April 2011

Genome Biology: Tsunami

Like the ripples from that dropped block of concrete, a tsunami is actually a series of waves, usually spaced about 15-20 minutes apart, with troughs in between them. To the observer on shore, the approach of a tsunami often begins with a rapid receding of the shoreline, much further out than normal. This is followed, 8-10 minutes later, by the first wave, which surges onto the shore, often traveling a half a mile or more inland. As the cycle repeats, the first wave recedes, carrying anything loose back out to sea. Then the next wave hits. In Thailand, Sri Lanka and Indonesia, where the worst damage occurred, many people who survived the impact of the first wave were swept out to sea as it receded, or were killed by one of the surges that followed. But what fascinates me the most about tsunamis is that, until they reach land, they are practically unnoticeable on the surface of the ocean. Their amplitude in deep water is often only a meter or less. An ocean liner or a fishing vessel would pass right over them, completely unaware that underneath it a force was racing onward that, when it surfaced, could obliterate an entire country.

I’ve been thinking a lot about that sort of thing recently, because it seems to me that it’s a pretty good metaphor for what is going on in science. I started writing this column because I believed that genomics was like a tsunami: a force that, when it crested, would change everything, and I wanted to have an excuse to think about what that would mean. The true impact of the genomics revolution is only starting to be apparent now, and it’s very different from what it was predicted to be when the Human Genome Project began in the late 1980s. It has not had a significant impact on human health yet - the disease genes that have been discovered have generally come from specific individual research programs, and pharmacogenomics has initially focused on polymorphisms in genes that were already identified before the human genome was sequenced. Genomics has produced technology, such as cDNA microarrays and mass spectroscopy-based proteomics, that is likely to play a major role in diagnostics in the near future, but not necessarily in treatment. No, the major effects, which are now rolling across biology like a series of waves, are cultural.

Because of genomics, data gathering and analysis is now valued highly - in some instances above hypothesis-driven research. Because of genomics, targeted big science projects, such as structural genomics, that aim to produce easily appreciated results (usually in the form of large amounts of data), are consuming a large chunk of funding that would otherwise go to individual investigator-initiated basic research. Because of genomics, there is a perception in some quarters that when you have analyzed something you have understood it; mathematical modeling of biological processes is beginning to become a substitute for experimental probing. Because of genomics, a kind of mysticism is creeping back into biology: we use terms, like ‘systems biology’ and ‘emergent properties’, that have echoes of vitalism in them - almost as though we are starting to believe that we cannot explain the behavior of living systems in terms of the physics and chemistry of their component parts. We can argue about whether this is good or bad for our field. We can argue about how we should react to it. But we cannot ignore it. None of this could have been appreciated in 1990. It was all moving beneath the surface, moving rapidly and inexorably and now it is upon us. Until the next tsunami comes along, genomics, like molecular biology before it, will change our scientific world whether we like it or not.

So one of the lessons I take from what happened on 26 December is the folly of believing that things will remain as they are today. We go about our lives and our careers unaware of the great forces that move, unseen, beneath the usual tide of events. Until they crest they are almost undetectable, so we don’t talk about them or plan for them. And once they do crest, they can change our careers and our lives in a very short time. It would seem that, of all the qualities we need to survive and thrive in an unpredictable world, flexibility - adaptability if you will - might just be the most valuable. The other lesson is a practical one. If you’re standing on shore, looking out at what seems to be a perfectly calm ocean, and you suddenly see the shoreline receding rapidly, exposing the sea bottom much farther out than usual, turn around and run like hell away from the water. You need to get a half mile inland; a mile would be better. You have, if you’re lucky, maybe 10 minutes.

*This commentary was reprinted with permission from Genome Biology (2005) 6, 104.

Gregory Petsko (petsko@brandeis.edu) is the Gyula and Katica Tauber Professor of Biochemistry and Molecular Pharmacodynamics at Brandeis University.

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