“A golden age of biomedical research.”

An oral history of the lasting impact of the Clinton administration’s efforts through the National Institutes of Health (NIH).

On Tuesday, March 29, the Clinton Foundation and the University of Arkansas Clinton School of Public Service hosted “Investing in a Healthier Future,” an installment of the Kumpuris Distinguished Lecture Series presented through the Clinton Presidential Center.

President Bill Clinton, Dr. Donna E. Shalala, Dr. Harold Varmus, Dr. Francis Collins, Dr. Anthony S. Fauci, and other nationally recognized experts discussed the lasting impact of the Clinton administration’s efforts through the National Institutes of Health (NIH), including the creation of the Vaccine Research Center, monumental gains made in the fight against HIV/AIDS, and creating “a new standard of excellence in biomedical research.”

Below, we’ve adapted their remarks as part of an oral history of an era of unprecedented investments and advancements in scientific and medical research.

President Clinton, former Health and Human Services Secretary Donna E. Shalala, and former director of NIH Dr. Harold Varmus on building a bipartisan movement for expanded investments in medical research — including the Vaccine Research Center.

SECRETARY DONNA SHALALA: I came to HHS in 1993 from the University of Wisconsin at Madison. And during those years, I also sat on the NIH advisory committee to the director appointed by Secretary Sullivan. I’ve always believed that the president’s most important legacy was his commitment to science, to the NIH. The bipartisan efforts to successfully almost double the NIH budget unleashed a golden age of biomedical research. But for me, it was not just the doubling but what the leadership did with that money.

Second, it was the leadership we recruited and those we retained, and the impact of training grants on preparing a new generation of scientists.

DR. HAROLD VARMUS: The NIH has been in existence for over a century. Today it’s a federation of 27 institutes and centers, each of which receives its direct appropriations. The budget for the NIH today is about 43 billion. When the Clinton administration started, it was a little under 11 billion, increased steadily, and initiated a five-year doubling process.

The NIH is a health-related science agency that doesn’t do direct healthcare. Instead, it provides basic and clinical research opportunities, training, and infrastructure to the nation’s medical research establishment. About 10 percent of the NIH’s research is done by government scientists, mainly on the campus in Bethesda. The rest is done through grants and contracts to institutions, medical schools, and universities in all states and some abroad. And these grants and contracts are issued, importantly, through competitive peer review. Like all agencies, NIH has an annual appropriation. Still, it’s important to note that the NIH does its research through multi-year grants and contracts and works on very long-term problems, which means that support from the administration to keep its budget strong is incredibly important.

We’ve had support at the NIH from both sides of the aisle for many years. And in general, we have a good working relationship with both the executive and the legislative branches. There are two ways in which the executive branch, especially the White House, provides comfort and support to the NIH during an administration. First is the support for that long-term, ongoing work that supports the biggest medical research enterprise in the world. During the Clinton administration, there was strong support for many aspects of basic research, all of which can lead to improved health over many years, even many decades. There are many examples of advances in cancer treatments and improved outcomes of cardiovascular disease and stroke, and many other things.

From my perspective, as the NIH director during most of the Clinton administration and as a scientist who’s dependent on NIH all the time for my own work, I look back on the Clinton years as the golden years in medical research for many reasons.

First, we had the enthusiasm of not just the president but the president’s family. Indeed, the first family member to come visit us was the First Lady, who came to the NIH for a day-long tutorial about genetic research and virology. And she then brought the President out for his Saturday tutorial after giving a radio address about the Family Leave Act. And he heard about the research going on in AIDS and genomics and cancer research. And that persuaded the first daughter to turn up and spend several days working in a lab run by one of our outstanding female scientists. So, as a result, we still have vials labeled CC1, CC2, and CC3 for mutants of a bacterial protease that she isolated.

The second reason is the strength of the budget proposals. The president said to me many times, “I’m not proposing everything I want you to have, but I know that Congress will double your increase, even when Republicans are in charge.”

And he followed that prescription for many years and helped start the five-year doubling in 1998. The third aspect was the quality and attitude of our partners in the US government during the administration.

