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Dr. J. John Cohen

A Short Story

Mini-Med School

Teaching the Love of Killer Cells and Suicide Genes: J. John Cohen, MD, CM, PhD

Lecture titles like "Murder and Suicide in the Immune System" might prompt one to peg Dr. J.J. Cohen as a murder mystery writer, which he is. His research and publications opened up the whole field of programmed cell death studies. But Cohen's approach to work and life is anything but morbid. In fact, his real passion is bringing immunology to life for his Health Sciences Center students—and anyone else within earshot.

"Immunology is a hated and feared and dreaded subject at most medical schools," Cohen explains. "And it is very complicated," he concedes. Cohen's mission is to get students to see "the gorgeous beauty of immunology" and its organizing principles and to inspire them to read articles about the subject after earning their degree—in short to provide tools for lifelong learning.

Judging from the number of teaching awards he's won, his mission has been successful. His self-description as "an amateur teacher" notwithstanding, in addition to being a President's Teaching Scholar, Cohen has received dean's and chancellor's teaching awards, has won the Excellence in Teaching Award every year since 1982 (more often than any other teacher in the CU system), and has been named Teacher of the Year five times.

When asked to describe his teaching style, he immediately responds, "storytelling. I really think the human mind evolved listening to stories." In addition, he spends "a huge amount of time trying to think of working analogies. Analogies are incredibly powerful." To illustrate, he takes a set of keys out of his pocket and notes that all keys have a specificity part (the shaft) and a functional part (the head) that allows one to use the specificity part. "An antibody is exactly like that," he explains, with a specific and functional part, both of which must be operative to work properly.

Cohen holds strong views about who should teach large lecture classes. Perhaps because all his large classes at McGill University were taught by famous professors—he recalls being "spellbound" by Donald Hebb in Psych 100—Cohen believes that "only absolute stars should be teaching freshmen." Rather than making large courses "punishment," faculty should "earn their right" to lecture in the big halls, he says.

Among the largest classes Cohen teaches are those in CU's Mini Med School (see article at left). In addressing that highly diverse audience, Cohen employs a couple of general teaching principles that he claims all good teachers adhere to. "You have to start from the assumption that the people there are every bit as smart as you are, but their background is different." Then you determine how much new material they can absorb in an hour and present the one or two most crucial concepts in "ordinary English. But I don't pull any punches on the complexity of it. The worst thing you can do in that circumstance is talk down, because it's not justified."

A Born Scientist

Cohen always knew he would become a scientist. At age six he was "blowing up" his parents' basement with experiments. He landed his first hospital lab job at 11 and worked as a lab technician in Montreal during summers from age 12 through high school. A PhD and MD at McGill followed.

Although he thought seriously about becoming a clinician, "Sometime during my internship, I came to the conclusion that, over a lifetime, I could help more people being a researcher and a teacher than I could being a clinician. It was a very, very tough decision for me. I think I decided, as a clinician, that there wasn't anything that I could do that an awful lot of other people couldn't do, but that, maybe as a researcher and teacher, I could do something unique." And he has.

Cohen is most noted for his groundbreaking work on programmed cell death (PCD), or apoptosis. His lab has been studying the phenomenon continuously for longer than any other in the world. The first paper identifying the research area appeared in 1972. In 1980, the Scottish researcher Andrew Wyllie published a paper in Nature on a specific phenomenon of cell death in thymus cells from mice. Cohen thinks he may have been the only one who read the article. At the time, his lab was interested in why thymus cells die.

If Wyllie is the father of apoptosis, Cohen is the uncle. After seeking and receiving Wyllie's blessing to conduct follow-up studies on thymus cell death, Cohen and his team discovered that, at its daily peak concentration in the blood, cortisol, which is produced by our adrenals, will kill thymus cells. They wondered how the body could make a substance that's lethal and then realized that this phenomenon explained the huge turnover of thymus cells. Thymus cells, Cohen explains, have to be exactly right for an individual's system, but only about one percent of the cells that develop are right. All the rest are "either no good or downright dangerous, and they have to be killed." Once a day, the cortisol kills the inadequate thymus cells, leaving the survivors to mature into the T cells that control our immunity.

