Dr. Steven J. Collins, whose research into the molecular genetics of myeloid leukemias changed the way scientists thought about cancer cells and led to the development of one of the earliest targeted therapies, died May 25. He was 69 and had been living with gastrinoma, a malignant pancreatic neuroendocrine tumor, for nine years.
An emeritus member of Fred Hutchinson Cancer Research Center’s Human Biology Division, he held the Madeline Dabney Adams Endowed Chair in AML Research, only the second chair to be endowed at Fred Hutch, from 2003 until his retirement in 2012. His research laid the groundwork for the development of retinoic acid therapies for acute promyelocytic leukemia, or APL, a subtype of acute myeloid leukemia.
In both types of leukemia, immature cells in the bone marrow lose their ability to mature, or differentiate, into infection-fighting white blood cells. Collins showed that retinoic acid, a vitamin A derivative, can trigger a series of molecular actions that drives immature APL cells to develop into healthy ones. Until then, researchers had focused on toxic agents that would kill the immature cells.
“The idea that you could cause a leukemia cell to differentiate and use drugs that were nontoxic to treat it — no one had thought of that,” said Dr. Fred Appelbaum, Fred Hutch executive vice president and deputy director. “Everyone thought about killing the cell, not inducing the cell to grow up. It was a change in how to think about cancer cells. Suddenly it opened up a whole area of research.”
For all of Collins’ laboratory firsts, Appelbaum and others this week mourned the loss not just of a remarkable scientist but of an “incredibly generous” colleague, slyly humorous friend, genuinely caring physician and devoted husband and father.
Leukemia researcher Dr. Jerald “Jerry” Radich started out in Collins’ lab in 1988. He knew right away he wanted to work with Collins, he said, and not just because “he was clearly a brilliant guy.”
“There are a lot of brilliant guys,” Radich said. “But you could tell right off the bat that he was exceedingly thoughtful. He was kind. He was patient. He was generous to a fault. He had a hugely infectious laugh.”
To describe his mentor, Radich turned to a quote from cowboy humorist Will Rogers. “It’s great to be great,” the quote goes, “but it’s greater to be human.”
According to colleagues, Collins achieved both.
An Ohio native who won biology prizes in high school, Collins received his medical degree in 1973 from Columbia University and did his oncology internship at the University of Michigan. That is where he first met Appelbaum, then one year ahead of him. After their internships, both young clinician-researchers did stints at the National Cancer Institute. Collins worked in the lab of Dr. Robert Gallo, an eminent leukemia researcher who went on to become world famous in 1984 for co-discovering HIV as the cause of AIDS.
While in Gallo’s lab, Collins developed a famous cell line called HL-60, which remains a workhorse cell line for the study of leukemia, and began his lifelong work on APL.
He also began studying the disease model for chronic myeloid leukemia, or CML, after moving to Seattle to work as a medical oncologist at the Veterans Administration Medical Center. There he met Fred Hutch molecular biologist Dr. Mark Groudine, who was then on the VA center tumor board. Interested in exploring molecular biology, Collins accepted an invitation to spend a sabbatical in Groudine’s lab.
While there, Collins was the first to observe the amplification — or increase in the number of copies — of an oncogene in a cell line, Groudine said. This observation provided an alternate mechanism for increasing the amount of oncogene expression.
Collins returned briefly to the VA, but Groudine and others succeeded at luring him to the Hutch for good in 1986. Groudine and Collins went on to write much-cited papers on CML, which originates from a blood-cell genetic abnormality called the Philadelphia chromosome.
Collins was named director of the Hutch’s Molecular Medicine Division in 1995, a position he held until it was renamed the Human Biology Division in 1999, bringing together researchers with expertise in molecular medicine, cancer biology and genetics.
Despite all of his accomplishments, Groudine described Collins as “totally unpretentious.”
“This was one of those guys who didn’t care about the spotlight,” Groudine said. “He just wanted to work and get some answers.”
He also wanted to help others find answers. In his 30-plus years at the Hutch, Collins became known for his sound advice, even in fields that were outside his wheelhouse.
“He was willing to spend hours and hours with colleagues helping with their grants,” said Appelbaum. “He had great scientific taste, broad knowledge and a critical eye for how questions should be posed and addressed and what you should do after you got answers from your first set of experiments. He was incredibly generous with his time.”
Dr. Colleen Delaney, a leader in cord blood transplants who has held the Madeline Dabney Adams Endowed Chair since 2013, recalls first meeting Collins when she was a fellow and still figuring out what she wanted to do with her life.