Long-term science pays off. Long-term investments in the studies of infectious agents, including HIV, have led to the culmination of those efforts during the Clinton years, with our ability to prevent transmission of HIV from mothers to infants, the development of protease inhibitors, and the development of highly effective therapies against AIDS.

When the Clinton administration began, the program run by government scientists in Bethesda was under some criticism. And a report from outside scientists arguing that one thing we needed to do was revitalize clinical research at the Clinical Center in the NIH intermural program led to a recommendation that was given due scrutiny by the Office of Management and Budget.

Then head of the Office of AIDS Research, Bill Paul, unfortunately, deceased a couple of years ago, led to a proposal we put together a vaccine research center on campus. And one day, the president and Al Gore had me and Tony Fauci come down and chat with him about what needed to be done in AIDS research. He immediately caught on to this idea of building a vaccine research center and made that part of an address he gave at Morgan State [University]. And that persuaded Congress to proceed with an investment that paid off in many ways.

PRESIDENT CLINTON: You made a case that we have to get broad-based support if we want to continue this, and I’ll give you both within the Congress and the larger country. In the Congress, Harold [Varmus], I’ve always given you credit for this. I don’t know if you deserve it, but you’ll give it to somebody else if you don’t.
But we got waxed in the ’94 presidential election because I tried and failed to get health care reform, allowing its history to be rewritten. And because I tried and succeeded in getting the assault weapons ban, the 10-bullet ammunition clip limit, and the Brady Bill passed. But I talked to Newt Gingrich one day, and he had 100 members of his new majority who didn’t have a passport and were proud of it and thought the government would mess up a two-car parade, and the purpose was to have less of it. I knew he was interested in science because he had given me a copy of EO Wilson’s book on ants.

I said to Newt, “Well, we got to get these people on the research bandwagon. You need to take them to NIH.” But when they got there, these people who thought the government was some sort of amorphous, evil mob, whoever was responsible for the tour these freshman congressmen took, started them in a hospital bed. And they lay in a bed and looked at the films saying what all the NIH was doing on the TV in the hospital room. And it was an elemental political observation, which is that everyone wants to go to heaven this morning, but nobody wants to die. We all want to live as long as we can. And it was brilliant. And all of a sudden, we had no problems getting the Republicans to vote for the NIH budget.

I would say that we had a couple of years where the Christian evangelical community leaders were involved in mainstream politics, talking to everybody. I brought them in 2000 on the millennial debt relief initiative and had worked with a couple of them who were friends of mine. And they all supported relieving the debt of the world’s poorest countries if they put the savings into healthcare, education, or development. President Bush later institutionalized this. But they weren’t quite ready for AIDS yet. They weren’t quite past the, oh, we just got to talk about prevention and abstinence and nothing else.

But by the time he got to the point where we had the votes in Congress because of their support to pass the PEPFAR program, which I love. We tripled overseas AIDS assistance when I was president, and we were giving 25 or 30 percent of what the world was giving, but it was peanuts. Nothing. And so, after he did that, I want to give him credit for something else that a lot of people don’t know. In the beginning, they were only working, I think, in seven or eight countries because they were requiring PEPFAR to purchase, for these countries, medicine that big pharma was making. And they’d give them a discount, but it was like 150, $1,500 a year, which was less than the 10,000 or so we were paying in Harlem, but way more than 150 or so we were already down to with the prices we had negotiated through the Clinton Health Access Initiative.

Once President Bush said, “Talk to me about what you’re doing on AIDS.” And so, I did. And I said, “You ought not to make these countries buy generic drugs, but you ought to give them the option to take the money you give them and spend it on generics.” And he said, “Well, I’m told that they’re not as effective.” I said, “I know they tell you that. And I know they’re important to you politically, but it’s not true.” I said, “What if I were to submit to the FDA every single drug we put in any human body, in any country, for review and approval. If they get approved, would you okay the money?” He said, “It sounds like a fair deal to me.” It was just the two of us talking, and no lobbyist had a chance to talk him out of it. He just cared about whether poor people were going to live or die. And I could tell he cared.

So, we submitted 22, as I remember, 22 different products, and the FDA immediately approved 19. He didn’t slow walk it. He didn’t do anything; he played it straight. They just reviewed them and approved them. And all of a sudden, PEPFAR was in more than twice as many countries, treating a hugely greater number because he did that, and he had the support of the Christian evangelical community.

