Two events persuaded FDA Matters to write another column on biological complexity and its implications for medical research, drug discovery, and personalized medicine. First was the release of a remarkable study on gene mutations in cancer tumors. It is a stellar and sobering example of how biological complexity confounds our expectations that rapid advances in science will quickly lead to cures. 

Second was the multiple comments from readers of last week’s column suggesting that drug discovery (and biomedical advances generally) are so hard because “the low-hanging fruit has been picked.” This is a persistent and dangerous myth that devalues past breakthroughs and distorts the challenges bio-medicine faces over the next decade.

This past week’s New England Journal of Medicine contained an original article on cancer tumor heterogeneity. According to Reuters, the study showed:

“…about two-thirds of genetic mutations in samples from primary tumors of kidney cancer patients were different from one another, even if they were taken from the same tumor…Researchers also found even more genetic differentiation in biopsies of secondary tumors. The findings suggest that using samples from a primary tumor as a basis for treatment decisions may not be good enough, researchers said.”

An accompanying NEJM editorial, as well as a Wall Street Journal article and comments,  both pointed to this as a setback for matching treatments to the genetic make-up of a person’s tumors (i.e. personalized medicine). Their comments didn’t surprise me.

Over 2 ½ years ago, I put personalized medicine in perspective by comparing it to the long history of biotechnology. I didn’t predict the cancer gene mutation discovery. I just pointed out what history tells us: biological complexity is greater than we imagine, making promising areas of discovery appear closer to maturity than they really are. The truth of this was on prominent display in these new research results on cancer tumors.

This provides a near-perfect context to respond to those who thought the answer to last week’s column, “Why is Drug Discovery So Hard (and Expensive)?” is “because the low-hanging fruit has been taken.” They suggested: what remains to be accomplished in human biology and drug discovery is incredibly difficult because all the easy questions have been answered and the easy drugs and biologics have already been developed.*

As near as I can tell, a great many very smart people believe this. And they could not be more wrong. The challenges ahead are, indeed, quite difficult….but so were yesterday’s challengesbefore we solved them.

The “low-hanging fruit theory” is truly insulting to a generation of bioscientists whose record of accomplishments over the last 50 years was achieved by their hard work and dedication, as well as their brilliance. If anything, they might argue that it is easier now—given the new knowledge and the new tools that researchers have to work with.

Beyond that, the view of the past as low-hanging fruit–“easy and less expensive”–distorts our view of the future…that somehow we face challenges greater than other people have faced before us. We don’t.

Human biology is complex and biomedical research is slow and time-consuming. Most new knowledge raises as many questions as it answers (as is certainly true with the new cancer tumor research). None of this is new. And it is true no matter where you stand in the continuum of biological knowledge, whether you are Pasteur or one of today’s biotechnology “rock stars”.

I am not pessimistic or discouraged about biomedical discovery or opposed to personalized medicine, just concerned we see them in a realistic light. I conclude that:

  • More biological knowledge is always better than less.
  • Having more knowledge doesn’t tell you whether the next task is easier or harder (and often it is both).
  • Having more knowledge doesn’t tell you whether success is near or far.

These three observations are controlling principles in biomedical research’s quest to lessen the burden of disease and provide all of us with a higher quality of life.

Since this is FDA Matters blog, how does FDA fit in? The agency works closely with companies developing drugs and devices and is one of the final arbiters in whether biological knowledge has, indeed, been turned into benefit for mankind.

The agency needs the tools, the resources and the top scientific minds to stay ahead of the ongoing flood of new biomedical knowledge. It needs to be ready to stimulate, then evaluate, what we hope will be a torrent of new, ground-breaking drugs and devices that will, over time, arrive.

adapted and republished with permission by FDA Matters, a weekly blog covering FDA policy and regulation