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[s-A] Unraveling the DNA Myth

 

 

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" mindfulprophet " <MindfulProphet

Unraveling the DNA Myth

 

UNRAVELING THE DNA MYTH

The spurious foundation of genetic engineering

Barry Commoner / Harper's Magazine Feb02

 

Barry Commoner is senior scientist at the Center for

the Biology of Natural Systems at Queens 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 sending

a request to cbns.

 

 

 

Update from Dr. Commoner

30 Jan 2003

 

Greetings,

 

It is now several months since you commented (in a

letter to the editor or by e-mail to CBNS) on the

publication of my article, " Unraveling the DNA Myth, "

in the February 2002 issue of Harper's. I regret the

long delay in responding to your comments; because

of the large number of them that we received, it was

impossible to respond to them individually. (By

September 2002 there were over 400 responses to the

article, commenting on it and/or requesting the list

of references.) Instead, my colleague, Dr. Andreas

Athanasiou, and I have taken the time to prepare an

analytical response to the comments as a whole and a

summary of how the value judgments (positive/negative)

expressed in these comments were distributed among

several identifiable groups of respondents. These

analyses are now available on the new web site

http://www.criticalgenetics.org which we have just

established to facilitate the work of our Critical

Genetics Project.

 

The Critical Genetics Project is one of the programs of the Center for

the Biology of Natural Systems at Queens College, City University of

New York. The Project responds to the need to consider new ways of

understanding the roles of the living cell's molecular constituents,

such as DNA, RNA and protein, in the biology of inheritance. We plan

to establish a searchable database of the relevant research and to

prepare ongoing critical analyses of such research in publicly

accessible forms. We invite you to visit our web site, initially for

our analysis of the responses to the Harper's article and, over time,

for its ongoing program as well.

 

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 subatomic 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 Dolly1, the fatherless sheep cloned directly from her

mother's cells; these techniques have now been applied,

unsuccessfully, to human cells. ANDi2, 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.3 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.4

 

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.5 ANDi, 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.6 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.

 

Glossary of terms

 

Alternative splicing

Reshuffling of the RNA transcription of a gene's nucleotide sequence

that generates multiple proteins.

 

Cell

The fundamental, irreducible unit of life.

 

Central dogma

A theory concerning the relation among DNA, RNA, and protein in which

the nucleotide sequence of DNA exclusively governs its own replication

and engenders a specific genetic code trait.

 

Chaperone protein

Folds new strung-out proteins into the ball-like structure that

specifies their biochemical activity.

 

Gene

A term applied to segments of DNA that encode specific proteins that

give rise to inherited traits. Human DNA contains about 30,000 genes.

The term's meaning has become increasingly uncertain.

 

DNA

Deoxyribonucleic acid. A large molecule composed of a specific

sequence of four kinds of nucleotides found in the nucleus of living

cells.

 

Nucleotide

The four kinds of subunits of which nucleic acid is constructed.

 

RNA

Ribonucleic acid. Its various forms transmit genetic information from

DNA to protein.

 

Spliceosome

A specialized group of proteins and ribonucleic acids that carries out

alternate splicing.

 

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.7 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. By any

reasonable measure, the finding (published last February) signaled 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 " 8 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.

 

Since Crick first proposed it forty-four years ago, the central dogma

has come to dominate biomedical research. Simple, elegant, and easily

summarized, it seeks to reduce inheritance, a property that only

living things possess, to molecular dimensions: The molecular agent of

inheritance is DNA, deoxyribonucleic acid, a very long, linear

molecule tightly coiled within each cell's nucleus. 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:

 

Guided by Crick's theory, the Human Genome Project was intended to

identify and enumerate all of the genes in the human body by working

out the sequence of the three billion nucleotides in human DNA. 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. " Walter

Gilbert, one of the project's earliest proponents, famously observed

that the 3 billion nucleotides found in human DNA would easily fit on

a compact disc, to which one could point and say, " Here is a human

being; it's me! " 9 President Bill Clinton described the human genome as

" the language in which God created life. " 10 How could the minute

dissection of human DNA into a sequence of 3 billion nucleotides

support such hyperbolic claims? Crick's crisply stated theory attempts

to answer that question. It hypothesizes a clear-cut chain of

molecular processes that leads from a single DNA gene to the

appearance of a particular inherited trait. The explanatory power of

the theory is based on an extravagant proposition: that the DNA genes

have unique, absolute, and universal control over the totality of

inheritance in all forms of life.

