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September 3rd, 2013 at 2:00 pm

Peter Rabins on Causality and Evolution

“That a construct described 150 years ago is still so central to scientific thinking on the matter is a tribute to Darwin’s genius and, more importantly, evidence of the power of the proposal that he made.”—Peter Rabins

book cover

This week our featured book is The Why of Things: Causality in Science, Medicine, and Life, by Peter Rabins. Today, we are featuring an essay by Peter Rabins on causality and evolution.

You can also enter our book giveaway for a chance to win a free copy of The Why of Things

One hundred and fifty years after he proposed it, Charles Darwin’s theory of evolution remains one of the great breakthroughs in science. The combination of Darwin’s extraordinary observational skill as a descriptive naturalist (at that time a cutting edge method of science) and an ability to infer from these observations a broad theory that had powerful explanatory power is the basis of his persisting reputation.

Although the power of Darwin’s ideas was in their breadth and comprehensiveness, the idea that confirmation and refutability are two cornerstones of the scientific method were not established when Darwin was writing. There were kernels of each in Francis Bacon’s 17th century description of science, but data from such disparate fields as fruit-fly genetics, paleontology, and molecular biology have continued to uphold not only the basic concept of evolution but also many of his related ideas.

Darwin did not propose a mechanism by which evolution worked. He was very likely unaware of the work of his contemporary Mendel, the Augustinian Monk who single handedly identified the major of principles of heredity. Darwin did suggest that heredity occurred by a blending of characteristics, an idea based on his observations and the history of animal breeding.

Mendel’s work suggested a different model, one in which individual units of heredity were passed on in the familiar dominant and recessive modes. One hundred years after their work, Ernst Mayr and others brought together the approaches of Mendel, Darwin and their successors in a “grand synthesis” that combined heredity acting on individuals with evolution acting on groups. Herbert Spencer introduced the term “survival of the fittest” as a short hand for Darwin’s model, and it is this phrase that remains as the public’s view of the Darwinian model.

Watson and Crick’s 1953 demonstration that 4 distinct elements, nucleotide bases adenosine (A), guanine (G), cytosine (C) and thymidine (T), are the basic elements of the code that transmitted genetic information and that they are arranged in two strands that separate at the time of reproduction was one of the great scientific discoveries of the twentieth century. Within a decade the mechanism by which these 4 bases coded for the 20 amino acids that are needed to make the proteins of the human organism was deciphered and further advances in sequencing these 4 bases allowed for the sequencing of the human genome in 2001.

What has happened in the decade since access to complete genome sequencing became available is extraordinary. Darwin’s idea that heredity worked by blending has been upheld in a general sense, although Mendel’s proposal of a unit of heredity, later named the gene, has been confirmed as well. Perhaps the most amazing discovery has been the identification of a level of complexity to genetics that had been unrecognized.

Two examples illustrate the extraordinary ferment that is currently going on in genetics. In 1990 Mary Claire King identified mutations in the BRCA gene on chromosome 17 as the basis of a heredity form of breast cancer. This idea builds right out of Mendel (there are distinct units of heredity) and Watson-Crick (base pair differences have biological significance). Her subsequent research has identified another gene, BRCA2, which also contributes to genetic risk. Within these two genes, many distinct mutations cause disease and the specific mutation differs from family to family. This was already known to be true of cystic fibrosis, another genetic disease. For both of these diseases there is a limited number of mutations (several hundred), although many thousands of families are affected, and for cystic fibrosis, the severity of illness is partly determined by which mutation that family carries. Thus, it is the abnormal gene that contributes to both disease, and multiple abnormalities within each gene that can lead to abnormal function. This combines the Mendelian idea of a single unit of heredity and a mechanism by which graded variation, the concept of blending, might both be correct.

Many cases of breast cancer do not involve abnormalities in these genes, a situation that is true of many common diseases, which are caused by inherited mutations in some people, new mutation in the same genes in others, have abnormalities in the processes dependent upon the normal function of those genes in spite of not having a genetic abnormality, or are not associated with (or at least so far have undiscovered) gene changes. Mendel’s idea that there are units of heredity still explains such disorders although in a more complex fashion than he imagined or than geneticists conceived of before 2000.

A second new insight is that many normal traits and many diseases are associated with differences in many, sometimes hundreds, of genes, and that variation in any single gene contributes a very small amount of the overall variation. This contradicts the “unit of heredity” approach of Mendel, in which traits are attributable to single genes, and strongly supports Darwin’s concept of blending by suggesting a mechanism for it. Future research may better explain this phenomenon but the finding that illnesses as diverse as diabetes, bipolar disorder, and Parkinson disease follow this pattern of changes in many genes contributing or to or “explaining” many cases of disease is a revolutionary concept. The same is true for normal traits. Height, for example, among the most heritable of human attributes, is influenced by over 700 genes, none of which contributes more than a small amount to the overall trait. This is even stronger support for Darwin’s idea of blending.

This brief overview illustrates the magnitude of Darwin’s great idea. That a construct described 150 years ago is still so central to scientific thinking on the matter is a tribute to Darwin’s genius and, more importantly, evidence of the power of the proposal that he made. The classification of Darwinian evolution raises an interesting question, though. Is it a theory, a Law of Nature, a description of nature, a causal mechanism? I suggest it has elements of all of these, but that at its heart it is a causal mechanism. Darwin proposed to identify the Origin of Species and the Descent (evolutionary emergence) of Man. He was addressing the question, how did the earth come to be inhabited by the life forms that it now has? This was and is one of the overriding questions of biology.

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