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Out of Order: Attention to detail
When I was in graduate school, I remember reading a paper that discussed the crystal structure of an enzyme called a GTPase—in this case, a signal transduction protein that undergoes a conformational change when it hydrolyzes GTP to GDP and inorganic phosphate (Pi). Two pages into the paper, I quickly grabbed my scissors and cut out a figure that illustrated the molecular bonds between the protein's active site and the GTP analogue.
It was a thing of beauty. Almost every atom of the GTP molecule 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 anniversary of the elucidation of another molecular structure—part crystallography, part Tinker Toy thought puzzle—the double-helical structure of DNA. A watershed moment by any yardstick, its impact on our world has been less about how we think about biology and more about what we realized we could do with biology.
It was a thing of beauty—an inherent simplicity of structure, and yet one that was capable of so many things. It was a figurative winding staircase to heaven for biologists and biochemists, and much later, for computational biologists. And it was something that the public could understand, if only at a very superficial level.
I would expect that almost everyone on this planet have been exposed to a zipper. Everyone knows how easily a zipper can get jammed and the impact this has on its function. How delicate and yet how strong a zipper can be. Congratulations, you now understand probably 50 percent or more of human disease.
By the same token, however, the simplicity and approachability of the double helix has had some negative repercussions. The beauty of its details has led many of us—scientific and lay people alike—to take the focus away from the big picture: human health, sustainable food sources and diverse ecosystems. This may sound like anathema to some (and perhaps signals my last commentary in ddn), but the elegance of the double helix opens the door to hyperbole about its ability to cure all our ills.
The most common metaphor for DNA is a blueprint, the belief being that all of the information required for an organism lay within its DNA and simply waits to be unlocked. It codes for the designers and workers, as well as how to combine the construction materials.
In a vacuum, this might be true. A single conversation with identical twins, however, will tell you it's not that simple. If it were, they would be identical in all aspects, but I have yet to meet identical twins that are one human in two bodies. Other factors weigh in.
DNA has a cult following; it has taken on godlike features for some. And as a society, I think it has led us to stop thinking of (or at least overlook) simpler solutions to our problems.
While one group of scientists and health professionals spends decades trying to come up with a vaccine or drug treatment for a scourge like parasitic guinea worm, another group has come in the back door and said, "what if we just filter the drinking water that contains the guinea worm eggs?" The Carter Center did this, and has practically eliminated guinea worm infection worldwide.
Because we have access to DNA, and can manipulate DNA, we often become fixated on a biological solution in the belief that we will tackle the root cause of a problem. In actual fact, most problems are like trees in that they almost never have one root. And it is important to be aware of all of those roots, so we can identify a solution that will not only work, but also work as soon as possible.
As I recently wrote in another forum, attention to detail is craftsmanship; fixation on detail is neurosis. As scientists, as corporate executives, as clinicians, as regulators, we have to make sure that we function on the side of craftsmanship, and not slip into neurotic fervor.
Molecular biological advances have changed our world for the good, and I am the first to jump up and applaud them. But it is equally important that we don't let the volume of that applause drown out the voices that offer alternative solutions.
Editor's note: For more on this issue, don't miss Willis' special report on the 60th anniversary of the DNA discovery in the June issue of ddn.
Willis is the features editor of ddn. He has worked at both ends of the pharmaceutical industry, from basic research to marketing, and has written about biomedical science for almost two decades.