Biography of Nancy Hopkins BIOGRAPHY eneticist Nancy Hopkins, professor of biology at the Massachusetts Institute of G Technology (MIT; Cambridge, MA), has achieved unprecedented suc- cess in cloning vertebrate developmental genes by exploiting zebrafish as an ideal model organism. By using insertional mutagenesis, a technique pioneered in invertebrate animals such as Drosophila but long considered impossible to use in vertebrates, Hopkins’s laboratory has cloned hundreds of genes that play a role in creating a viable fish embryo. This research has earned her several accolades, including 1998 election to the American Academy of Arts and Sciences and 1999 election to the Institute of Medicine. Hopkins has gained addi- tional recognition for her revolutionary work on gender equity issues in science, including many awards and more than 400 requests to speak on the topic. GENETICS In 2004, Hopkins became a member of the National Academy of Sciences. In Nancy Hopkins her Inaugural Article (1), published in this issue of PNAS, she and her col- leagues describe 315 zebrafish genes es- about life,’’’ said Hopkins. ‘‘I also geneticist Mark Ptashne, a former sential for early development. Hopkins thought it was ultimately going to lead teaching assistant for one of Hopkins’s and members of her laboratory cloned to a cure for most human diseases.’’ classes at Harvard. these genes by using insertional mu- Hopkins quickly switched plans from ‘‘I couldn’t relate to the whole process tagenesis, and they estimate that they using applied science in medical school of just going to get a Ph.D. so you could have identified approximately 25% of to performing basic biological research. have some career. I was relating only to the genes essential for early zebrafish After the lecture, she raced to Watson’s solving particular research problems in development. The genes Hopkins’s team laboratory at Harvard to inquire about science,’’ she said. Regretful about leav- has identified not only reflect an ex- working there. For the next year and a ing Harvard, but heeding Watson’s ad- traordinary level of evolutionary conser- half, Hopkins finished her course work vice, Hopkins began a doctoral program vation from lower organisms, such as at Radcliffe while performing research at nearby Yale University in New Ha- yeast and Caenorhabditis elegans, but in Watson’s laboratory on bacterio- ven, CT. She soon found that no one at also they may play a vital part in identi- phage, a model organism considered to Yale was interested in isolating the re- fying the genetic basis for many human have the most accessible genes. Her pressor, which was then considered a diseases. work exposed her to many distinguished daunting task. Consequently, after a scientists who passed through the labo- year and a half, Hopkins left her pro- Masterful Mentors ratory, such as Francis Crick and Sydney gram without a degree to join Ptashne Hopkins was born in 1943 in New York, Brenner. Although women of Hopkins’s at Harvard and work as his technician. NY, into a family with several engineers generation were rarely encouraged to Ptashne successfully isolated the isotopi- and scientists; an uncle and a great un- pursue science as a career, Watson nur- cally labeled repressor about 6 months cle were both chemists, and another un- tured Hopkins’s interests and supported later (2). cle was an engineer. However, she did her strong scientific leanings. ‘‘He told Upon completion of her work with not seriously consider becoming a scien- me, ‘You should be a scientist. You Ptashne, Hopkins received a friendly tist until her undergraduate years at have a one-track mind, just like me,’’’ lecture from Watson. ‘‘Jim said, ‘Okay, Radcliffe College (Cambridge, MA), the she recalled. you’ve had your fun, now you have to go After she graduated from Radcliffe in formerly all-women annex of Harvard back to graduate school.’ The next day, 1964, Watson encouraged Hopkins to University. (Radcliffe College, now I was enrolled in Harvard,’’ she said. coed, is currently known as Harvard’s continue her education in graduate For the next several years, Hopkins con- Radcliffe Institute for Advanced Study.) school. However, she was reluctant to tinued to study the repressor, character- Fond of art, math, and science, Hopkins leave her friends and mentors in izing its properties and interactions with briefly considered architecture and med- Watson’s laboratory and the research operators. For her thesis, she used ge- icine as possible careers. Then, in her projects with which she had become junior year, she attended a lecture given deeply involved. At the time, her stron- by the famous geneticist James Watson. gest interest lay in a project to isolate This is a Biography of a recently elected member of the The topic of the day was DNA. ‘‘After 1 the lambda phage repressor, a protein National Academy of Sciences to accompany the member’s hour, I