On November 27, 2006, members of the CRI Postdoctoral Fellowship Review Committee gathered for a private ceremony to honor CRI Scientific Advisory Council Associate Director Dr. Benvenuto Pernis, for his 28 years of dedication to the council and exemplary service on the Postdoctoral Fellowship Review Committee. Dr. Pernis stepped down from the committee in early 2006. In the following interview, Dr. Pernis reflects on his career and his experience at CRI.
When did you become interested in science?
My early scientific career began more than fifty years ago when I studied silicosis, a disease of the lungs involving what we now understand to be an innate immunological response against inhaled dust particles. At the time, very few believed the disease’s symptoms were caused by immune-related inflammatory responses, but we now know this to be the case.
CRI: What attracted you to immunology?
Dr. Pernis: Around that time (this was in the mid-1950s) Nobel Laureate Sir Frank Macfarlane Burnet published his clonal selection theory, an extension of the theories developed by his contemporary, immunologist and Nobel Laureate Niels Jerne, which explains how lymphocytes target antigens for destruction. This idea laid the fundamentals of immune tolerance, or the ability of the immune system to recognize “self” (safe) from “non-self” (dangerous), and catapulted the field of immunology into the scientific spotlight. Young scientists like myself realized that immunology was where the exciting new science was happening, so naturally I gravitated to it. It was the right choice, because it is my general view, as informed by my background, that the immune system’s sophistication and complexity ultimately will be required to fight a disease as complex as cancer.
CRI: What were some of your contributions to the field?
Dr. Pernis: The genetics field was also advancing at this time, and I and others began to explore the genetic underpinning of immunity. While I continued to publish data on the immune-based causes of diseases associated with dust and particulate inhalation, I also strove in my earlier work to understand the body’s ability to produce a nearly infinite number of antigen-specific antibodies from a finite number of genes. I identified the genetic markers associated with antibody production and, beginning in 1964, published several papers in which I identified various immune cells found in the spleen that produce antibody (also called immunoglobulin). These are now known as B cells, and their vital function in immunity has been well characterized. I discovered that each cell only activates one of the two genes that control each immunoglobulin chain by a process called allelic exclusion.
CRI: Where did you conduct your research?
Dr. Pernis: I began my work in Italy, where I taught at universities in Cagliary, Milan, and Genoa. In 1972, I became a member of the Basel Institute of Immunology in Switzerland, under the direction of Dr. Jerne. The Institute was dedicated to exploring the then newly emerging technologies related to molecular biology, gene cloning, and development of mouse models. I continued my exploration in Basel of the genetic controls of immunoglobulin production until 1976, when I accepted a professorship at Columbia University in New York City. I realized that I missed teaching and decided to return to it.
“I am devoted to education and strongly believe that it is vitally important to cultivate young minds and help them to get established in science.”
CRI: Why teaching?
Dr. Pernis: I derive great personal satisfaction from teaching. It is immediately gratifying when I sense that a lecture hall full of students understands the information I am conveying to them. I am rewarded by the knowledge that 10 or even 100 students now know a little bit more, than they did before they entered the room. I am devoted to education and strongly believe that it is vitally important to cultivate young minds and help them to get established in science.
CRI: Are there any notable people whose scientific careers you helped establish?
Dr. Pernis: I have had the pleasure of having trained and worked with many very talented scientists during my career, too many to mention. However, one of them in particular stands out, and that’s Linda Buck, who won the Nobel Prize in Physiology or Medicine in 2004 along with Richard Axel, a colleague of mine at Columbia. Linda joined my lab as a postdoctoral fellow in 1980 to continue her studies into the production of B cell surface immunoglobulins that are used as antigen receptors. I recall having had many conversations with her about the genetic basis of antibody production. She would later go on to discover the genetic basis for olfactory odorant receptors, and I like to think that she carried with her into her further work some of the knowledge gained from our conversations.
CRI: How did you become involved with the Cancer Research Institute?
Dr. Pernis: I first learned of the organization through its Scientific Director, Dr. Lloyd Old. He was and continues to be a luminary in the field of cancer immunology, and I’d met him during my many trips to the United States when I was still in Europe. He invited me to join the CRI Scientific Advisory Council in 1978, and specifically to sit on the Postdoctoral Fellowship Review Committee, which Lloyd had recently formed. I accepted his invitation and remained a member of the committee until stepping down last year.
CRI: How was your experience as a member of the CRI Postdoctoral Fellowship Review Committee?
