Bucking the Zeitgeist

Today's biology is a frenzy of convergence. Driven by huge datasets and the tools to analyze them, comparative genomics and systems biology are being used to define the common basis of life and the dazzling variations on its central theme. Given the spirit of the times, any attempt to advance a grand unifying theory of biology would get a reasonable hearing today.

Rewind 10 years to 1997, however, and the zeitgeist of biology was quite different. Reductionism was king. Excellence in molecular biology was a major driver, and research was more noticeably compartmentalized, with the focus on providing a full description of the discrete pieces of the puzzle of life. For example, Science magazine's "Breakthrough of the Year" in the mid-90s featured p53, DNA repair and cloning. How would a theory that dared to span the breadth of biology be received in such a reductive setting?

That question was tested by the submission of a paper to Science called "A General Model for the Origin of Allometric Scaling Laws in Biology." ¹ Two biologists - Jim Brown and Brian Enquist - and a physicist, Geoffrey West, shared a common interest in why rates and times scale as a fourth powers of body mass, and had developed a metabolic theory that they said could predict fundamental characteristics of vertebrate cardiovascular and respiratory systems, plant vascular systems and insect tracheal tubes.

I'm in a good position to tell you how that theory was received: I was the editor at Science who handled the original research paper, a process that is etched vividly upon my memory. Bucking the zeitgeist is never easy, and the divisions riven by the work were immediately evident.

The two members of the Board of Reviewing Editors had diametrically opposite reactions, and we decided to send the paper out for formal peer review. The first two reports were enthusiastic: "A real breakthrough" and an "original theoretical approach. But the third, an expert in fluid flow who took longer to identify was unimpressed, finding the work "fundamentally flawed."

This negative reviewer declined to consider a revised manuscript, so two further expert views were sought. They raised some further grumbles, but these were not fundamental. As the editorial team, we felt justified in proceeding to publication with one ecstatic, two enthusiastic, two lukewarm and two implacably negative reviews.

Despite 728 citations, the article polarizes opinion to this day. The work of its authors is profiled here. Over the course of the decade their theory has extended tentacles across the entire spectrum of biological (and potentially biomedical) phenomena, including energy and resource use, genome length, and life span. A recent Nature article described the work as "breathtaking in its ambition and scope." ² West recently widened the ambition and scope still further-to social organizations-with a brief essay in Harvard Business Review reporting that "cities manifest power-law scaling similar to the economy-of-scale relationships observed in biology: a doubling of population requires less than a doubling of certain resources. The material infrastructure that is analogous to biological transport networks-gas stations, lengths of electrical cable, miles of road surface-consistently exhibits sublinear scaling with population." ³

It would appear that August Everding, the German opera director, was wrong when he said, "Whoever marries the zeitgeist will be a widower soon" - at least when it comes to biology.