When I was in graduate school, I remember reading a paperthat discussed the crystal structure of an enzyme called a GTPase—in this case,a signal transduction protein that undergoes a conformational change when ithydrolyzes GTP to GDP and inorganic phosphate (Pi). Two pages into the paper, Iquickly grabbed my scissors and cut out a figure that illustrated the molecularbonds between the protein's active site and the GTP analogue.
It was a thing of beauty. Almost every atom of the GTPmolecule was touched by at least one atom of the protein—hydrogen bonds,hydrophobic interactions, ionic interactions. It was amazing. And on that day,I decided I wanted to know that much about something by the time I graduated.
I think of this moment as we approach the 60th anniversaryof the elucidation of another molecular structure—part crystallography, partTinker Toy thought puzzle—the double-helical structure of DNA. A watershedmoment by any yardstick, its impact on our world has been less about how wethink about biology and more about what we realized we could do with biology.
It was a thing of beauty—an inherent simplicity ofstructure, and yet one that was capable of so many things. It was a figurativewinding staircase to heaven for biologists and biochemists, and much later, forcomputational biologists. And it was something that the public couldunderstand, if only at a very superficial level.
I would expect that almost everyone on this planet have beenexposed to a zipper. Everyone knows how easily a zipper can get jammed and theimpact this has on its function. How delicate and yet how strong a zipper canbe. Congratulations, you now understand probably 50 percent or more of humandisease.
By the same token, however, the simplicity andapproachability of the double helix has had some negative repercussions. Thebeauty of its details has led many of us—scientific and lay people alike—totake the focus away from the big picture: human health, sustainable foodsources and diverse ecosystems. This may sound like anathema to some (andperhaps signals my last commentary in ddn),but the elegance of the double helix opens the door to hyperbole about itsability to cure all our ills.
The most common metaphor for DNA is a blueprint, the beliefbeing that all of the information required for an organism lay within its DNAand simply waits to be unlocked. It codes for the designers and workers, aswell as how to combine the construction materials.
In a vacuum, this might be true. A single conversation withidentical twins, however, will tell you it's not that simple. If it were, theywould be identical in all aspects, but I have yet to meet identical twins thatare one human in two bodies. Other factors weigh in.
DNA has a cult following; it has taken on godlike featuresfor some. And as a society, I think it has led us to stop thinking of (or atleast overlook) simpler solutions to our problems.
While one group of scientists and health professionalsspends decades trying to come up with a vaccine or drug treatment for a scourgelike parasitic guinea worm, another group has come in the back door and said, "whatif we just filter the drinking water that contains the guinea worm eggs?" TheCarter Center did this, and has practically eliminated guinea worm infectionworldwide.
Because we have access to DNA, and can manipulate DNA, weoften become fixated on a biological solution in the belief that we will tacklethe root cause of a problem. In actual fact, most problems are like trees inthat they almost never have one root. And it is important to be aware of all ofthose roots, so we can identify a solution that will not only work, but alsowork as soon as possible.
As I recently wrote in another forum, attention to detail iscraftsmanship; fixation on detail is neurosis. As scientists, as corporateexecutives, as clinicians, as regulators, we have to make sure that we functionon the side of craftsmanship, and not slip into neurotic fervor.
Molecular biological advances have changed our world for thegood, and I am the first to jump up and applaud them. But it is equallyimportant that we don't let the volume of that applause drown out the voicesthat offer alternative solutions.
Editor's note:For more on this issue, don't miss Willis' special report on the 60thanniversary of the DNA discovery in the June issue of ddn.
Willis is the featureseditor of ddn. He has worked at both ends of the pharmaceutical industry, frombasic research to marketing, and has written about biomedical science foralmost two decades.