Cohen had serious difficulty publishing this theory in the beginning. "Everybody thought it was totally nuts, and it sounds nuts, but it turns out to be totally true, although it took 20 more years, practically, to find that out." The self-effacing researcher says he was "lucky to have a group of the brightest people on the face of the earth in the lab at the time," and they soon took the next step and discovered that cortisol itself doesn't kill the cells but that it turns on "suicide genes" in the cells. "Then we were hooked. We gave up everything else we were doing to follow that trail." Cohen's discoveries led to numerous other new ideas about cell death, including the hypothesis, proven by other researchers, that cancer is the manifestation not only of excessive cell growth but also of insufficient cell death.

Even after Cohen's lab discovered these "mind-boggling" principles in 1980, publications on PCD were rare, but their numbers grew exponentially during the late eighties, and by 1998, 25 new papers were published on the subject each day. Cohen's database contained 21,580 papers on PCD by the end of 1998.

Why is the study of cell death important? For starters, under normal conditions, approximately 25 million cells die per second, so it's a fundamental biological function. The phenomenon is also critical to understanding and treating many different diseases. Most serious chronic brain diseases, for example, involve abnormal cell death. "If one knew what the trigger was . . . one could figure out ways to interfere with it." The inverse situation—too little cell death—is implicated in cancer and probably other conditions and developmental disorders.

These days, instead of competing directly with larger, more heavily funded labs, Cohen's group uses a more adventurous approach, which has proven its merit: "We try to find areas in our field that aren't fashionable and develop them."

The People Behind the Science

Although he always knew he'd become a scientist, Cohen credits influential people more than innate ability with the successful development of his career. "My career and character has been shaped by memorable teachers and mentors," he says. "Without them you don't get educated."

First in a long line of mentors was Martin Hoffmann, the endocrinologist who let Cohen do research in his lab at age 11. Then, "by the best possible luck on the face of the earth, when I was a third-year medical student, I was assigned to the ward that he ran. He was feared because of his ferocity for truth. People were petrified of him, and I loved him because he pushed me as hard as he could. . . . The biggest sorrow of my life was that he died a few years ago, and I never got a chance to tell him how important he was to me."

Another mentor influenced his choice of immunology as a specialty. When Cohen had to decide what lab to work in as a graduate student, immunologist Max Richter invited him to join his team. Richter "seemed like an interesting, jolly guy to work with," so Cohen accepted the offer and "fell in love with the subject" even though "immunology was pretty boring back then."

CU emeritus immunology Professor David Talmage is another role model. "He taught me the most important thing, which was: It's not important who's right; it's important what's right."

Cohen remembers that Talmage, "one of the most visionary thinkers I've ever met," would come to meetings with postdocs and present a new theory of immunology, which the younger immunologists would critique. Talmage would accept their criticism and then come up with a new model. "He wasn't trying to show how smart he was; he was trying to get at what was right. And he didn't care if it was him who got the best theory. Most people say that he came up with the idea that won two other guys the Nobel Prize. . . . And Dave is the least bitter individual I've ever met in my life. And I think he's delighted that his idea turned out to be right. That's my idea of a real hero. I'm not as good as he is, but I would like to be."

Now that he is the mentor to graduate students and postdocs, Cohen says, "I care about their development as people as much as I care about their development as scientists." To that end, he tries to "create an environment in which they are comfortable and can work at the level they're happy working at. . . . I think the most important thing of all is to be comfortable, is to feel secure and valued, and you will do what you can do. . . . My lab is an extreme in that regard. I'm not trying to win marbles. I want people to be really happy and to have happy lives while they're in my lab doing science." He admits that some peers criticize him for not "toughening them up for the real world," but Cohen contends that one should be "scientifically aggressive but not at the expense of other people's happiness."

He also wants those who leave his lab to be good teachers and bemoans medical students' lack of opportunities for teaching and for learning about teaching. Most of his students, however, are capable of teaching a whole course on immunology, and, he says, "so far, most of them have, and I'm really, really proud of that."

Peg Squier, PhD, MD, who has worked as a postdoc in Cohen's lab for two years, says he is "just as good a mentor and boss" as he is a teacher. Squier says, "I've heard people say good managers bring in good people and then let them do what they do best. He does that, but he also keeps tabs on what's going on. He's more a team leader than a boss."

