Dangerous Misprints

M.F. Perutz

We are now within reach of being able to map all the genes on the human chromosomes, some hundred thousand of them maybe, and to decipher all the genetic information that defines a human being. This will include its sex, the chemistry of its body and its predisposition to a variety of diseases, but not, at least not yet, its personality. All this information is laid down in the human germ cells. Each of them contains 46 chromosomes, worm-like objects only just visible under a good light microscope. Each chromosome is made up of two chains of deoxyribonucleic acid, DNA for short, combined with protein. Along these chains, the genes are spread out in a linear order. A complete genetic map might tell us, for example, that the gene for little Johnny’s brown eyes is number 1349 on chromosome 23, but it would not explain why Johnny tells so many lies. So what use would that map be to you and me? Not much, as long as we keep in good health, but many serious scientists believe that such a map would be of signal benefit to medicine. On the other hand, it would also face us with formidable new moral, social, financial and legal problems. This book recounts some of the scientific adventures that brought the Genome Project into being and presents the cases for and against it, but without attempting any judgment about their relative merits.

The remarkable new scientific developments which it describes originate from a discovery by Oswald Avery, an American bacteriologist of English parents who devoted his life to finding out why some of his pneumonia patients recovered, while others died. In 1943, very near the end of his career, he solved the problem. His patients were liable to be infected by two different strains of pneumococci, distinguished by the presence and absence of only a single gene. To his own and the entire scientific world’s surprise, Avery and his collaborators found that the lethal gene was made of DNA. At first few scientists believed that so simple a molecule could specify genetic information, but its role became clear when Francis Crick and Jim Watson in Cambridge determined its three-dimensional structure. Their famous double helix showed how the genetic information is written on DNA and how it is copied every time a cell divides. Some years after this, scientists also deciphered the genetic code.

Occasionally, very rarely in fact, an error occurs in the copying of the message that makes up a gene. Even more rarely, such an error manifests itself in a malfunction or absence of the protein specified by that gene, and gives rise to a congenital disease. Queen Victoria, for instance, carried the gene for haemophilia which surfaced in some of her male descendants as a malfunctioning of a protein needed for the clotting of blood: consequently several of them bled to death.

Thanks to discoveries made over a span of many years, the genes responsible for haemophilia and several other congenital diseases have recently been mapped. The scene was set by an apparently irrelevant observation made in 1952 by Jean Weigle, a Swiss biologist in California. Weigle was puzzled by a virus that thrived in one strain of coli bacteria, languished at first in another closely-related strain, and then mysteriously regained its former vigour. Years later, another Swiss biologist, Werner Arber, decided to follow up Weigle’s seemingly trivial observation. Arber found that Weigle’s second strain restricted the virus’s growth, because it contained a scissor-like enzyme that cut its DNA. After a while the virus mobilised its defences against the bacterial scissors and thrived as before. The enzyme did not cut the DNA randomly, but at a specific word which, like ‘madam’, read the same either way and which the enzyme evidently recognised.

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