An Amazing Week

I have been told many times, “It is amazing what people will do for you when you want to accomplish something.” For some reason, people tend to listen to what I say and go along for the ride. It is part of my personality to be extroverted and rally people around an idea. But I also try to be fair and listen to what everyone thinks before selecting the best way to move forward.

The idea to organize the International Society for Stem Cell Research (ISSCR) came about at a Keystone symposium on stem cells in 2001. The same group of scientists always attended these meetings, but because we were in different fields, we had little contact in between. I suggested we should have a society to bring us together and tackle some of the ethical, political, and educational issues surrounding stem cell research. At the first annual meeting of the ISSCR we had 700 members; 3 and 1/2 years later, we are up to 2200. I am absolutely happy with how it turned out.

That was the second community I worked to organize. In the early 1990s, I arranged several meetings to get the zebrafish genome initiative off the ground. I thought it was an essential step for establishing the zebrafish as a model organism. In both cases, there was a small group of labs training all the people in the field, and it was necessary for the groups to organize themselves for the fields to move forward.

Zebrafish was a huge risk when I started working on it. A lot of people told me I was making a mistake. I began studying GATA-1, a blood cell-specific transcription factor, as a postdoc with Stuart Orkin at Children's Hospital in Boston. After establishing my own lab in 1991, I looked for a system to determine how GATA-1 was induced in embryos, as a way to understand stem cell development. For 8 years I worked first in the mouse and then the frog. Then, in one amazing week, a number of events converged to take me in a different direction.

At a conference, one of my competitors suggested that zebrafish might be a good system for understanding the genetics of stem cells regulation. Upon my return to the lab, a scientist who had expertise with antartic fish asked to join my group on a sabbatical. At the same time, a friend from Harvard called me to say that he had a zebrafish mutant that could not make blood and asked me if I wanted to work on it.

In collaboration with Christiane Nusslein-Volhard, we started isolating several other bloodless mutants. But many questioned the relevance of the work asking, “How do you know fish make blood same way as humans?” Once we showed that mutating the gene for congenital sidero-blastic anemia in zebrafish resulted in an animal model of the disease, we figured that fish probably do make blood similarly to humans. But then people said, “We already knew about that gene.” So, we isolated a novel gene that encodes a protein that transports iron from the intestine into the circulation and found that mutations in the homologous gene in humans cause type-4 hemo-chromatosis. This was the first time that a gene identified in zebrafish had been used to predict a human disease. And in 2003, we identified another new gene that participates in the generation of blood stem cells during embryogenesis. Thus, it took us roughly 10 years to contribute something novel to the stem cell field using zebrafish.

We are now using zebrafish to find cancer stem cells. Part of the motivation for going in this direction is that my mother passed away from breast cancer when I was in medical school. I always thought that if I could find the right system to study the disease, I would do it.

What these experiences have taught me, and I try to teach my students and postdocs, is the value of taking risks. Too many people work on what is already known. I am also a big believer in establishing your own identity as an independent scientist. I don't think it is a good idea to continue the same work that you did as a postdoc.

I enjoy mentoring and take it seriously. The key is to recognize that everyone has a certain skill set and personality and to try to work with that. I tell my students and postdocs to use their skill set to be successful, and either try to bypass their flaws or improve on them. I don't expect them to do what I do. That would be unfair.

Outside of research and medicine, my main passion is music. I play with the Longwood Symphony Orchestra every Thursday night. It has been a great outlet for the ups and downs of research. When I was doing my undergraduate at Muhlenberg College, I played the trumpet 7 hours a day. But I knew enough to realize that there were many good trumpet players out there, and I was probably not going to be among the top ones. Instead, I thought medicine would allow me to contribute something truly unique. So I decided to enroll in medical school at Thomas Jefferson University. I certainly never suspected I would end up working on fish!