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Lethal Chemistry at Harvard
Grad School Pressure

19 FEBRUARY 1999

Is graduate school too intense? Talk back in discussions.

Next Wave Editor's Note: When we read this piece in The New York Times last November, it struck a chord with those of us here at Science who have been through graduate school. We realize that not all of you may have had the opportunity to read it, so we're republishing it here on Science's Next Wave.

From: 29 November 1998, New York Times, Sunday Magazine Desk.
Except for one-time personal use, no part of any New York Times material may be reproduced by any mechanical, photographic, electronic process, or in the form of phonographic recording, nor may it be stored in a retrieval system, transmitted or otherwise copied for public or private use without written permission of The New York Times Permissions Department.

In death as in life, Jason Altom managed to be both extremely methodical and extraordinarily good-hearted. On the warm, humid day in mid-August when he ended his life, he walked up to the third-floor bedroom of the Somerville, Mass., house he shared with two fellow graduate students at Harvard University, drank a liquid laced with cyanide procured from the very chemistry laboratory where he was considered an unusually gifted student and lay down on his bed. Having accounted for the remote possibility that his own death might endanger others, the 26-year-old doctoral candidate left a warning note on the bed. ''Do Not Resuscitate,'' it read. ''Danger: Potassium Cyanide.'' As one of his roommates explained to me later, ''I think he was worried, in his meticulous way, that someone might try to give him mouth-to-mouth resuscitation.''

It is not for that note, but rather for the three suicide notes Jason left on the nightstand next to his bed, that his death has had reverberations far beyond Harvard. One was addressed to his parents, a second to the chairman of Harvard's chemistry department and the third to his graduate adviser, the Nobel laureate Elias J. Corey. Work in the chemistry labs ground to a halt that weekend as word of Jason's death swept through one after another of Harvard's 16 chem lab groups and then, by phone and E-mail, out into the tightknit international community of chemists, some 600 of whom had trained with Corey over the last half century. Any suicide is shocking, but this one was especially so: widely known and well liked, Jason was by all accounts the golden boy of the Corey group, perhaps the finest synthetic organic chemistry laboratory anywhere in the world.

The following Monday morning, Corey, a vigorous 70-year-old, delivered the devastating news to the department chairman, James G. Anderson. ''He was just shocked and dismayed and heartbroken,'' Anderson said later. ''I had never seen him so distraught.'' Four weeks later, the Altom family shared with The Harvard Crimson the contents of Jason's suicide note to the chemistry department chairman. The paper published excerpts in its Sept. 14 issue.

''This event could have been avoided,'' the note began. ''Professors here have too much power over the lives of their grad students.'' The letter recommended adoption of a three-member faculty committee to monitor each graduate student's progress and ''provide protection for graduate students from abusive research advisers. If I had such a committee now I know things would be different.'' It was the first time, a columnist for The Crimson observed later, that a suicide note took the form of a policy memo.

Like a raw, angry Rorschach blot, the notes inspired different interpretations in different quarters. Some graduates of Harvard's chemistry program volunteered the opinion that Altom's letter eerily and lucidly confirmed longstanding concerns about the pressures of the Harvard chemistry program in general and the Corey lab in particular. As every ensuing bit of coverage dutifully noted, it was the second suicide to hit the Corey group in less than two years and the third since 1980. Others felt Corey was being unfairly tarnished.

By the time I went up to Cambridge, the much-publicized suicide had already inspired a number of changes, including the three-member thesis committee suggested by Jason, a program of lectures to stress alternative careers for Ph.D.'s, more opportunities for social interaction between students and free confidential access to a therapist, with Harvard picking up the tab. The suicide note, in short, had catalyzed major changes.

But as I began to speak with Jason's friends and colleagues, I quickly learned that the situation was more complicated than the notes had implied. The people who knew Jason Altom best were as stunned and confused by the anger of his letters, which Jason's family later shared with them, as by his death. No one had had the slightest inkling that Jason felt unfairly treated by his adviser -- not the roommate who watched TV with him the night before his death, not the postdoc with whom he shared a lab (and who marveled at the amount of attention Jason received from Corey), not the six friends with whom he socialized during his five years in Cambridge, not the other roommate who furiously pedaled his bicycle home on a Saturday morning in August when he'd been told that something terrible had happened. That roommate, Andrew Black, could imagine a burglary, a fire, a calamity to another resident in the house, but never something to do with Jason. ''I can't tell you how shocking it was,'' he said.

