Harvey Lodish's membrane biology research and his scientific leadership roles caught our attention. Curious to know more, BioTechniques contacted him to find out about the ambitions, character, and motivations that led to his success.Focusing on What's Important
How did you begin your scientific career?
When I was in high school, Ethel Laughlin— a teacher at my public high school in Cleveland Heights, OH—introduced me to a chemistry project on red cell membranes and membrane transport. I wondered then how membrane proteins were made, but there was no way of looking at it. Later on, some early work at MIT with David Baltimore showed that enveloped viruses, such as vesicular stomatitis virus, encoded a single glycoprotein that was involved in budding of the virus particle from the cell surface. In the early '70s, before recombinant DNA methods and really in the dark ages of molecular and cell biology, we studied the biosynthesis of this viral envelope protein, showing that it was made in the endoplasmic reticulum, moved to the Golgi apparatus, and then resided on the plasma membrane.
Then in the late '70s, it became apparent that one could clone genes, which was a novel concept. I started a project to clone abundant membrane protein genes and we soon reported the cloning of the erythrocyte glucose transporter GLUT1, followed by GLUT2 and GLUT4. GLUT1 was the first mammalian protein demonstrated to transport glucose across a membrane, instigating studies of the molecular biology of metabolism and expanding the field of membrane transport proteins. The GLUT4 transporter responds to insulin and its cloning began the field of molecular biology of diabetes and glucose transport.
It seems that you have refocused your research several times during your career. What prompted this?
We really didn't know we were going to be studying glucose metabolism, but the cloning of GLUT1 simply opened the whole field; a succession of people came to the lab to work on glucose transporters. A little later, a postdoc in my lab, Alan D'Andrea, cloned the erythropoietin receptor despite the belief that it was almost impossible to isolate the gene for such a rare receptor. Well, we did it and opened the field of red cell signaling. Later we reported the cloning of the TGFβ receptor with Bob Weinberg (MIT), starting that field. One more example is that about 10 years ago, I realized that we needed more information on hematopoietic stem cells and their growth factors. Again, some postdocs came to the lab and identified cells in the fetal liver that supported expansion of hematopoietic stem cells and cloned a series of growth factors that stimulated them. This culminated in the ability to grow human cord blood cells in culture, a study that will soon begin clinical trials in Singapore. So, really what I've done is look for areas that are interesting and important and determine where the main problems in those fields can be approached by the molecular and cell biology techniques I use.
Another aspect of my shifting focus is that I let my postdocs take their research with them. I have what I call the two-year rule: when postdocs leave my lab, we have a conversation where they tell me realistically what they are interested in doing for the next two years, and that is theirs. I never compete with my former postdocs. As a consequence, my lab changes focus over a 5–10 year period, allowing us to work on new ideas and enabling those who actually did the work to successfully start their own labs. I learned a long time ago that this training philosophy provides a lot of motivation. I've trained 150 postdocs and graduate students, many of whom are spectacular. There aren't too many faculty who can boast of a Nobel Prize and four members of the National Academy of Sciences.
I understand that you have also served on several scientific advisory boards. How did you get involved?
I have been involved with Children's Hospital (Boston, MA) for 40 years and serve on the Board of Trustees, which is a little odd for a cell biologist. I attended Kenyon College and later was on their board for 18 years. And I organized the scientific advisory board for the Massachusetts Life Sciences Center, which is Governor Deval Patrick's ten-year, billion-dollar initiative in life sciences.
The governor proposed the plan to great acclaim in June 2007, but it was basically going nowhere in the legislature. As you know, these things are heavily embedded in politics. At the Whitehead Institute's 25th anniversary celebration, we were getting our pictures taken and I said, “Governor, I like your ideas, but you better get yourself a scientific advisory board to ensure that the money goes to appropriate things.” Much to his credit, he listened and connected me with the group that was organizing the program. They asked me to put together the scientific advisory board, which I did. And I'm very proud of it; it's composed of outstanding academics with business experience and leading scientists in business and venture capital. I enjoy working on policy. Dealing with state politics is a whole new world.