Reflections

This section collects the essays from Reflections from the Frontiers (Explorations for the Future: Gordon Research Conferences 1931-2006), GRC's 75th anniversary commemorative publication.

Illustrations of Life
Rakesh K. Jain
Rakesh K. Jain
Harvard Medical School / Massachusetts General Hospital
Seminal Findings and an Allergy to Black Flies

I am pleased and honored to contribute to this festschrift in celebration of the seventy-fifth anniversary of the Gordon Research Conferences. I have had the privilege of participating as a speaker, discussion leader, and organizer at more than twenty Gordon Research Conferences since 1990. These meetings have spanned areas as diverse as cancer, chemotherapy, radiation oncology, angiogenesis, vascular biology, microcirculation, drug delivery, and optics. They have allowed me to learn from the leaders in all these fields, to initiate new collaborations, and to present provocative ideas to the best brains in the business.

Although I had previously heard of these prestigious meetings and had seen their program announcements in Science, it was not until 1990 that I received my first invitation to speak at a Gordon Conference–on solute exchange in microcirculation and on drug delivery. I attended the Drug Carriers in Biology and Medicine Conference in New Hampshire in June. On the third day my mentor, Pietro Gullino, invited me to join him on a hike to the White Mountains during the afternoon break. We had a delightful time hiking in the hills and enjoying the scenery. By evening I was feeling a little tired but nevertheless prepared for the session, and I sat in the front row next to Pietro. After a short time I began to feel dizzy and excused myself to lie down. Soon I lost my vision and told Pietro I was feeling ill. The next thing I knew, I was in the hospital getting adrenaline. I had had an allergic reaction to being bitten by black flies. So my first lesson from the GRC was that I am allergic to insect bites. Since then I have limited myself to canoe trips.

Beyond this seminal finding I was quite struck by the caliber of the speakers, the cutting-edge nature of the work presented, the extent of formal and informal discussions, and the opportunity to mingle with the participants. I was equally struck by the fact that these two groups, microcirculation and drug delivery, were not taking advantage of one another’s expertise, although they were addressing complementary questions. This lack of communication among different disciplines became even more vivid when I attended the Cancer Conference in 1991 and the Chemotherapy of Experimental and Clinical Cancer Conference in 1992.

In the majority of presentations cancer biologists viewed solid tumors–the cause of over 85 percent of cancer-related deaths–as a collection of cancer cells. However, from our own work and that of others, we knew that a solid tumor is made up of more than just cancer cells: it is composed of cancer cells, host cells, and blood vessels, all of which are embedded in an extracellular matrix. The tumor is an organ–albeit an abnormal one–but there was no GRC that treated it as such.

I saw an opportunity to combine these different areas–microcirculation, drug delivery, cancer, and chemo-therapy–and proposed a new GRC called Angiogenesis and Microcirculation. I approached Judah Folkman with this idea and asked him to be my cochair. He was enthusiastic. We presented our proposal to Alexander Cruickshank and Carlyle Storm of the GRC, and our proposal was accepted. The first GRC on this topic was held in August 1995 at Salve Regina University, and these meetings have remained popular ever since: they continue to be oversubscribed! This is only one example of how the GRC has enabled scientists to develop new, interdisciplinary areas of study.

In June 2001, at a Cancer Chemotherapy Gordon Conference, I proposed that antiangiogenic therapy not only prunes tumor vessels but also normalizes the tumor vasculature and makes it more efficient for drug delivery. This new and provocative concept received a mixed response from the audience, which galvanized my thinking even more. I went home the next week and wrote a commentary for Nature Medicine, outlining this hypothesis and its implications. I also began several new clinical and preclinical studies. The discussion at the GRC and the Nature Medicine commentary that ensued have served as guides for the current phase of my work. Emerging preclinical and clinical data from various laboratories now provide compelling evidence in support of the normalization hypothesis. Thus, the Gordon Conferences have been critical to my career development and growth and have provided a new direction for the field of angiogenesis.

In short, my own experience is a good example of how the seventy-five years of the GRC have allowed the fruitful association of areas of research and how the conferences have been the ideal forum for presenting new concepts. I believe the conferences are a benefit for all of us, and I look forward to their continuance in the years to come.