If Jason's death may not have had much to do with the incendiary accusations contained in his letters, as many of his friends seemed to suggest, it was nonetheless inextricably linked to the pressures of graduate-school life -- not just at Harvard but at every top-flight university where competitive overachievers aspire to become scientists. And if it were indeed an avoidable death, the reasons may have less to do with the reforms already in place and more to do with chemistry of a different sort -- not the textbook chemistry of orbitals and bonds, but the more mysterious and nuanced kind between two extremely bright human beings locked in a typically intense graduate-school relationship.

Every year in October, when the Nobel Prizes in chemistry, physics and medicine or physiology are announced, the predictable parade of American honorees is reported on television and in the papers with a combination of patriotic glee and almost total befuddlement about the nature of the work being honored. Hardly anyone pauses to think about the educational system that has been so fabulously productive in turning out scientists in this country. It is a system limited to about 120 research institutions, and at the upper, rarefied reaches of that system are the elite universities. As James Anderson, chairman of Harvard's chemistry department, puts it: ''The students here are spectacularly good, very bright, very committed. They want to win Nobel Prizes, and some of them will, and some of them want to do it before they're 30.''

Graduate study in the sciences, however, is a very unsentimental education. It requires the intellectual evolution from undergrad who can ace tests of textbook knowledge to original thinker who can initiate and execute research about which the textbooks have yet to be written. What is less often acknowledged is that this intense education involves an equally arduous psychological transition, almost a second rebellious adolescence. The passage from callow, eager-to-please first-year student in awe of an often-famous faculty adviser to confident, independent-minded researcher willing to challenge, and sometimes defy, a mentor is a requisite part of the journey.

Harvard's Mallinckrodt Laboratory is one of the premier factories for producing outstanding academic and industrial chemists. The building stretches for an imposing length of Oxford Street in Cambridge, its formal entrance flanked by stolid white pillars, its double green doors topped by an entablature with all the modesty of a Federal Reserve bank. On its four floors, and in two adjoining buildings that form the complex of chemistry buildings at Harvard, corridors open on laboratory upon laboratory, reagents stacked on shelves, the ventilated work areas known as hoods constantly sucking fumes away, the entire building literally throbbing with ventilation. There are 16 professors with lab groups in these buildings, in organic and inorganic and physical chemistry, with expertise ranging from the composition of the ozone hole to the enzymatic reactions of creatures on the ocean floor. To people who have spent enough time here, each group has its distinct smells (depending on the chemistry being done) and each its distinct social tone (depending on the personality and style of the lab chief). At this level of achievement, there are no more A's for effort. As a sign in one lab had it: ''Don't Try. Do.''

The young people who walk through those green doors enter a world that has aspects both of a foreign country, with its own language and customs, and of Dante's nine circles of hell, complete with acrid odors and licking flames. In any given year, there are roughly 350 young scientists -- half of them graduate students, half postdoctoral fellows -- who toil in the buildings. For the five or six years it typically takes to acquire a Ph.D., time is both a burden and a gift. Aside from taking classes their first year, students have the freedom to pursue original research. Their monthly stipends, after taxes, amount to little more than $1,000 a month. They are expected to work 60 to 80 hours a week. ''If it's felt that you're not working hard enough, you feel that pressure more from the group than from your adviser,'' said Reed Konsler, a fifth-year graduate student and co-chairman of the chemistry department's Quality of Life Committee.

These pressures are not unique to Harvard. At the country's other elite graduate chemistry programs -- at the Massachusetts Institute of Technology, the University of California at Berkeley, the California Institute of Technology, Stanford University and the Scripps Research Institute -- the stresses are said to be comparable, but according to some experts, they may be getting worse. ''The life of the graduate student is so pressured because the future is so uncertain,'' said Dr. Edward M. Hallowell, a psychiatrist who took courses in chemistry at Harvard as an undergrad and is now on call to the university's chemistry department. ''Whether you're a graduate student in English literature or a graduate student in chemistry, there's no guarantee that you're going to be able to find a job. And then you add the self-imposed pressures of the students themselves. They want to win a Nobel Prize yesterday.'' In some fields of chemistry, the job market has never been better, but Hallowell argues that coping with the overall pressure has become more difficult. ''I think the kind of supports that used to be there for people aren't there anymore, like family and extended family and community and religion, so you get more isolation,'' he said, ''and isolation is the big enemy.''

