A loss to the field...he will be missed.
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boston.com
Noted gene therapist Isner dies
Led cardiovascular research program
By Alice Dembner and Anne Barnard, Globe Staff, 11/1/2001
Dr. Jeffrey Isner was making a comeback.
A year and a half after federal regulators shut down his pioneering heart disease research citing safety concerns, the Boston cardiologist was back, armed with a new $10 million grant to expand on his idea of using gene therapy to grow new blood vessels for weak hearts.
Yesterday morning, the 53-year-old Isner died suddenly of a heart attack, sending shock waves through his hospital and the community of gene therapy researchers who recognized him as one of the most creative minds in their emerging field.
''Jeffrey is an outstanding visionary scientist who ... generated a lot of excitement,'' said Dr. Savio L.C. Woo, past president of the American Society for Gene Therapy. ''If this field succeeds in the future, it will be his legacy.''
Indeed, Isner's return had been viewed by some researchers as a sign of renewed confidence in gene therapy, in which scientists alter patients' genetic makeup to treat diseases. The long-touted field was shaken by the 1999 death of a healthy Arizona teenager, who volunteered for a University of Pennsylvania gene therapy study.
''This is definitely a big loss to the field of gene transfer,'' added Dr. Sonia Skarlatos, director of the program at the National Heart Lung and Blood Institute that awarded Isner a ''center of excellence'' award in September.
Isner's death is also a loss for St. Elizabeth's Medical Center in Brighton, where he created a nationally known cardiovascular research program, attracted many talented doctors, and built a dedicated following of patients. The president of Caritas Christi, the hospital's parent chain, last year called Isner ''the Pedro Martinez of our research staff.''
Yesterday, Caritas president, Michael Collins, said he was also mourning the death of a friend. Collins committed the hospital ''to honor Jeff's legacy and fulfill the promise of the research he so brillantly pioneered.''
Isner, who had no history of heart disease himself, had been working for years to coax blood vessels to grow in patients whose hearts were too sick for bypass surgery and whose blood-starved limbs were threatened with amputation.
He was inspired by Dr. Judah Folkman of Children's Hospital, whose groundbreaking work discovered proteins, called vascular endothelial growth factors, that promote the growth of blood vessels. Folkman's aim was to block the growth factors in cancer patients, to starve tumors of their blood supply. Isner thought of using them the opposite way for heart patients, to stimulate growth of blood vessels.
Folkman said yesterday that Isner's ''accomplishments will have lasting influence in the care of patients with cardiovascular disease and those with cancer.''
St. Elizabeth's invested more than $10 million in Isner's work and joined him and other investors in creating a private company in 1997 to develop and eventually market his research.
By the fall of 1999, several of Isner's heart patients were convinced they had been given a second chance. Erling Linnerud, 72, was back on his feet handing out Gideon Bibles, cutting way back on the 10 to 12 nitroglycerin pills he had taken nightly. Floyd Stokes bought a new peanut farm, to replace the one he sold when he was denied another bypass operation and was sure he was going to die.
Then disaster struck. The death of Jesse Gelsinger in a gene therapy experiment at the University of Pennsylvania in 1999 brought new federal scrutiny to the field of gene therapy.
Within months, Isner, too, fell under scrutiny. In February 2000, the FDA shut down his clinical trials, finding he had failed to report the death of a patient to the hospital's safety review board and had endangered the lives of other patients by improperly enrolling them in his studies.
For Isner and his staff, it was a severe blow.
''I didn't take any short cuts,'' he said in an interview a few weeks before his death. ''We put a lot of genuine sweat and blood into this at a time when no one thought it would amount to a hill of beans. For people to insinuate that we were sloppy or didn't care about patients - that was really hard to take.''
Isner also came in for criticism over the deaths of two patients he treated. While the patients both suffered cardiac arrest within a day of the gene therapy surgery, Isner insisted they succumbed to their underlying illnesses. Regulators have not disagreed.
The Tufts University professor also became a lightning rod for criticism of gene researchers' financial conflicts of interest. Patients' families criticized him for failing to tell them he had a financial stake in the experiments. And the American Society for Gene Therapy adopted ethics standards saying its members should not have equity in the companies that sponsored their experiments. Isner and St. Elizabeth's agreed to disclose their interest to patients, but did not divest.
Through it all, Isner persevered.
''He was a real entrepreneur in a positive sense and developed innovative strategies for treating heart disease,'' said Dr. Ronald Crystal, a competitor in gene therapy who works at New York Hospital/Cornell Medical Center and had also come in for milder federal criticism of his studies.
In August 2000, the journal Circulation printed Isner's report that nine of 13 patients with advanced heart disease showed evidence that inactive heart muscle returned to normal function after his treatment. That November, Isner was reinstated as an investigator for research by the biotechnology company Genzyme. And in the past few months, he had gotten FDA approval to move ahead with his research after agency officials were satisfied he had taken steps to ensure the problems would not recur.
In awarding the $10 million grant, NIH's first to Isner for gene therapy in patients, Skarlatos said the agency was sure all rules to protect patients would be followed. NIH planned to have a special safety board monitoring the work and St. Elizabeth's had arranged for an independent organization to keep track of patient records and research protocols.
Isner said a few weeks ago that he didn't feel the need to apologize for anything. `I'll never spend one day of my life questioning whether we didn't do everything we could to communicate with and take care of these patients,'' he said.
Over the summer, a group of patients who credit him with saving or enriching their lives gathered at St. Elizabeth's to fete him. Andrew Guerini, 72, of Milton was among them. Since his treatment last January, Guerini says he can walk to the post office without getting angina. ''I think he was on to something,'' Guerini said.
This story ran on page B1 of the Boston Globe on 11/1/2001.
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