In this interview, Michael N. Hall talks about scientific prizes, the discovery of regulated cell growth and his career.
On the long list of scientific prizes that you have received, the most prominent is missing. Do you expect to win the Nobel Prize?
Friends tell me that I can expect to win it, but that is what friends do. Do I personally expect it? I suppose that I am considered. However, I would be surprised if I won it. There are probably many who are considered every year. There are many deserving scientists. How can one expect it?
What do the prizes that you received mean to you?
They mean a great deal. On a personal level, prizes are a very nice compliment, but in the broader sense, they are important as validation of our work and that it is recognized internationally. As scientists, we work very hard and invest ourselves personally so it is very gratifying to receive such validation.
Do your colleagues treat you differently because of the prizes you received?
Not the long-term colleagues who know me well and who saw how the whole story developed. Others sometimes approach me as if I were a celebrity and probably treat me with a little too much respect. I dislike this because it creates a barrier between you and people. Sometimes, I say silly things just to remove that barrier and make people more comfortable. I do not like hierarchy among scientists.
“I do not like hierarchy among scientists.”
How was the groundbreaking discovery that cell growth is controlled initially received by the scientific community?
For a very long time, people did not even understand what we were saying, let alone accept or dismiss it. We discovered that TOR (Target of Rapamycin) controls growth in the mid-nineties. If you at that time read a paper about cell growth, it meant cell division. When we went around telling others we discovered this controller of cell growth, people said “Come on, we have known about that for years. It is cyclin-dependent kinase”. I realized that we had to re-define the term “growth” and make a distinction: what cyclin-dependent kinases control is increase in cell number, but cell growth means increase in cell size.
A given space can be filled with many smaller parts or fewer larger parts.
Yes, it is so logical in retrospect. At that time, growth was not studied because it was not thought to be a regulated process. I also had to remind people that the process of getting more cells is a combination of cell growth and division. Cyclin-dependent kinases are extremely important and I would say TOR is also important, given that cell growth and division go hand-in-hand. TOR receives many inputs and then controls even more outputs – as if it were the brain of the cell.
Why did your lab start working on Rapamycin in yeast?
It was an exciting time in medicine because of the development of transplantation surgery, which was made possible by immunosuppressive drugs such as rapamycin. There was a lot of interest in finding out how these drugs worked, particularly in mammalian cells. Joseph Heitman, who was a postdoc in the lab, got very interested in these drugs. He and Rao Movva, a collaborator at Sandoz, remembered that Rapamycin was initially shown to be an antifungal agent. So, they made the assumption that whatever the underlying mechanism is, it must be conserved from yeast to human. We viewed yeast as a better experimental system than mammalian cells because it was genetically tractable, unlike mammalian cells at that time.
Rapamycin was the first drug found to extend the lifespan of mammals. Did you consider using it for that purpose?
No, I do not consider anything like that. When that publication came out, the sales of Rapamycin produced for research purposes skyrocketed. Apparently, people started dosing themselves.
One meaning of “Tor” in German is fool, did you sometimes feel like a fool in the early days of TOR research?
Of course, this is part of the research process. You work very hard to get Mother Nature to reveal her secrets to you. You get it in little bits and pieces and often you feel like you are not making much progress.
Did you always want to become a scientist?
I wanted to do something that involved creativity. When I was a young student, I wanted to be an artist but then decided I could not be because it was too unstructured. Also, you need to be really courageous to be an artist. Then medical school was too structured, so I had to find another way. To me, science is a compromise that combines structured productivity and creativity.
“To me, science is a compromise that combines structured productivity and creativity.”
What is for you the major difference between science and art?
An artist is unconstrained, whereas a scientist is constrained by truth. We are looking for the truth of how nature works. An artist can create anything and is limited only by the medium, for example, the edges of a canvas, but not by the concept.
Did you ever have a Plan B to becoming a professor?
I briefly thought about a Plan B as a postdoc. My PhD studies were not a particularly stressful period because my experiments worked well and I was able to publish several papers. Everything came very naturally. I knew that I wanted to become a professor someday but was not thinking too far ahead. When I became a postdoc, I then realized the pressure was on. I knew I would have about four years to have a story that would allow me to sell myself on the job market. I had many sleepless nights as a postdoc, wondering whether I was going to make a discovery or not. There is a lot of built-in anxiety there that you have to learn to deal with. I did not want to take any chances and worked extremely hard. When things were not going that well during the postdoc, I was very fortunate to have friends and my wife, who helped me out and supported me.
How did your wife deal with your career?
If you are a scientist and married to a non-scientist, your spouse needs to be an extremely understanding person. Doing science is a passion so you invest many more hours than only from nine to five, and even when you are home, you are usually thinking about science. You are absent mentally a lot of the time, as well as physically due to traveling.
“There is a lot of built-in anxiety there that you have to learn to deal with.”
Why did you come from the US to the Biozentrum in Basel to start your research group?
I came here after my studies and postdoc in America, but I was much less American than most of my American colleagues. I felt more global because I grew up in South America, so I was more open to looking for positions outside of America. After my PhD, I did a mini postdoc in Paris and during this time I met my wife who is Parisian. Then we went to San Francisco together, where I did my real postdoc, and when the time came to look for jobs, because my wife was European, I looked in Europe too. I was looking in French speaking areas in Europe and had offers from institutions in Paris and Lausanne.
