Scientist’s work at Jackson Lab lauded

Posted Aug. 31, 2009, at 10:25 p.m.
Last modified Jan. 30, 2011, at 11:57 a.m.

Doug Coleman never meant to stay in Maine for 51 years. The plan, back in 1958 when he arrived at The Jackson Laboratory in Bar Harbor as a newly minted Ph.D., was a year or two at most.

“I thought I’d learn what I could, pick up a few things about cancer and genetics and immunology, then move on,” recalls Coleman, 78. “But now that I look back on it, my work couldn’t have been done anywhere else.”

That “work” at Jackson Lab — accomplished during a remarkably innovative period of research with fat laboratory mice back in the 1960s and early 1970s — is now internationally recognized as key to modern understanding of the biology of obesity and diabetes.

On Oct. 7 in Hong Kong, Coleman will put on a tux and accept the 2009 Shaw Prize in Life Science and Medicine, awarded “in equal shares to Douglas L. Coleman and Jeffrey M. Friedman for their work leading to the discovery of leptin, a hormone that regulates food intake and body weight.”

The prestigious prize, widely regarded as the “Nobel of the East,” carries a $1 million award and jointly recognizes the achievements of Rockefeller University’s Friedman, whose groundbreaking obesity research in the mid-1990s built on Coleman’s discoveries of two decades earlier.

Retired from the laboratory since 1991 with the title of emeritus professor, Coleman has been recognized with other top honors, including election to the National Academy of Sciences in 1998 and the 2005 Gairdner Foundation Award, an annual prize for research achievement by Canadian scientists.

The road to Jackson Lab

It’s a long way from Hong Kong to Stratford, Ontario, where he was born during the Depression. The only child of hardworking English immigrant parents who didn’t finish high school, Coleman tinkered with a chemistry set and pondered how things worked and what they were made of. But he never dreamed of spending his entire working life in the lab.

“My career was not a straight path; there were a lot of forks in the road,” Coleman said during an interview this summer. “But I took the right forks most of the time.”

One of those forks led to McMaster University in Ontario, where he fell in love with biochemistry and with his future wife, Beverly, “the only girl to graduate in chemistry in the Class of 1954.” After graduation, the couple headed to the University of Wisconsin at Madison, a “mecca of biochemistry” where he earned his doctorate in 1958.

He heard about the job at Jackson Lab from Andrew Kandutsch, a Wisconsin alumnus and fellow biochemist who then was working in Bar Harbor with George Snell, the pioneering immunologist who went on to win the Nobel Prize in 1980.

The Colemans moved to Seal Harbor on Mount Desert Island for their anticipated short stay, only to put down roots there for the next 28 years, raise a family of three sons, and charm their Maine neighbors as “the new folks from Canada.”

Jackson was “a marvelous place” in those early years, “a stimulating environment for a young person to come into,” he says. Fully recovered from the devastating fire of 1947, the laboratory had a tight-knit, colorful staff that included Snell, director Earl Green and his scientist wife, Margaret, and geneticist Elizabeth “Tibby” Russell. Founder Clarence Cook Little, who retired in 1954, was still a regular presence.

“All the disciplines rubbed off on each other,” Coleman says. “In a university, you’d be isolated in a department. But at the lab, I had collaborations with almost everyone on the staff. It was just so smooth and intellectually stimulating, not so competitive and technology-driven like it is today.”

Hands-on researcher

Coleman already was exhibiting the traits that would characterize his research style and lead to his success in the developing field of biochemical genetics. There was the bulldog pursuit of answers, the facility for identifying unknowns. “I could focus on the meat of a problem, I could get there fast,” he says.

There was the hands-on approach to laboratory research. Coleman was a self-described “loner” who conducted most of his own experiments, in contrast to the modern research model that relies heavily on assistants and postdocs to do the legwork.

Edward Leiter, a leading diabetes researcher at Jackson since 1974 who credits Coleman as a mentor, says, “He taught me unswerving honesty with the data and complete openness about his current findings. He was always willing to share.”

It was a collaboration with Jackson colleagues that launched Coleman along another fork in the road, toward his research into the underlying causes of obesity in certain strains of grossly fat mice that had appeared as spontaneous mutations in the lab’s extensive colonies.

In a series of elegant experiments with the ob (obese) and db (diabetes) mouse models, Coleman proposed the existence of a blood-borne “satiety” factor that regulates appetite and body weight, and he showed that both strains of fat mice had defects in this same control system.

The ob mouse couldn’t produce the factor, and the db mouse was resistant to it. But the result was the same: Both mice kept eating after normal mice would stop. Obesity is often associated with insulin resistance and type 2 diabetes, with the linked conditions sometimes called “diabesity.”