 

In order to control inheritance, Crick reasoned, genes would need to

govern the synthesis of protein, since proteins form the cell's

internal structures and, as enzymes, catalyze the chemical events that

produce specific inherited traits. The ability of DNA to govern the

synthesis of protein is facilitated by their similar structures-both

are linear molecules composed of specific sequences of subunits. A

particular gene is distinguished from another by the precise linear

order (sequence) in which the four different nucleotides appear in its

DNA. In the same way, a particular protein is distinguished from

another by the specific sequence of the twenty different kinds of

amino acids of which it is made. The four kinds of nucleotides can be

arranged in numerous possible sequences, and the choice of any one of

them in the makeup of a particular gene represents its " genetic

information " in the same sense that, in poker, the order of a hand of

cards informs the player whether to bet high on a straight or drop out

with a meaningless set of random numbers.

 

Crick's " sequence hypothesis " neatly links the gene to the protein:

the sequence of the nucleotides in a gene " is a simple code for the

amino acid sequence of a particular protein. " 11 This is shorthand for

a series of well-documented molecular processes that transcribe the

gene's DNA nucleotide sequence into a complementary sequence of

ribonucleic acid (RNA) nucleotides that, in turn, delivers the gene's

code to the site of protein formation, where it determines the

sequential order in which the different amino acids are linked to form

the 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-that is, the

genome must therefore represent the whole of a person's inheritance,

which distinguishes a person from a fly, or Walter Gilbert from anyone

else. 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 includes a second doctrine, which he originally called

the " central dogma " (though this term is now generally used to

identify his theory as a whole). The hypothesis is typical Crick:

simple, precise, and magisterial. " Once (sequential) information has

passed into protein it cannot get out again. " 12 This means that

genetic information originates in the DNA nucleotide sequence and

terminates, unchanged, in the protein amino acid sequence. The

pronouncement is crucial' to the explanatory power of the theory

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. " 13

 

Crick was aware of the brashness of his bet, for it was known that in

living cells proteins come into promiscuous molecular contact with

numerous other proteins and with molecules of DNA and RNA. His

insistence that these interactions are genetically chaste was designed

to protect the DNA's genetic message-the gene's nucleotide

sequence-from molecular intruders that might change the sequence or

add new ones as it was transferred, step by step, from gene to protein

and thus destroy the theory's elegant simplicity.

 

Last February, 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. " 14 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-hardly an adequate basis for distinguishing among " life as a fly,

a carrot, or a man. " In fact, an inattentive reader of genomic CDs

might easily mistake Walter Gilbert for a mouse, 99 percent of whose

genes have human counterparts.15

 

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 the " ultimate

description of life " than the genes, on their own, can tell us.

 

Scientists and journalists somehow failed to notice what had happened.

The discovery that the human genome is not much different from the

roundworm's led Dr. Eric Lander, one of the leaders of the project, to

declare that humanity should learn " a lesson in humility. " 17 In the

New York Times, Nicholas Wade merely observed that the project's

surprising results will have an " impact on human pride " and that

" human self-esteem may be in for further blows " from future genome

analyses, which had already found that the genes of mice and men are

very similar.16

 

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 is " so discordant with our predictions " was described,

in full, last February in Science as follows: " nearly 4096 of human

genes are alternatively spliced. " 18 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 the distinctive nucleotide sequence of

a single gene encodes the amino acid sequence of a single protein.

According to Crick's sequence hypothesis, the gene's nucleotide

sequence (i.e., its " genetic information " ) is transmitted, altered in

form but not in content, through RNA intermediaries, to the

distinctive amino acid sequence of a particular protein. In

alternative splicing, however, 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.

 

The molecular events that accomplish this genetic reshuffling are

focused on a particular stage in the overall DNA-RNA-protein

progression. It occurs when the DNA gene's nucleotide sequence is

transferred to the next genetic carrier—messenger RNA. A specialized

group of fifty to sixty proteins, together with five small molecules

of RNA-known as a " spliceosome " —assembles at sites along the length of

the messenger RNA, where it cuts apart various segments of the

messenger RNA. Certain of these fragments are spliced together into a

number of alternative combinations, which then have nucleotide

sequences that differ from the gene's original one. These numerous,

redesigned messenger RNAs govern the production of an equal number of

proteins that differ in their amino acid sequence and hence in the

inherited traits that they engender. For example, when the word TIME

is rearranged to read MITE, EMIT, and ITEM, three alternative units of

information are created from an original one. Although the original

word (the unspliced messenger RNA nucleotide sequence) is essential to

the process, so is the agent that performs the rearrangement (the

spliceosome).19

 

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.20 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.21

 

Alternative splicing thus has a devastating impact on Crick's theory:

it breaks open the hypothesized isolation of the molecular system that

transfers genetic information from a single gene to a single protein.