“Steve was an incredibly approachable faculty member, and I can remember seeking his advice on many occasions early in my career at the Hutch,” she said. “He was easy to talk to and gave great advice. His friendly demeanor and willingness to help junior faculty stood out. I thank him for that.”
Mike Rubin, now a 54-year-old philanthropic gift officer at Fred Hutch, knew another side of Collins. Thirty years ago, Rubin underwent a bone marrow transplant to treat AML. Collins was one of his physicians.
Given the stress and blur of that time, Rubin remembers his nurses, who remained constant through his three-month treatment, more than his doctors, who rotated through. That’s why it surprised him to find how well Collins remembered him.
When Rubin celebrated his 18th transplant “birthday” in 2005 (in Hebrew, the number 18 is the word for life and so an extra special anniversary), Collins came. He asked about Rubin’s sister, not only recalling that she had been his donor but that she had taken leave from Brown University to be there.
“All that mattered was that he cared about me,” Rubin said. “And that was really clear.”
Constancy was a theme for Collins. Dr. Gordon Starkebaum, a rheumatologist and emeritus professor at UW Medicine, is another longtime friend who, like Groudine, first met Collins when the two worked at the VA hospital. They played tennis every Friday night for decades and shared long bicycle rides. (Collins talked Starkebaum into doing the first Obliteride together five years ago, with the money raised going to Radich’s lab.)
They also raised families together. Starkebaum knew Collins as the admiring husband of Kathy, a noted watercolor artist, and devoted dad to Jeff, Greg and James, delivering a supportive —and hilarious — speech just last year at James’ wedding.
Not surprisingly, Collins researched his rare cancer when he was diagnosed nine years ago, Starkebaum said. An experimental treatment bought him years of remission. When the cancer returned, he retired from his lab but for as long as he could, continued to attend seminars and conferences on campus. He was “sharp as a tack,” Starkebaum said, but annoyed by his powerlessness to stop the cancer.
Still, “he never was bitter,” Starkebaum said. “He never complained.”
Radich, who remained close friends and golfing buddies with Collins after starting his own lab at the Hutch, reflected in conversations with Collins on the irony of a cancer researcher having cancer.
“Most of us were hoping that if we chose this line of work, somehow that would account for something and get us off the hook,” Radich said. “It doesn’t work that way. He would actually laugh about the irony. But he did remarkably well. He was nine years with this thing. He did ‘outside the box’ well.”
Radich keeps on his pin board three items that Collins bequeathed him from his own “wall of fame” — photos and clippings that had been not so much cut as ripped out and tacked up for his inspiration and amusement. They are an old photo of Don and Dottie Thomas, a magazine picture of Bob Dylan in his eye-makeup phase arm-in-arm with boxer and activist Muhammad Ali and a typical bungled quote from former Vice President Dan Quayle: “If we don’t succeed, we run the risk of failure.”
“That smorgasbord of very different things is pretty much him,” Radich said.
A few weeks ago, Radich returned from an errand to find Collins waiting in his office. He knew why his old friend and mentor was there.
“We didn’t say our goodbyes, per se,” Radich said. “We talked about family and other stuff. But it was clear what was going on.”
For Appelbaum, the goodbye came in a touching letter from Collins. Tucked into the envelope was a gift certificate for a round of golf. Along with Radich, he and Collins had been regular “dew sweepers,” first off the tee at a public course in West Seattle at 5:30 a.m. to fit in a round of golf and be in their labs by 8:30.
“It’s been my gain to have been friends with him,” Appelbaum said. “It’s been all of our blessing to have had him here for as long as we did.”
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The Collins family will hold a memorial service with a buffet supper on Thursday, July 20, from 6:30 to 9 p.m. at the Center for Urban Horticulture, 3501 NE 41st Street, Seattle. The family requests that memorial gifts be designated to Fred Hutchinson Cancer Research Center. Memorials can be made online at www.fredhutch.org/memorial or mailed to Fred Hutch, P.O. Box 19024, Mail Stop J5-200, Seattle, WA 98109.
Mary Engel is a former staff writer at Fred Hutchinson Cancer Research Center. Previously, she covered medicine and health policy for the Los Angeles Times, where she was part of a team that won a Pulitzer Prize for Public Service. She was also a fellow at the Knight Science Journalism Program at MIT. Follow her on Twitter @Engel140.