Both those examples show you why we need to keep working to build broad-based support for the work of the NIH. Our common humanity can sometimes be found when we’re sick, or someone we love has something wrong with them. And even when it’s not available anywhere else.

Dr. Anthony Fauci on the creation of the White House Office of National AIDS Policy, when he first knew the tide was turning on the HIV/AIDS epidemic, and a commitment to making treatments available worldwide.

DR. ANTHONY FAUCI: In preparation for my remarks about this, I just went through my mind the other day, almost on a year-by-year basis, the extraordinary advances that we experienced, literally from the day President Clinton set foot into the White House. One of the first things that he did in 1993 was to establish the White House Office of National AIDS Policy or ONAP, which is still exerting an important function. We never had that before [President Clinton] came into the White House.

And then, though, it was also when the toll of morbidity mortality was accelerating in the country—by 1994, AIDS had become the leading cause of death among all Americans aged 25 to 44. But then, things started to turn around with regard to therapy. We remember the famous ACTG 076 results, the first time that we showed that you could interfere with the transmission of HIV from a pregnant mother to the baby. That has to be one of the true hallmarks of iconic studies done at the NIH under his leadership as president. The years that were so exciting—all eight of them—but there was a cluster of a few in the middle that, from my standpoint, was transforming, from 1995 to 1996. That’s when we went from one and then two and then three drugs in combination, culminating with the first time use of protease inhibitors, the third drug in the three-drug combination.

What happened then was something that I have to say, without hyperbole, every time I reflect on that, I still get little bits of goosebumps because I had been taking care of persons with HIV for years from 1981 right up until the time in 1996 when that combination proved to be completely transforming in turning around the lives of people with HIV. At the 1996 Summer Vancouver International Aids Conference, those results were presented. It shook the world in a positive way because from that time onward, the idea of hospices was a thing of the past for people with HIV.

I have a photograph that I show at many meetings of Harold [Varmus] and President Clinton and I and Vice President Gore and Bill Paul in the Oval Office. I was presenting a schematic of a brand-new discovery of a co-receptor called CCR5 for HIV. President Clinton got very wonky because he wanted to know the details of that receptor was. But at the end of the scientific discussion, President Clinton said, “By the way, Tony. It’s 1996, December the third. We had HIV since 1981, and the virus was discovered in 1983 and ’84. Why don’t we have a vaccine?” That’s when we got into the discussion of the possibility of having a vaccine research center. And, he said he would do something about it.

I thought he was just trying to be nice. But to our great surprise, in May of 1997, he announced at a commencement address at Morgan State [University] that the administration would support the building of a vaccine research center at NIH. The years went on, and things got better and better.

One of the things President Clinton did do that that led to the success in a subsequent administration of the PEPFAR program, but even as he was president, he issued an executive order to assist developing countries in importing and producing generic HIV treatments so that they could have available to them treatments that were costing tens of thousands of dollars here. And importantly, when he left the presidency, through the Clinton Foundation, he continued pushing to have the availability of drugs to people in lower-middle-income countries.
So, it was an extraordinary run. And I’m so proud to have been a part of it.

Dr. John Gallin and Dr. Gary Nabel on the administration’s impact on the NIH Clinical Center, upholding “a new standard of excellence for biomedical research,” and how the work continues.

DR. JOHN GALLIN: The NIH Clinical Center opened in 1953. And since its opening, incredible teams of basic and clinical scientists, in close partnership with very courageous patients, often in the scariest moments of their lives, has resulted in an outstanding history of accomplishment, improving the health care of the nation and the world. A few examples of early accomplishments include chemotherapy for cancer, cure of childhood leukemia, lithium for depression, fluorides to prevent teeth decay, identification of cholesterol as a risk factor for heart disease, the first three treatments of AIDS, and the discovery of hepatitis viruses B and C that caused cirrhosis and liver cancer that led to a vaccine for hepatitis B and tools to prevent, to protect the blood supply from and to treat hepatitis C. Dr. Baruch Blumberg received the Nobel Prize in 1976 for the discovery of hepatitis B. And Dr. Harvey Alter from the Clinical Center, in partnership with Doctors Michael Houghton and Charles Rice, shared the Nobel Prize in 2020 for the co-discovery of hepatitis C.