In the fall of 1993, 43 students entered the graduate program in chemistry at Harvard. By happenstance, seven of them met at a department-sponsored ice cream social and became fast and lasting friends. Andrew Black, a broad-shouldered and genial Australian who loved rowing as much as chemistry, had arrived from Sydney. Rebecca Jackman and Curtis Keith, from Canada, knew each other from their undergraduate studies at McGill University in Montreal. Katie Queeney, a graduate of Williams College, had just spent a year abroad as a Fulbright scholar. Michael Grogan, a tall and deceptively droll Midwesterner, had studied at Notre Dame. Alexis Borisy came from the University of Chicago; he ultimately left Harvard in 1995 with a Master's degree, one of about 11 students from the class of 1993 who left school. And then there was Jason Altom.

He was exactly the kind of student Harvard and every other top-notch science department looks for: bright, outgoing, likably confident, intellectually mature, and with an inner reserve of self-reliance that is indispensable to any researcher working on the cutting edge. Jason was born in Oak Ridge, Tenn., the son of Donald and Dianna Altom. He attended the University of North Carolina with the intent of studying business, according to friends, but graduated in 1993 as one of its most accomplished chemistry students ever. With a long, narrow face and an engaging grin, he was known for his good sense of humor, the methodical way in which he threw himself into any task (including hobbies) and a taste for setting the highest goals and challenges for himself and the unrelenting drive to achieve them. He was the kind of person who attended to every detail, no matter how small, in both his science and his spare time: when assigning friends to bring wine for one of the wine-tasting parties he occasionally threw, he parenthetically provided the correct pronunciation of ''chianti.''

Every fall each laboratory in Harvard's chemistry department holds an open house for the incoming graduate students, a high-end version of a fraternity rush. There is always competition to get into the hot lab each year, and the exercise often provides graduate students with their first taste of the mythologies that pervade life in the lab. Among them is the phenomenon known as ''back pressure,'' where graduate students want to be in labs with a constant influx of new students, since it puts pressure on the lab to push out Ph.D.'s in a timely fashion. By December of the first year, graduate students have often made perhaps their most fateful decision: deciding on a faculty adviser, the person who will dominate their lives for the next five or six years.

More than most chemistry departments, Harvard's has the reputation for having a very autonomous faculty. ''The way it's set up at Harvard, notwithstanding these recent changes, your primary adviser was solely responsible for deciding when you graduate,'' said Thomas James, who received a Ph.D. in chemistry from Harvard in 1995. ''That gave the adviser inordinate power over the graduate student's life. They hold your paycheck in one hand and your letters of professional recommendation in the other, and in academic chemistry, letters of recommendation are everything. At Harvard, the message that's sent loud and clear is that one person decides when you graduate and what your prospects will be.''

There is courtship on both sides, of course. Working with a Nobel laureate or a rising young star is not only scientifically exciting, it can also burnish a student's future prospects. So students strive mightily to impress their mentors, and sometimes they never stop. On the faculty side, advisers seek gifted and motivated students -- they are the ones, after all, who do much of the science in the lab. For junior faculty members, the quality of their graduate students might make the difference between getting tenure or not. So while students have the illusion of choosing, it is the advisers who ultimately make the choice.

Yet for all the weight this relationship must bear, it is often arranged on a limited amount of information -- not exactly a mail-order marriage, but close. And the fundamental inequality in power between an adviser and a student requires responsibility and even psychological astuteness on both sides. The graduate student is agreeing to be pushed to his intellectual and physical limits by someone he barely knows.

By the beginning of 1994, after only four months of graduate study, the students in Jason Altom's class chose which adviser they wanted to work with. Jason and another member of ''the Seven,'' Michael Grogan, were two of three new graduates students accepted that year into the laboratory of E.J. Corey.

'E.J. Corey is one of the most important chemists of our century,'' says Peter Dervan of Caltech. Born in Methuen, Mass., and educated at M.I.T., Corey is one of the most prolific organic chemists of this century. His area of specialty is synthetic organic chemistry -- that is, developing new reactions and building naturally occurring chemical compounds from scratch. In the course of a career whose productivity is almost without precedent, he and the members of his lab have synthesized more than 100 naturally occurring chemical compounds, many of them with significant medical or industrial implications. ''He was born brilliant and he'll die brilliant,'' says A.I. Meyers of Colorado State University. ''I would rank him as one of the two or three greatest scientists in the century, and the entire pharmaceutical industry has been living off his chemistry for years.'' The extended family of Corey group members has published, by one estimation, a phenomenal 100,000 scientific papers.

