The DNA Myth

What’s in a name? by Grain

The central dogma of the Life Science industry was first put forward by Watson and Crick in the 1950s. It says that our genes, aligned on a double helix of two chains of nucleotides (DNA), can be read like the code of a computer programme. The code is said to be simple and universal, with each trait determined by one or more genes: one gene one protein one function. But recent advances in molecular biology, in particular the mapping of the genomes of humans and other organisms, have not revealed the “secret of life”, rather they have revealed our ignorance in the face of life's profound complexity. We now know that biological function results from a much more complex model of genetic interactions taking place within the cell and between the organism's genome and its larger (virtually limitless) environment. Yesterday's so-called “junk DNA”, the large amount of DNA that does not code directly for a protein, is now recognised as playing a critical function in modulating gene function.

But as molecular biology moves towards a more ecological understanding of living organisms, in which the gene hinders the understanding of biologists, the gene continues to dominate scientific and popular discourse. Scientists and industry, clinging to outdated, linear genetic determinism, still speak about genes as the wellsprings of cures for disease and hunger. Every week comes a new announcement about the ‘discovery' of some gene for some application. Money changes hands and stock prices go up. While the gene's currency is declining in scientific circles, it remains the centerpiece of a multi-billion dollar industry, whose future depends on a clean cut, predictable gene. Acknowledging the true complexity of genes and heredity would mean opening a Pandora's box of regulatory and biosafety nightmares, and death to the industry.

Throughout almost all the 10,000 year history of agriculture, “plant breeder” was synonymous with “farmer”. The patient and careful work of millions of farmers produced an endless wealth of crops and varieties, with their myriad colours, flavours, needs, uses, adaptive characteristics, sub-products, growth habits, and so on. Then, around one hundred years ago, scientists decided that farmers did not know a thing and claimed a monopoly over plant breeding. Farmers were told they were ignorant and their seeds worthless, while seeds bred by scientists (using the very same seeds of farmers they said were useless) were presented as all that were worth planting.

Unraveling the DNA Myth by Barry Commoner

There is a crucial problem in molecular genetics and in its applications to agriculture, medicine and the production of pharmaceutical drugs. This science is based on a 50-year old theory that says DNA alone governs inheritance. Molecular genetics is now confronted with a growing disjunction between this widely accepted premise and an array of discordant experimental results that contradict it. But this disparity remains largely unacknowledged and experiments with transgenic plants and animals (many of which are not even recognised to be experiments) continue on a massive scale.

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 Science of the Century, and it stands poised to assume godlike powers of creation, calling forth artificial forms of life. 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, [1] the fatherless sheep cloned directly from her mother’s cells; these techniques have now been applied, unsuccessfully, to human cells. ANDi, a photogenic rhesus monkey, recently was born carrying the gene of a luminescent jellyfish. [2] 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 US have been genetically engineered to survive the application of powerful herbicides.

Our leading scientists and scientific entrepreneurs (two labels that are increasingly interchangeable) assure us that these feats of technological prowess, though marvellous 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. [3] ANDi, perversely, has failed to glow like a jellyfish. Genetically modified pigs have a high incidence of gastric ulcers, arthritis, enlarged hearts, 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, the plant’s own genetic system has been unwittingly altered as well, with potentially dangerous consequence. [4] The list of malfunctions gets little notice; biotechnology companies are not in the habit of publicising 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 characterise 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 genes – should fully account for its characteristic assemblage of inherited traits. [5] Since Crick first proposed it forty-four years ago, the Central Dogma has come to dominate biomedical research. Simple, elegant, and easily summarised, it seeks to reduce inheritance to molecular dimensions. The molecular agent of inheritance is DNA, deoxyribonucleic acid, a very long, linear molecule tightly coiled within each cell’s nucleus (see diagram opposite). DNA is made up of four different kinds of nucleotides, strung together in each gene in a particular linear order or sequence. Segments of DNA comprise the genes that, through a series of molecular processes, give rise to each of our inherited traits.

But the premise of the Central Dogma, unhappily, is false. Tested between 1990 and 2001 in one of the largest and most highly publicised 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. By any reasonable measure, the finding (published in February 2001) signalled the downfall of the Central Dogma. It also destroyed the scientific foundation of genetic engineering and the validity of the biotechnology industry’s widely advertised claim that its methods of genetically modifying food crops are “specific, precise, and predictable” [6] and therefore safe. In short, the most dramatic achievement to date of the $3 billion Human Genome Project is the refutation of its own scientific rationale.

