Assisted by the robots and other complex machinery, scientists are studying what happens to the cells as each of the roughly 22,000 human genes is turned off. They hope to find the genes involved in different diseases, the starting point for creating a drug.
It is a merger of sophisticated biology and brute force made possible only because the Human Genome Project provided the identity of all the human genes. But as with so much else that has spun off from the genome project, it is also an expensive gamble, with success far from assured.
“Can I point to a single drug right now that this has facilitated?” said Michele Cleary, Merck’s senior director for automated biotechnology. “No, because we are in the early stages of this. There’s information feeding into the early stages of the pipeline that we’ll see the fruits of in years to come.”
Ten years after President Bill Clinton announced completion of the first draft of the Human Genome Project, in June 2000, its application to drug development is still, at best, a work in progress. But while many genetics scientists outside the drug industry say the project has had few medical benefits, industry researchers urge a wait-and-see patience.
In fact, some of the first drugs based on genomic studies are now starting to reach the market. Several new “targeted” cancer drugs, for instance, block the effects of genetic abnormalities that spur tumor growth. A drug from the biotech giant Amgen, an osteoporosis treatment called Prolia, was approved two weeks ago. The company got its initial clue for the drug by making different genes in mice overactive. Mice with one particular overactive gene had unusually thick bones.
And the drug company Human Genome Sciences, founded in 1992 as the genome project was just getting under way, applied last week for approval of Benlysta, which could be the first new drug in decades for treating lupus.
That is nothing like the cornucopia of new drugs that some experts predicted the genome project would yield. A decade ago, drug companies spent billions of dollars equipping themselves to harness the newly revealed secrets of human biology. Investors bid the stocks of tiny genomics companies to stratospheric heights.
That “genome bubble” has long since popped. And not only has there been no pharmacopeia, but some experts say the Human Genome Project might have at least temporarily bogged down the drug industry with information overload.
As the head of Novartis’s pharmaceutical business lamented in 2000, “Data, data everywhere, and not a drug, I think.”
Indeed, even though research and development spending by major pharmaceutical companies has roughly doubled in the decade since the genome project was largely completed, reaching $46 billion last year, the number of new drugs approved each year has stayed about the same. There were 25 in 2009.
Genomics is not the only reason for the decline in the bang from the research buck. A big factor has been stiffer testing requirements by the Food and Drug Administration.
For all that, drug industry executives say it is simply a matter of time before the Human Genome Project pays off. They note that because it can take 15 years or more to go from a basic discovery to a marketed drug, it is too early to expect many drug approvals yet.
Moreover, pharmaceutical executives say that even if there are not many drugs yet, the genome project has transformed the way research is done.
“It’s become a very standard part of what we do,” said Peter S. Kim, the executive vice president in charge of research at Merck.
The company spent $1.1 billion in 2006 to acquire Sirna Therapeutics, which is developing the RNA interference technology that Merck uses to turn off genes. Dr. Kim said that having the genome sequence gave scientists “the ability to do science at a different level.”
At Bristol-Myers Squibb, two-thirds of the drugs being developed have been “touched” in some way by genomics, said Elliott Sigal, president of research and development.
At Genentech, one-third of the drugs in clinical trials and two-thirds of the newer compounds earlier in development “have been enabled in a significant way” by the genome project, said Marc Tessier-Lavigne, executive vice president for research at Genentech, a unit of Roche.
One of those ways, he and others said, is allowing the potential side effects of a drug to be detected earlier. Often, drugs meant to inhibit one protein in the body also inhibit other fairly similar proteins, causing unintended effects. Knowing the genes can enable companies to find these similar proteins in advance and make sure their drug interacts with only the intended target.
“By having the genome sequence you can make better drugs, more specific drugs,” Dr. Tessier-Lavigne said. “In the old days you would only discover the side effects much later in the process and the drug would die.”
Many drug companies now collect and analyze the DNA of patients in clinical trials, hoping to find genetic signatures that will allow drugs to be better tailored to specific patients. It was recently discovered, for example, that patients with a certain variation in a gene called CYP-2C19 did not respond well to the widely used anticlotting drug Plavix, leaving them at a higher risk of having a heart attack.
Still, some executives concede the genome project has not lived up to expectations, and in some ways might have even made life more difficult for drug companies.