By rearranging the single gene's nucleotide sequence into a

multiplicity of new messenger RNA sequences, each of them different

from the unspliced original, alternative splicing can be said to

generate new genetic information. Certain of the spliceosome's

proteins and RNA components have an affinity for particular sites and,

binding to them, form an active catalyst that cuts the messenger RNA

and then rejoins the resulting fragments. The spliceosome proteins

thus contribute to the added genetic information that alternative

splicing creates. But this conclusion conflicts with Crick's second

hypothesis—that proteins cannot transmit genetic information to

nucleic acid (in this case, messenger RNA)—and shatters the elegant

logic of Crick's interlocking duo of genetic hypotheses.22

 

The Precise Duplication of

DNA is accomplished by the

living cell, not by the DNA

molecule alone

 

The discovery of alternative splicing also bluntly contradicts the

precept that motivated the genome project. It nullifies the

exclusiveness of the gene's hold on the molecular process of

inheritance and disproves the notion that by counting genes one can

specify the array of proteins that define the scope of human

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. Perhaps this is why

the crucial role of alternative splicing seems to have been ignored in

the planning of the project and has been obscured by the cunning

manner in which its chief result has been reported. Although the

genome reports do not mention it, alternative splicing was discovered

well before the genome project was even planned—in 1978 in virus

replication23, and in 1981 in human cells.24 By 1989, when the Human

Genome Project was still being debated among molecular biologists, its

champions were surely aware that more than 200 scientific papers on

alternative splicing of human genes had already been published.25

Thus, the shortfall in the human gene count could—indeed should—have

been predicted. It is difficult to avoid the conclusion—troublesome as

it is that the project's planners knew in advance that the mismatch

between the numbers of genes and proteins in the human genome was to

be expected, and that the $3 billion project could not be justified by

the extravagant claims that the genome—or perhaps God speaking through

it would tell us who we are.26

 

Alternative splicing is not the only discovery over the last forty

years that has contradicted basic precepts of the central dogma. Other

research has tended to erode the centrality of the DNA double helix

itself, the theory's ubiquitous icon. In their original description of

the discovery of DNA, Watson and Crick commented that the helix's

structure " immediately suggests a possible copying mechanism for the

genetic material. " Such self-duplication is the crucial feature of

life, and in ascribing it to DNA, Watson and Crick concluded, a bit

prematurely, that they had discovered life's magic molecular key.27

 

Biological replication does include the precise duplication of DNA,

but this is accomplished by the living cell, not by the DNA molecule

alone. In the development of a person from a single fertilized egg,

the egg cell and the multitude of succeeding cells divide in two. Each

such division is preceded by a doubling of the cell's DNA; two new DNA

strands are produced by attaching the necessary nucleotides (freely

available in the cell), in the proper order, to each of the two DNA

strands entwined in the double helix. As the single fertilized egg

cell grows into an adult, the genome is replicated many billions of

times, its precise sequence of three billion nucleotides retained with

extraordinary fidelity.28 The rate of error—that is, the insertion

into the newly made DNA sequence of a nucleotide out of its proper

order—is about one in 10 billion nucleotides. But on its own, DNA is

incapable of such faithful replication; in a test-tube experiment, a

DNA strand, provided with a mixture of its four constituent

nucleotides, will line them up with about one in a hundred of them out

of its proper place. On the other hand, when the appropriate protein

enzymes are added to the test rube, the fidelity with which

nucleotides are incorporated in the newly made DNA strand is greatly

improved, reducing the error rate to one in 10 million. These

remaining errors are finally reduced to one in 10 billion by a set of

" repair " enzymes (also proteins) that detect and remove mismatched

nucleotides from the newly synthesized DNA.29

 

GENETIC INFORMATION ARISES NOT

FROM DNA ALONE BUT THROUGH

ITS ESSENTIAL COLLABORATION

WITH PROTEIN ENZYMES

 

Thus, in the living cell the gene's nucleotide code can be replicated

faithfully only because an array of specialized proteins intervenes to

prevent most of the errors—which DNA by itself is prone to make—and to

repair the few remaining ones. Moreover, it has been known since the

1960s that the enzymes that synthesize DNA influence its nucleotide

sequence. In this sense, genetic information: arises not from DNA

alone but through its essential collaboration with protein enzymes—a

contradiction of the central dogma's precept that inheritance is

uniquely governed by the self-replication of the DNA double helix.

