LEWIS CANTLEY has made significant advances in cancer research, stemming from his discovery of the signaling pathway phosphoinositide 3-kinase (PI3K). His pioneering research has resulted in revolutionary treatments for cancer, diabetes, and autoimmune diseases. He is the author of more than 400 original papers and more than 50 book chapters and review articles. He conducted his postdoctoral research at Harvard University, where he became assistant professor of biochemistry and molecular biology. He later became a professor of physiology at Tufts University, but returned to Harvard Medical School as a professor of cell biology. He became chief of Harvard’s new Division of Signal Transduction, and a founding member of its Department of Systems Biology, in 2002.
What is the book (or books) you’ve given most as a gift, and why? Or what are one to three books that have greatly influenced your life?
I read fairly widely, but particularly enjoy and give or recommend to my friends and family books written by three contemporary writers: Richard Rhodes, Neal Stephenson, and Philip Kerr.
The Making of the Atomic Bomb by Richard Rhodes is a masterpiece of
explaining the sequence of discoveries that led to the development of the atomic bomb in an historical context. During my graduate studies at Cornell, I minored in theoretical physics and took courses from Hans Bethe and other luminaries, so I had met several of the physicists in the book. Yet I learned more physics from the book than I did in my courses.
Neal Stephenson is an incredible writer who manages to create fictional characters who reveal the eccentricities and absurdities of real-life scientists and mathematicians as they go about their work of creativity. Were I to teach a course on the history of science, The Baroque Cycle would be required reading. It is way over the top in capturing the character of Newton and his contemporaries, and the science sometimes (intentionally) becomes magical, but with the interwoven sex and violence, it is way too much fun to put down.
Finally, I have read everything Philip Kerr has written about the fictional Berlin policeman Bernie Gunther, struggling to survive as the Nazis take over Germany. These books are a contemporary warning for our own future in America.
How has a failure, or apparent failure, set you up for later success? Do you have a “favorite failure” of yours?
An important failure for me was my failure to obtain tenure at Harvard in 1985. As an assistant and associate professor in the Biochemistry and Molecular Biology Department, I worked on the proteins and lipids that make up the barrier between the inside and outside of cells, and how they are involved in cell regulation. This was not very fashionable, as everyone was jumping onto the revolution of genetics and molecular biology. My move to Tufts Medical School and, later, Harvard Medical School led to collaborations with scientists at those institutions, notably Tom Roberts and Brian Schaffhausen, who appreciated the importance of understanding the biochemical pathways involved in cancer. Ultimately, it was work done at those institutions that led to the discovery of PI 3-kinase, a central mediator of cell growth, involved in both diabetes and cancer.
What is one of the best or most worthwhile investments you’ve ever made?
My best investment was the eight years I spent getting undergraduate and graduate degrees in chemistry and biophysical chemistry. While my current research focuses on developing cures for cancers, the insights I have into how cancers evolve and how to develop drugs to treat cancer come from my understanding of the rules of chemistry and biochemistry. This insight has not only facilitated breakthroughs in my own laboratory, but also allowed me to start companies such as Agios and Petra, which are developing drugs against novel targets for cancer therapy.
What is an unusual habit or an absurd thing that you love?
I relax by playing solitaire on my iPad. Trying to develop strategies to beat the odds focuses my mind and eliminates all other thoughts.
The even more nerdish thing that I do [in my work] is try to read the function of proteins from their linear sequence of amino acids. A protein is a string of amino acids with approximately the same amount of information as is found in the 500 or so letters that make up a typical paragraph in a book. There is no reason why we shouldn’t be able to teach ourselves how to “read” the information in a protein the way we read paragraphs in English or French or Chinese. The problem is to establish the rules. My lab focuses on breaking down the protein into short strings of five or ten amino acids called “motifs” that are conserved through evolution and often found in multiple proteins. Often these motifs are ways for proteins to communicate with other proteins. So once we know the function of the motif, we can predict how the protein communicates with other proteins in our bodies. When someone tells me about the protein they are excited about in regard to a disease, I immediately look up the sequence and search for motifs that might help explain the link of the protein to the disease. This approach is responsible for many of the discoveries from my laboratory.
In the last five years, what new belief, behavior, or habit has most improved your life?
Moving from Cambridge to New York City has allowed me to live without having an automobile. My walk to work is ten minutes regardless of the weather or traffic. I don’t need to shovel snow, scrape ice from a car window, or look for a parking spot. It’s wonderful. It probably saves me at least an hour every day, and walking is healthy.
What advice would you give to a smart, driven college student about to enter the “real world”? What advice should they ignore? My advice is to choose a profession that is really easy for you to do and that also allows you to be creative. If it is easy for you to do and somewhat difficult for your peers to do, you will not have to work too hard to be successful and you will have enough spare time to enjoy life. You will also be able to put in extra hours to blow out the competition every now and then, should that be necessary.
If, on the other hand, you have to work long hours all the time just to be competitive, you will burn out and not enjoy life.
One should not pursue a profession just because it is viewed, at the time you begin college, as the one that will have the most jobs or where you will make the most money. Technologies and infrastructures in the world are changing at an unprecedented rate. No one can predict what will be the best profession four years from now. If you are uncertain of your talent, get a broad education that does not narrow your options. The best skill is to be able to communicate efficiently both in writing and speaking. The two college courses that were probably most important for my career were a course in literature and composition and a course in logic (an advanced math course). These courses taught me how to reach the correct conclusion from a set of facts and how to communicate that conclusion to a diverse audience.
If you could have a gigantic billboard anywhere with anything on it, what would it say and why?
My message would be: “Sugar is toxic.” Sugar and other natural or artificial sweeteners are among the most addictive agents in our environment. When consumed in quantities that exceed the rate of metabolism in muscle or the brain, sugar is converted to fat, resulting in insulin resistance, obesity, and an increased risk of many other diseases, including cancers. While consuming fats and proteins evokes a feeling of satiety, consuming sugars induces a desire for more sugar within an hour or so. We evolved this addiction because, in the not-so- distant past, adding fat to our bodies at the end of a growing season when fruits were ripe was essential for surviving until the next growing season. But today, sugar is available all year round and is one of the cheapest foods available. So we continually add fat to our bodies. We may be approaching a time when sugar is responsible for more early deaths in America than cigarette smoking. I have written and lectured extensively on this subject over the past ten years as our understanding of the biochemical basis for the toxicity of sugar, especially the link to cancer, has become more clear.
What are bad recommendations you hear in your profession or area of expertise?
The worst recommendation is to keep your ideas and data secret until you have a paper describing these results accepted in a journal. Anytime I have a crazy idea or see an unexpected result, I talk about it with my colleagues to see if they have seen anything similar and whether they think my idea is crazy. This is the fun of science. Multiple scientists with different experiences and expertise can collaborate and get to the right answer much faster than a single scientist.
When you feel overwhelmed or unfocused, what do you do?
I play solitaire, which clears my mind, allowing me to fall asleep. After six hours of sleep I spontaneously wake up and everything seems simple and possible.