Somewhere, Charles Darwin is smiling

In 1990, Craig Tuerk and Larry Gold, biologists at the University of Colorado, published a paper in the journal Science heralding a new process they called SELEX: Systematic Evolution of Ligands by Exponential Enrichment. Using the principles of Darwinian evolution — variation, selection and replication — they successfully produced an RNA molecule that bound a key viral protein extraordinarily well. Given the astounding, superficially irreducible complexity of specific molecular binding, this was a revolutionary discovery.

During the last 15 years, other scientists have used this procedure to produce similar molecules that bind disease-related proteins with what one investigator described as “exquisite” affinity. So far, scientists have been able to inhibit the replication of the Hepatitis C virus; detect anthrax spores and inhibit the replication of the feline immunodeficiency virus, the Type-1 human immunodeficiency virus, bacterial cell invasion, cancer angiogenesis and much more — all using this technique in the laboratory. While many of these experiments were done in test tubes, others were performed in living organisms with great success, and several SELEX-derived therapeutic compounds are in Stage III clinical trials and will likely reach the drug market within the next year. One drug, Macugen, is already on the market and is an effective treatment of age-related wet macular degeneration, a debilitating disease of the eyes.

Exciting as these visionary biomedical innovations are, they also present scientists, public policy makers, pharmaceutical companies and ordinary citizens with new ethical dilemmas.

The keystone of SELEX is the theory of evolution, and it could never have come into being without the theoretical work of Charles Darwin. SELEX takes a randomized library of nucleotide strands, determines which strands bind a given protein and then replicates these tightly binding sequences using an enzyme that is a ubiquitous constituent of cells. Because this enzyme has a given error rate, some of the newly produced nucleotide polymers are capable of binding the protein even more strongly than their parents. When the process is iterated many times and the produced nucleotides are selected for their ability to bind to the protein, remarkable, and therapeutically promising, molecules emerge.

What is so striking about SELEX is how similar it is to the natural process of evolution that, barring a clever joke by an omnipotent deity, appears to have unfolded on this planet over the past 4.5 billion years. All that’s required to create something so complicated as a molecule that can reverse wet macular degeneration is variation, selection and molecular polymers with differential “reproductive success.” The same ingredients and forces are likely responsible for producing the unfathomably complicated creatures we find today in nature.

If, as the references above suggest, molecular medicines synthesized using this technique (like Macugen) make it past FDA vetting and are marketed to homo sapiens, what ethical obligations do pharmaceutical companies have to consumers when it comes to reporting the research and development techniques that were used in production? In a country where, according to a November Gallup poll, 45 percent of Americans reject Darwinism and believe that God created human beings “pretty much in their present form” within the last 10,000 years, it is decidedly unethical to market Darwinian treatments without first obtaining informed consent from patients.

An ethical move would be to place warning labels on the medicines themselves, as the drug delivery system permits. A terrifying, black and white rendering of Darwin’s head would serve this purpose admirably. It would effectively alert patients of the origins of their medications and allow them to make health care decisions in accordance with their religious beliefs.

Unfortunately, if history is a reliable guide, drug companies will take the road of maximal profit, meaning that the evolutionary origins of these therapies will be obscured, resulting in a morally contradictory situation for a large number of patients.

For this reason, I believe politicians must introduce legislation ensuring our right to know how medications were produced before more drugs made using evolutionary principles reach the market.



Matthew Gillum is a first-year graduate student in molecular and cellular physiology. His column appears on alternate Fridays.

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