 

Another important divergent observation is the following: in order to

become biochemically active and actually generate the inherited trait,

the newly made protein, a strung-out ribbon of a molecule, must be

folded up into a precisely organized ball-like structure. The

biochemical events that give rise to genetic traits—for example,

enzyme action that synthesizes a particular eye-color pigment—take

place at specific locations on the outer surface of the

three-dimensional protein, which is created by the particular way in

which the molecule is folded into that structure. To preserve the

simplicity of the central dogma, Crick was required to assume, without

any supporting evidence, that the nascent protein—a linear

molecule—always folded itself up in the right way once its amino acid

sequence had been determined. In the 1980s, however, it was discovered

that some nascent proteins are on their own likely to become

misfolded—and therefore remain biochemically inactive—unless they come

in contact with a special type of " chaperone " protein that property

folds them.

 

The importance of these chaperones has been underlined in recent years

by research on degenerative brain diseases that are caused by

" prions, " research that has produced some of the most disturbing

evidence that the central dogma is dangerously misconceived.30 Crick's

theory holds that biological replication, which is essential to an

organism's ability to infect another organism, cannot occur without

nucleic acid. Yet when scrapie, the earliest known such disease, was

analyzed biochemically, no nucleic acid—neither DNA nor RNA—could be

found in the infectious material that transmitted the disease. In the

1980s, Stanley Prusiner confirmed that the infectious agents that

cause scrapie, mad cow disease, and similar very rare but invariably

fatal human diseases are indeed nucleic-acid-free proteins (he named

them prions), which replicate in an entirely unprecedented way.

Invading the brain, the prion encounters a normal brain protein, which

it then refolds to match the prion's distinctive three-dimensional

shape. The newly refolded protein itself becomes infectious and,

acting on another molecule of the normal protein, sets up a chain

reaction that propagates the disease to its fatal end.31

 

The prion's unusual behavior raises important questions about the

connection between a protein's amino acid sequence and its

biochemically active, folded-up structure. Crick assumed that the

protein's active structure is automatically determined by its amino

acid sequence (which is, after all, the sign of its genetic

specificity), so that two proteins with the same sequence ought to be

identical in their activity. The prion violates this rule. In a

scrapie-infected sheep, the prion and the brain protein that it

refolds have the same amino acid sequence, but one is a normal

cellular component and the other is a fatal infectious agent. This

suggests 'that the protein's folded-up configuration is, to some

degree, independent of its amino acid sequence and therefore

determined, in part, by something other than the DNA gene that

governed the synthesis of that sequence. And since the prion protein's

three-dimensional shape is endowed with transmissible genetic

information, it violates another fundamental Crick precept as well—the

forbidden passage of genetic information from one protein to another.*

Thus, what is known about the prion is a somber warning that processes

far removed from the conceptual constraints of the central dogma are

at work in molecular genetics and can lead to fatal disease.**

 

* Although Crick localizes the protein's genetic information

in its amino acid sequence, it must also be found in the protein s

three-dimensional folded structure, an the surface of which the highly

specific biochemical activity that generates the inherited trait takes

place.

 

** In 1997, when Prusiner was awarded the Nobel Prize, several

scientists publicly denounced the decision because that the prion,

through infectious, is a nucleic-acid-free protein contradicted the

central dogma and was too controversial to warrant the award. This

bias impeded not only scientific progress but human health as well.

Although Prusiner's results explained why the prion's structure

resists them, conventional sterilization procedures were nevertheless

relied on to fight mad cow disease in Britain, with fatal results.

 

By the mid 1980s, therefore, long before the $3 billion Human Genome

Project was funded, and long before genetically modified crops began

to appear in our fields, a series of protein-based processes had

already intruded on the DNA gene's exclusive genetic franchise. An

array of protein enzymes must repair the all-too-frequent mistakes in

gene replication and in the transmission of the genetic code to

proteins as well. Certain proteins, assembled in spliceosomes, can

reshuffle the RNA transcripts, creating hundreds and even thousands of

different proteins from a single gene. A family of chaperones,

proteins that facilitate the proper folding— and therefore the

biochemical activity—of newly made proteins, form an essential part of

the gene-toprotein process. By any reasonable measure, these results

contradict the central dogma's cardinal maxim: that a DNA gene

exclusively governs the molecular processes that give rise to a

particular inherited trait. The DNA gene clearly exerts an important

influence on inheritance, but it is not unique in that respect and

acts only in collaboration with a multitude of protein-based processes

that prevent and repair incorrect sequences, transform the nascent

protein into its folded, active form, and provide crucial added

genetic information well beyond that originating in the gene itself.

