Julia Draznin Maltzman, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 14, 2005
This year at ASCO, a new award was created in an attempt to recognize the important contribution that basic and translational scientists make to the field of oncology. The Science of Oncology Award attempts to highlight the importance of basic and translational science to improve the understanding of this complex field and to advance the development of new diagnostic tools, therapeutics, and even technology.
Harold Varmus, MD is the first recipient of this prestigious award. Dr. Varmus was chosen because of his lifetime commitment to science and his pioneering research on the genetic origins of cancer. Over twenty years ago, while working in the laboratory of Dr. J. Michael Bishop, Dr. Varmus first identified that normal human cells harbor genes within them that could transform them into cancerous cells. Specifically, they proved the cellular origin of the oncogene of the chicken retrovirus. This work was truly revolutionary, as it led to the discovery and understanding of many more genes that control growth and development and are frequently mutated in human cancers. It is for this concept that Drs. Bishop and Varmus were recognized with a Nobel Prize in Physiology and Medicine in 1989. Under the Clinton administration in 1993, Dr. Varmus directed the National Institutes of Health (NIH), a position he held until 1999. Under his directorship, the budget of the NIH almost doubled from just over ten billion to almost twenty billion dollars. He erected many new buildings, hired new leadership, and revolutionized how we think about basic and translational research.
Dr. Varmus opened his lecture by pointing out that, although he began his scientific career thirty years ago, he feels it is only now that the field of molecular genetics is entering its most interesting phase. When he began, he claimed that the realms of molecular cancer genetics and clinical oncology were two totally separate worlds: each as different as "religion and science", he said. One could perceive one world as potentially irrational, and the other as potentially irrelevant.
It was not until the early 1990&'s that these two separate worlds started to collide. Dr. Varmus cites the introduction of DNA-based testing in CML, the introduction of monoclonal antibodies, and the more recent clinical risk assessment profiles looking for inherited gene mutations. In the last few years, larger gene expression profiles used for diagnosis, prognosis, and therapeutic approaches have further brought together these two seemingly disparate worlds.
The current ASCO meeting is filled with examples of new drugs/therapies available that attempt to inhibit the product of these mutated genes or oncogenes that drive cancer. Dr. Varmus sees a future in which all risk, prevention, prognosis, and treatment will be based on a known molecular damage incurred by the individual patient. This is how he sees these two worlds not only combining, but totally overlapping. Only under these conditions, Dr. Varmus notes, will all of our actions be rational, reasonable, judicious, and sensible.
Dr. Varmus outlines a plan on how to achieve the ideal state. First, he noted that we must strive to better understand what we already know and learn how to apply it. Second, we need to define and map out the complete genotype of cancer, just as we have succeeded in mapping the normal human genome. Thirdly, he notes that we must develop new strategies for prevention and diagnosis of cancer. Dr. Varmus admits he does not know exactly what those are, but acknowledges that more work is needed in this capacity. And finally, he calls for a change in the culture of cancer research. He notes that we need to find improved ways to disseminate new knowledge to everyone in order to better educate the students of oncological sciences.
In an attempt to understand what has been done in the past thirty years, Dr. Varmus pointed to three main concepts. One idea, very familiar to most of us, is that cancer is likely the result of multiple mutations that add up over time. The three most common types of mutations that may lead to cancer include: a gain of function within a cell; a loss of tumor suppressor function; and a loss of DNA integrity/inability for DNA repair. A second accomplishment has been the understanding of the various types of proteins which these mutated genes produce. What is their function when mutated and causing cancer, and what is their function when not mutated and part of the normal cellular physiology? Finally, the third important concept on which we frame our current understanding of cancer physiology is that oncogenes not only initiate a cancer, but maintain it. In other words, cancer cells become dependent on mutations for survival.
Dr Varmus claims that as our knowledge of cancer physiology grows, it is only natural to strive towards a greater goal: to map out the entire cancer genome, in much the same way the human genome project has succeeded in mapping the normal physiologic genome. Critics claim that this would be an expensive (about 1 billion dollars) and lengthy endeavor. For example, lung cancer may have multiple mutations, even within one single gene. Furthermore, as drug resistance becomes more prevalent, new mutations would arise, and thus this map would require constant upkeep and maintenance. However, Dr. Varums claims that this cost, although substantial, is not so great relative to the entire NIH annual budget. He also notes that, although this process may be lengthy, it is well worth the challenge, as the data that it would yield is invaluable.
To make all this work, it has become very clear to Dr. Varums that we will need a team approach. He touts the importance of people who can translate the basic science to clinical medicine. He believes that someone who has an intimate knowledge of the clinical disease course as well as very grounded knowledge in the biological sciences could more clearly identify the potential for new therapeutics and technology. They could then focus the science in the context of a particular disease. Dr. Varmus claims that we need individuals who could act as intermediaries between the two worlds of science and clinical medicine.
Dr. Varmus closed his speech by noting the importance of changing the current culture of science and medicine. He noted that the Internet has created the opportunity to disseminate large amounts of information very quickly and thus has provided us with the opportunity to access an enormous public library. He noted sharply that access to information should be unhampered in order to ensure that science and medicine continues to grow and prosper for the good of society collectively as well as for each of us as individuals.