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Bigger of the “core” members whose labs are genes that may reveal how and why the based primarily at the Broad, leads the disease occurs and may also give When a first draft of the human ge- medical and population program, a guide for developing treatments. nome was sequenced in 2001, biology sud- which studies such genetic di≠erences. Psychiatric diseases, very few of which denly became much bigger. The — One of its key goals is to understand the have any known cause or mechanism, are three billion DNA “letters” long— genetic basis of complex diseases like dia- perfect candidates for genetic analysis. contains an incredible amount of data. But betes and heart disease. Altshuler, who Edward Scolnick, senior lecturer on ge- until recently, medical biology had been trained as a diabetes clinician, became netics, the former president of Merck Re- concerned with drilling down to the frustrated by the lack of knowledge about search Laboratories, has changed direc- finest details of how the body works. the disease’s origins. “So many of my pa- tion in his career to address this problem. With genomics, on the other hand, it is tients had parents and siblings and chil- Now, as director of the Broad’s psychi- now possible to get a wide-angle view of dren with type II diabetes, and we could- atric disease initiative, his goal is to human biology. “Fifteen years ago, we n’t explain it at all,” he says. “And it change the way such diseases are treated. thought of the human genome as this seemed to me amazing that in this era of The e≠ort focuses on schizophrenia and infinite, unbounded territory,” says Eric genetic information, we didn’t know what bipolar disorder, which seem the most Lander, a faculty member at MIT who is was causing it.” likely to be heritable. Scolnick says that also professor of at Har- Standard biology has been very good at knowledge of the biological basis of psy- vard Medical School and head of the explaining the so-called Mendelian ge- chiatric diseases is woefully lacking: at Harvard and MIT. “The netic diseases, in which inheriting a mu- “There is no chemical test or physical test rendered it finite, tated gene leads something in the body to or biological test that allows you to make just big. So now you can ask questions go awry. Complex diseases, however, seem a diagnosis of these diseases.” The best like, ‘What are all the genes that confer to be a messy combination of genes and way to get at the biology is through ge- risk for diabetes? What are all the muta- environment. No one gene “causes” a dis- netic studies, he says. “To really under- tions that might give rise to cancer? What ease like diabetes, but several genes might stand function you have to understand are all the genes that are essential to make put a person at higher risk for developing how the genes a≠ect that function.” a cell infectable by HIV?’” it in the presence of certain behaviors or Genetic studies on this scale have be- The Broad (the name rhymes with road) environmental factors. To tease out risk come feasible only in the past year, and the is a joint venture among Harvard, MIT, genes, researchers collect DNA samples first papers are just being published. It is the Whitehead Institute for Biomedical and clinical information from large groups likely that genomics will quickly shed Research (also located in Cambridge), and of people with and without the disease light on some diseases, while others may the Harvard-a∞liated hospitals that aims and look for statistical di≠erences in their remain a muddle of data. But the Broad to answer some of those big-picture leaders insist that, whatever the questions. “We have a really clear The Broad Institute’s outcome, science will benefit from a hundreds of staff mission,” Lander says. “We want to scientists and wide-angle view of the relationship fulfill the power of genomics for technicians work on between genes and disease. .” Announced in 2003 and genomics problems An ambitious application of that o∞cially launched in 2004, the best addressed by principle is the cancer genomics research teams. Broad focuses on interpreting the group, led by Broad core member information in the genome in a way Todd Golub, associate professor of that can be applied to human pediatrics. The group uses genomics health. It also serves as a kind of ser- to study and classify di≠erent types vice center for scientists at the two of cancers. This is not as simple as it schools who want to apply the tools sounds: part of what defines a can- of genomics and other large-scale cer cell is a genome that is irregular technologies to their own work. and unstable. Not all cancer re- Making the genome useful is a searchers believe it will be easy to much bigger task than sequencing make sense of erratic cancer it. The Human Genome Project pro- , but Golub says that it’s duced a single DNA sequence, but important to try. “Most cancer re- in reality there is no “one” human search involves finding a gene in- genome. For genomics to be useful volved in some aspect of cancer and to medicine, it must tackle the studying it in great depth,” he says. di≠erences among people that lead Entire careers are spent cataloguing one person to get a disease and an- every aspect of a gene’s function. “If other to avoid it. David Altshuler, that’s the only approach you take, associate professor of genetics, one there’s the possibility you don’t get

