Random Molecular Permutations

How much predictive power does our DNA have? Let’s say that you and I have never met. If I had your complete genome mapped out would I be able to make any serious predictions about you? Hair color? Height? Weight? Personality? Career path? Many scientists believe that DNA can give us a really good idea of the type of person you are. There are a few scientists that disagree – Rupert Sheldrake is one of them. The latest issue of New Scientist magazine details the bet made between Rupert and Lewis Wolpert on this topic. At stake is a “fine case of port”.

Here is Rupert’s statement. A link to the entire article is below.

Lewis Wolpert’s faith in the predictive power of the genome is misplaced. Genes enable organisms to make proteins, but do not contain programs or blueprints, or explain the development of embryos.

The problems begin with proteins. Genes code for the linear sequences of amino acids in proteins, which then fold up into complex three-dimensional forms. Wolpert’s wager presupposes that the folding of proteins can be computed from first principles, given the sequence of amino acids specified by the genes. So far, this has proved impossible. As in all bottom-up calculations, there is a combinatorial explosion. For example, by random folding, the amino-acid chain of the enzyme ribonuclease, a small protein, could adopt more than 1040 different shapes, which would take billions of years to explore. In fact, it folds into its habitual form in 2 minutes.

Even if we could solve protein-folding, the next stage would be to predict the structure of cells on the basis of the interactions of millions of proteins and other molecules. This would unleash a far worse combinatorial explosion, with more possible arrangements than all the atoms in the universe.

Random molecular permutations simply cannot explain how organisms work. Instead, cells, tissues and organs develop in a modular manner, shaped by morphogenetic fields, first recognised by developmental biologists in the 1920s. Wolpert himself acknowledges the importance of such fields. Among biologists, he is best known for “positional information”, by which cells “know” where they are within the field of a developing organ, such as a limb. But he believes morphogenetic fields can be reduced to standard chemistry and physics. I disagree. I believe these fields have organising abilities, or systems properties, that involve new scientific principles.

The Human Genome Project has itself set back the hopes it engendered. First, our genome contains only between 20,000 and 25,000 genes, far fewer than the 100,000 expected. In contrast, sea urchins have about 26,000, and rice plants 38,000. Moreover, our genome differs very little from the chimpanzee’s genome, the sequencing of which was completed in 2005. As Svante Pääbo, director of the Chimpanzee Genome Project, commented: “We cannot see in this why we are so different from chimpanzees.”

Second, in practice, the predictive value of human genomes turns out to be low. Everyone knows tall parents tend to have tall children, and recent studies on the genomes of 30,000 people identified about 50 genes associated with being tall or short. Yet together these genes accounted for only about 5 per cent of the inheritance of height. This is not the only example of “missing heritability”. Steve Jones, professor of genetics at University College London says that “hubris has been replaced with concern”, and he suggests the present approach is “throwing good money after bad”.

Wolpert is not alone in believing in the predictive value of the genome. Governments, venture capitalists and medical charities have bet and are still betting billions of dollars on it. More than a case of fine port is at stake.

What can DNA tell us? Place your bets now

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