When asked to identify the most valuable thing she's learned from Cohen, Squier, who also wrote her thesis under Cohen's supervision, struggled to offer a single answer. "I've learned an awful lot, not just about science but just in terms of how to work in science," she began. "I think it's his approach to science and to working. He approaches them as a teacher and a student. He's always willing to learn new things." Even though he's a consummate lecturer, for example, Cohen invites critiques of his teaching that could improve it.

Squier sees that attitude in every dimension of Cohen's life, including interactions with friends and those he supervises: "Throughout his life, he's always teaching." Cohen's daughter Zoe provides yet another example of his penchant for sharing a love of science with everyone who crosses his path: She is working on a PhD in physiology with an immunology minor.

Cohen's respect for and support of peers, students, and postdocs inspire those around him to do their best at even mundane scientific tasks. In praise of Squier, he says, "She is so good, smart, loyal. . . . When we were between grants once, rather than tell me we had had to let our dishwasher go, she would sneak in on weekends to wash the dishes, so I never found out till years later." Such anecdotes unwittingly illustrate one of his most significant and natural talents: an ability to cultivate the community in that entity we call the "scientific community."

A Short Story

The first year CU offered the Mini Med School, the Health Sciences Center PR office sent a news release to local media. The day after an article about the MMS appeared in a Denver paper, 1,200 people called to sign up—triple what the school's largest lecture hall could hold and well beyond the "20 or so" people Cohen originally expected.

One prospective student was so disappointed that he called Cohen, who remembers a "tiny little voice" telling him that he'd wanted to be a doctor "all his life." The voice belonged to 12-year-old Jarrod Little. Cohen arranged for Jarrod and his mother to occupy the "house seats" he had at his disposal and then watched the boy, who sat in the front row at every session, furiously take notes.

This past December, Cohen received a certificate of appreciation from the University of Texas Medical School at Houston "in recognition of true interest and enthusiasm in the recruitment of able students to the field of medicine." Entering students had been asked to "nominate persons whose influence, encouragement and attitude directly and indirectly led to their consideration of medicine as a profession." The first-year medical student who nominated Cohen for the award was Jarrod Little.

Mini Med School

Fall 1998 marked the 10th anniversary of the Health Sciences Center's Mini Med School, which provides to the community a series of free lectures representing what medical students learn in their first two years. With assistance from his campus PR office, Dr. J.J. Cohen initiated the program, which has sold out every year.

On eight consecutive Wednesday nights, CU faculty present a lecture and take questions on one of eight fields of knowledge from the first two years of medical school: anatomy and physiology, cell biology, immunology, cancer, molecular biology, virology, pharmacology, and neurobiology. Cohen teaches the first four sessions listed.

Participants—who range from adolescents to seniors—include parents of medical students, prospective med students (roughly 20 percent), people related to medical professionals (10 to 15 percent), retirees (especially engineers), and individuals with medical problems. Cohen says, "It's probably the most interesting mix that I ever get to talk to."

Although many similar programs now exist, CU was the first school in the country to offer such a program, and Cohen is acknowledged as the concept's father. In 1996 he received the BankOne award for community service and the Colorado Healthcare Communicators Gold Leaf Award in recognition of his MMS work.

When asked what he gains from the MMS, Cohen immediately replies, "the pure plain fun" of it. "I love to teach. I'll knock people out of my way if there's a chance to teach," he laughs. Then he mentions the program's original goal: "to pay back the community for their support." (The original impetus for the MMS came from a desire to provide not just clinical outreach but also outreach that represented the campus's scientific activity.)

Another source of satisfaction is knowing the "incredible impact this has on the people who come. It's emotional for everybody." Take Marsey Kay, for example, a 1998 MMS student, whose father and grandfather earned medical degrees at CU. She says it was "one of the most influential and life-changing experiences of my life. . . . [Cohen] is not only a good speaker, a good teacher, but he put together a marvelous program. You could tell he spent a lot of time choosing the information to cover in these topics. Each one was a wower."

Program Director: Mary Ann Shea   360 UCB, Boulder, CO 80309-0360   Phone: (303) 492-4985   E-mail: MaryAnn.Shea@Colorado.EDU