Is Pasteur's day past?

There has always been an intimate relationship between medicine and biology. Experiments in the 19th century identified infectious agents as the source of disease, discovered sterile techniques for surgery and developed effective anaesthetics. I’m lucky they did: I can sit and type this article five days after my angry appendix and I parted ways in a Seattle operating room. In 1850 I wouldn’t have heard the soil raining down on my coffin. Others are not so lucky. Five years ago my father died of metastases from esophageal cancer, and three months ago AIDS carried off my dear friend Mark Miller. For both, the best of modern medical science bought them perhaps a year. Why do these diseases still confound 20th century biology, despite all our progress? In part, as Tony James argued so eloquently in this space, we are slowed by our inability to tackle problems collaboratively, rather than as an enormous number of competing independent research groups. But reading a little about the 19th century shows that this cannot be the only factor slowing the development of a brave new medicine. Pasteur was certainly a hero, driven to the point of ruining his own health in his search for cures for infectious diseases, but he was no angel of collaborative science. He competed vigorously and ruthlessly with others for results and reputation, and he conducted human experiments that lay at the very border of his time’s medical ethics, and far beyond ours. So why can’t we make dramatic advances like those of the 19th century? The obvious answer (which we use as our excuse to a public hungry for progress) is that Pasteur, Koch, Lister, Fleming, et al. solved the easy problems and left the hard ones to us. This is irrefutable. There are many more differences between our cells and those of a bacterial pathogen than between a normal and a malignant human cell. But there are other causes we talk about less willingly. One is the explosion of information that makes it almost impossible for anyone to know about all of the medicine, biology and chemistry relating to a single disease, let alone all diseases. Pasteur’s contributions spanned the whole of science. He invented stereochemistry, disproved spontaneous generation, and developed safe vaccines for human and animal diseases. His work required an understanding of a wide range of scientific disciplines, not just an awareness of the known facts. I think part of our current problem is a fundamental confusion between facts and ways of manipulating them in our minds. The facts are the data; the ways of manipulating them are described by words like interpretation and understanding. In the past it has been so hard to determine the facts of biology that we haven’t thought much about the process by which successful biologists convert facts into understanding. But modern biology and chemistry are now generating such huge streams of data that our traditional misty methods of turning small numbers of facts into knowledge seem certain to be overwhelmed. We need a revolution in thinking about thinking about biology before, for example, pharmacology can really form the interface between genomics and combinatorial chemistry. Our intellectual difficulties make us retreat into simplistic solutions for the very problems (above) that we talk of as complex. The suggestion that we can cure cancer by putting a wild-type p53 gene in every malignant cell sounds as plausible to me as the 1930s political dream of solving the great depression by putting a chicken in every pot. The offering of simple solutions for complex problems is in part influenced by venture capital. At a recent symposium on genetic models for human disease, though some talks were fine, others were largely data-free appeals for commercial funding. Does practical research have to be done this way? The British government’s response to the need for an accurate method to determine longitude (in the 18th century) was to create a prize for the first affordable, effective solution, and give financial help to competitors with promising initial data. Perhaps it would work again. The final reason for our failure to make effective progress on medical problems is the hardest to account for: the feeling that applied research is in some way inferior to basic research. This attitude is rooted in a fundamental prejudice that the most abstract research area is the most difficult and most noble. Most biologists think that physicists are smarter than biologists, for example. Within biology, applied research has been equated with biotechnology, and has suffered in the debates between those too pure to sully their hands with industrial money and those accused of sleeping with the enemy for financial gain. Although many of those who initially appeared to be purists can now be found on the advisory boards of companies, the prejudice against applied research lingers like a long and painful hangover. Perhaps the current (and to me equally wrongheaded) belief that there are no interesting problems left in biology will convince more people to try and emulate Pasteur by combining the basic and applied aspects of biology to tackle real and pressing practical problems.