New York Times
April 22, 2013
Cancer Centers Racing to Map Patients’ Genes
By ANEMONA HARTOCOLLIS
Featuring: Dr. James Crawford, Chair, Pathology, North Shore-LIJ Health System
Electric fans growl like airplanes taking off and banks of green lights wink in a basement at Mount Sinai’s medical school, where a new $3 million supercomputer makes quick work of huge amounts of genetic and other biological information.
Just a couple of miles away, a competitor, Weill Cornell Medical College and NewYork-Presbyterian Hospital/Weill Cornell hospital are building a $650 million research tower. Across the street is a newly completed $550 million tower housing labs for another competitor, Memorial Sloan-Kettering Cancer Center.
Major academic medical centers in New York and around the country are spending and recruiting heavily in what has become an arms race within the war on cancer. The investments are based on the belief that the medical establishment is moving toward the routine sequencing of every patient’s genome in the quest for “precision medicine,” a course for prevention and treatment based on the special, even unique characteristics of the patient’s genes.
Among other projects, Harvard Medical School has its Center for Biomedical Informatics, which among a broad array of approaches uses mathematical modeling to predict when genetic information could lead to more effective treatment. Phoenix Children’s Hospital opened the Ronald A. Matricaria Institute of Molecular Medicine in December, recruiting researchers from Los Angeles and Baltimore and planning to sequence the genomes of 30 percent of their childhood cancer patients in their search for better therapies.
Johns Hopkins, with its focus on public health, wants to develop a “systematic genomic sequencing program” over the next two years that will combine genomic analysis with a patient’s environmental exposure, family history and other factors to support preventive medicine, said Scott Zeger, vice provost for research.
“There will be a moment in time when whole genome sequencing becomes ubiquitous throughout health care,” said Peter Tonellato, director of the Harvard personalized medicine lab and a clinical investigator in pathology at Beth Israel Deaconess Medical Center in Boston. “Let’s say we figure out all the individuals who might have a cancer, and we can predict that with a relatively high level of accuracy. Then presumably we can take steps to avoid those, let’s say, decades of treatment.”
Sequencing an entire genome currently costs in the neighborhood of $5,000 to $10,000, not including the interpretation of the information. It is usually not reimbursed by insurance, which is more likely to cover tests for genetic mutations that are known to be responsive to drugs. The treatments themselves, which are sometimes covered, typically cost several times that.
Even optimists warn that medicine is a long way from deriving useful information from routine sequencing, raising questions about the social worth of all this investment at a time of intense fiscal pressure on the health care system.
“What’s the real health benefit?” said Dr. Robert C. Green, a Harvard professor and a medical geneticist at Brigham and Women’s Hospital in Boston. “If you’re a little bit cynical, you say, well, none, it’s foolish.”
Dr. Green is part of a federally sponsored research project that is looking at the economic and medical impact of whole genome sequencing. “One of the most prominent downsides is you start chasing risks for a whole lot of disease you’ll never have, and generate a lot of cost for little benefits,” he said.
He was not ready to dismiss the efforts of Mount Sinai and others, though. “The other side of the question is, what was there to look up on the Internet when the first person got a personal computer? Very little.”
The race entails large sums spent not only on construction and technology but also recruitment, salaries and incentives for scientists like Weill-Cornell’s Dr. Lewis Cantley, who was lured from Harvard, or Eric E. Schadt, plucked from the biotech world to head the Mount Sinai Institute for Genomics and Multiscale Biology.
NewYork-Presbyterian/Weill Cornell announced a new Institute for Precision Medicine, headed by a prostate cancer expert, in January. (The newly fashionable term “precision medicine” is an updated version of another genomics buzzword, “personalized medicine.”) “I am not in this for competition,” said Dr. Laurie Glimcher, dean of Weill Cornell Medical College. “I consider it collaboration, and I think we all have the same goal in mind, which is to cure disease.”
As Weill Cornell was courting Dr. Cantley, Memorial was pursuing another Harvard eminence, Dr. José Baselga, to be its physician in chief. “It’s a small world,” Dr. Baselga, a breast cancer specialist, said, recalling that he and Dr. Cantley had exchanged notes on what each was being offered.
Memorial sequenced 16,000 tumors last year, mainly in lung cancer patients, Dr. Baselga said. In addition to the research building just completed on East 68th Street, a new outpatient building on East 74th Street, to be finished in 2018, will have whole floors dedicated to early-phase clinical trials.
The promise of whole genome sequencing can be seen in trials like one for bladder cancer at Memorial, where the effects of a drug normally used for breast cancer were disappointing in all but one of about 40 patients, whose tumor went away, Dr. Baselga said. Investigators sequenced the patient’s whole genome. “The patient had a mutation in one gene that was right on the same pathway as the therapy,” Dr. Baselga said. “And that explained why this worked.”
At Mount Sinai, Dr. Schadt, 48, an all-around risk aficionado who rides a BMW S 1000 RR Superbike, says he will use the mathematical principles of weather and markets forecasting to assess the risk of disease, and, given a disease, determine the subtype and best drugs to use.
Mount Sinai has collected what it calls an electronic “biobank” of information on 24,000 patients, who have agreed to participate in DNA sequencing and research over their lifetimes.
Some of that information will be fed into the supercomputer, which is named Minerva, after the Roman goddess of wisdom. Data storage alone is a challenge: one genome is 300 gigabytes of raw data per patient sample. Minerva’s supervisor is Patricia Kovatch, 44, a computer engineer who led the team that built Kraken, the world’s third fastest computer, in 2009, while working for the University of Tennessee at Oak Ridge National Laboratory.
So much hiring has been going on surrounding personalized medicine at Mount Sinai, she said, that “it feels like a start-up.”
At this point, scientists have only an imperfect understanding of how snippets of genetic material can determine a patient’s chances of getting many diseases, especially more common ones. And patients are often reluctant to enroll in clinical trials of drugs still in development. But by setting up the right infrastructure — collecting and sequencing patient DNA, identifying patients who could benefit from a particular drug and aggressively recruiting patients for trials — the academic medical centers hope to play a bigger role in the development of new drugs, which could lead to lucrative patent royalties.
“The pharmaceutical companies need the expertise of academic medical centers, they need our patient groups to participate,” said Dr. Dennis Charney, dean of the Icahn School of Medicine at Mount Sinai.
Those groups could include patients like Kieran P. Holohan, a 45-year-old lawyer who received a diagnosis of acute myeloid leukemia in 2009. After his chemotherapy and the disease’s remission, his original doctor pushed him to have a bone-marrow transplant to prolong the remission. A friend from his rugby club, a geneticist, told him that “this has a lot to do with chromosomes,” he recalled, and sent him to a doctor at Weill Cornell, Gail J. Roboz.
A relatively new laboratory test found that Mr. Holohan’s leukemia had a mutation that meant that his chances of survival would not necessarily improve with the risky transplant. So he opted for more chemotherapy, and his cancer is still in remission.
“They didn’t go with a suit off the rack,” he said. “This was bespoke medicine.”
His doctor is more cautious. “Unfortunately, cancer is cured three times a day in the media,” she said. But that does not mean that there might not be truly customized treatments for cancer 10 years down the line, she said.
Dr. James M. Crawford, chair of pathology at Hofstra North Shore-LIJ School of Medicine, said his institution, a competitor in some ways with the Manhattan medical centers, was “quite literally on the fence” about whether to join the race or to “let more data emerge before we decide we are going to commit more resources to this.”
“What is the ultimate utility of this personalized medicine?” he said. “As a medical profession but also as a society we have not answered this question to our satisfaction.”