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MARGINALIA

Winter 1859

A single 30-day span begat much of modern biology

Robert L. Dorit

The First Case

Pasteur, of course, was right, but with one major exception. If we think of contemporary organisms in the present, life begets life, and like begets like. But if we look into the past, we quickly realize that there must have been at least one time when Pasteur’s dictum did not hold. Some 3.8 to 4 billion years ago, life on Earth emerged from nonlife. Astonishingly early in the history of this planet, its abiotic chemistry assembled into the rudiments of living systems. Those early systems, capable of organizing their chemical reactions, defining an inside and an outside, storing information, encoding their own history and, crucially, evolving, would irreversibly alter Earth’s surface and history.

The origin of life is a crucial question for modern biology. It is also a material question to be addressed with material explanations. I am certain that biology, together with chemistry and information theory, will unravel the question of how life may have originated. As scientists, however, we are not equipped to explain what the origin of life “means” or what its “purpose” is. Instead we are taking on the challenge of understanding how organized chemistry emerges from spontaneous chemistry, and how transient organization becomes transmitted information—in short, how nonlife becomes life.

We are making progress, and have over the past decade come to understand that early in the history of life (unlike the current state of affairs), function and information may have been deeply and sloppily intertwined. But to make things more complicated, the line between the living and the nonliving is not as sharp as we once thought. Gone are the days when we spoke of élan vital or of exalted vegetative forces, but we are not quite sure what to claim in their place as the exclusive hallmarks of living systems.

The rise of a new field in biology, synthetic biology, may shed light on these issues. The goal of this emerging subfield is to show that a working organism, one that has never before existed, can be assembled in the lab. The genomes of these new creatures are under construction—they are being assembled in numerous labs by stitching together selected genes from a variety of existing organisms. The comparisons to Dr. Frankenstein’s creation are tempting, but this is an altogether less sinister undertaking. At its core, the justification for this effort is utterly pragmatic: to custom-design organisms (bacteria, primarily) that exhibit features we deem desirable. We can easily imagine the benefits of a bacterium that readily transforms cellulose into ethanol, or one that takes toxic chemicals and breaks them down into less harmful products. And we now believe we can custom-build the organisms we need. Much like that fateful winter in 1859, a new discovery in synthetic biology might soon alter the path of scientific research and discovery in many disciplines for many years to come.

These efforts to assemble a completely new organism in the lab are, in unexpected ways, tests both of Pasteur’s and of Darwin’s rules. If we succeed in building a new organism from the genes of existing organisms—or from modified versions of those genes—we will in effect be building life from life, and in so doing, remaining faithful to Pasteur’s tenets. We are betting, of course, that genes that work well in the organism in which they evolved will also function in a completely different context—and function in the ways we want them to. This conception of genes as self-contained and context-independent units of information remains to be fully tested.

But let me be clear: There are no metaphysics here. I am not arguing that genomes are endowed with some ineffable and untestable quality. Instead, the question we are asking is whether real genomes are more than the sum of their gene parts. Genes in existing organisms, after all, have traveled together in a genome for millions of generations. We will soon find out whether the evolution of genomes involves a subtle, or perhaps a not-so-subtle, ongoing conversation among the genes that compose a genome. Take the genes entirely out of context, pair them with other genes evolved in wholly different settings, and something important may be lost.




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