The net outcome is that no single DNA gene is the sole source of a

given protein's genetic information and therefore of the inherited trait.

 

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.

 

The delay in dethroning the all-powerful gene led in the 1990s to a

massive invasion of genetic engineering into American agriculture,

though its scientific justification had already been compromised a

decade or more earlier. Nevertheless, ignoring the profound fact that

in nature the normal exchange of genetic material occurs exclusively

within a single species, biotech-industry executives have repeatedly

boasted that, in comparison, moving a gene from one species to another

is not only normal but also more specific, precise, and predictable.

In only the last five years such transgenic crops have taken over 68

percent of the U.S. soybean acreage, 26 percent of the corn acreage,

and more than 69 percent of the cotton acreage.32

 

That the industry is guided by the central dogma was made explicit by

Ralph W.F. Hardy, president of the National Agricultural Biotechnology

Council and formerly director of life sciences at DuPont, a major

producer of genetically engineered seeds. In 1999, in Senate

testimony, he succinctly described the industry's guiding theory this

way: " DNA (top management molecules) directs RNA formation (middle

management molecules) directs protein formation (worker molecules). " 33

The outcome of transferring a bacterial gene into a corn plant is

expected to be as predictable as the result of a corporate takeover:

what the workers do will be determined precisely by what the new top

management tells them to do. This Reaganesque version of the central

dogma is the scientific foundation upon which each year billions of

transgenic plants of soybeans, corn, and cotton are grown with the

expectation that the particular alien gene in each of them will be

faithfully replicated in each of the billions of cell divisions that

occur as each plant develops; that in each of the resultant cells the

alien gene will encode only a protein with precisely the amino acid

sequence that it encodes in its original organism; and that throughout

this biological saga, despite the alien presence, the plant's natural

complement of DNA will itself be properly replicated with no abnormal

changes in composition.

 

In an ordinary unmodified plant the reliability of this natural

genetic process results from the compatibility between its gene system

and its equally necessary protein-mediated systems. The harmonious

relation between the two systems develops during their cohabitation,

in the same species, over very long evolutionary periods, in which

natural selection eliminates incompatible variants. In other words,

within a single species the reliability of the successful outcome of

the complex molecular process that gives rise to the inheritance of

particular traits is guaranteed by many thousands of years of testing,

in nature.

 

In a genetically engineered transgenic plant, however, the alien

transplanted bacterial gene must properly interact with the plant's

protein-mediated systems. Higher plants, such as corn, soybeans, and

cotton, are known to possess proteins that repair DNA miscoding;34

proteins that alternatively splice messenger RNA and thereby produce a

multiplicity of different proteins from a single gene;35 and proteins

that chaperone the proper folding of other, nascent proteins.36 But

the plant systems' evolutionary history is very different from the

bacterial gene's. As a result, in the transgenic plant the harmonious

interdependence of the alien gene and the new host's protein-mediated

systems is likely to be disrupted in unspecified, imprecise, and

inherently unpredictable ways. In practice, these disruptions are

revealed by the numerous experimental failures that occur before a

transgenic organism is actually produced and by unexpected genetic

changes that occur even when the gene has been successfully transferred.37

 

Most alarming is the recent evidence that in a widely grown

genetically modified food crop—soybeans containing an alien gene for

herbicide resistance—the transgenic host plant's genome has itself

been unwittingly altered. The Monsanto Company admitted in 2000 that

its soybeans contained some extra fragments of the transferred gene,

but nevertheless concluded that " no new proteins were expected or

observed to be produced. " 38 A year later, Belgian researchers

discovered that a segment of the plant's own DNA had been scrambled.

The abnormal DNA was large enough to produce a new protein, a

potentially harmful protein.39

 

One way that such mystery DNA might arise is suggested by a recent

study showing that in some plants carrying a bacterial gene, the

plant's enzymes that correct DNA replication errors rearrange the

alien gene's nucleotide sequence.40 The consequences of such changes

cannot be foreseen. The likelihood in genetically engineered crops of

even exceedingly rare, disruptive effects of gene transfer is greatly

amplified by the billions of individual transgenic plants already

being grown annually in the United States.