In the mythologies that germinate and spread among graduate students, the Corey lab had the reputation of being predominantly male, extremely hard-working and very traditional. (Corey was said to discourage listening to anything other than classical music in the labs.) Corey's office, at the end of a long corridor running along the south wall of the Conant Laboratory, was behind a blue door that was often closed. If you wanted to speak with the lab chief, according to former students, you would knock on the door and take your cue from a pair of red and green lights beside the door frame. Despite the unusual traffic signals, Corey also had the reputation of being very accessible.

Even his most unforgiving critics admit Corey is a gifted chemist with great intuition, passionate about science above all else, caring and loyal toward students who show the same passion; but even his most unabashed admirers admit that his lab is an intense place. ''It is stressful,'' says K.C. Nicolaou, a chemistry professor on the faculties of both the University of California at San Diego and the Scripps Research Institute. ''To do a Ph.D., very infrequently does one have a pleasant ride all the time. But I would do it all over again with Corey. He's a great mentor.'' Meyers agrees: ''He is just an incredibly bright guy, and he expects everyone around him to perform at a similar level.''

A stressful environment is, at some level, precisely the desired effect: serving to separate those who have the emotional as well as intellectual toughness to become scientists from those who don't. The problem, according to a former graduate student who asked not to be named, was that Corey cares so much that ''he doesn't realize the emotional effects of his driving. When you're a professor, you're not just doing research,'' this student said. ''You're dealing with people during a very difficult transition in their lives. In the Corey lab, those things don't come into the calculation. It's just chemistry.''

Despite the angry insinuation of Jason's suicide notes, however, there is one thing upon which everyone agrees: Jason never expressed those sentiments in life. ''To Jason, E.J. was like God,'' said Rebecca Jackman. ''I think E.J.'s was the only opinion about chemistry that mattered to Jason,'' said Katie Queeney.

By their second year, graduate students have usually selected a research problem. Jason wanted to pursue an academic career at the highest level after receiving his doctorate -- an ambition whose soaring trajectory is always pointed into an uncertain future. So he felt he needed an especially ambitious research project. Corey suggested several possibilities, but Jason surprised his adviser by asking him for an even more challenging project. Corey suggested the total synthesis of a molecule called haplophytine.

Once they choose a research project, graduate students essentially fend for themselves -- there are no courses, no tests, no timecards, no guardrails. ''When you leave Harvard, you better be prepared to perform in the outside world as a scientist,'' said James Anderson, the department chair. ''Students will feel that in the early stages they aren't getting the guidance. But if you ask them two or three years into their postdoc what it was that they valued most, quite often they say: 'Well, I really was introduced to what it meant to do independent science. Thank God I wasn't treated like a hothouse plant, because if I was, I would have failed miserably as a postdoc.'''

In scientific research, whether chemistry or molecular biology or physics, the graduate student's journey from ignorance to expertise is like a trip without a compass. ''In my experience, it's completely self-motivated, and there are no landmarks in the landscape,'' said Curtis Keith one day over a soda in the Greenhouse, a student cafeteria in the Science Center across the street from Harvard's chemistry labs. ''There are no rewards along the way, no stages when you get evaluated. It feels like there's a long period where you don't have any landmark to see where you are.''

As they spiral deeper into the well of intellectual inquiry, students become especially susceptible to a kind of hearsay mythology about the system, about lab chiefs, about potential calamities -- mythologies that retain their power, one former student remarked, precisely because they are rooted in at least partial truths. At Harvard, they heard stories about the student who had spent five years in one lab before being told he wouldn't be receiving his Ph.D. They heard the story about the fifth-year graduate student who decided to go to medical school; his adviser barely spoke to him after he announced the decision. They spoke of ''submarine science,'' in which graduate students feel obliged to spend their days doing experiments suggested by their adviser -- even if they are certain they won't work -- and wait until after hours to try what they wanted in the first place.

In some labs, they even resorted to little tricks to impress the lab chief. The extra jacket on a hook in the lab, so it looked as if you were around even if you'd gone home. Having someone open your lab door and turn on the lights in the morning, so it looked as if you were already in. Putting a stirrer -- a magnetic object that stirs liquids together -- in a flask, so it would look as if you had a reaction going on. One student told me he never left a note to a fellow student open on the desk, because it might suggest you weren't around; notes were folded over, with an X on top, to indicate there was a message within.

