A crapshoot is defined as a risky or uncertain matter; something that could produce a good or bad result. President Obama’s moonshot on cancer is different in terms of its greater complexity and higher moral purpose — but unfortunately, not in its probability of success.
The Audacity of Scope
President Obama has asked Congress for $755 million to “focus” on immunotherapy, combination therapy, vaccines that prevent cancer causing viruses, and early detection techniques. According to Vice President Joe Biden, who will coordinate 13 government institutions in this research, “Our job is to clear out the bureaucratic hurdles, and let science happen.”
It is hard not to welcome such an initiative. Cancer has deposed heart disease as the number one killer in 22 American states. Experts project the number of global cancer cases will double in the next 15 years. But we are better at projecting the demand for innovation than we are at producing it; and we are even better at making promises we can’t keep and polices that don’t work.
President Roosevelt created the National Cancer Institute in 1937. Nixon declared a “war on cancer” with the National Cancer Act in 1971. The Bush administration spoke in 2003 of spending $600 million per year to rid the world of cancer by 2015. Obama and Biden made campaign promises to fight cancer in 2008, and should be lauded for trying to keep them, but their approach needs a lot of work.
The underlying assumption is that we should spend as much money, and use as many public and private constituencies to do as much as we can on as many paths as possible. There are three things wrong with this: first, $755 million is a measly sum under the current paradigm drug development. It can cost a company up to $5 billion and a full decade to bring one cancer-fighting drug to market. Second, we have tried this strategy before. Doing the same thing again, only harder, will lead to numerous failures whose cost will be passed on to the insurance companies and their customers in the form of high drug prices. Third, the answer is right in front of us.
We use the term moonshot to reference JFK’s successful space program, but don’t apply its deepest insights. We in the cancer fighting community lack that program’s predictive models, which were the key to its success. Despite severe technological limitations, NASA believed in predictive models based in math, engineering and physics. They modeled, for example, gravity’s influence on earth launches, moon landings, and human tissue. The models told them exactly what tools were needed to do the job. Only then did they build spacecraft to accomplish our goals.
Meanwhile, back on earth, we build tools before we understand the problem of cancer. Two-thirds of published research cannot be reproduced. In the post-genomic era, the FDA approves only 7% of drugs that enter cancer clinical research. Over the past five years, twice as many trials have resulted in only a 10% increase in approvals. Industry investment in R&D has gone backwards, and with it comes a soaring cost of innovation that drives drug prices. Imagine the public tumult, the demand for our leaders to resign, if only one in 14 of rockets carried our astronauts safely!
Great Strategy is Reconciling what Others Believe are Opposites
The discussion we should be having is how to cure cancer and lower drug prices at the same time. Cancer is a multidimensional, ever-changing disease of the entire cell system. The standard focus on individual targets — while supporting publications to drive academic careers and intellectual property that supports high-risk industry investment — has failed. The secrets of biology lay in the interactions between molecules: the dynamics. We need to hack into a human cell as if it were a computer and decode the operating system: switch these proteins off to cure pancreatic cancer, turn others on to end heart disease, and deliver smart growth factors to regenerate neural tissue.
If predictive engineering was the impetus behind space travel, then systems biology can spur innovation and foster initiatives of “cell exploration.” Systems biology is the method of building models of complex biological environments so we can design the right drug from the start. These drugs would have fewer off-target effects and last longer at the disease site. They would also cost less because the cost of failure of the present “scattershot” system of drug discovery would not be passed along to the consumer.
The NIH is a national treasure that houses the tiny National Centers for Systems Biology, a network of our top academic institutions and thought leaders who are already on the path to uncovering cellular secrets. But last year, of the $25 billion in grants supported by the NIH, those aimed at the truly transformational opportunity of systems biology totaled a mere $8 million, or .032% of the total.
Many of us now know that a “war on cancer,” campaign promises massive infusions of capital, top-down political coordination and even the genomic revolution do not come close to the value created by a greater understanding of systems biology. If we call it a moonshot, but don’t comprehend the real key to putting a man on the moon, how is that different than a crapshoot?
Robert Mulroy is a founder and the CEO of Merrimack, a systems biology company based in Cambridge Massachusetts whose pancreatic cancer drug was approved by the FDA in October.