By Isha Jain ’12, thurj Staff

Harvard Medical School Professor George Church is what many would call ‘a renaissance man’ in the biological sciences. He has published papers in fields ranging from synthetic biology to sequencing technologies to bioethics, and he helped found the modern science of genomics. But aside from his groundbreaking research, he has also been advisor to 27 different companies. His latest endeavor is the Personal Genome Project, which involves sequencing the genome of 100,000 volunteers. Dr. Church sat down with thurj and told us about his life, his research and his views on science and technology in the genomics era.

Image Credit - Edge Research

Q: You have a strong background in both computer science and biology. How did these interests merge and develop?

A: When I was very young, I got interested in computers. It was really hard, because I wasn’t exactly in an intellectual hotbed. I would play with electrical parts that I could scrounge from construction sites. By 9th grade I managed to get into a better educational system. We had some sort of a toy network that connected Dartmouth to our high school and I learned a lot. I was constantly looking for a way that I could connect my interest in math and computers with biology and medicine. My freshman year of college I found the only guy who was working in biology in the computer science department. Sophomore year I found the only guy in the biology department doing work in computer science. I worked on solving the crystal structure of tRNAs. One of the programs I wrote was still in use thirty years later and is only now fading away.

Q: How did this lead to your later work with sequencing and the Human Genome Project?

A: At one point we wanted to know if the structure we had determined for our tRNA was applicable to the other ones that had been sequenced. I typed in all the nucleotide sequences of the known tRNAs and asked if they could fold up to fit our determined structure. I thought it was so cool that we could just type in the sequence of a tRNA and have it fold up. Then I thought, how cool would it be if we could type in the sequence of a human being and have people “fold up”?

Q: So you actually started thinking about the Human Genome Project at that point?

A: Yeah, it was a very vague and immature way of thinking about it. Looking back it was kind of visionary, but it was really just stupid at the time. So I started becoming obsessed with how we would actually sequence all this DNA. Sequencing struck me as very unsolved, but very solvable. At that time no one used computers in biology, except for maybe a little bit in crystallography or neuroscience. There was actually a bit of a sidetrack at this point that some people find amusing. I finished college two years early and then flunked out of graduate school. I was working so hard on the crystal structure of tRNAs. I figured I had already proven that I could take hard courses and do well in them; did I have to do it again? So, I flunked out of Duke and for some reason Harvard let me into graduate school.

Q: What kind of interdisciplinary projects are you working on now?

A: Probably the most interdisciplinary project we have is the Personal Genome Project. We have actually had to innovate in these fields. We got to the point that we needed a lot of holistic human data. Many previous studies had been very “tunnel-vision”: looking at this liver enzyme or this liver disease. By specifically recruiting people that are okay with public disclosure, We made a new paradigm in medical research.

Q: What criteria were involved in selecting the PGP10 (the first 10 experimental subjects of the Personal Genome Project)?

A: They were board members of genomic companies or a chief scientific officer or CEO of a sequencing instrumentation facility. The IRB (Institutional Review Board) wanted it to be very likely that they knew what they were getting themselves into by having published about genomics or made public statements. We wanted them to be diverse within that definition, so that if I was missing something, they could provide another set of advisers. There are certain things in science that you just can’t do yourself. One of the problems with the old way of thinking was that you would put your work in a vault and then only let the people who think the same way you do, see it. Maybe the person with the answers is a school teacher in England – not American, and with no scientific background. The most likely person to think outside of the box is the least likely person to have the credentials.

The PGP-10 From left to right, George Church, John Halamka, Esther Dyson, Misha Angrist, Keith Bachelder, Steven Pinker, Kirk Maxley, Rosalynn Gill, Stanley Lapidus, and James Sherley. (Credit: Personal Genomics, Inc.)

Q: Perhaps I could ask you about some of your other projects? Could you tell us something about your ‘aging project’?

A: We have been working on the aging project for a few years. We have one of the best comparative zoology databases. What we ideally want are two animals that are really close to each other in sequence but have very different longevities. Two species that have very similar sequences are the mouse and the naked mole rat. The mouse is an ideal human surrogate. It turns out that the typical mouse lives just over two years and the naked mole rat lives about twenty years. So what we are doing is taking big chunks of DNA from the mole rat and putting them into the mouse, replacing the mouse gene with the mole rat gene to see if we can increase its longevity.

Q: How direct is your involvement with businesses and companies, and what is your motivation for developing biotech products?

A: You can choose to just publish [your research] and hope that someone pays attention, which is increasingly not the case. In the early days of molecular biology, companies would make the enzymes for you [the academic researcher]. And then that wasn’t enough. So then the companies would make a kit for you. And then even that wasn’t enough. And eventually they would build a device that would implement the kit. This has made it easier for scientists to use a wide variety of tools, but you can’t always hide in the ivory tower. You need to make sure that you have enough control over whatever method you are developing, and work with a company to ensure they don’t botch it. You don’t want to micromanage your company just like you don’t want to micromanage your lab, but you do want to manage it.

Q: You have a very eclectic range of topics. How do you keep track of them?

A: Well, to me they all fit into one thing. There are a relatively small number of applications that make sense to me. For example, I say if you have to pick a disease, what is the thing that everyone dies of? When you are between the age of 20 and 45, not much happens to your body. It is only once you start aging that almost every organ system starts fading. Aging is really the fundamental problem and all the other things are just symptomatic.

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