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the big picture. You see only the bits you and MIT access to its technical capabilities, lege of Cornell University—to further know about; there may be vast pieces of which are organized into “platforms”: facil- focus genomic technology on understand- information that remain.” ities specializing in techniques like genome ing and treating cancer.) sequencing, genetic analysis, and chemical The Broad currently has an operating By bringing together an impressive biology. Instead of relying solely on its budget of about $125 million, with most of array of technologies under one roof, the graduate students and postdocs for techni- its funding coming from the National In- Broad has created a new kind of resource cal skills, the Broad employs a dedicated stitutes of Health (NIH) and other federal for Boston’s biomedical community. Lan- sta≠ of research scientists to run its plat- sources. It has won major federal grants, der likens it to NASA’s Jet Propulsion Lab- forms. These scientists, who have no acade- including $14 million to identify common oratory in California, based at the Califor- mic duties, are wholly involved in collabo- genetic variations called single-nucleotide nia Institute of Technology. A grad student rative research with other researchers. polymorphisms (SNPs); $18 million to at Caltech may come up with an idea for Some scientists are concerned that cen- study heart, lung, blood, and sleep disor- sending something to Mars, but when it ters like the Broad promote a “bigger is ders; and $12.6 million to study cancer ge- comes time to build the rocket, she relies better” attitude that values massive data- nomics. About 5 percent of its budget on the expertise of the laboratory. “We sets and expensive techniques over de- haven’t got a tradition of that in biology,” tailed investigation. Although the Broad’s Lander says. “That’s what the Broad is. We studies are conducted on a scale beyond are trying to put jet rockets under smart what a single lab can accomplish, its lead- young faculty, postdocs, and grad stu- ers stress that they do not push “big sci- dents.” ence” over traditional investigator-led re- Until now, biology simply hasn’t had search. David Altshuler says that, “For many tools equivalent to jet rockets. But most kinds of research, the form that fol- in the past several years, the technology lows the function is probably what it’s al- available to biologists has become more ways been: the individual lab working powerful—and expensive. Genomic se- with the professor, because the problem quencers are the resource most people as- is best tackled in that way.” The Broad, he sociate with this kind of research, but said, is devoted to questions that are best other technologies also help to answer answered by teams working together. questions on a large scale: DNA “chips” can report which genes are turned on or Lander says that the vision for the Broad o≠ in a particular cell; RNA interference came from uno∞cial collaborations be- allows scientists to turn o≠ selectively tween scientists at Harvard and MIT that each of thousands of genes in a cell; and emerged while he headed the Whitehead “libraries” of chemicals let researchers Institute, a major center for sequencing quickly screen many di≠erent molecules the human genome. As the project came to to identify potential candidates for future a close, “this growing culture of collabora-

drugs. With automation, machines can tion was so powerful, we felt we needed a RICK FRIEDMAN perform in hours or days tasks that might way to institutionalize it.” The idea took comes from the two universities. The have taken an individual months or years. years to become a reality. Eli and Edythe Broad has also sought partnerships with The Broad’s leaders argue that a new Broad, who were funding a minor project pharmaceutical companies for some of its kind of organization is needed to enable at the Whitehead, made a chance visit projects. Whether part of a public or pri- researchers to access resources like these there on a Saturday and were impressed vate partnership, results of the Broad’s and answer the big questions that ge- by the buzz of activity and conversations work are all made publicly available. nomics poses. Traditionally, biology is or- going on. After many discussions with Though MIT handles the administration ganized into laboratories run by individ- leaders at Harvard, MIT, the Whitehead, for the institute, it is governed by both ual investigators and sta≠ed with and the teaching hospitals, they agreed to universities. The science community of graduate students and postdoctoral fel- fund Lander’s vision in Boston with a Boston and Cambridge is already collabo- lows—young scientists in training who $100-million founding gift, which was rative, and connections have been forged take on projects and then leave after a few later doubled. (As this issue went to press, among schools and science departments at years. Investing in new technologies is a the Starr Foundation of New York City Harvard, between Harvard Medical major e≠ort, so laboratories specialize in announced a $100-million gift to fund a School and its a∞liated hospitals, and be- certain techniques, but not in others. five-year consortium linking the Broad to tween Harvard and MIT. Some of these Often the large-scale questions go unan- four New York research centers—Cold connections are informal, some are “vir- swered, except by large centers that al- Spring Harbor Laboratory, Memorial tual” research centers, and some are educa- ready have the resources to address them. Sloan-Kettering Cancer Center, Rocke- tional connections like the Health Sciences The Broad o≠ers researchers at Harvard feller University, and Weill Medical Col- and Technology joint M.D.-Ph.D. program

