TCS Daily

Abundant Goodness

By Charles Murtaugh - February 28, 2003 12:00 AM

In his famous Natural Theology of 1800, English theologian William Paley advanced the so-called argument from design on behalf of the existence of God: if I should come across a watch, lying in a field, would I not know that it had a maker?

[W]hen we come to inspect the watch, we perceive . . . that its several parts are framed and put together for a purpose. . . [I]f the different parts had been differently shaped from what they are, of a different size from what they are, or placed after any other manner or in any other order than that in which they are placed, either no motion at all would have been carried on in the machine, or none which would have answered the use that is now served by it. . . The inference we think is inevitable, that the watch must have had a maker.

It would be nice, perhaps, if the molecular biologist felt a similar confidence about the object of his or her study, such that by observing the mechanism of a biomolecule one could immediately see the connection between its construction and its function. It is true enough that living things appear to act purposefully, and that their constituent parts, like human machines, serve functions. What is less apparent for an enzyme, say, than for a watch, is the connection between its structure and its function.

As often as not, I find molecular structures alien and incomprehensible, and I suspect I'm not alone: structural biologists - the folks who actually crystallize macromolecules and decipher their three-dimensional shapes - form a distinct cadre within molecular biology, closer to physicists than to stamp collectors like myself. The problem is that the pictures they generate convey too much information and too little: many macromolecules are mostly scaffolding, with only a small amount of functionally-specific structure tucked away here and there, hard to find unless you already know what you're looking for. Moreover, biological molecules tend to be very coy, binding substrates and partners only transiently, via weak bonds that are easy to exclude or overlook in a crystal structure. This gives biomolecules critical flexibility, of the sort that human designers can only dream about (and this applies in spades to nanotechnologists), but it also reduces the visual impact of the average structure. Looking at a 3-D picture of hemoglobin is not quite the same as opening up the back of a pocket watch.

The wonderful thing about structural biology, though, is that it can surprise you with insights unforeseen by conventional biochemistry. If structural biology served no purpose other than aesthetic, there wouldn't be so many structural biologists, and this week marks the fiftieth anniversary of their greatest triumph: James Watson and Francis Crick's double helix structure for DNA.

Even overlooking their ethically-questionable use of a colleague's data, it is easy to give Watson and Crick too much credit: by the time that they set out, it was already known that the genetic material consisted of DNA, that this material was contained in the chromosomes, and that genes were arranged linearly on those chromosomes. (This last finding, made by Alfred Sturtevant as an undergraduate, is my personal choice for the past century's most important biology discovery.) Nonetheless, one can imagine the frustration felt by the microscopist staring at the chromosomes, or the geneticist counting her fruit flies, so close and yet so far from the material basis of inheritance. Everyone could talk about genes, but without knowing their structure at an atomic and chemical level, no one could do anything about them.

What made the double helix so immediately compelling? First, it reduced the problem of biological information to a single line of code, in the form of base pairs, which might correspond to the linear structure of proteins. Second, as the authors famously wrote, "it has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." That is, because the information contained in the double helix is equally represented on each strand, it could be duplicated, when a cell divides, simply by peeling the molecule apart and synthesizing new strands to match the old ones.

And here was where the fun got started, from the perspective of molecular biology: the two strands of the helix line up with each other by virtue of their complementarity, displaying a sort of molecular fidelity that could be readily exploited in the lab. If I have two samples of DNA, A and B, I can tell whether they match by heating them until their weak base pairing interactions fall apart, and then mixing them: if A strands bind to B strands, I know they are similar, and by varying the temperature and time during their mixing, I can get an idea of just how similar they are. Once biologists figured this out, they were off to the races: gene cloning, DNA fingerprinting, genome microarrays, behind all the buzzwords of modern biology is the double-helical nature of DNA.

In this way, one can see the Watson and Crick finding as the beginning of an almost uninterrupted string of good luck for molecular biologists. What if the structure of DNA had been a triple-helix, with some bizarre, non-linear coding and binding properties? It's easy enough now to say that such a molecule could never have served for genetic material, but the fact is that until we discover little green men from outer space, we'll never know if there could have been a different, more complicated and less useful (from the biologist's point of view) way of constructing our chromosomes.

And since Watson and Crick? Most biologists are unsympathetic to William Paley's argument from design, but perhaps they might be susceptible to an even older argument for the existence of God, based on the abundant goodness of the world. They might say, if the DNA had been a double helix, but there hadn't been bacteriophages around to help us understand its function, that would have been enough. And if there had been bacteriophages, but no restriction enzymes to let us cut and paste DNA in the lab, that would have been enough. And if there had been restriction enzymes, but no reverse transcriptase to let us capture genes in action, that would have been enough. And if there had been reverse transcriptase, but no green fluorescent protein to light up the inside of the living cell, that would have been enough. And if...

It's not the worst argument I've heard on God's behalf, and it contains a ready rebuke to anti-biotech activists: if we're doing something against God's will, why did He give us such good tools to do it with?

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