In 1990, James Watson described the Human Genome Project as “the ultimate description of life”. It will yield, he claimed, the information “that determines if you have life as a fly, a carrot, or a man.” How could the minute dissection of human DNA into a sequence of 3 billion nucleotides support such a claim? Crick’s crisply stated Central Dogma attempts to answer that question. It hypothesises a clear-cut chain of molecular processes that leads from a single DNA gene to the appearance of a particular inherited trait. Crick’s second hypothesis neatly links the gene to the protein. This “sequence hypothesis” states that the gene’s genetic information is transmitted, altered in form but not in content, though RNA intermediaries, to the distinctive amino acid sequence of a particular protein. It follows that in each living thing there should be a one-to-one correspondence between the total number of genes and the total number of proteins. The entire array of human genes must therefore represent the whole of a person’s inheritance. Finally, because DNA is made of the same four nucleotides in every living thing, the genetic code is universal, which means that a gene should be capable of producing its particular protein wherever it happens to find itself, even in a different species.

Crick’s theory is based on an extravagant proposition: that genes have unique, absolute, and universal control over the totality of inheritance in all forms of life. According to Crick, genetic information originates in the DNA nucleotide sequence and terminates, unchanged, in the protein amino acid sequence. The pronouncement is crucial because it endows the gene with undiluted control over the identity of the protein and the inherited trait that the protein creates. To stress the importance of this genetic taboo, Crick bet the future of the entire enterprise on it, asserting that “the discovery of just one type of present-day cell” in which genetic information passed from protein to nucleic acid or from protein to protein “would shake the whole intellectual basis of molecular biology.” [7] Crick was aware of the brashness of his bet, for it was known even then that in living cells proteins come into promiscuous molecular contact with numerous other proteins and with molecules of DNA and RNA. He insisted that these interactions are genetically chaste.

In February 2002, Crick’s gamble suffered a spectacular loss. In the journals Nature and Science and at joint press conferences and television appearances, the two genome research teams reported their results. The major result was “unexpected.” [8] Instead of the 100,000 or more genes predicted by the estimated number of human proteins, the gene count was only about 30,000. By this measure, people are only about as gene-rich as a mustard-like weed (which has 26,000 genes) and about twice as genetically endowed as a fruit fly or a primitive worm. [9] The surprising results contradicted the scientific premise on which the genome project was undertaken and dethroned its guiding theory, the Central Dogma. After all, if the human gene count is too low to match the number of proteins and the numerous inherited traits that they engender, and if it cannot explain the vast inherited difference between a weed and a person, there must be much more to Watson’s “ultimate description of life” than the genes alone can tell us.

Scientists and journalists somehow failed to notice what had happened. The project’s scientific reports offered little to explain the shortfall in the gene count. One of the possible explanations for why the gene count was “so discordant with our predictions” was described in Science as follows: “nearly 40% of human genes are alternatively spliced.” [10] Properly understood, this modest, if esoteric, account fulfills Crick’s dire prophecy: it “shakes the whole intellectual basis of molecular biology” and undermines the scientific validity of its application to genetic engineering. Alternative splicing is a startling departure from the orderly design of the Central Dogma, in which a single gene encodes the amino acid sequence of a single protein. In alternative splicing, the gene’s original nucleotide sequence is split into fragments that are then recombined in different ways to encode a multiplicity of proteins, each of them different in their amino acid sequence from each other and from the sequence that the original gene, if left intact, would encode. Alternative splicing can have an extraordinary impact on the gene/protein ratio. 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. [11]

Alternative splicing thus has a devastating impact on Crick’s theory: it breaks open the hypothesised isolation of the molecular system that transfers genetic information from a single gene to a single protein. It also contradicts the theory that proteins cannot transmit genetic information to nucleic acid (in this case, messenger RNA). [12] The discovery of alternative splicing also nullifies the exclusiveness of the gene’s hold on the molecular process of inheritance. The gene’s effect on inheritance thus cannot be predicted simply from its nucleotide sequence – the determination of which is one of the main purposes of the Human Genome Project.

Grain website

Barry Commoner's Critical Genetics Project

Note: What’s in a name? by Grain Unraveling the DNA Myth... Grain website Critical Genetics Project