But perhaps the biggest problem at Harvard, and probably at a lot of other institutions, is that graduate students felt they had limited interaction with faculty members. In 1995, David Evans, then the department chairman, invited the student Quality of Life Committee to propose changes that would improve monitoring progress toward a degree. The students responded in November 1995 with a detailed proposal recommending that each student should have a committee of three faculty members following them during their graduate-school career.

The faculty discussed the proposal at a meeting but did not institute any changes. The students were ''pretty disappointed that it was clearly not a priority,'' said Katie Queeney, a former member of the committee. But they also realized that mentoring is not the reason faculty get tenure at major research institutions like Harvard. ''Science is what they're hired for,'' said Kateri Paul, current co-chairwoman of the committee, ''and science is what they're admired for.''

But perhaps the most striking paradox is that two of Jason's closest friends, Rebecca Jackman and Katie Queeney, were leading figures on the Quality of Life Committee pushing for those reforms. Yet the first indication that Jason shared their concerns, they said, came in the suicide notes.

Room 318 is long and narrow, with a long black-topped table top, or bench, running along each wall, one for each student. This is where the hours, the days, the years, the Friday nights and the holidays all disappear. This is where Jason spent most of the last five years of his life.

No more than 10 paces from Corey's office, the room opens on either side of the doorway onto two hoods -- the hearth of a chemistry lab, as it were, where large, round-bottomed flasks, boiling furiously with a dark broth of reagents, send vapors up long glass condensation tubes to the small flask -- about the size of a decorative light bulb -- in which the solvents used in the synthetic reactions that win dissertations and tenure-track jobs are collected. In the popular imagination, chemistry is the province of goggles and Bunsen burners, but in the creative precincts of synthetic organic chemistry, it is more like doing sculpture on an atomic scale.

Haplophytine, the molecule Jason Altom chose to synthesize, is, in the words of his lab mate, ''an obscenely complex compound.'' It is a potent insecticide made by plants and was the subject of intense research during World War II. Haplophytine is actually two smaller compounds joined together. ''So it was a really tough challenge,'' explained Brian Stoltz, the postdoc who shared a lab with Jason. ''Either one, to me, would have been tough. To make both of the parts and then stick them together was even harder.''

The strategy for synthesizing complex organic molecules was one of the reasons Corey received a Nobel Prize in 1990. As Stoltz explains it: ''You look at a compound from the start, and then you think, in a backward sense, how you'd put the compound together. That's called retrosynthetic analysis. You can't run reactions backward, but you can do a logical disconnection, step by step, until you get to readily available starting materials.'' Jason's path was not without some initial bumps, but the work proceeded steadily. He had divided the total synthesis into two smaller parts, and by the spring of 1997, while many of his colleagues were struggling, he had already achieved a coup by completing one of the subunits. ''Jason's synthesis was very elegant and very quick,'' said Stoltz. ''And it worked. From the day he completed the first half, two years earlier, he had the option to write it up as his thesis.''

But that wasn't good enough for Jason. ''He felt it was necessary to complete the molecule,'' Michael Grogan, his roommate and fellow group member, told me, ''in order to be certain that his graduate career would be recognized as notable, to be certain that he could do what he wanted to do with his degree.''

Even when the work was going reasonably well, there were signs that Jason held himself to almost impossibly high standards. He came into the lab around 8 or 9 in the morning, and often didn't leave until 10 at night. He pursued several outside activities, like running and wine-tasting and salsa dancing, but he almost seemed to strive for enjoyment. He good-naturedly endured the teasing of his roommates when he went through a familiar ritual before going out on a date. ''If he went out,'' Black recalled, ''he'd spend days planning the whole process -- where they'd go for dinner, what they'd do after dinner. He'd be saying, 'It's gotta be fun.' He was really sort of methodical about having fun. It was rare, if ever, that he went out and did something for the hell of it.''

Then, one day in February 1997, Jason was shocked by a sudden, violent event in the Corey lab. While Jason was still working on the first half of the molecule, a first-year graduate student from Hong Kong named Fung Lam was found unconscious in a room adjacent to Room 318; he died two days later. Known as ''Mike,'' Lam had joined the Corey lab less than two months earlier. His death was later ruled a suicide, and several students claimed he used potassium cyanide.

