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Archive for July, 2009

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

Codex Sinaiticus Goes Online

Codex Sinaiticus is one of the most important books in the world. Handwritten well over 1600 years ago, the manuscript contains the Christian Bible in Greek, including the oldest complete copy of the New Testament. Its heavily corrected text is of outstanding importance for the history of the Bible and the manuscript – the oldest substantial book to survive Antiquity – is of supreme importance for the history of the book.

From the press release: Codex Sinaiticus is one of the most important witnesses to the Greek text of the Septuagint (the Old Testament in the version that was adopted by early Greek-speaking Christians) and the Christian New Testament. No other early manuscript of the Christian Bible has been so extensively corrected. A glance at the transcription will show just how common these corrections are. They are especially frequent in the Septuagint portion. They range in date from those made by the original scribes in the fourth century to ones made in the twelfth century. They range from the alteration of a single letter to the insertion of whole sentences.

One important goal of the Codex Sinaiticus Project is to provide a better understanding of the text of the Codex and of the subsequent corrections to it. This will not only help us to understand this manuscript better, but will also give us insights into the way the texts of the Bible were copied, read and used. By the middle of the fourth century there was wide but not complete agreement on which books should be considered authoritative for Christian communities. Codex Sinaiticus, one of the two earliest collections of such books, is essential for an understanding of the content and the arrangement of the Bible, as well as the uses made of it.

The Greek Septuagint in the Codex includes books not found in the Hebrew Bible and regarded in the Protestant tradition as apocryphal, such as 2 Esdras, Tobit, Judith, 1 & 4 Maccabees, Wisdom and Sirach. Appended to the New Testament are the Epistle of Barnabas and ‘The Shepherd’ of Hermas. The idiosyncratic sequence of books is also remarkable: within the New Testament the Letter to the Hebrews is placed after Paul’s Second Letter to the Thessalonians, and the Acts of the Apostles between the Pastoral and Catholic Epistles. The content and arrangement of the books in Codex Sinaiticus shed light on the history of the construction of the Christian Bible.

The ability to place these ‘canonical books’ in a single codex itself influenced the way Christians thought about their books, and this is directly dependent upon the technological advances seen in Codex Sinaiticus. The quality of its parchment and the advanced binding structure that would have been needed to support over 730 large-format leaves, which make Codex Sinaiticus such an outstanding example of book manufacture, also made possible the concept of a ‘Bible’. The careful planning, skillful writing and editorial control needed for such an ambitious project gives us an invaluable insight into early Christian book production.

Codex Sinaiticus Online