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at and MIT. sociate members keep their full teaching zontal connector” cutting through the The Broad aims to take collaboration a and research responsibilities, but shuttle vertical structure of isolated departments step further. Its founders say it is both a between the Broad and their home insti- and institutions. Altshuler adds, “We are real and a virtual institution. Its sleek tutions, sometimes maintaining labs at not trying to create another silo in new building in Kendall Square provides both places. Memberships have two-year Boston, by which I mean an organization labs and o∞ce space where people from renewable terms, and members are ex- that exists for itself only. If the Broad be- di≠erent institutions can “work together pected to collaborate with others, attend comes a silo, it will be a failure.” cheek by jowl,” as Lander puts it. In addi- weekly program meetings, and otherwise The Broad’s team-based structure al- tion to its full-time sta≠ of 625 and six contribute to the Broad community. In re- lows young scientists to lead projects, core faculty members (expected to reach turn, Lander says, they are given only the and Lander believes this quality will de- 12 in the near future), the Broad has a net- right to propose collaborative projects. termine its success. Certainly many of the work of more than 100 “associate mem- With its private funds, the Broad main- Broad’s junior members have already bers” in the Harvard and MIT commu- tains an internal grant-making mecha- benefited. Three junior members, with nity, helping it reach beyond its walls. nism that can help researchers launch pro- help from Lander and the Broad, were Core members have faculty appointments jects without facing the onerous process able to collect $18 million to build a re- and maintain full teaching responsibili- of applying for grants from the National source for RNA interference, a new tech- ties at one or both schools; Lander, for in- Institutes of Health. These internal funds nology for turning genes o≠ in cells. Nor- stance, has been teaching MIT’s intro- can nurture early or risky projects until mally, a senior would be in ductory biology class for 15 years, and they can find support elsewhere. charge of such a venture. Stuart Schreiber, Loeb professor of chem- Forging an institutional marriage be- The collaborative approach is attractive istry, teaches organic chemistry at Har- tween Harvard and MIT was challenging to young scientists who like teamwork— vard. They also supervise undergraduate enough. But the Broad is also intended to though it challenges the traditional model and graduate students in their labs. New help bring together Harvard’s widely sep- of training in biology, which values well- core members are hired through academic arated science community. In July, a re- rounded scientists who do much of their searches with university or hospital de- port from the University Planning Com- work independently. Pardis Sabeti, M.D. partment leaders. mittee for Science and Engineering at ’06, for example, a postdoctoral fellow at The Broad solicits nominations for asso- Harvard noted how boundaries between the Broad who worked with Lander as an ciate members from department heads, institutions, schools, and departments in- undergraduate at MIT and won a presti- school leaders, or the researchers them- hibit collaboration (see “Sweeping gious Burroughs Wellcome Fund Award selves, and a group of 10 core and associate Change for Science,” September-October, after earning her medical degree, says that members act as a selection committee. As- page 71). Lander calls the Broad a “hori- Lander has created “this sort of can-do at-

Women are un- men in the same field to patent discoveries—an important pre- derrepresented cursor to commercialization. So concluded Waverly W. Ding Sciences and Gender in academic sci- (Haas School of Business, University of California, Berkeley), ence and engi- Fiona Murray (MIT Sloan School of Management), and M.B.A. neering, according to a report issued in September by the Na- Class of 1975 visiting professor of business administration Toby tional Academies, not because of a lack of talent or other E. Stuart, in research published in the August 4 issue of Science. intrinsic factors, but because of “unintentional biases and out- The authors found that male academic scientists have richer moded institutional structures” that hinder their advancement. networks of colleagues and industry collaborators, and that The report, “Beyond Bias and Barriers” (www.nationalacade- women scientists gain patents at only 0.4 times the rate of their mies.org), advocated changes in hiring, evaluation, and promotion equivalent male peers. Collegial support and institutional assis- processes, and support for faculty members who have family tance, they found, helped encourage women to seek more caregiving responsibilities—recommendations consistent with patents. The gap, the researchers also noted, is narrowing as those of Harvard’s Office of Faculty Development and Diversity younger women build more robust networks that lead to com- (see “Developing a Diverse Faculty,” September-October, page mercial connections for their work. 76). Among members of the committee that produced the report were Harvard Corporation member Nannerl O. Left to right: Nannerl O. Keohane, Barbara J. Grosz, Elizabeth Spelke Keohane, president emerita of Duke University and Welles- ley College; Higgins professor of natural sciences Barbara J. Grosz, who is also dean of science at the Radcliffe Institute; and Berkman professor of psychology Elizabeth Spelke. Consistent with that finding, a separate study revealed that women in academic life sciences are far less likely than FROM LEFT TO RIGHT: STEPHANIE MITCHELL; ROSE LINCOLN/HARVARD NEWS OFFICE