40 years after the Clinical Center opened, the hospital infrastructure could barely sustain modern clinical care and science, and the Clinical Center came under scrutiny. In 1994, a report on the NIH intermural program to the NIH director, Harold Varmus, by a committee chaired by Dr. Gail Cassell and Dr. Paul Marks recommended for the first time a new Clinical Center be constructed as promptly as possible. The same year, Vice President Gore’s reinventing government initiative said the Clinical Center should be critically reviewed and re-engineered to improve its effectiveness and efficiency.

In response to this recommendation, the Department of Health and Human Services, under Secretary Donna Shalala, convened a team coordinated by Dr. Helen Spitz to conduct a review. And the review reiterated the earlier recommendation to build a new Clinical Center. As a result, with the support of the president’s administration and Congress, plans to construct a new Clinical Center were initiated.

Key events in moving the process forward included President Clinton’s visit to the Clinical Center in August of 1995. On September 30, 1996, Congress approved funding for the new hospital named the Mark O. Hatfield Clinical Center. Construction began in 1999 and was completed in August of 2004. And on September 22, 2004, a patient speaker, the late Susan Butler, called the Clinical Center, The House of Hope, highlighting what the Clinical Center means to the patients and the public.

The opening of the new Mark O. Hatfield Clinical Research Center enabled the continuation of great accomplishments that continued to improve the health of the nation to today. These include cell-based immune therapy for cancer, new treatments for kidney cancer, a new drug for depression, ketamine, first in human studies for the Ebola and COVID vaccines, the discovery of a new category of diseases called autoinflammatory diseases, and new drugs to treat them, gene therapy for several rare diseases, including sickle cell disease, and the creation of the undiagnosed diseases program, where patients from across the nation with unexplained medical problems are brought to the Clinical Center for evaluation and advice for treatment.

In 2011, the Clinical Center received the Mary Woodward Lasker-Bloomberg Award for public service for serving since its inception as a model research hospital, providing innovative therapy and high-quality patient care, treating rare and severe diseases, and producing outstanding physician-scientists whose collective work has set a standard of excellence for biomedical research.

DR. GARY NABEL: When we think back to the AIDS crisis, as our memories fade, we sometimes forget the unimaginable toll that that crisis took on human life. Not only the toll on human life but the quality of life for victims and families and the profound effect economically and politically throughout the world. More than 39 million people have died in the epidemic so far, more than five times the numbers we’ve faced with COVID. Despite the gravity of the global health threat and significant investments in the science at the time, by the late 90s, despite the pronouncement from Margaret Heckler and the Reagan administration, her pronouncement that we’d have a vaccine a few months back in the early ’80s, the vaccine remained elusive. And yet it remained the best way to prevent and contain the epidemic.

Now, the reason for it is the biology of HIV. This was an insidious virus. And it posed an unprecedented scientific challenge for vaccine development. And the reason for that is because it had such enormous genetic diversity, and it also could camouflage many of its important viral entry proteins. As a result, there are more variants of HIV in a single person infected with the virus than there are in the entire planet and the whole population of the world during a single year of an epidemic like COVID or flu. Compared to licensed vaccines, where there may be three to 10 components at most, this complexity posed a daunting challenge, thwarted the best and the brightest of scientists working in individual labs around the world.

So it was really in this context that Harold and Tony, and Bill Paul, with support from Secretary Shalala, approached President Clinton and decided that the best thing to do was to develop a dedicated Vaccine Research Center (VRC) to be built at NIH to overcome the scientific, technical, and early development challenges facing HIV and other emerging global health threats.

The room where it happened was the Oval Office of the White House. And I think it’s important to note that this group that met there really served as a brain trust that started the process and, importantly, remained involved and nurtured its growth.

The VRC was an innovative model for supporting scientific research in three ways.

