Plenty of factors can conspire to slow down progress in molecular diagnostics and personalized medicine. There’s never enough money to run all the experiments scientists can imagine, it’s hard to gather data that squares with traditional medical evidence standards, and society is willing to pay a lot more money for drugs than diagnostics.
But there’s another factor increasingly limiting diagnostics entrepreneurs and the investors who back them—a scarcity of high-quality tissue samples.
Samples—everything from tumor biopsies to blood and urine to feces and saliva—are the crucial raw material that goes into the whiz-bang science of seeking diagnostic answers. Microscopes, real-time PCR machines, next-generation gene sequencers—they all depend on high-quality samples. In this case, “high quality” means it’s been stored in a central place, preserved the right way, shipped and handled properly, and ideally, matched with a patient’s long-term medical records. Sometimes, those records might even say something about how that patient’s case ended up so researchers can connect the dots between genes that are out of whack and a state of disease.
I’ve been hearing lots of anecdotal comments over the past year from entrepreneurs and investors about how tricky it can be to get ahold of enough high-quality samples to advance their visions for genetic-based personalized medicine. Sue Siegel, the former managing director at Mohr Davidow Ventures now with GE, called biological samples “liquid gold” at a genomics event I organized last October. Brook Byers, the partner at Kleiner Perkins Caufield & Byers, said at the Personalized Medicine Conference last November in Boston that his firm has gone so far as to connect its portfolio companies with “sample hunters” to help the companies get access to precious samples.
There are many reasons why samples are scarce, and valuable. There’s a surge in understanding of basic biology, which is creating demand for more samples to run through experimental instruments. When patients go in to see the doctor, nobody wants the patient to get poked, prodded or asked to come to the clinic for repeat sample donations any more than necessary. It also takes money, manpower, and a long-term organizational focus to really manage a biobank so that it’s truly a great resource for physicians and researchers.
Like many other things in life, this is really about supply and demand. The supply of good samples is short, and the demand is increasing.
“Cancer screening is getting more and more aggressive,” says Brad Gray, the CEO of Seattle-based NanoString Technologies, which is developing a digital gene expression test to gauge breast cancer risk. Physicians today “catch tumors early, and we catch them when they are small. That’s good. But it means you’re starting with a small amount of tissue, and the amount of things you want to know keep going up as our understanding of the molecular biology of cancer is going up.” And, obviously, once a small tumor biopsy gets used in an experiment, it can’t be used again. “This is a non-renewable resource,” Gray says.
Lung cancer is a great example of the sample bottleneck. Since the lungs are a sensitive internal organ, getting samples of tumor tissue there isn’t easy, and is generally done by a physician with a tool to scrape out as little tissue as he or she needs for analysis. There are traditional pathology tests that need some of that sample to classify the tumor, but beyond that, there are now single-purpose tests to look for EGFR status, or a mutation to the ALK gene, to see whether the patient is a good candidate for a certain targeted therapy. Each of those diagnostics consumes a little bit of the precious sample.
Hospitals and physicians know how rich in information their samples are, but the first priority is going to be using the supply to best manage the patient’s care. Research, especially the really exploratory kind, doesn’t always