Dr. Pernis: It has been one of the most rewarding experiences in my lifetime. As a member of this committee, I have had the opportunity to have first-had access to the newest ideas emerging from the youngest immunological researchers. It has been quite fascinating to oversee the dynamic evolution of immunology through the scope of the fellowship committee. Moreover, I have thoroughly enjoyed some of the discussions—some of them quite heated—among the committee members during our review meetings. Every session was stimulating; I made it a point to never miss a meeting in the 28 years I served on the committee.
CRI: What were some of the significant changes in research direction within immunology as seen through the fellowship applications?
Dr. Pernis: It has been fascinating to witness entire areas of research take a step back before moving forward again. For instance, the concept of immune regulation was one that took hold early on with the theoretical existence of what were then called suppressor T cells. That view was completely negated for a time until the re-emergence of the concept decades later through the discovery of what we now call regulatory T cells. Naturally the projects proposed in the fellowship applications reflected this changing landscape of current scientific thinking. It was beautiful to see the logic of the system played out through the fellowship applications.
CRI: Were there any other significant movements within immunology that you can recall being played out in this manner?
Dr. Pernis: Perhaps the most significant one—which, in my opinion, is still only beginning to take hold—is the shift away from studying solely the adaptive immune response to infectious disease and cancer to include also the exploration of the innate immune system and its role in defense against cancer. You see, the study of adaptive immunity is largely concerned with the ability of the body to generate immune responses specific to a foreign invader through the generation of antigen-specific T cells and is also characterized by the body’s ability to “remember” how to recognize quickly such invaders upon reinfection. It’s the basis of vaccination as we have known it. A lot of work has been accomplished to help apply our knowledge of adaptive immunity to cancer therapy.
“…We are only now beginning to ask how the innate immune response can be applied to cancer, and this is an area of study that I believe is going to attract the greatest attention for young cancer immunologists over the next decade.”
CRI: When did this shift toward the study of innate immunity begin?
Dr. Pernis: As recently as 1989, when Charles Janeway, a Yale professor of immunobiology, first theorized that the body possesses a first-line defense against foreign invaders like viruses and bacteria. Dr. Janeway posited that this immediate immunity is based on pre-existent or innate abilities of some immune cells to recognize molecular structures commonly associated with infectious agents. This theory was quickly proven and formed the basis for a new field of study on innate immunity. Within a few years, we began to receive fellowship project proposals seeking to explore innate immunity and its response to infection. However, we are only now beginning to ask how the innate immune response can be applied to cancer, and this is an area of study that I believe is going to attract the greatest attention for young cancer immunologists over the next decade. I should note that I find it particularly interesting to remember that cancer immunology began with Dr. William B. Coley’s investigations of what we now know was an innate immune response against cancer.
CRI: Would you please elaborate on this?
Dr. Pernis: Certainly. Dr. Coley observed that cancer patients with advanced tumors sometimes underwent complete tumor regression following infection and fever. He developed a mixed bacterial toxin—by all rights the first cancer immunotherapy—that he then injected directly into tumors with the express intention of summoning the body’s general immune defenses. He reported complete regression in some patients, but his results were not easily reproducible. Meanwhile, chemical and radiation therapy for cancer took predominance in medical practice and Dr. Coley’s immunological work went largely unnoticed. However, thanks to the work of his daughter, Helen Coley Nauts, and the Cancer Research Institute, which she founded, we now have a clearer understanding of the immunological mechanisms Dr. Coley’s toxin set in motion, namely, that his bacterial toxin attracted innate immune responders to the tumor site. In the process of attacking the bacteria, these innate immune sentinels triggered a cascade of other immune events within the tumor environment, resulting in long-term immunity to cancer. Essentially, Dr. Coley predicted more than 100 years ago that innate immunity would play an important role in the control of cancer.
CRI: What are you doing these days?
Dr. Pernis: I retired from my teaching position at Columbia, but I am still dedicated to research and to reaching out to young scientific minds and piquing their interest in immunology. I am preparing a publication at the moment on the subject of the innate immune response to crystals, specifically cholesterol crystals and their possible role in the development of atherosclerosis. Science keeps me alive—it is my passion, and I plan to continue carrying out my research as long as possible.
CRI: Do you have any closing comments about CRI’s fellowship program?
Dr. Pernis: Only to say that CRI is doing a beautiful job helping young scientists become established. There is no wiser investment of donor dollars that I can think of than investing in the future leaders of cancer immunology. I am grateful for the opportunity to serve on the Scientific Advisory Council, and for the kind recognition given me when I stepped down from the Fellowship Committee. It has been an honor and pleasure to serve with such distinguished colleagues.