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2 April 2009

The end of nature’s mystery

Michael Barrett, a leading research scientist, spends his days stripping life down to its chemical c

By Michael Barrett

In the beginning, God created the heaven and the earth. He then spent six days knocking together everything upon earth: millions of living species and even more now extinct ones. Yet it is not easy for biologists to believe in God the Creator; 50 years of extreme reductionism have removed much of nature’s mystery. We know all about the genetic code, and how the chemical composition of DNA can be translated into the panoply of proteins that shape cells and drive the chemical reactivity that defines each species. My job involves stripping tiny microscopic parasites down to their bare chemical components, which I compare to those of mammalian cells. I seek subtle differences that could allow us to construct molecules that interfere with parasite, but not human, chemistry. These experiments, we hope, will lead to the formulation of new drugs in our fight against disease.

Spending one’s time deconstructing life to its chemical components does, however, lead one to ask just what it is. If I took each and every chemical that comprises a cell and mixed them together, I would create nothing more than a chemical goo. There are, of course, organising principles that make life far more than the sum of its chemical parts. For some, an intelligent

designer could do this. Elsewhere, a relatively young discipline called systems biology aims to combine knowledge of the cellular chemical parts list with high-power computation to try to identify whether those organising principles themselves are no more than a mathematical consequence of self-assembled parts and time.

So far, for all our posturing, no one has come close to creating a living organism from a non-living, “abiotic” start. Craig Venter, famed for his profit-driven efforts to sequence the human genome, is making much fanfare about his attempts to “create” a new life form. In reality, however, all Venter is aiming to do is add a new, synthesised, genetic blueprint to a preorganised cellular system. This is an extreme version of the genetic engineering of microbes that has been going on for several decades now.

When Charles Darwin published On the Origin of Species in 1859, he conspicuously evaded an explanation of man’s position in the evolutionary tree. He also failed to touch on just how the whole thing got going. Naturally, he did have thoughts on the subject. “But if (and oh what a big if) we could conceive in some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, &c. present, that a proteine [sic] compound was chemically formed ready to undergo still more complex changes,” he wrote to his friend the botanist Joseph Hooker in 1871.

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By the early 20th century the great British geneticist J B S Haldane had transmuted Darwin’s “warm little pond” into the so-called “primordial soup theory”, evoking a watery planet, warm and rich in gaseous chemicals such as ammonia, hydrogen, methane and carbon dioxide. In 1953, the American Stanley Miller tried to

re-create such a primordial soup in the laboratory. He set up a series of test tubes containing water, many of the proposed gases and a supply of electric sparks to mimic the lightning-charged atmosphere of early earth. Remarkably, those simple gases were easily converted into some of the basic organic chemicals typically found in living organisms. Miller’s success led to the hope that it would be only a matter of time before simple biochemicals could be turned into the more complex molecular strings characteristic of living cells today. But decades of ever more sophisticated experimentation have failed to yield significant advances.

Proponents of the “abiotic” origin of life point out that the four to five billion years of earth history is rather longer than the 56 years since Miller’s experiment. Some scientists believe that life could have evolved anywhere in the universe and then been carried on comets from solar system to solar system, from planet to planet. Such astrobiological origins would lead to a vastly increased probability that conditions suitable to spark life were met somewhere.

As a biochemist, I retain faith in the notion that life evolved through spontaneous chemical reactivity. One theory points to life emerging during the Hadean Aeon in the hot depths of the ocean. This era covers the first half-billion or so years of Planet Earth’s history, when volcanic matter was constantly spewing up through the ocean floor, heating water and causing an extraordinary mix of chemical constituents. The problem with this idea, however, is that the molecules forming in such conditions diffuse throughout the ocean, so diluting them to negligible levels.

The British geologist Mike Russell and Bill Martin, an American evolutionary biologist, adapted the so-called iron-sulphur world theory to try to lead us from simple chemical reactions to entities recognisable as living cells. Iron-sulphur complexes are among the best chemical catalysts that we know today, and iron and sulphur are abundant in volcanic exhalations. Many of the proteins (called enzymes) that catalyse the reactions of cellular life today use little iron-sulphur clusters, buried deep within their structures.

According to Russell and Martin, iron-sulphur deposits within tiny cavities in Hadean rocks (think, for example, of the holes in pumice stone – only smaller) could have catalysed the for­mation of a multitude of biochemicals. In the enclosed environment of those cavities, these chemicals could accumulate. Some molecules can actually catalyse their own production. Many evolutionary biologists today believe that some time after the first chemical burst, the emergence of so-called ribonucleic acids (RNAs) provided a huge expansion in self-replicating and, critically, mutating chemistry. Today, we know that RNA can fold in ways to drive its own assembly, and to catalyse the formation of other molecular configurations as well. Complex novel chemicals could emerge. Among these would be the structures we know as lipids, which are capable of forming self-sealing membrane bags. These lipid bounded bags could then free the chemical reaction chambers from their rocky confines. The first free living cells would be born. The processes of Darwinian evolution would then select those that were able to survive and replicate the best.

The individual steps of Russell and Martin’s theory are feasible. But did they happen? Obviously it is difficult to obtain definitive proof for events that occurred billions of years ago. So we have to accept that many of the steps in this, and other origin theories, as is often said, “could happen given enough time and the right conditions”. Divine interventionists can rightly argue that the abiotic, chemical view is no more proven than the existence of their omnipotent Creator.

The unrelenting deconstruction of life’s mysteries to their chemical bare bones, however, leaves me believing that we really are no more than a bag of chemicals; our oldest ancestors no more than a string of self-assembling molecular building blocks; our very consciousness nothing more than the output of a chemically driven series of electrical impulses, selected ultimately, perhaps, to ensure the propagation of a seminal chemical reaction.

Michael Barrett is professor of biochemical parasitology at the University of Glasgow

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