Why "magic molecule" no "magic bullet" (25/8/2003)

Recently we carried a letter from Dr Patricia Elliott responding to a piece in the Financial Times by Greg Conko and Henry I Miller.

Dr Elliott accused Conko and Miller, who had claimed the safety of GM foods was more than proven and their benefits were 'legion', of 'bad science' - making claims unsupported by credible research - and she challenged them to identify any research regarding the effects on human health of any GM product.

Alan Malcolm of the Institute of Biology subsequently replied to Dr Elliott's challenge (GM products can be the best option, Financial Times, Aug 21, 2003), using the examples of GM insulin and Factor IX.

In her reply (item 1 below) to Malcolm, Dr Elliott contrasts how such GM products are regulated in the medical field with the safety testing, or lack of it, for agricultural products.

But the excerpt (item 2 below) from a recent article by Richard Lewontin, the evolutionary geneticist and Alexander Agassiz Research Professor at Harvard University, makes clear how the approval of products like GM insulin itself raises questions about the safety of genetically engineered products.

Prof Lewontin's article is worth reading in full. He shows how DNA has been mythologised. Properties are attributed to it (principally, that of making proteins and of self-replication) that biologists know to be false. DNA, Lewontin shows, has been turned into a "magic molecule" but only by divorcing it from all the complexity of its actual context - biological, environmental, social, and economic.

Ignoring these complexities is a dangerous game - one that guarantees results other than the ones predicted. This is why, says Lewontin, we do not have a single case of a successful cure for a disease by means of gene therapy. And even if at some point in the future that is achieved, it is likely to be of very limited value. The claim that the manipulation of DNA is the path to general health is totally unfounded. It is actually irrelevant to the majority of instances of human ill health.

On the other hand, the possibility of using genetically transformed organisms for the commercial production of biologically useful molecules has been realised, notably in the case of genetically engineered human insulin. But, says Lewontin, when we begin to look at the complexity of this product's clinical, biological and economic context, we discover that it is far removed from a magic bullet. For some, in fact, it is life threatening.

Lewontin's article available in full here:
Worth reading in conjunction with Barry Commoner's article on DNA
replication, Unraveling the Secret of Life

1.LETTERS TO THE EDITOR: GM safety first
2.The DNA Era - Richard Lewontin
3.Coma dangers to 15,000 switched to GE human substitute
1.LETTERS TO THE EDITOR: GM safety first
Financial Times, Aug 25, 2003
By Patricia Elliott
Sir, May I thank your correspondent Alan Malcolm, (Letters, August 21) for responding to my request for any research evidence supporting the claim that genetically modified products were safe when consumed by humans.

His reference to GM insulin and Factor IX reminds us that such products, when used for medical treatment, have had to meet stringent safety standards and are continuously monitored after approval. So far, no GM food product has met these standards. The new European Union directive has improved the requirements that have to be met and the statutory post-marketing monitoring plan, if properly enforced, would help to bridge the gap, though the practical difficulties are much greater than in the medical field.

Patricia Elliott, Saffron Walden, Essex
2.The DNA Era
by Richard C. Lewontin [EXCERPTS]

The last fifty years have seen the reorganization of most of biology around DNA as the central molecule of heredity, development, cell function and evolution. Nor is this reorganization only a reorientation of experiment. It informs the entire structure of explanation of living processes and has become the center of the general narrative of life and its evolution. An entire ideology has been created in which DNA is the "Secret of Life", the "Master Molecule", the "Holy Grail" of biology, a narrative in which we are "lumbering robots created, body and mind" by our DNA. This ideology has implications, not only for our understanding of biology, but for our attempts to manipulate and control biological processes in the interests of human health and welfare, and for the situation of the rest of the living world.

The first step in building the claim for the dominance of DNA over all living processes has been the assignment of two special properties to DNA, properties that are asserted over and over again, not only in popular expositions but in textbooks. On the one hand, it is said that DNA is self-replicating; on the other, that DNA makes proteins, the molecular building blocks of cells. But both of these assertions are false - and what is so disturbing is that every biologist knows they are false.

...the possibility of using genetically transformed organisms as factories for the commercial production of biologically useful molecules, has been realized in practice. The most famous case, the mass production of human insulin by bacteria, is particularly instructive.
Insulin for diabetics was originally extracted from cow and pig pancreases. This molecule, however, differed in a couple of amino acids from human insulin. Recently, the DNA coding sequence for human insulin has been inserted into bacteria, which are then grown in large fermenters; a protein with the amino acid sequence of human insulin is extracted from the liquid culture medium. But amino acid sequence does not determine the shape of a protein. The first proteins harvested through this process, though they possessed the correct amino acid sequence, were physiologically inactive. The bacterial cell had folded the protein incorrectly.

A physiologically active molecule was finally produced by unfolding the bacterially produced protein and refolding it under conditions that are a trade secret known only to the manufacturer, Eli Lilly. This success, however, has a severely negative consequence. For some diabetics this "human" insulin produces the symptoms of insulin shock, including loss of consciousness. Whether this effect is caused by a manufacturing impurity, or because the insulin is not folded in the same way as in the human pancreas, or because the molecule is simply too physiologically active to be taken in large discrete doses rather than internal, continuously released amounts calibrated by a normal metabolism, is unknown.
The problem is that Eli Lilly, which holds the patent on the extraction of insulin from animal pancreases, no longer produces pig or cow insulin. Hypersensitive diabetics for whom Eli Lilly's standard treatment is dangerous no longer have an easily obtainable alternative supply.
3.Report highlighted coma dangers to 15,000 sufferers who were switched to genetically-engineered human substitute

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