Then Jeff Schatz asked me to look at a position at the Biozentrum in Basel and I could not decline his invitation. I went to visit with zero expectations. I spent a couple of days there and discovered that the Biozentrum was a great place in terms of science and the quality of the students and postdocs. It seemed like a fantastic place to do science and to develop one’s career. However, I had to convince my wife and myself to come to German speaking Switzerland, which was a very different place in the mid-eighties than it is now. We decided to give it a try for three years and if we did not like it, go somewhere else. We ended up liking it and stayed.
How was living in Basel after living in San Francisco?
In the very beginning, there were not that many positive sides and we were in a kind of a shock. At that time, there were like three official days per year when people moved apartments. We arrived just after one of these and it was challenging to find a good apartment. There were all these rules like not taking a shower after a certain time, which we were not used to coming from San Francisco. It was also within months of the Chernobyl explosion and the Schweizerhalle accident that polluted Europe and the Rhine, respectively. Things were bleak in the beginning.
You grew up in South America until age thirteen when your parents sent you to boarding school in New England. How was this transition for you?
That was a far bigger shock than moving to Basel. I was leaving my parents for the first time, moving to a country where there was winter and going from a completely carefree childhood in the tropics to a very regimented environment in that school. This changed me a lot and it was sort of an intellectual awakening because when I was growing up in the tropics, school was not that important to me. I did well in school, but it was more of a place where I met my friends. This idea of going to school to learn something and to acquire knowledge, and having a life of consequence … I did not think about these issues in the tropics as a child.
Did you encourage your children to become scientists?
No and I am not disappointed that they did not. My parents never pressured me to do anything and never said you should become a doctor or go into business, etc. Somehow, they had this deep-seated trust that I would find out by myself what I wanted to do. This is the same approach I have with my children. I want them to find their own interests to pursue.
You once said that the rational scientific approach can lead to difficult situations outside of science. Can you elaborate on this statement?
I think, as scientists, we do not get super happy when good things happen and also not very sad when things go the wrong way. We analyze and move on. In the real world, people want you to show emotions and, as scientists, we do not do that very much.
What was a useful career advice you received?
I cannot think of any explicit advice. I have many role models who gave me advice via how they behaved and handled things. My role models also changed during my career. My immediate role models were my advisors and as more distant role models I would name François Jacob and Jacques Monod.
What advice would you give young scientists?
My advice for anybody young is very cliché: follow your passion. However, that is not the hard part. The hard part is finding it. So, expose yourself to as much as possible, trying to figure out what you are going to do for the rest of your life. If you find what you like to do, your life will be a wonderful experience.
Throughout your career, did you notice the students changing?
Yes, they are less focused because there are more distractions in their lives. We did not have social media and smartphones and all these types of things, which add up and distract. To me, it seems that our human brains are not wired to handle all the distractions that are out there now.
I tell my graduate students that the phase that they are going through is the transition from a student to a professional. This big transition requires a high degree of dedication. To me, it is like a Buddhist monk going to the mountaintop to meditate until he achieves enlightenment. He is up there with no distractions and focused. This is the way I went through graduate school and I then stayed focused my entire life.
“Follow your passion. However, that is not the hard part. The hard part is finding it.”
What was one significant change in research you witnessed over your career?
When they sequenced the genome, this sort of took all the mystery out of biology to me, because then we knew the boundaries. We would never again isolate a gene which had not been seen before and would never discover a protein that had not already been known. When I was a student and you would isolate a mutant or a protein, it was something that had never been seen before and then you had to figure where it fit in the big picture.
Have you been tempted to have your genome sequenced to know more about your disease risks?
Yes, but not for that reason. I have been tempted from the perspective to know more about my family background. My grandparents immigrated to America and before that there is little family history recorded. It would be interesting to know what our roots are.
Another significant change in research was the development of CRISPR-Cas gene editing. Can you comment on the CRISPR babies?
I think this is a disaster and completely unethical. We need the trust of the public because the public finances our research. If things like this become more common, it will be hard to convince the public to fund science and funding science is essential.
How should scientists react in a debate when confronted with non-factual arguments?
You should never use a condescending or insulting tone of voice. This precludes being convincing. You have to be calm and go by the numbers.
Michael N. Hall obtained his PhD from Harvard University in 1981 and conducted his postdoctoral research at the Institute Pasteur in Paris and the University of California in San Francisco. In 1987, he joined the Biozentrum in Basel as an Assistant Professor, where he was promoted to Full Professor in 1992. He is a member of the U.S. National Academy of Sciences, the European Molecular Biology Organization and a fellow of the American Association for the Advancement of Science. For his scientific achievements, he received numerous prizes and awards including the Louis-Jeantet Prize for Medicine (2009), the Marcel Benoist Prize (2012), the Breakthrough Prize in Life Sciences (2014), the Canada Gairdner International Award for Biomedical Research (2015), the Albert Lasker Basic Medical Research Award (2017) and the Sjöberg Prize (2020).
Interview: Dominik Theler