Interview with John I. Gallin, M.D.

Former NIH Clinical Center Director Reflects on His Career at NIH

BY LAURA STEPHENSON CARTER

John Gallin, who is retiring in March 2023 after 52 years at NIH, has been an Editor for The NIH Catalyst since it began in 1993. Here he talks with the Catalyst about his involvement with the publication and about his own career. After graduating from Weill Cornell Medical College (New York) and completing his residency at New York University’s Bellevue Hospital, he came to NIH in 1971 as a Clinical Associate in the National Institute of Allergy and Infectious Diseases’ (NIAID’s) Laboratory of Clinical Investigation. In 1976, he became a Senior Investigator in NIAID, Chief of the Laboratory of Host Defenses (1991-2003), and later NIAID’s Scientific Director (1985-1994). He became the 10th—and longest serving—Director of the NIH Clinical Center in 1994. During his term as Director (1994-2017), he oversaw the construction of a new addition to the hospital (the Mark O. Hatfield Clinical Research Center, which opened in 2005); established the Department of Bioethics; developed a new curriculum for clinical research training that is now offered worldwide; and started the Bench-to-Bedside Awards. In 2011, the NIH Clinical Center was awarded the Lasker-Bloomberg Public Service Award “for serving…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 in biomedical research.”

Gallin is retiring as the NIH Associate Director for Clinical Research, as Chief Scientific Officer of the NIH Clinical Center, and as Chief of the Clinical Pathophysiology Section in the Laboratory of Clinical Immunology and Microbiology, NIAID. You can read more about his career at https://www.nih.gov/about-nih/who-we-are/nih-director/statements/statem….

The following interview has been lightly edited for clarity.

CATALYST: How did you get involved with The NIH Catalyst?

GALLIN: NIH Director Bernadine Healy [NIH Director, 1991-1993], near the end of her term, did a competition for the Deputy Director for Intramural Research [DDIR], after Ed Rall retired in 1990. I applied for that and in the application, she asked for an essay of what would you do as DDIR. I said I thought the NIH needed a campus newsletter about intramural research and suggested that it be called the Catalyst. She liked that idea, but she picked Lance Liotta as DDIR [in 1993]. She encouraged him to pursue the newsletter idea and he did. He was the Editor and invited me to be the Deputy Editor. I thought Lance did a great job. He had some interesting ideas, such as his column on emerging technologies.

CATALYST: How has the Catalyst changed over the years?

GALLIN: It started off as black and white and we weren’t allowed to share it with anyone outside of NIH. The Editors and the Editorial Advisory Board met several times a year and we would talk about, just as you do now, topics to cover. Sometimes we would invite someone to write an article. When Michael Gottesman became the DDIR [in 1994], it underwent some transformation and modernization. He was very interested in the whole idea of the Catalyst and began writing columns for almost every issue, which I thought were special. The Catalyst became more of a newsletter that chatted with the community. That was the goal—telling people who was there, what was happening. I think transitioning to online and later to color was a big improvement. In the Clinical Center, the Catalyst is distributed to bins; they clearly get taken and read. It’s become a real part of the intramural program. I think people would be upset if it suddenly stopped.

CATALYST: Most of our writers are volunteers—postdocs and postbacs.

GALLIN: It points out the [alternative] career path opportunities in science and in medicine—from being an illustrator to being a newspaper reporter to being a Sanjay Gupta.

CATALYST: What made you decide to go to medical school?

GALLIN: I didn’t apply initially. I wanted to get a Ph.D. and I was excited that I’d been accepted into some graduate programs. My dad urged me to apply to medical school because he thought it might open doors and provide more opportunities. So I listened to him and applied. I was delighted when I was accepted at Cornell. It was wonderful fatherly advice to a son.

CATALYST: Why did you choose to come to NIH?

GALLIN: In my senior year of medical school I was introduced to a visiting speaker—Sheldon “Shelly” Wolff, head of NIAID’s Laboratory of Clinical Investigation; he later recruited me. He had this ability to recruit young people, many of whom became really successful, like Tony Fauci. I once asked Shelly, “How do you do that? How do you pick these winners, these young people?” He said, “I look for people who played on a team, either as an athlete or as a musician, [someone] who had a sense of team activity.” He said that was very important because in those days, during the Vietnam War, he could pretty much pick anybody—the cream of the crop of the medical schools. I think it was a good piece of advice. Talking about team science and all of that, that was special. [Gallin played ice hockey in high school and college and played clarinet in a band.]

CATALYST: You’ve had a longstanding interest in chronic granulomatous disease (CGD). What is that research about?

GALLIN: CGD is a rare genetic disorder in which the phagocytes cannot kill certain bacteria and fungi. As a result children with the disorder are highly susceptible to frequent and sometimes life-threatening infections. These children lack a key enzyme for making reactive oxygen species [ROS], which is important in host defense against infection as well as in inflammation. ROS can cause all sorts of problems when not properly regulated ranging from atherosclerosis to cancer to traumatic brain injury. Sometimes patients with rare diseases serve as windows to common diseases.

