What if a simple blood test could detect any cancer early, when it was still easy to treat?
It sounds like science fiction. But Illumina ILMN +1.20%, the $24 billion (market cap) biotechnology company that has pioneered cheap, efficient sequencing of DNA, says it could be a reality in a few years. It is launching a new startup, GRAIL (because such a test would be a holy grail for cancer doctors), with $100 million in funding. Illumina will hold a majority share. Other backers include Sutter Hill Ventures, ARCH Ventures, Jeff Bezos’ Bezos Expeditions and Bill Gates. The startup could have vast medical, economic and societal implications–if the technology really works.
“Everything here is directed at being a pan-cancer test, something that is a universal test,” says Jay Flatley, who has been Illumina’s chief executive for sixteen years and has improved the power of DNA sequencing at a rate that exceeds improvements in microchips over the same period of time.
“It’s our largest investment ever,” says Robert Nelsen, a partner at ARCH, says of GRAIL. Nelsen helped found Illumina, and, more recently, some of the the most well-funded startups ever, including cancer company Juno Therapeutics, which raised $310 million before its IPO, and Denali Therapeutics, focused on brain diseases, which raised $217 million last year.
“It remains to be proven,” Nelsen asserts, “but it’s likely to be the case that you will be able to know deep and large amounts of information about multiple cancers with a single test.”
Flatley says that the idea for GRAIL was hatched eighteen months ago when Illumina researchers were trying the company’s DNA sequencers out on blood. They found that as the company’s sequencers became increasingly powerful, they were able to detect trace amounts of DNA in those samples.
That got Flatley and another top Illumina executive, Richard Klausner, excited.
“There’s a phenomena that we now know that tumors put out, at very early stages, their DNA into the circulation,” Klausner said at the Forbes Healthcare Summit in Decemebr 2014. “We can now measure that with incredible precision. I think one of the biggest breakthroughs we can see in cancer in the next few years is this possibility that there could be a blood test or a urine test that detects early-stage cancer.”
Cancers start out having the same genetic code as the people they afflict. But what makes them into cancers is a slow buildup of mutations in their DNA. These changes mean that the cells no longer listen to the body’s commands to die or stop growing. They develop cloaking devices to avoid the immune system, and commandeer their host’s energy stores.
But tiny bits of this changed DNA are present in the blood, perhaps from an early stage. Flatley says his researchers think they can find this DNA, and by identifying dozens or hundreds of different genetic mutations, tell with an amazingly high degree of certainty if someone has cancer, without causing scares for healthy people. Right now, though, that’s only a technologist’s guess.
The proof needed for such a test will be vast and expensive to create. Flatley imagines a study that would include tens of thousands of patients, with their genes sequenced hundreds of thousands of times. Instead of sequencing entire genomes thirty times, as is done to look for genetic changes, samples from these patients might be sequenced hundreds or thousands of times to look for changes that might indicate cancer.
Each year, the study might identify small numbers of patients who had cancer. At first, many of them would be in the late stages of the disease, Flatley says. But as time passed, the study should start only identifying patients in the early stages of cancer, because the tumors were always being caught when they are new.
Critics are likely to see problems. Will the test detect small cancers that would be kept in check by people’s immune systems, meaning people would receive treatment who didn’t need it? Will it simply be wrong sometimes? Can GRAIL, even with such a deep war chest, really prove that such a test works? The challenges are vast.
Flatley concedes the company may need to take some smaller steps. One possibility would be to combine the GRAIL test with mammography. Mammograms have a high false positive rate. If a blood test could help point out women who don’t need painful biopsies, or detect cancers the mammograms miss, that would be a big deal on its own.
And for now, this test doesn’t even really exist. Flatley is confident it will within a year. GRAIL has to talk to the FDA. It needs a CEO. Klausner, the former NCI chief, is leaving Illumina, but remaining with GRAIL as a director. For now, this new company will probably be consolidated into Illumina’s financials.
That the effort is nascent isn’t stopping Flatley and Nelsen from dreaming big. They both imagine that maybe someday the test would not only identify cancer, but provide the key to killing it. Maybe the DNA mutations identified by such a test could be inserted in the killer white blood cells being engineered by Nelsen’s other company, Juno, and injected into the patient. Then they would hardly ever know they had cancer.
This dream serves both to show the awe-inspiring scope of their project and how much has to be done. Juno’s first treatments, which indiscriminately kill all of the body’s B-cells, an immune cell type that goes awry in some cancers, won’t hit the market for a few years. Such custom designs are a long way away.
Flatley says he plans to move fast, though. The giant clinical trial of GRAIL’s still unfinished test? He expects to start it next year. One thing Flatley is known for is not missing deadlines.
The cancer world is changing, Nelsen says. “I think these things will converge pretty rapidly. If I was a big pharma with a minimally effective, medium toxicity chemotherapy drug I would be nervous. I think it’s going to be really a fascinating time.”