Zebrafish and Cancer: What's the Connection?

Nancy Hopkins has made large contributions to the fields of developmental biology and cancer research. But her model organism, and to some degree her particular slant on molecular biology, were a matter of serendipity, as she relates to this MIT Museum audience.

When Hopkins was 10, her mother developed a form of mild cancer, terrifying to her, but also a catalyst for her interest in medical research. Later in college, after a lecture about DNA by James Watson, Hopkins realized that “the secret of life was being placed in front of you, that molecular biology someday had the potential to explain everything worth knowing: the meaning of life, why I looked like my mother...”

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After obtaining a Ph.D. in molecular biology, Hopkins was determined to enter the field of cancer research, although colleagues warned it would be the “end of my career.” Fortunately for her, Richard Nixon was just as energized about finding cures for cancer, and poured money into the field. Even better, scientists had begun to make some key discoveries about the source of some cancers. After years working on viruses and oncogenes, Hopkins “thought it would be fun to move on to something else.” On sabbatical in Germany to study the genetics of behavior, she encountered zebrafish in her colleague’s lab. The evolution of the zebrafish from fertilized egg to adult occurs in five days, and Hopkins found it a perfect subject for studying an organism’s early development.

In her own words, she came back to MIT completely obsessed with finding all the genes “that make things work properly” in the zebrafish. After years of painstaking study, Hopkins and her team figured out how to remove one gene at a time from the zebrafish (with its 20,000-25,000 genes), in order to understand what those genes did. She built 4,200 fish tanks with almost 100 thousand fish, and ended up with 550 mutant lines of fish.

Then “a funny thing happened to bring me back to cancer,” says Hopkins. A lab assistant noticed some fish were developing tumors. She screened 17 mutant lines and found a family of cancer genes that appeared comparable to a group of human cancer genes. This discovery may explain the genetic basis for other human tumors.

As she continues work with her fish, Hopkins embraces new and faster technologies to accomplish genetic screens, as well as better detection and imaging capability. “I look forward to the day when I can just sit at home and do experiments with existing data,” she says.