 

The degree to which such disruptions do occur in genetically modified

crops is not known at present, because the biotechnology industry is

not required to provide even the most basic information about the

actual composition of the transgenic plants to the regulatory

agencies. No tests, for example, are required to show that the plant

actually produces a protein with the same amino acid sequence as the

original bacterial protein. Yet this information is the only way to

confirm that the transferred gene does in fact yield the

theory-predicted product. Moreover, there are no required studies

based on detailed analysis of the molecular structure and biochemical

activity of the alien gene and its protein product in the transgenic

commercial crop. Given that some unexpected effects may develop very

slowly, crop plants should be monitored in successive generations as

well. None of these essential tests are being performed, and billions

of transgenic plants are now being grown with only the most

rudimentary knowledge about the resulting changes in their

composition. Without detailed, ongoing analyses of the transgenic

crops, there is no way of knowing if hazardous consequences might

arise. Given the failure of the central dogma, there is no assurance

that they will not. The genetically engineered crops now being grown

represent a massive uncontrolled experiment whose outcome is

inherently unpredictable. The results could be catastrophic.

 

Crick's central dogma has played a powerful role in creating both the

Human Genome Project and the unregulated spread of genetically

engineered food crops. Yet as evidence that contradicts this governing

theory has accumulated, it has had no effect on the decisions that

brought both of these monumental undertakings into being. It is true

that most of the experimental results generated by the theory

confirmed the concept that genetic information, in the form of DNA

nucleotide sequences, is transmitted from DNA via RNA to protein. But

other observations have contradicted the one-to-one correspondence of

gene to protein and have broken the DNA gene's exclusive franchise on

the molecular explanation of heredity. In the ordinary course of

science, such new facts would be woven into the theory, adding to its

complexity, redefining its meaning, or, as necessary, challenging its

basic premise. Scientific theories are meant to be falsifiable; this

is precisely what makes them scientific theories. The central dogma

has been immune to this process. Divergent evidence is duly reported

and, often enough, generates intense research, but its clash with the

governing theory is almost never noted.

 

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.41 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 to store information

produced 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.

 

DNA

did not create life;

life created DNA

 

Why, then, has the central dogma continued to stand? To some degree

die theory has been protected from criticism by a device more common

to religion than science: dissent, or merely the discovery of a

discordant fact, is a punishable offense, a heresy that might easily

lead to professional ostracism. Much of this bias can be attributed to

institutional inertia, a failure of rigor, but there are other, more

insidious, reasons why molecular geneticists might be satisfied with

the status quo; the central dogma has given them such a satisfying,

seductively simplistic explanation of heredity that it seemed

sacrilegious to entertain doubts. The central dogma was simply too

good not to be true.

 

As a result, funding for molecular genetics has rapidly increased over

the last twenty years; new academic institutions, many of them

" genomic " variants of more mundane professions, such as public health,

have proliferated. At Harvard and other universities, the biology

curriculum has become centered on the genome. But beyond the

traditional scientific economy of prestige and the generous funding

that follows it as night follows day, money has distorted the

scientific process as a once purely academic pursuit has been

commercialized to an astonishing degree by the researchers themselves.

Biology has become a glittering target for venture capital; each new

discovery brings new patents, new partnerships, new corporate

affiliations. But as the growing opposition to transgenic crops

clearly shows, there is persistent public concern not only with the

safety of genetically engineered foods but also) with the inherent

dangers in arbitrarily overriding patterns of inheritance that are

embedded in the natural world. through long evolutionary experience.

Too often those concerns have been derided by industry scientists as

the " irrational " fears of an uneducated public. The irony, of course,

is that the biotechnology industry is based on science that is forty

years old and conveniently devoid of more recent results, which show

that there are strong reasons to fear the potential consequences of

transferring a DNA gene between species. What the public fears is not

the experimental science but the fundamentally irrational decision to

let it out of the laboratory into the real world before we truly

understand it.

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2: ANDi.

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Crick 1958 (above), page 153.

 

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page 1305

 

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Watson J.D. and Crick F.H.C. Molecular structure of nucleic

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Monsanto Company Product Safety Center. Confidential Report

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39: Abnormal host DNA in transgenic soybeans.

Windels et al 2001 (above).

 

40: Transgenic plant's enzymes rearrange the alien gene's

nucleotide sequence.

Kohli A, Leech M, Vain P, Laurie DA, Christou P. Transgene

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41: DNA did not create life; life created

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Commoner B. Biochemical, biological and atmospheric evolution. Proc

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from: http://www.mindfully.org/GE/GE4/DNA-Myth-CommonerFeb02.htm

 

 

 

 

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