St. Louis. Genetics researchers at Washington University, one of the world’s leading centers for work on the human genome, were devastated. Dr. Lukas Wartman, a young, talented and beloved colleague, had the very cancer he had devoted his career to studying. He was deteriorating fast. No known treatment could save him. And no one, to their knowledge, had ever investigated the complete genetic makeup of a cancer like his.
So one day last July, Dr. Timothy Ley, associate director of the university’s genome institute, summoned his team. Why not throw everything we have at seeing if we can find a rogue gene spurring Wartman’s cancer, adult acute lymphoblastic leukemia, he asked? “It’s now or never,” he recalled telling them. “We will only get one shot.”
Ley’s team tried a type of analysis that they had never done before. They fully sequenced the genes of both his cancer cells and healthy cells for comparison, and at the same time analyzed his RNA, a close chemical cousin to DNA, for clues to what his genes were doing.
The researchers on the project put other work aside for weeks, running one of the university’s 26 sequencing machines and supercomputer around the clock. And they found a culprit — a normal gene that was in overdrive, churning out huge amounts of a protein that appeared to be spurring the cancer’s growth.
Even better, there was a promising new drug that might shut down the malfunctioning gene — a drug that had been tested and approved only for advanced kidney cancer. Wartman became the first person ever to take it for leukemia.
And now, against all odds, his cancer is in remission and has been since last fall. While no one can say that Wartman is cured, after facing certain death last fall, he is alive and doing well.
Wartman is a pioneer in a new approach to stopping cancer. What is important, medical researchers say, is the genes that drive a cancer, not the tissue or organ — liver or brain, bone marrow, blood or colon — where the cancer originates.
One woman’s breast cancer may have different genetic drivers from another woman’s and, in fact, may have more in common with prostate cancer in a man or another patient’s lung cancer.
Under this new approach, researchers expect that treatment will be tailored to an individual tumor’s mutations, with drugs, eventually, that hit several key aberrant genes at once. The cocktails of medicines would be analogous to HIV treatment, which uses several different drugs at once to strike the virus in a number of critical areas.
Researchers differ about how soon the method, known as whole genome sequencing, will be generally available and paid for by insurance — estimates range from a few years to a decade or so. But they believe that it has enormous promise, though it has not yet cured anyone.
With a steep drop in the costs of sequencing and an explosion of research on genes, medical experts expect that genetic analyses of cancers will become routine. Just as pathologists do blood cultures to decide which antibiotics will stop a patient’s bacterial infection, so will genome sequencing determine which drugs might stop a cancer.
“Until you know what is driving a patient’s cancer, you really don’t have any chance of getting it right,” Ley said. “For the past 40 years, we have been sending generals into battle without a map of the battlefield. What we are doing now is building the map.”
Large drug companies and small biotechs are jumping in, starting to test drugs that attack a gene rather than a tumor type. Leading cancer researchers are starting companies to find genes that might be causing an individual’s cancer to grow, to analyze genetic data and to find and test new drugs directed against these genetic targets. Leading venture capital firms are involved.
For now, whole genome sequencing is in its infancy and dauntingly complex. The gene sequences are only the start — they come in billions of small pieces, like a huge jigsaw puzzle. The arduous job is to figure out which mutations are important, a task that requires skill, experience and instincts.
So far, most who have chosen this path are wealthy and well connected. When Steve Jobs had exhausted other options to combat pancreatic cancer, he consulted doctors who coordinated his genetic sequencing and analysis. It cost him $100,000, according to his biographer. The writer Christopher Hitchens went to the head of the National Institutes of Health, Dr. Francis Collins, who advised him on where to get a genetic analysis of his esophageal cancer.
Harvard Medical School expects eventually to offer whole genome sequencing to help cancer patients identify treatments, said Heidi L. Rehm, who heads the molecular medicine laboratory at Harvard’s Partners Healthcare Center for Personalized Genetic Medicine. But later this year, Partners will take a more modest step, offering whole genome sequencing to patients with a suspected hereditary disorder in hopes of identifying mutations that might be causing the disease.
Whole genome sequencing of the type that Wartman had, Rehm added, “is a whole other level of complexity.”
Wartman was included by his colleagues in a research study, and his genetic analysis was paid for by the university and research grants. Such opportunities are not available to most patients, but Ley noted that the group had done such an analysis for another patient the year before and that no patients were being neglected because of the urgent work to figure out Wartman’s cancer.
“The precedent for moving quickly on a sample to make a key decision was already established,” Ley said.
Ethicists ask whether those with money and connections should have options far out of reach for most patients before such treatments become a normal part of medicine. And will people of more limited means be tempted to bankrupt their families in pursuit of a cure at the far edges?
“If we say we need research because this is a new idea, then why is it that rich people can even access it?” asked Wylie Burke, professor and chairwoman of the department of bioethics at the University of Washington. The saving grace, she said, is that the method will become available to all if it works.
The New York Times