Albert Lasker
Basic Medical Research Award

Mr. James W. Fordyce, members of the board of the Albert and Mary Lasker Foundation, Dr. Joseph Goldstein, members of the Awards Jury, and not least, all of the guests that are here with us to celebrate this special occasion, it is an enormous honor to have been selected as one of your recipients for the 2001 Lasker Prize.

We are at the beginning of a new century, a new millennium and soon to reap many of the harvests accrued from the molecular biology revolution. It may not be too presumptuous to anticipate that this coming century will be noted by future historians as the Age of Biology. This revolution started on April 25, 1953.

I am a child, a product of the age of molecular biology. From its outset molecular biology was a new breed of science and scientists. Devotees from physics, chemistry and biology joined its ranks. Everything was new. There were no limitations. The guiding premise was that the most complex biological phenomena could, with persistence, be understood in molecular terms. Genetics, along with molecular biology, became the principal means for dissecting complex biological phenomena into workable subunits. Initially, the focus of molecular biologists was bacteria and bacterial viruses. Soon all organisms, including ourselves, came under their scrutiny.

I was first exposed to molecular biology at MIT. As an undergraduate at Antioch College, majoring in Chemistry and Physics, every alternate quarter we packed up our bags and set off for a new city to participate in work experience. I worked for several quarters in Dr. Alex Rich's laboratory, at MIT. In addition to experimental work, I also had the opportunity to take courses from Salvador Luria, Boris Magasanick, and Cyrus Leventhal. They were not only great figures of that era, but tremendous teachers.

For my graduate studies, I decided to go to Harvard University and work for James Watson. Professor Watson had a profound influence on my career. He personified molecular biology. His bravado encouraged self-confidence in those around him. His stark honesty made our quest for truth uncompromising. He taught us not to bother with small questions, for such pursuits were likely to produce small answers.

Doing science in Jim's laboratory was a blast. As a graduate student I was provided with what appeared to be limitless resources. I could not be kept out of the lab. We were cracking the genetic code, determining how proteins were synthesized and isolating the enzymatic machinery required for transcription. At this time, Walter Gilbert was also working in Jim's laboratory. Jim and Wally complemented each other brilliantly because they had such different approaches to science. Jim was intuitive, Wally quantitative. As students, we received the benefits of both.

From Jim's laboratory, I joined the faculty at Harvard Medical School and from there went to the University of Utah. When contemplating leaving Harvard and going to Utah, which most thought was quite rash, I asked Jim what he thought about the prospect of such a move. He looked at me and said that I could do good science anywhere. The move turned out to be a good decision. In Utah, I had the luxury to be able to pursue long-term projects, including gene targeting, that were not possible at Harvard, a bastion of short-term gratification.

I do not have time to go into a description of our contributions to gene targeting. For those who are interested in this history, I recommend to you articles soon to be published by Nature Medicine. Instead, I tried to recreate for you an image of an era that inspired and led to our experiments, and to give tribute to a few of the great figures that influenced my journey.

Though I was advised not to, I want to close by thanking three people in this audience. First, my mentor, Jim Watson, who taught me not so much how to do science, but the essence of science; Dr. Kirk Thomas, who has been a dear colleague in my laboratory for many years, and in particular during some of the crucial years when the development of the gene targeting technology occurred; and finally my wife, Laurie Fraser, who has had the patience to put up with me for so many years. I do some of my wildest thinking starting around 2:00 a.m. In my excitement, I nudge my wife. She awakens and says "What?" And I begin my story. By 5:00 a.m. I am satisfied that I have provided sufficient details to make the story compelling and then promptly fall to sleep. As I wander off into dreamland, I hear her whisper, "My God!"

Thank you for your patience. I wish to again express my gratitude to all of you for conferring this great honor upon me. Thank you.