Saturday, December 01, 2007

Genetic Engineering Part 4

The Spurious Foundation of Genetic Engineering

by Barry Commoner

Biology once was regarded as a languid, largely descriptive discipline, a passive science that was content, for much of its history, merely to observe the natural world rather than change it. No longer. Today biology, armed with the power of genetics, has replaced physics as the activist Science of the Century and it stands poised to assume godlike powers of creation, calling forth artificial forms of life rather than undiscovered elements and sub-atomic particles. The initial steps toward this new Genesis have been widely touted in the press. It wasn't so long ago that Scottish scientists stunned the world with Dolly, the fatherless sheep cloned directly from her mother's cells: these techniques have now been applied, unsuccessfully, to human cells. AND, a photogenic rhesus monkey, recently was born carrying the gene of a luminescent jellyfish. Pigs now carry a gene for bovine growth hormone and show significant improvement in weight gain, feed efficiency, and reduced fat. Most soybean plants grown in the United States have been genetically engineered to survive the application of powerful herbicides. Corn plants now contain a bacterial gene that produces an insecticidal protein rendering them poisonous to earworms.

Our leading scientists and scientific entrepreneurs (two labels that are increasingly interchangeable) assure us that these feats of technological prowess, though marvelous and complex, are nonetheless safe and reliable. We are told that everything is under control. Conveniently ignored, forgotten, or in some instances simply suppressed are the caveats, the fine print, the flaws and spontaneous abortions. Most clones exhibit developmental failure before or soon after birth, and even apparently normal clones often suffer from kidney or brain malformations. AND, perversely, has failed to glow like a jellyfish. Genetically modified pigs have a high incidence of gastric ulcers, arthritis, cardiomegaly (enlarged heart), dermatitis, and renal disease. Despite the biotechnology industry's assurances that genetically engineered soybeans have been altered only by the presence of the alien gene, as a matter of fact the plant's own genetic system has been unwittingly altered as well, with potentially dangerous consequences. The list of malfunctions gets little notice; biotechnology companies are not in the habit of publicizing studies that question the efficacy of their miraculous products or suggest the presence of a serpent in the biotech garden.

The mistakes might be dismissed as the necessary errors that characterize scientific progress. But behind them lurks a more profound failure. The wonders of genetic science are all founded on the discovery of the DNA double helix - by Francis Crick and James Watson in 1953 - and they proceed from the premise that this molecular structure is the exclusive agent of inheritance in all living things: in the kingdom of molecular genetics, the DNA gene is absolute monarch. Known to molecular biologists as the "central dogma" the premise assumes that an organism's genome - its total complement of DNA genes - should fully account for its characteristic assemblage of inherited traits. The premise, unhappily, is false. Tested between 1990 and 2001 in one of the largest and most highly publicized scientific undertakings of our time, the Human Genome Project, the theory collapsed under the weight of fact. There are far too few human genes to account for the complexity of our inherited traits or for the vast inherited differences between plants, say, and people.

DNA has been assumed to be the blueprint of characteristics of an organism What the Genome project revealed was that this assumption is too simplistic and there are unknown (interactive) factors at work that influence the development of an organism. What does this mean for genetic engineering?

Alternative splicing can have an extraordinary impact on the gene/protein ratio. We now know that a single gene originally believed to encode a single protein that occurs in cells of the inner ear of chicks (and of humans) gives rise to 576 variant proteins, differing in their amino acid sequences. The current record for the number of different proteins produced from a single gene by alternative splicing is held by the fruit fly, in which one gene generates up to 38,016 variant protein molecules.

In other words, the results are unpredictable.

The credibility of the Human Genome Project is not the only casualty of the scientific community's stubborn resistance to experimental results that contradict the central dogma. Nor is it the most significant casualty. The fact that one gene can give rise to multiple proteins also destroys the theoretical foundation of a multibillion-dollar industry, the genetic engineering of food crops. In genetic engineering it is assumed, without adequate experimental proof, that a bacterial gene for an insecticidal protein, for example, transferred to a corn plant, will produce precisely that protein and nothing else. Yet in that alien genetic environment, alternative splicing of the bacterial gene might give rise to multiple variants of the intended protein - or even to proteins bearing little structural relationship to the original one, with unpredictable effects on ecosystems and human health.

Because of their commitment to an obsolete theory, most molecular biologists operate under the assumption that DNA is the secret of life, whereas the careful observation of the hierarchy of living processes strongly suggests that it is the other way around: DNA did not create life; life created DNA. When life was first formed on the earth, proteins must have appeared before DNA because, unlike DNA, proteins have the catalytic ability to generate the chemical energy needed to assemble small ambient molecules into larger ones such as DNA. DNA is a mechanism created by the cell. Early life survived because it grew, building up its characteristic array of complex molecules. It must have been a sloppy kind of growth; what was newly made did not exactly replicate what was already there. But once produced by the primitive cell, DNA could become a stable place to store structural information about the cell's chaotic chemistry, something like the minutes taken by a secretary at a noisy committee meeting. There can be no doubt that the emergence of DNA was a crucial stage in the development of life, but we must avoid the mistake of reducing life to a master molecule in order to satisfy our emotional need for unambiguous simplicity. The experimental data, shorn of dogmatic theories, points to the irreducibility of the living cell, the inherent complexity of which suggests that any artificially altered genetic system, given the magnitude of our ignorance, must sooner or later give rise to unintended, potentially disastrous, consequences. We must be willing to recognize how little we truly understand about the secrets of the cell, the fundamental unit of life.

Barry Commoner is senior scientist at the Center for Biology of Natural Systems at Queen's College, City University of New York where he directs the Critical Genetics Project. Readers can obtain a list of references used as sources for this article by sendin a request to: cbns@cbns.qc.edu

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