When I came to NIH, I worked with others to begin to define the biochemical basis of CGD. In collaboration with Genentech, Inc., we showed that the drug interferon gamma dramatically decreased the number of infections those children got by 70% (Proc Nat Acad Sci USA 85:4874-4878, 1988).

The FDA licensed it very quickly. That was the first time I participated in a drug trial. With licensing of interferon gamma, the FDA stipulated that we do a phase 4 study looking at long-term effects of this drug because it was given [as a subcutaneous injection] three days a week to patients. There were side effects—many patients felt like they had the flu. We needed a better treatment. Ultimately we used bone-marrow transplantation, then gene therapy. Harry Malech, who was working with me from the very beginning, led the effort [Proc Nat Acad Sci USA 94:12133-12138, 1997].

CATALYST: What other diseases did you help find treatments for?

GALLIN: We were looking for patients who had recurrent infections that were unexplained. It was sort of the undiagnosed diseases program before it was in existence. We began to identify patients with different diseases and we named them. One disease was called neutrophil-specific granule deficiency [in which] the children lack one of the key granules inside the cell that’s important in host defense.

We defined the molecular basis of another disease that had been called the lazy leukocyte syndrome due to an abnormality of actin function with a defect in the protein called WDR-1. The patient’s neutrophils had defective chemotaxis. Actin is sort of the muscle of the cell. That pathway was broken in that patient.

We discovered another patient who did not manifest the clinical danger signals of inflammation such as fever, pain, redness, or swelling when she got infected. This was the first patient with a new primary immune deficiency due to IRAK-4 deficiency, a critical component of the Toll-like receptor pathway. We figured out the genetic basis of her disease which contributed to understanding both the molecular pathway and clinical importance of the Toll-like receptor pathway in signaling the innate immune response.

Then there’s Job’s syndrome [a rare, primary immunodeficiency with symptoms of atopic dermatitis, recurrent skin staphylococcal infections, and recurrent pulmonary infection] associated with elevation of IgE [immunoglobulin E]. We defined a lot of the features of that disease. Later Steve Holland figured out the basis of Job’s syndrome. Steve also began to work on atypical mycobacterial infections in other patients and he described a spectrum of deficiencies related to the interferon gamma pathway.

As genetic capabilities began to emerge, we began to figure out what the genetic basis of those diseases were. In some cases, treatments.

Phil Murphy was then a clinical fellow working in the lab on receptors on neutrophils that respond to chemotactic stimuliwith directed migration of leukocytes. Phil was describing several chemoattractants. He had one that he was very interested in, but he couldn’t figure out what it did. I thought he was spending too much time on it. I said, “Phil, just stick it in the freezer, and someday you’ll figure it out.” Sure enough, a little later, Bernie Moss called me up and asked, “Do you guys know anything about chemotactic receptors?” [I told him about Phil Murphy]. He says, “Well Ed Berger in my lab thinks he may have the coreceptor for HIV. He thinks it might be similar to a chemotactic receptor.” So Ed Berger got together with Phil Murphy and sure enough that thing that Phil had put in the freezer was the coreceptor for HIV.

CATALYST: What’s the most satisfying part of your career?

GALLIN: It’s the rewards of caring for patients in an environment where you could do some research and help them as a result of the research. I was lucky. We identified several different disorders of phagocytes. First just phenotypically, through their clinical manifestations of the disease and functional abnormalities of the cells, and then genetically. For some patients, we developed treatment strategies that clearly made a difference in the quality of their lives. Now, with the teams that we started, including people like Harry Malech and Steve Holland, bone marrow transplantation and gene therapy are being used to cure some of these patients.

CATALYST: What were your administrative roles?

GALLIN: I was a lab chief. I was a scientific director of the National Institute of Allergy and Infectious Diseases with Tony Fauci [Fauci was the Director of NIAID from 1984-2022]. Then I was the Director of the Clinical Center for 22 years. Those were phenomenally rewarding experiences. When I was first asked to do those things, I was advised by Shelly Wolff, “Don’t do them unless you’re ready to change and dedicate a big portion of your life to trying to help others.” If you are not ready to do that, you’re not going to be any good at it. I was ready to do that. I had also complained about some of the things in the Clinical Center, and thought “I should be willing to serve to try to improve things.” So I accepted those responsibilities and it turned out that I really enjoyed them. I was able to continue some of my research and clinical activities, too. I thought it was perfect.

CATALYST: Did being the Director of the NIH Clinical Center affect your own research?

GALLIN: I decided to cut back on my research lab activities. NIAID leadership split my lab into three labs and made made Phil Murphy, Harry Malech, and Steve Holland lab chiefs. Suddenly three of the young people in the lab became NIH lab chiefs. That made me very proud.

CATALYST: Why did you stay at NIH for 50 years?

GALLIN: I enjoyed the special environment of being able to take care of patients and do some clinical research. I also enjoyed the environment of helping to participate in the management of the NIH Clinical Center—the largest single clinical research program in the world—watch it grow, and watch some new programs get started. So I had the good fortune of being in a position [in which] things were changing.

