The Joy of Discovery

Going back to the beginning, why experimental science?

Growing up, you often question yourself about what you’re good at. And it became clear to me as I progressed through high school that I was good at science and mathematics. In 1955, I had the opportunity to spend a summer at The Jackson Laboratory (www.jax.org) and it introduced me to the huge potential of experimental science. It was very inspirational and essentially determined the rest of my life.

When I went to graduate school (Massachusetts Institute of Technology) back in 1960, I looked at what people were doing in experimental science; the most interesting work was being done with viruses, particularly ones that grow in bacteria. But I thought that the field was very limiting. I wanted to see if viruses could be used as a probe for the behavior of animal and human cells. I left MIT to go to Rockefeller University because there was a professor there – Richard Franklin – whose work was very closely aligned with my aspirations.

Later on, I met with Renato Dulbecco – one of the people bringing animal virology into the late 20th century – and he invited me to join him at the Salk Institute in La Jolla. I moved there in 1965, where I spent two and a half years before moving back to MIT.

You achieved a great deal at MIT. What are your highlights?

The discovery of reverse transcriptase in 1970 was the biggest; nothing beats that. But we did move into cancer research where we discovered that the Abelson virus made an oncoprotein that phosphorylated tyrosine. It stays with me as a great moment because we had found a new kind of protein modification that was linked to cancer. It eventually led to the “miracle drug” Gleevec.

Next, I decided to move the laboratory into immunology. A highlight there was our discovery of RAG genes, which encode the proteins that recombine DNA and give the immune system its variability – and ability – to react. And we also unearthed the NF-kappa B transcription factor – plus a whole host of other transcription factors that control immune function. It was a period of incredible and important protein discovery on the part of the post-doctoral group I was working with. And there is no higher high than a discovery.

But you won a joint Nobel Prize in 1975 for “discoveries concerning the interaction between tumor viruses and the genetic material of the cell” – that must have been a high point...

The main highlight there was that the call came from my wife! She was at a scientific meeting in Europe and heard before the official announcement, and she called me – woke me up, in fact. Going to Sweden for the ceremony was like entering fairyland. I was treated like nobility and given the Prize by the King of Sweden.

Did your research focus change after receiving the prize?

The prize was coincident with my movement into immunology, but it wasn’t the reason for the move. I had already made the decision based on the rise of recombinant DNA methods. Indeed, the new ability to use recombinant DNA methods to understand mammalian cell biology was very real in 1975. And at that point I decided to enjoy myself and take advantage of the new methodology to work on the adaptive immune system.

What are you focusing on right now?

After stepping down as president of the California Institute of Technology in 2005, I decided to try something a little different. I wanted to see if we could translate some of our findings from the laboratory into humans – either as therapeutics or prevention. In particular, I focused on gene therapy methods. We’ve been doing that now for the last 10 years and we have several projects in clinical development; cancer and HIV are major focuses.

As gene technologies advance, what are the major concerns?

One concern of mine dates back to my early experience with recombinant DNA methods. Indeed, when they were developed, I was part of the group that produced the Asilomar Meeting in 1975 to address the potential dangers that might arise from this new technology. Now that genome-editing technologies have appeared, the concern is a reality rather than a theoretical concern. I was also part of a group that called on the National Academy to take some action to limit the use of these technologies until we could at least come to a consensus about what’s right, what’s appropriate and what’s inappropriate. That of course is always a judgement in the context of technology. The National Academy is now actively evaluating the technology and the larger societal concerns that surround gene editing.

What advice would you give to today’s scientists?

Science today is such a different world than it was when I started out. But in retrospect, I think I made some pretty good decisions back in the 1960s; I found the right places to work, and the right people to work with. The most important consideration should be your scientific environment and the people around you.

Today, I think that science has been so ‘professionalized’ that some of the joy of discovery is lost. Anything we can do to give young scientists an opportunity to be independent and to express their own particular notions about science and creativity is positive for the forward movement of science.