Molecular Medicine (1 of 3)

I had the good fortune to attend (thanks to FI Center) the “Molecular Medicine Tri-Conference” in San Francisco last week. The attendees were researchers, executives of biotech and pharmaceutical companies, a few scientists from NCI or NIH, and me—as far as I can tell, the single NGO nonprofit person. (That’s not to say all the companies present are turning a profit—far from it.)

Molecular medicine: an intriguing idea. It goes with the term “molecular oncologist” that now appears in the scientific literature. But, in layman’s terms, what’s the relationship between molecules, medicine and health? When I go to the doctor it’s still pretty hands-on (“Okay, turn your head an cough.”) But increasingly the underpinnings of our understanding of disease and our means to treat it involve intimate understanding of the complex molecules that comprise the sub-systems of living things. If this conference is any indication, the tongue depressor is on the way out, in a manner of speaking, and an Affymetrix chip is on the way in. These terms indicate how fully the frontiers of medical science have shrunk toward intense study of disease at the molecular level (it’s the post-genomic era, if nobody told you yet) and cancer is at the very focal point of the effort. I didn’t run into anyone claiming to be a molecular oncologist, but the #1 topic of discussion was cancer. Cancer, cancer, cancer. The molecular transformation of well-behaved cells obeying well-constrained limits into malignancy is perhaps the biggest challenge—and biggest market opportunity—in commercial medical development today.

There were three facets of molecular medicine at the conference that caught my attention: 1) the raw science, 2) the raw business, and 3) the raw socio-economico-legal process of change. In my opinion all three are equally important. Anyone with an interest in cancer control today needs to realize that conquering cancer involves an extraordinarily complex interplay of these three things. There’s a lot of sophisticated science to do; it’s going to be done by the real world mechanism of health care products ultimately coming from the profit-making sector; and the rate of change is so great that the legal and social rules for enabling it are up in the air. Dealing with cancer is, in my opinion, a matter of influencing the interactions of these three components in the way that gets the most out as expeditiously as possible. Part of what’s interesting is that the wave of recent scientific breakthroughs is turning into a “rush to the clinic,” as it is known, and it’s about as orderly as the rush across the Bay Bridge at 5:00. Sometimes the rush can be premature. There is a kind of desperation in pharmaceuticals these days because, to continue in the game, they have to produce profits as well as treat disease.

The Science
Interestingly, there were no declarations at this conference that the “revolution” is just around the corner or that miraculous disease cures are at hand. These are people who have been struggling for years to convert scientific knowledge into real-world outputs that can be taken off the shelf and make people feel better. They’ll settle for less than revolutionary progress.

A basic condition that drives scrutiny of disease at the molecular level is the increasing evidence that most disease is heterogeneous. That is, many diseases—especially cancer—differ in significant ways in their expression because of alternative molecular processes. We’ve long said that cancer is not one but 100 diseases, but now it seems clear that even within a category like breast cancer or leukemia there are many more sub-categories that are clinically significant. Finding the right effective treatment process may require differentiating small genetic differences and having treatment approaches specific to those differences. The ultimate end of this is “personalized medicine”: every person’s disease may differ somewhat in its character and take different treatment. The trick is to identify significant traits precisely and to find corresponding “targeted” approaches. To find a way that is both effective and safe is very complex.

Indeed, cancer is perhaps the champ in a category of diseases referred to in biotech circles as “complex, polygenic” diseases. That means the disease is very complex in its fundamental biology, and it has more than one significant genetic factor. No one-gene diseases in this class of bad boys; a whole handful of genes may play a significant role. Moreover, they may fluctuate over time and dealing with the disease may mean affecting a whole set of genetic factors.

So sessions at the conference went into depth on work underway at biotech and pharma labs on diagnostic arrays, DNA markers to predict response to drugs, proteomics, new technology for biological assays of various types, epigenetics, blood-based biomarkers, molecular profiles that indicate pre-malignant states for earlier detection of cervical cancer, all kinds of biomarkers for drug development, and on and on. Pick up a copy of Nature at your newsstand to follow the shoptalk.

Many of the sessions were suggestive of tools and techniques to be brought to market in the future that will be of help in the detection and treatment of cancer. Tests, devices and techniques are in the works to provide information for all phases of disease processes: predisposition to disease, disease differentiation, disease progression, drug selection, dose selection, drug reaction, and toxicity. All in all, the premise is that it is possible to make the diagnosis of disease and prescribing effective interventions more rational. Instead of prescribing and then waiting to see the reaction, the whole thing should be made more precise and predictable.

But it was apparent from the excruciating refinement of some of the lab work and the tentative way they described the road ahead that no one should rush out to proclaim that The Cure for anything is just around the corner. The sessions are a confrontation with reality: making even incremental progress is hard, hard work and going from the lab to the clinic is no certain thing. The complex diseases are being chipped away at. Nothing about it is easy. And yet you have to feel optimistic. There is tantalizing progress on many fronts and there’s got to be payoff down the road. And nothing is getting more attention than cancer.

Next: The Molecule Biz