said, ‘That’s it; that’s going to that controls the expression of other Inaugural Article on page 12792. answer every question I’ve ever had lambda genes. The project was led by © 2004 by The National Academy of Sciences of the USA www.pnas.org͞cgi͞doi͞10.1073͞pnas.0405554101 PNAS ͉ August 31, 2004 ͉ vol. 101 ͉ no. 35 ͉ 12789–12791 Downloaded by guest on September 28, 2021 netics to define the operators that the she was recruited by Salvador Luria and though many of the mechanisms of can- repressor binds to, and then she isolated David Baltimore, and she shared an of- cer had been elucidated based on RNA DNA from operator mutants. Her re- fice with the newly recruited Phil Sharp. tumor virus research, findings by Harold sults showed that various mutations af- All three of these scientists were Nobel Varmus, Mike Bishop, and others had fected the repressor protein’s ability to Prize winners, the latter two for work shown that oncogenes, and not viruses, bind to DNA (3, 4). Hopkins completed done at MIT. However, instead of con- were the major cause of human cancers. her Ph.D. in 1971. tinuing her research on DNA tumor vi- ‘‘The field of the molecular biology of ruses, Hopkins changed her focus to cancer was clearly in good hands, and A Dynamic Career RNA tumor viruses, considered then to I wanted to make a change,’’ said The accessibility of genes in lambda be a likely cause of many human can- Hopkins. phage originally drew Hopkins to genet- cers. Such a career shift would be diffi- After months of consideration, she ics. However, as her studies progressed cult for a junior faculty member to decided that her new focus would be the she became interested in applying her make today; switching tracks could genetics of vertebrate behavior, a field knowledge of genetics to a larger prob- alienate familiar funding sources or that had long interested her but was lit- lem. Inspired by the fear she had felt lengthen the time to achieve tenure. tle studied at the time. ‘‘From the day I when her mother contracted a mild ‘‘But back then, funding was easier to first heard about DNA in that classroom form of skin cancer when Hopkins was obtain, I suspect, and, to me, the two at Harvard, the three problems I wanted a child, she decided that her next step viruses seemed very similar and similar to work on were control of gene expres- would be to research the genetics of ani- even to phage lambda,’’ she said. ‘‘Intel- sion, cancer, and behavior,’’ she said. ‘‘I mal tumor viruses. Because of recent lectually, a virus is a virus.’’ just hadn’t known when the latter two successes in studying bacteriophage Hopkins and her students set out to would become accessible. So I decided genes, a small group of scientists was determine what features influence the to go and see if the genetics of behavior confident that cancer genes could even- host range for mouse RNA leukemia might have become accessible by now.’’ tually be just as accessible. viruses, an important factor in under- To begin her studies, Hopkins searched By the time Hopkins completed her standing why viruses cause cancer. Her for a suitable vertebrate model. In a Ph.D. at Harvard, Watson had estab- early studies in this area were some of stroke of luck, she heard at a cocktail lished the Cold Spring Harbor Laboratory the first genetic research on mouse party at Cold Spring Harbor that Ger- in Cold Spring Harbor, NY, particularly RNA tumor viruses. In a pivotal article man researcher Christiane Nusslein- for studying tumor viruses. ‘‘I don’t (5), published in the Journal of Virology Volhard had begun genetics studies on think I ever talked to him about my in- in 1977, Hopkins and her colleagues zebrafish. terest in tumor viruses. We were just obtained evidence that the viral capsid Hopkins had been awed when she independently on the same track,’’ said protein p30 was the determinant of the read about Nusslein-Volhard’s previous Hopkins. However, when she decided to B- or NB-tropism of murine leukemia discoveries on genes necessary for early begin tumor virus research at Cold viruses, determining whether the viruses development in the fruit fly, work that Spring Harbor, many colleagues in the could grow well just on type B mouse eventually earned her the Nobel Prize in phage field advised her against it. ‘‘A cells or on both type N and type B cells. Physiology or Medicine (8). Sensing that number of people who were still work- The result was surprising, because host Nusslein-Volhard’s nascent zebrafish ing on bacterial viruses said, ‘Goodbye, range was commonly thought to involve research held the key to performing we’ll never hear from you again,’ be- proteins located on the surface of a vertebrate genetics, Hopkins went to cause they thought cancer research is virus; the p30 protein was known to Germany in the late 1980s to plan be- the end of people’s careers, it isn’t ready reside deep inside the virus particle.