On a balmy day the thermostat in Nancy Hopkins’ lab in the Center for Cancer Research on the MIT campus is set to a temperature that is uncomfortably warm-for humans, anyway. It’s fine for the other occupants: minnow-sized striped zebra fish that populate the plastic tanks stacked against one wall. Around here, what the fish need, the fish get. Hopkins is fervent about the fish because she believes that they will repay her with something of immeasurable value: a fundamental understanding of life and disease.
Hopkins is one of a growing number of researchers who have begun using the zebra fish as a tool for studying the developmental biology of vertebrates. It is, in some ways, a departure from her scientific roots. Hopkins grew up professionally along with the field of molecular biology, eventually learning the ways of viruses in an effort to uncover the genetic underpinnings of cancer. Now she has traded in viruses for fish-an exchange that reflects her enthusiasm for genetics and for being part of the early stages of a new discipline.
While most zebra-fish researchers are searching for a handful of genes important to particular organs or systems, Hopkins’ team plans to pinpoint 2,400 of them-enough to build an entire animal. The project is ambitious, but Hopkins is no stranger to daring science. Her first mentor was the audacious co-discoverer of the structure of DNA, James Watson. Since her days as an undergraduate in Watson’s classroom and as a researcher in his labs, Hopkins has kept what she calls “impeccable scientific company,” working side by side with some of biology’s most influential players. Hopkins reminisced about the early days of DNA with TR Associate Editor Rebecca Zacks, and looked ahead to an extraordinary fishing expedition.
You were involved with molecular biology at its very early stages-was that more accident or design?
More age, I think. I was old enough to be there at the right time. I came in in 1963, 10 years after the structure of DNA was determined, and the genetic code was still being cracked. People were still trying to figure out what DNA triplet coded for which amino acid, and Jim Watson would come rushing into class waving triplets. At that time, we couldn’t imagine the answers to questions like what type of gene would the first cancer gene or oncogene be. Now we know some dozens of genes that can be cancer genes, but the very first time you find one out, your whole brain somehow changes, your world changes, the way you view nature changes.
I’d seen those changes come in the early days of molecular biology every couple of years. Generally the day somebody told you their experimental result, you knew that person would win the Nobel Prize. And they did, they always did. You could tell they would because your whole way of thinking was changed by that one instant. Now the discoveries fall more into a framework that’s familiar: Somebody gets another gene for another disease; it’s always fantastic and sometimes it’s very surprising, but it’s another one, not the first one.
Why did you make the transition from viruses to zebra- fish research?
I had the feeling that the field I was in had finished this first phase that had been super exciting, and the second phase didn’t fit as well in my lab. The possibility of applying genetics in the zebra-fish system-actually finding the genes that were responsible for developmental processes and for behaviors in a vertebrate animal-was something people hadn’t imagined you might really be able to do. I thought it would be fun to see whether one could make that possible, I was drawn to that.
What is your lab’s goal with the fish?
We have a very sharp focus, and it’s very big but very simple, very clear: We just want to understand how you start with a single cell and make an animal, that’s all. And we know that it is done by genes.
If you think about early development, you’re really talking about two processes: one cell becoming many (cell division), and how those cells organize themselves in three-dimensional space to make such an incredibly complex thing as a hand, a face, a brain, a pancreas. When the process of cell division goes out of control it becomes the process of cancer, and when the process of cellular organization goes awry you end up with birth defects. So if you could understand how genes allow development to occur normally and abnormally, you would understand life and illness.
We know that there are about 2,400 genes that are essential to make a normal zebra-fish embryo. If we have enough resources and enough energy, we’d love to get them all.