Jason seemed morbidly interested in Mike Lam's death, according to his roommate Andrew Black, and discussed its details at great length. ''I was really worried about Jason around that time,'' said Black. ''He went out and bought a book with a title something like ''Understanding Depression,'' so he might recognize the symptoms in somebody else better. But it turned out more to be a book about how to recognize depression in yourself.'' Most of the Seven had some outside passion to balance their intense lives in the lab. Andrew Black had his rowing, Katie Queeney had her book group, Mike Grogan liked to cook and give dinner parties and several had relationships to go home to. Curtis Keith had a different, more sobering distraction; his father had developed a terminal illness, and he'd made frequent trips home to spend time with him.

According to The Harvard Crimson, Lam had returned from a lecture by Corey shortly before his suicide. Corey expressed his sorrow in a 1997 interview with The Crimson, but it is another remark from the same interview that struck me as emotionally oblique. Corey had inspected Lam's lecture notes after his death, according to the story, and felt it was important to note that they were ''beautifully done.''

Sooner or later, at some point in virtually every young scientist's career, he or she hits a wall. ''Frustration is a huge part of research,'' James Anderson explained, ''and that's never described adequately.'' For a while, it seemed Jason was charmed never to find that place. In February of this year, he completed the synthesis of the second part of the molecule. Not quite five years into his graduate work, all that separated Jason from the goal of a total synthesis was a single bond. But bringing the two parts together meant solving the most difficult part of the problem -- forming a bond with what's known as a ''quaternary carbon,'' a carbon atom with highly complex, tightly packed structures surrounding the bonding site.

''There are not a lot of ways to do that,'' Brian Stoltz told me. ''You have two pieces you're trying to put together, and there are a certain number of things in the toolbox to try. They didn't work. The toolbox is empty. So then you have the toolbox in the brain. Every day we sat down and thought about different strategies, Jason with me, Jason with other people in the laboratory, Jason with Professor Corey. I don't know how many reactions he tried, but it was a lot. A couple hundred maybe. Always trying to make that bond.''

And always failing.

Months passed without success. At one point during the summer, when a reaction went bad and turned brown, Corey popped his head in the lab and, according to Jason's friends, made the suggestion that all the compounds in the black tar needed to be analyzed. Without the slightest bit of irony, Jason printed up a large sign -- ''Characterize Everything,'' it read -- and attached it above his desk. ''To me, it was just bizarre that he would do that,'' said Andrew Black, who saw the note in Jason's lab one day. ''It was like he was chastising .himself about not being diligent enough. But it was odd, because no one was more diligent and methodical and precise than Jason.'' Yet following a July 19 meeting with Corey to discuss his future, Jason told both Brian Stoltz and Mike Grogan that he had his adviser's full support.

Toward the end of July, Jason tried the umpteenth permutation of the reaction to make the last bond. For one brief moment, it looked as if he might have gotten over the hump, recalled Brian Stoltz, who was in the lab at the time. ''We both sat there and looked at the data,'' said Stoltz, ''and we thought it worked. It looked like we had it.'' Jason immediately reported the news to Corey, but like the good scientist he already was, he ran further tests on the compound. In the parlance of chemistry, it was ''behaving peculiarly,'' and by Aug. 1 he discovered that an unwanted bond had formed.

''I think that was certainly a low day,'' Stoltz said quietly. ''To think you have the solution to your problem, and then to figure out that you don't -- that's pretty frustrating. He dealt with it the way you deal with these things -- you start thinking about another solution. But in general, he must have been very good at hiding his emotions.''

On the Saturday he discovered the mistaken coupling, Jason, extremely distraught, phoned his parents in Tennessee. ''There was a clear concern that he had misidentified the compound and had provided misleading information to Professor Corey,'' Donald Altom said in an interview. ''He didn't know how to discuss that with Professor Corey.'' He was so upset, according to his parents, that they considered traveling immediately to Cambridge, but when he seemed better during a phone call the following Monday, Aug. 3, they felt that he was going to be O.K.

At some point in his last two weeks, his friends now believe, Jason's sense of self-worth became inextricably entangled with making that final bond. ''That's the lonely place you end up in when your experiments aren't going well,'' Kateri Paul said. ''There's no one to talk to. It's just you and the molecule.'' In his suicide note to Corey, which several friends read, Jason implied that Corey told him he had made ''no intellectual contribution'' to the haplophytine project, even though Corey remained optimistic that the final coupling could be made. Still, he seemed to feel that he no longer had Corey's respect.

