Editor's Note: Philip Skell's Opinion in the Aug. 29, 2005 issue,"Why do we invoke Darwin?" (19 [16]:10)generated a tremendous response from readers. Here we present a selection of edited letters. Please continue the discussion in our new forum on The Scientistwebsite athttp://media.the-scientist.com/talkingpoints/.

Philip Skell's opinion highlights the proximate vs. ultimate causation dichotomy that's so familiar to biology students. One might conclude that the question is unfair in asking evolutionary theory to address proximate issues rather than those it is more appropriately concerned with – questions about why something is the way it is.

Philip Skell is ignoring the agent who "makes sense" in the famous Dobzhansky quote. Some experimental biologists don't "need" an understanding of the role the process they are investigating plays in evolution because they are so specialized and mentally narrow that they operate as technicians, however competent, not PhDs. Anyone can drive...

Skell's finding that Darwin has had no effect on his research results from his peculiar point of view as a chemist who dabbles in biology. As a biologist who dabbles in chemistry, I have a different point of view. Darwin, of course, had no effect on any of my chemical research. Darwin also had little or no influence on my research on blood clotting or cancer. The other half of my research has been on skin, where Darwin had a major influence on my choice of projects, research design, and interpretation of the results.

Philip Skell was unduly selective in his choice of eminent scientists and areas of biology to cite with regard to the role that evolutionary theory played in how they conducted their scientific work. My field, comparative physiology, has proven highly fruitful in investigating, from an explicitly evolutionary perspective, such diverse biological topics as nerve function (a Nobel Prize for that), muscle contraction (another Nobel Prize), digestion, environmental adaptation, neurophysiological mechanisms, endocrine function (another Nobel Prize), vision (another Nobel Prize), and a host of other topics (and several more Nobel Prizes).

Some small parts of biology may be able to ignore evolutionary biology, but when we try and understand how these parts fit together, it is difficult to see how we can avoid using it as a heuristic framework, unless we replace it with another. Will Skell be suggesting an alternative?

It is unfortunate that chemist Philip Skell chose to air his ignorance of biology in public. Chemistry is fortunate in that its basic tenets are not under attack from religious fundamentalists. But you never know, some folks may come up with the idea of "intelligent ions" and want to teach it in the public schools as an alternative "theory" to "Daltonism," and want to put disclaimers in chemistry text books stating that atomic theory is "only a theory."

Philip Skell somewhat misleadingly conflates two complementary epistemological tools offered by Darwin's "theory" (better referred to as "Darwin's established scientific fact") of evolution of species by means of natural selection. The first is the appearance of adaptation under environmental and other pressure – this is, indeed, not a useful heuristic in biological research because natural selection does not yield the optimal, but only the improved. The second is the relatedness of all life forms on earth through an evolutionary tree, and the differential selective pressure on essential vs. species-specific processes.

My field of immediate technical expertise – the biology of genome control in eukarya – has benefited from this latter heuristic immensely. Nothing in genome biology makes sense except in light of evolution because core genome regulatory processes are conserved and related, and their comparison across taxa (most notably, between E. coli, budding yeast, fruit fly, and mouse), has single-handedly revolutionized our understanding of genome control.

In fields such as ethology, ecology, and evolution, Darwinian evolution has without doubt provided more than just a "fruitful heuristic." The study of sociality is just one area where evolutionary explanations (particularly kin selection) have been supported by experimental evidence, as recent high profile papers in Nature and Science have demonstrated.12

In answer to "Why do we invoke Darwin?" Even though tools are the forces that set off revolutions in science when there are no paradigms to be overthrown, the Darwinian concept of evolution has provided, without doubt, an enormous "heuristic." Why is there this intense effort to sequence not just the entire genome of humans, but also the genomes of many other species? Now, scientists all over the world can read the billions – nay trillions of nucleotides: This is the amazing recording of how evolution – the blind watchmaker – designed all living matter. Darwinian evolution is no longer a theory. It is a documented fact. Go and scrutinize the comparative genomes and after a few years of study tell me that this is not a tangible breakthrough.

An emerging field in biotechnology field stands to challenge Skell's assertion: the field of directed molecular evolution, also thought of as "Darwinian evolution in the test tube." Directed evolution aims at improving proteins (or nucleic acids), by mimicking the basic steps of the Darwinian evolution process: creating a genetic diversity, then selecting a subset of "adapted" genes. Over the last decade, a number of important proteins have been produced by directed evolution in academic labs and private companies: highly specific and affine antibodies against virtually any target, enzymes active at low temperature for laundry, thermostable enzymes for various industrial purposes, and others.

Philip Skell responds: My essay about Darwinism and modern experimental biology has stirred up a lively discussion, but the responses still provide no evidence that evolutionary theory is the cornerstone of experimental biology. Comparative physiology and comparative genomics have certainly been fruitful, but comparative biology originated before Darwin and owes nothing to his theory. Before the publication of The Origin of Species in 1859, comparative biology focused mainly on morphology, because physiology and biochemistry were in their infancy and genomics lay in the future; but the extension of a comparative approach to these sub-disciplines depended on the development of new methodologies and instruments, not on evolutionary theory and immersion in historical biology.

One letter mentions directed molecular evolution as a technique to discover antibodies, enzymes and drugs. Like comparative biology, this has certainly been fruitful, but it is not an application of Darwinian evolution – it is the modern molecular equivalent of classical breeding. Long before Darwin, breeders used artificial selection to develop improved strains of crops and livestock. Darwin extrapolated this in an attempt to explain the origin of new species, but he did not invent the process of artificial selection itself.

It is noteworthy that not one of these critics has detailed an example where Darwin's Grand Paradigm Theory guided researchers to their goals. In fact, most innovations are not guided by grand paradigms, but by far more modest, testable hypotheses. Recognizing this, neither medical schools nor pharmaceutical firms maintain divisions of evolutionary science. The fabulous advances in experimental biology over the past century have had a core dependence on the development of new methodologies and instruments, not by intensive immersion in historical biology and Darwin's theory, which attempted to historicize the meager documentation.

Evolution is not an observable characteristic of living organisms. What modern experimental biologists study are the mechanisms by which living organisms maintain their stability, without evolving. Organisms oscillate about a median state; and if they deviate significantly from that state, they die. It has been research on these mechanisms of stability, not research guided by Darwin's theory, which has produced the major fruits of modern biology and medicine. And so I ask again: Why do we invoke Darwin?

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