Landmark paper

Published in 1973, Coleman’s research provided some of the earliest evidence that obesity was not just about willpower and eating habits but also involved chemical and genetic factors, thus setting the stage for modern scientific inquiry into the increasingly prevalent condition.

He expresses surprise “that what I thought was an interesting set of observations would turn out to have such a major impact in the field of obesity” In fact, it was more than 20 years before that impact was assured by another innovator in a vastly different technological climate in genetics research.

In 1994, after eight long years of laboratory sleuthing, Jeff Friedman –– who characterizes Coleman as “a scientist’s scientist” –– found the defective gene in the ob mouse. A year later, he identified the satiety factor as a hormone he named leptin, for the Greek word leptos, which means thin.

Friedman showed that leptin originates in fat cells, the first proof that these cells –– long viewed as “dumb” storage reservoirs –– are dynamic communicators with the brain in a complex, interwoven system for regulating metabolism and the body’s energy balance. He is continuing his research into leptin’s role in human obesity and other conditions.

“Obesity and diabetes are reaching epidemic proportions,” says Rick Woychik, president and CEO of Jackson Laboratory. “Further study of the pathways underlying diabesity, enabled by the discoveries of Doug Coleman and Jeff Friedman, could lead to therapeutic strategies to combat this health crisis.” He points out that Coleman’s pioneering work laid the foundation for the lab’s current major emphasis on obesity and diabetes research.

No regrets

Coleman continued his work at Jackson for another 18 years after his landmark paper appeared, but he walked away from it all at age 60 with “no regrets.” Never much for computers, he only recently began e-mailing to handle all the communications involved with the Shaw Prize.

“Bev and I wanted to travel, to pursue our interest in native cultures, and that’s what we did,” he says. “We started in the Arctic, then the Galapagos, Peru, Guatemala, Mexico, Honduras, Belize. The Inuits, the Incas, the Mayans, it was great to actually see and feel their environments.”

And there was the couple’s “Mixed Woods” waterfront property in Lamoine to enjoy. The Colemans moved there from Seal Harbor in 1986 and became actively involved in land conservation issues locally and statewide, including establishment of a 50-acre sustainable woodlot that they placed under a conservation easement.

He still owns the Lamoine property, and today there are handicapped-accessible trails through the woods, and a well-tended Beverly Coleman Memorial Garden full of native wildflowers that she transplanted from around the property so that visiting schoolchildren “could see them all in one place,” he says.

Beverly died in late April after a long struggle with Alzheimer’s, and Coleman still radiates sadness at the sound of her name. He moved to a retirement community in Bar Harbor to be near her in the last year, but has tentative plans to return to Lamoine.

How would she react to news of his award? “Oh, Bev would have been very excited and enthusiastic,” he says softly. “I heard after she died that she had told someone I did the best and brightest research in the world.”

His whole family will be flying to Hong Kong for the October ceremony: sons David and Tom, and Tom’s wife, Sarah, and their young son Benjamin. A third son, John, died in 1971 at age 11 from bone cancer.

The Shaw Prize

The Shaw Prize — first awarded in 2004 through a foundation established by Hong Kong media mogul and philanthropist Sir Run Run Shaw — spotlights breakthroughs in scientific research that have “resulted in a positive and profound impact on mankind.” Unofficial projections have it that about one-third of the awardees will go on to win Nobel Prizes.

Coleman has no interest in such speculation. “I got a great deal of joy out of research for its own sake. I think I came through science at the perfect time,” he says. “The peer recognition is nice, and I’m very grateful, but I haven’t sought awards.”

He plans to donate his entire $500,000 share of the prize to The Jackson Laboratory for education programs and diabetes research, and to McMaster University to bolster an existing scholarship in his and Beverly’s names. He also made a similar gift of his Gairdner prize money in 2005.

Coleman was, and is, very good at keeping things in perspective. Colleagues recall that his work focus was intense, that he would be in the lab every morning by 6:30 a.m. But he always left by 3:30 or so in the afternoon, to be with his family.

The internationally recognized scientist doesn’t take himself too seriously. There’s a widely reproduced photograph of Friedman and Coleman, side-by-side in a lab at Jackson in 1995 on the occasion of Friedman’s leptin discovery.

In the photo, Coleman is holding a mouse by its tail against the sleeve of his white lab coat, and the expression on his face is somewhere between a smile and a grimace.

“That mouse was biting me like crazy!” he says with a laugh.

Luther Young is a freelance writer in Blue Hill who works as a scientific grant writer at The Jackson Laboratory. He may be reached at loyoung@nasw.org.

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