CATALYST: What were some of those changes?

GALLIN: We brought a new clinical research information system to the Clinical Center—CRIS. That was very rewarding. Then we brought the biomedical translational research information system—BTRIS—to the Clinical Center, which is taking all the hospital data and merging it with the lab data that the institutes have and being able to massage the data. Those were rewarding. Building the Department of Bioethics was something I enjoyed watching happen, too. I asked Zeke Emanuel [Ezekiel J. Emanuel], who was at Harvard at the time, if he would come and build a department. He asked me what he had to do. I said, “It’s easy, just build the best bioethics department in the world.” He liked that challenge. [Emanuel was Chief of the Clinical Center’s Department of Bioethics from 1997 to 2011; Christine Grady succeeded him.]

CATALYST: How did you support the Clinical Center research?

GALLIN: During my time as Clinical Center Director, a number of departments flourished and interacted with the institutes and centers (ICs). I encouraged Clinical Center Investigators to get dual appointments in the ICs. I thought that would be a way to get more resources for them. It was rewarding to watch that happen and watch the discoveries and the accomplishments. I was very proud of Harvey Alter’s work. [Alter shared the Nobel Prize in Physiology and Medicine for the discovery of the hepatitis C virus.]

CATALYST: You started partnerships with outside organizations, too.

GALLIN: I started 10 partnerships and enjoyed that. One was with Howard University [a historically Black research university in Washington, D.C.] so students and faculty could conduct research with NIH PIs; NIH PIs could access the underrepresented minority patient populations at Howard.

CATALYST: What educational activities did you help launch?

GALLIN: In 1996, I started a seminar on the Principles and Practices of Clinical Research. There were about 25 students who took it in one of the conference rooms here in the Clinical Center. As it started to grow, it transitioned from a seminar room, to the Lipsett Amphitheater, to also being held online. We also started a Clinical Pharmacology Course—initiated by Art Atkinson—which has become part of our curriculum on clinical research. The curriculum also includes the course that Zeke Emanuel started on ethics and that Christine Grady now runs. Together the three courses make up our curriculum in clinical research and we reach over 25,000 students a year in more than 160 countries. We have textbooks for each of the courses. We’re preparing the Fifth Edition of Principles and Practices of Clinical Research. The publisher seems to like it and says the Science Direct Usage for the current edition is over 70,000. I was blown away by that.

CATALYST: What do you see as the future of clinical research at NIH?

GALLIN: The opportunities to do the science are just so phenomenal today. The development of the COVID-19 vaccine is just one dramatic example of how things can benefit the public health. Sometimes you’re not even aware of the importance of what you’re doing. I think the Clinical Center remains a unique place. We don’t bill and doctors don’t have someone telling them that they can only spend 15 minutes with a patient. This place is different. It’s recognized as such and should be more recognized.

I’m very excited thinking about the future and I see lots of young, really smart people doing great things. We have to preserve the special environment in the intramural program and at the Clinical Center. I think some of the tools that have been put in place over the last decade, such as protocol navigators that Dan Kastner was the first person to suggest, have helped the PIs write their protocols. As we look into the future, developing databases for clinical and research data will be critical for sharing information and allowing more rapid advances that will lead to therapeutic interventions.

CATALYST: Tell me about your involvement with the Children’s Inn and the Safra Family Lodge.

GALLIN: I’ve always been privileged to be part of the Children’s Inn, which was started in 1990 by Phil Pizzo [then Chief of the National Cancer Institute’s Pediatrics Branch]. When I was on the Inn’s board, I suggested—with input from the Clinical Center nurses—that we change the name to the Family Inn and that we get some resources and expand it to accommodate adults. The Children’s Inn was happy with their brand and did not want to change. Fortunately the Foundation for NIH spearheaded fundraising efforts to build the Safra Family Lodge, which opened in 2005.

CATALYST: Tell me about the Trailblazer Prize.

GALLIN: Five years ago, my wife and I worked with the Foundation for NIH [FNIH] to create the FNIH Trailblazer Prize for Clinical Scientists. [The prize recognizes the outstanding contributions of early career clinician-scientists whose research has the potential to or has led to innovations in patient care]. The idea is to find a young investigator anywhere in the country; institutions have nominated people. We have a wonderful jury that FNIH set up to review nominations. Every year, we give out a prize and now it’s being given out in concert with the FNIH Lurie Prize in Biomedical Sciences. I’m pleased that we could do that.

CATALYST: What’s next for you after you retire? [After this interview Gallin decided to become a part-time rehired annuitant and work in NIAID.]

GALLIN: I’ll be spending time with my wife and family. I’ll also be doing some educational activities and some research. I have a few research projects I would like to continue, especially on CGD. I am delighted NIAID is allowing me to return to this environment.

The Office of NIH History conducted oral history interviews with Gallin in 1993 and in 2019. Go to https://history.nih.gov/display/history/NIH+Oral+Histories and search the alphabetical listing for Gallin’s interview.