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mosphere, where everything is possible.” Boston’s scientific network, says Harold She explains that the Broad follows a Varmus, president of Memorial Sloan-Ket- collaborative, business-like model, in tering Cancer Center, former NIH direc- which people develop specialized skills tor, and a member of the Broad’s scientific and work together in teams. Sabeti, for advisory board. The institute is admit- instance, has developed techniques to tedly “operating on a scale that most of us identify areas of the genome that have would envy,” he adds, but there are other been honed through . centers around the world doing similar She also works with other scientists to work. But the Broad “has become a mag- analyze their data; for instance, she is part net…that seems very powerful at the mo- of a team led by Dyann Wirth, Strong ment,” he explains: collaboration between professor of infectious diseases at Har- Harvard and MIT is particularly useful be- vard School of Public Health and an asso- cause they have complementary re- ciate Broad member, that studies how the sources—Harvard has clinical expertise genome of the parasite that causes and access to patient information, while malaria varies around the world. The MIT has strengths in basic sciences and Specialized equipment and team, which includes Harvard and MIT computational science, which are needed techniques, arrayed on a large scale, members, was able to reach an answer to to make sense of large data sets. distinguish the institute’s operations. its question in a relatively brief eight Lander is characteristically excited months of collective work. about the potential for such a connection. gether, then the Harvard and MIT com- “If you can harness the diversity of exper- munity is just unstoppable,” he says. “It is What’s impressive is how the Broad tise by creating a community in which just the most powerful research commu- draws together the human resources of people are able to share and work to- nity in the world.” �courtney humphries

list. A single message can reach all of the THE UNDERGRADUATE subscribers in their House community. Se- niors laboring to find volunteers for their research can recruit and schedule subjects; event organizers can fill an entire Open for Business lecture hall or classroom with only a few keystrokes. By networking students with by casey n. cep ’07 like interests, these lists embolden their members. When a paper comes due or an exami- efore telegrams became Buried among their requests for stamps nation looms, students need only their scarce, the Japanese artist On and queries for directions, I suspect the re- house list to procrastinate. They can con- Kawara would send them with ality of a few hundred Harvard students tribute to an existing thread—as serious the message “I AM STILL who want the world to know they exist. as a debate on the Israel-Palestine conflict BALIVE.” Normally he would sign them House lists, as these open e-mail net- or as trivial as the e≠ort to revive Lobster with his name, and occasionally he would works are called, unite the residents of the Night in Harvard’s dining halls—or they vary their contents by replacing his stan- 12 undergraduate Houses in an immediate can initiate their own discussion by post- dard sentence with “I AM NOT GOING way. On the same day that freshmen re- ing some unlikely website or forwarding TO COMMIT SUICIDE.” Artists, cura- ceive their sophomore-year housing as- some provocative bit of news. The closer tors, and friends received them gratefully, signments, they also receive electronic in- one moves toward midterms or reading chiefly for the delight of knowing he really vitations to join their House’s open list, period, the more frequent the number of was “STILL ALIVE” and only secondarily, which enrolls them in an on-line commu- posts and replies. That same trend asserts I hope, for their future value as contribu- nity that often overshadows the physical itself in the hours after dark, when the tions to a conceptual project. walls that shelter them. The lists go dor- collective on-line activity of students still I think of Kawara’s telegrams and their mant in the summer, but during the acad- awake (despite their dwindling num- threadbare pleas for acknowledgment two emic year they receive 10 to 50 messages a bers) overwhelms the list. It is in the early or three times a day when I find e-mails in day. Publicity, procrastination, or pur- morning hours that one can expect to my in-box with the subject line “Pf- poseful pleas—these are the three princi- find ramblings mistakenly sent to the OPEN.” Surely the senders of those mes- pal reasons for posting to one’s house list. entire house list instead of the single re- sages wish only for the rest of Pforzheimer To publicize any cause or event, stu- cipient for whom they were intended, un- House to know they are “STILL ALIVE.” dents send virtual flyers to their house intelligible commentaries devoid of punc-

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