In the last week, his frustration with the elusive bond was apparent to all his friends. But if Jason was experiencing an unhealthy loss of perspective, no one noticed, and Corey -- for all his fabulous chemical imagination -- may have been the last person to see that Jason was on the verge of exhaustion. Corey did what he always did, which was to make suggestions and then ask what happened, and Jason did what he always did, which was to act on Corey's recommendations first. On the Thursday evening before his death, while munching pizza at a department function, Jason told Kateri Paul that he thought he might have found a solution to the haplophytine problem but felt obliged to pursue several of Corey's ideas first -- even though, he told Kateri, he didn't think they would work. Corey was checking on his progress twice a day, he said. ''If I drop a reaction on the floor or do the mental equivalent,'' he told her, ''I'll have to bust my butt to have something to say.''

Mike Grogan was the last person to speak with Jason. They had watched television Thursday night; at no point did Jason give a hint of the turmoil he was experiencing inside. ''I had a short conversation with him about what we were up to that day,'' Grogan recalled. ''He seemed tired and unsettled. I was concerned for him, but not at the level of clinical depression or suicide.''

The following morning, Jason called Grogan in the lab around 10 or 11 o'clock from home; members of the Corey lab were expected to turn in six-month research progress reports on Saturday, Aug. 15, and Jason typically stayed home to write them up. There was nothing unusual about that, his friends say, nor any particular stress attached to the task.

Jason made what turned out to be one last request of his roommate and fellow member of the Corey group. Perhaps out of habit, or perhaps out of a pathology of seeking approval that had become reflexive, he asked Mike Grogan to open the door of his lab and turn on the lights, so it would look as if he was in and working.

The question I kept asking Jason's friends was this: Even if the reforms suggested in his suicide note had been in place and there had been a committee mentoring him, might they have prevented his death? I wasn't entirely sure, and neither were some of his friends.

''It's not clear that it would have,'' Mike Grogan told me. ''I think he misunderstood his situation. I can't tell you why, but I think he did.'' Andrew Black said later: ''There was no real communication between them to make sure what the reality was. Neither of them understood the other beyond the science. Their relationship was wrapped around the science and nothing else.''

''Any time there's a situation like this,'' said Donald Altom, ''we feel there's a communication problem somewhere. We do not hold Professor Corey responsible per se. We think something went awry.''

Even E.J. Corey, who finally consented to an interview after declining several requests, admitted, ''I feel badly that I didn't know more about Jason's background and his day-to-day life.'' We spoke in his spacious, sunny, book-lined office on the third floor of Conant Lab, a plaque on one wall commemorating his Nobel Prize and numerous sticklike models of chemical structures appended like talismans to the bookshelves. When the subject was science, a smile came quickly to his face, but when it turned to suicide, he became guarded, his arms tightly crossed. Like everyone else, he insisted that he'd had no idea of the depth of Jason's distress.

''I would have done everything conceivable to help Jason if I had had any inkling of his problem,'' Corey said in his plain, soft-spoken voice. ''But I didn't. He was the last person in the world I would have expected to commit suicide.'' He recalled, by date and context, many of his extensive last conversations with Jason; described with evident pride his student's ''beautiful'' partial synthesis of haplophytine; remembered how he'd even asked Jason and a few other students from the lab to help him rescue a family cat from a tree at his home one Sunday afternoon in July, barely a month before the suicide. ''If he had troubles, personal troubles,'' Corey said, ''why wouldn't he seek help from me?''

One possible reason, I suggested, was the widespread atmosphere of fear I had encountered in the chemistry building. Almost every student I interviewed for this story was concerned about being quoted by name, even for the most generic or neutral remarks, and when I asked why, the answer was always the same: they weren't sure how their graduate advisers would take it, and it might affect their careers. Corey said he felt he had a partnership with his students that overrode constraints in communication, but as even he admitted, ''Because lines of communication are there doesn't mean there will be communication.''

In the end, despite all his scientific imagination and insight, Corey was no less confused than anyone else. ''The more I think about it,'' he said, ''the more helpless I feel to understand it. It's beyond my comprehension.''

Copyright (c) 1998 by The New York Times Company.

Reprinted by Permission

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