

Politician

Tony’s experiences as the streetwise kid growing up in Brooklyn undoubtedly helped him weather the storms of activist groups. He was the target of their criticism and even burned in effigy. Instead of being angry, Tony noted the pain of the people in these activist groups and approached them as a physician approaches a suffering patient. He began a dialogue that lasted for many years. Over time he won their trust and respect.

Tony is a great communicator. He has comforted the nation by appearing repeatedly on national television to explain one far-reaching crisis after another related to emerging and reemerging infectious diseases. On issues from AIDS, to anthrax, to SARS, to influenza, Tony provides confident, knowledgeable, realistic, and reassuring advice. He has earned the respect and trust of politicians on both sides of the aisle. He has advised every President from Ronald Reagan to the current George Bush. His knowledge, clarity, and frankness have made him so effective.

Personal traits

I had the privilege of working with Tony from 1985 to 1994 as his Scientific Director. Those were exciting years. Here is what I can tell you about Tony Fauci. Yes, he is very hard working. He is the best observer I’ve ever known. Nothing escapes him, nothing. He has a remarkable ability to contain his emotions.

Tony Fauci works hard and plays hard. He exercises about an hour every day. He enjoys fishing, occasional tennis, and cooking. To relieve stress in his office, he shoots hoops in a toy-sized net. One day as we were fishing on the Potomac River, he got so excited about a fish on the line that he flipped over our canoe. We survived, but I don’t believe he caught that fish.

I would describe Tony Fauci as a realistic optimist. He demands perfection and that is good. He delegates authority and responsibility effectively. He is very sensitive and loyal to his staff. He can keep his mouth shut. He never tells a secret, ever. He is a fabulous doctor and his patients adore him. When he talks he knows what he is talking about. He is wise. He cares about all people. He knows the names of the janitors, elevator operators, and animal caretakers. They all love and respect Tony Fauci because he talks with them, never at them. Tony Fauci is the kind of person you know you can call upon whenever you have a need, no matter what that need is.

And where do all these wonderful traits come from? I believe they come from his strong upbringing that instilled the importance of family. And that is reflected by his beautiful family. Tony met Christine Grady when she was a nurse at the NIH Clinical Center in 1983. They married two years later. Christine has gone on to build her own important career as one of the leading bioethicists in the world specializing on issues related to clinical research.

Christine and Tony have three fabulous children, Jennifer Ellen, a Harvard undergraduate, Megan Elizabeth, about to enter college, and Alison Christine, currently in high school (Figure ​(Figure7).7). Tony is phenomenally devoted and especially proud of his family, whom, in my opinion, gives him more satisfaction than anything else in life.

The AAP has made an incredible choice this year in selecting Anthony S. Fauci as their George M. Kober medalist. He is an exceptionally dedicated and talented physician, scientist, educator, administrator, spokesperson, politician, and advisor to our Congress and Presidents. His life’s work will profoundly affect generations to come. He is, quite simply, an extraordinary man. It is for all these reasons that I am so honored that Tony Fauci asked me to introduce him as the 2007 Kober Medalist, the highest award of the Association. Please join me in saluting Anthony S. Fauci, MD, on the occasion of his receiving this very prestigious award.