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UNRAVELING THE SECRET OF LIFE: DNA self-duplication, the basic precept of biotechnology, is denied

by Barry Commoner
GeneWatch
May-June 2003

References

Unraveling the DNA Myth: The Spurious Foundation of Genetic Engineering

by Barry Commoner
Harper's Magazine
February 2002

Synopsis
References

The Most Common Criticism

Viewed as mere elaborations upon the Sequence Hypothesis, it becomes difficult to notice that, in fact, by challenging the genetic sovereignty of DNA, the growing array of discordant observations contradicts Crick's authentic Central Dogma. This should have caused at least a few tremors in "the intellectual foundation of molecular biology." But stripped of the fundamental challenge inherent in Crick's conceptual taboo, the up-to-date, more detailed version of his Sequence Hypothesis acquires the aura of theoretical progress and, incidentally, seems to have immunized its adherents to the article's basic argument. A few examples of this common response follow.

The central dogma has been recognized for decades as an oversimplification of how nature works, and the [article's] cited counter examples are familiar to any undergraduate majoring in molecular biology.... Now he [the author] overstates the central dogma and then is shocked, shocked that a conceptual breakthrough from 1958 is no longer enough to describe all the complexity since discovered to occur in nature." (C.F., San Diego, CA)

"[H]is argument is based either on a mis-understanding or a deliberate misrepresentation of the present models of the flow of genetic information." (N.P., PhD, Dept. of Molecular and Cellular Biology, CA)

"Unraveling the DNA Myth was one of the most lucid and readable lay descriptions of genetic processes I have read.... However...his depiction of the commitment to an obsolete theory of most molecular biologists is irresponsibly sensational and misleading to an uninformed public.... I don't think there could have been anyone who had taken an undergraduate developmental biology or genetics course who would agree with the central dogma as Dr. Commoner states it, in its strictest form." (M.K., Ontario, Canada)

There is evidently a basic disagreement between the Harper's article and most of its critics as to the definition of the cental dogma. The article adopts the definition provided by Crick (1958), which consists of two closely related "hypotheses" (Crick's description): the Sequence Hypothesis and the Central Dogma. In contrast, the article's critics have restricted the scope of the central dogma solely to the Sequence Hypothesis, apparently even unaware that Crick had originally applied the term "Central Dogma" to the very hypothesis that they now ignore.

Additional mischief has been created by this disparity between the differing definitions of the central dogma. In the Nature Genetics editorial the truncated version is characterized as "the simplified shorthand they [molecular geneticists] sometimes employ in public pronouncements" - merely a dumbed-down version of modern molecular genetics, suitable only for pronouncements to an unenlightened public. It would appear that, confronted with the growing clash between the experimental evidence and their version of the central dogma, molecular geneticists, rather than granting Crick's original theory the dignity of seriously reevaluating it, have instead condemned it to the ignominious rank of public relations.

Here it is useful to cite further from Salzberg's response to the Harper's article:

"Commoner expresses the paranoid belief that scientists have somehow been conspiring to ignore evidence that contradicts the central dogma. In fact, hundreds of scientific articles have been published that refute the now-antiquated central dogma, and, despite Commoner's claims, these have been incorporated into modern theories."

This criticism is readily refuted. First, the article does not rely on a conspiracy to explain the disparity between experimental results and theory, but rather relies on the geneticists' failure to fully grasp the content of Crick's work. Second, the article's claim is amply supported by the published literature. The more than 9,500 papers in the U.S. National Medical Library's PubMed database that deal with alternative splicing - which, under the rules established by Crick's Sequence Hypothesis, represents a Central Dogma-forbidden increase in a gene's genetic information - is a good example. When the database is searched under the term "alternative splicing AND central dogma" (i.e., a relationship between these two terms), exactly one paper turns up.

Another common argument advanced by the critics of the Harper's article is that the actions of proteins, such as those in the spliceosome that - together with associated RNAs - cause alternative splicing, are themselves governed in this activity by the genes that influence their own amino acid sequences. But this argument does nothing to preserve the neat but fallible precept that the gene exclusively governs protein amino acid sequence. Instead, the genetic information in a protein and the trait it engenders is the commingled product of genetic information derived from its own gene, but also from the numerous other genes that govern the properties of the various proteins that collaborate in the overall process. The net outcome is that no single gene is the sole source of a given protein's genetic information or of the resultant inherited trait. Indeed, it is known that the polymerase enzymes that are essential to the accurate replication of DNA contribute crucially to the extraordinary fidelity of that process in the living cell. It can therefore be said that the nucleotide sequence of a DNA gene - its genetic information - is itself the commingled product of genetic information provided by the DNA template and that provided by the enzyme proteins. This sort of multiple causation has recently been directly demonstrated with respect to the regulation ("turning on or off") of gene activity. For example, a study that searched for genes that are activated in prostate cancer cells found some 200 of them.³

Surprisingly, some of the responses that are critical of the article's attack on the exclusivity of DNA's influence on heredity agree with my position on the dangers of biotechnology. For example, N.P. (PhD from a Department of Molecular and Cellular Biology), cited earlier with regard to the article's "gross misunderstanding" of the flow of genetic information, also writes: "I share Mr. Commoner's concerns about the use of transgenic organisms in agriculture." Similarly, M.K. (Ontario, Canada), who as cited earlier complained that the article was "irresponsibly sensational and misleading" also wrote that he wholeheartedly agreed with my "point of view and strong arguments for caution in genetic engineering." This is welcome news from the proponents of molecular genetics; but unfortunately it is indeed news, for to my knowledge, as a group, they have been publicly silent on this very public issue. Given that biotechnology is based on the one gene-one protein precept (a point that has been acknowledged by Craig Venter), which even these critics agree is obsolete, they should acknowledge their obligation to say so openly to the public.⁴

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