First of all, it provided a physical place, a physical laboratory, whereby you could bring the best and the brightest scientists together in one research center and where they could work in a multidisciplinary way to approach the problem because vaccine development is highly complex and involves many different types of approaches.
Secondly, it was a mission-driven research organization. We came to work each day knowing that a day saved in bringing a vaccine to the world saved 6,000 lives. Those efforts extended not only to HIV but also as we worked at the NIH to other emerging health threats, including the first SARS outbreak, avian flu, Ebola, Chikungunya, Zika, and now COVID.

And finally, it was a place where we could make clinical products and conduct human trials. It allowed us to operate independently of the constraints of the vaccine industry in undertaking vaccine development. And it’s important to recognize that, in large part, many of these vaccines are not developed because there’s a failure of the private markets to address global health challenges. So, it’s an important model for public and private partnership.

The center has succeeded in several ways. More than 100 clinical trials have been performed. Connections to the industry have made new vaccines accessible to the public. Perhaps the most tangible recent success has been its catalytic role in accelerating the development of the COVID mRNA vaccine. The VRC worked quickly internally and with the industry to advance prototypes and identify structure-based mutations that freeze the virus in a form that optimizes vaccine protection and gives us some protection that we’re now seeing across diverse strains.
And finally, at least from my perspective, the VRC is a gift that keeps on giving. The VRC has multiple productive collaborations with academic, biotech, and pharma labs. There’s now a diaspora of VRC scientists who have taken the training that they’ve received there and the spirit of the institution to new places where their work contributes to the continued preservation of global health. COVID vaccines have likely saved tens if not hundreds of millions of lives. And the VRC contributed in a foundational way to its development while progress continues to this day on HIV, Ebola, Chikungunya, and universal flu.

For me personally, it was an unparalleled and special opportunity to show how science and data can impact human wellbeing and save lives. To President Clinton, Secretary Shalala, Harold, and Tony, your leadership and wisdom have achieved significant goals, and I’m confident there is more to come. So, stay tuned. The work continues. And finally, I very much appreciate the opportunity to help build the center and serve.

Secretary Shalala, Dr. Fauci, Dr. Varmus on the decision to “go beyond HIV,” and the importance of cooperation in public health

SECRETARY DONNA SHALALA: Given the pressure everybody was under, you [Dr. Fauci] could have just made the vaccine center very narrowly focused on HIV/AIDS, but it seems that the decision to make it a vaccine center to cover more than just AIDS was critical for the future.

DR. ANTHONY FAUCI: That is an important issue. It became very clear to Gary and me. He was the director at the time. The talent that we had accumulated in the senior people and then their junior colleagues and acolytes was such that although we put a full-blown effort on HIV — the structural biology capability, the idea of structure-based immunogen design. It became apparent that it applied to RSV, that it was applicable to any of several viruses, that we did not want to constrain ourselves to just studying HIV.

So we went into flu, we did coronaviruses with the first SARS-CoV-1 and then MERS, and then the particular interest that Barney Graham had in respiratory syncytial virus, which was his love before he even came there, actually ultimately partnered with Peter Kwong to develop the immunogen design that led to the coronavirus. And so, it was just a beautiful symphony of people who were playing together, and it became very clear that it would go well beyond HIV, which it has.

DR. HAROLD VARMUS: I’ve got to make one footnote to that comment, Tony. Back in the first days of the Clinton administration, when things were not going very well in developing treatments and protections against AIDS, we had commissioned an outside group headed by distinguished virologist Arnie Levine to evaluate the AIDS program. One recommendation was that the development of immunology as a discipline was not being sufficiently applied yet to the study of HIV. And then Bill Paul, who had been director of the office of AIDS research, noted that we had tremendous strength in immunology, ranging from people like you, Tony, to many others on campus who could make a contribution to the development of vaccine research and people on campus began to gather. And next thing we knew, we had a proposal for a vaccine research center, and I’m very grateful to the president for saying this is not just going to be an HIV center. It was going to be a center for vaccine production. And it’s proven to be incredibly valuable along the lines that you’ve said.

SECRETARY DONNA SHALALA: Many people think that NIH is organized into silos. And it seems to me that the vaccine research center and the clinical center are two examples where the entire community of NIH came together. John, you would not have been successful if everybody hadn’t bought in.

DR. JOHN GALLIN: All the 17 centers and institutes in the intramural program use the hospital, interacting very closely.