What's the problem with genetic engineering (GE) now name-modified to genetic modification (GM)?
For a start in good old newspeak fashion modification became a more sexy marketing name than engineering, which successive governments and political culture had been painfully trying to dump throughout the 1980s, but its the same nomenclature.
Genetic engineering/modification (GE/M - it wants to be a gem but for the interruptive dash) is based on the assumption that you can interrupt the code sequences of DNA for one living organism and drop in an extra or alien piece of code from another living organism's DNA, which then becomes incorporated and expresses a particular function in the recipient (it might be herbicide resistance, insecticide resistance or it might be done to obtain a trait in corn that makes it more waxy so cornflakes don't get soggy when milk is poured over them in the morning). Science has of course managed to produce organisms, particularly plants (because they say plants are easier to deal with than mammals), that show every sign, more or less, of achieving modification for, usually, just one single trait. The big question mark for science remains as to how successful this process is. Some modified organisms only last for a few generations before the expressed trait falls silent or maybe ceases functioning. Questions are also posed in science as to how the modified DNA and the newly expressed trait interacts with the rest of the organism's cell chemistry. These are still largely unresolved problems of cell biology. Just because you can insert a piece of code into a long, long line of code and seem to get a particular trait expressed, doesn't mean the story ends there. Some argue that a modified organism is put under undue stress as a result of an extra bit of DNA being squeezed into it and an extra function being squeezed out of that. Far more research needs to be done at a laboratory level in the biological sciences before a comprehensive picture emerges. However, if you're in business and need to recoup research and development costs, you'll push anything into production for a buck if you can. And if research is reliant on private sector finance, even into the hallowed grounds of ye old universities, then prioritisation of pure and applied research will be geared to product solutions. By-products and other effects will be overlooked in this drive and science will suffer.
SUMMARY OF THE CAMPAIGN POSITION ON GM CROPS AND FOOD
GM crops are produced by a handful of multinational biotechnology corporations who patent the seeds and accompanying chemical inputs. Farmers are contracted into these agronomic regimes, which themselves are reliant upon severely large scale agricultural practice. Since GM crops are patented, farmers are not permitted to save seed. This taken together with restrictive contractual arrangements with the big companies involved, and the chemical inputs and their application, make the claims that GM crops will feed the world highly problematic. The control of land use and food production would effectively fall into the hands of a far narrower range of players. Cross-pollination with non-GM agricultural crops will lead to a multinational monoculture where consumers have no option but to eat GM food and farmers are in far less control of what they grow. The global trend of landlessness will be exacerbated.
There is an ongoing scientific debate on the safety of GM crops and food in terms of human health and environmental impacts. Until this debate is resolved no GM crops should be grown in the open environment and no GM ingredients allowed into the food chain.
The global control of the food supply needs to be challenged and resisted in the interest of everyone as a basic human right.
A Challenge to Gene Theory, a Tougher Look at Biotech - by DENISE CARUSO - New York Times, July 1 2007
THE $73.5 billion global biotech business may soon have to grapple with a discovery that calls into question the scientific principles on which it was founded. Last month, a consortium of scientists published findings that challenge the traditional view of how genes function. The exhaustive four-year effort was organized by the United States National Human Genome Research Institute and carried out by 35 groups from 80 organizations around the world. To their surprise, researchers found that the human genome might not be a "tidy collection of independent genes" after all, with each sequence of DNA linked to a single function, such as a predisposition to diabetes or heart disease. Instead, genes appear to operate in a complex network, and interact and overlap with one another and with other components in ways not yet fully understood. According to the institute, these findings will challenge scientists "to rethink some long-held views about what genes are and what they do." Biologists have recorded these network effects for many years in other organisms. But in the world of science, discoveries often do not become part of mainstream thought until they are linked to humans. With that link now in place, the report is likely to have repercussions far beyond the laboratory. The presumption that genes operate independently has been institutionalized since 1976, when the first biotech company was founded. In fact, it is the economic and regulatory foundation on which the entire biotechnology industry is built.
Innovation begets risk, almost by definition. When something is truly new, only so much can be predicted about how it will play out. Proponents of a discovery often see and believe only in the benefits it will deliver. But when it comes to innovations in food and medicine, belief can be dangerous. Often, new information is discovered that invalidates the principles - thus the claims of benefit and, sometimes, safety - on which proponents have built their products. For example, antibiotics were once considered miracle drugs that, for the first time in history, greatly reduced the probability that people would die from common bacterial infections. But doctors did not yet know that the genetic material responsible for conferring antibiotic resistance moves easily between different species of bacteria. Overprescribing antibiotics for virtually every ailment has given rise to "superbugs" that are now virtually unkillable.
The principle that gave rise to the biotech industry promised benefits that were equally compelling. Known as the Central Dogma of molecular biology, it stated that each gene in living organisms, from humans to bacteria, carries the information needed to construct one protein. Proteins are the cogs and the motors that drive the function of cells and, ultimately, organisms. In the 1960s, scientists discovered that a gene that produces one type of protein in one organism would produce a remarkably similar protein in another. The similarity between the insulin produced by humans and by pigs is what once made pig insulin a life-saving treatment for diabetics. The scientists who invented recombinant DNA in 1973 built their innovation on this mechanistic, "one gene, one protein" principle. Because donor genes could be associated with specific functions, with discrete properties and clear boundaries, scientists then believed that a gene from any organism could fit neatly and predictably into a larger design - one that products and companies could be built around, and that could be protected by intellectual-property laws.
This presumption, now disputed, is what one molecular biologist calls "the industrial gene." "The industrial gene is one that can be defined, owned, tracked, proven acceptably safe, proven to have uniform effect, sold and recalled," said Jack Heinemann, a professor of molecular biology in the School of Biological Sciences at the University of Canterbury in New Zealand and director of its Center for Integrated Research in Biosafety. In the United States, the Patent and Trademark Office allows genes to be patented on the basis of this uniform effect or function. In fact, it defines a gene in these terms, as an ordered sequence of DNA "that encodes a specific functional product." In 2005, a study showed that more than 4,000 human genes had already been patented in the United States alone. And this is but a small fraction of the total number of patented plant, animal and microbial genes.
In the context of the consortium's findings, this definition now raises some fundamental questions about the defensibility of those patents. If genes are only one component of how a genome functions, for example, will infringement claims be subject to dispute when another crucial component of the network is claimed by someone else? Might owners of gene patents also find themselves liable for unintended collateral damage caused by the network effects of the genes they own? And, just as important, will these not-yet-understood components of gene function tarnish the appeal of the market for biotech investors, who prefer their intellectual property claims to be unambiguous and indisputable?
While no one has yet challenged the legal basis for gene patents, the biotech industry itself has long since acknowledged the science behind the question. "The genome is enormously complex, and the only thing we can say about it with certainty is how much more we have left to learn," wrote Barbara A. Caulfield, executive vice president and general counsel at the biotech pioneer Affymetrix, in a 2002 article on Law.com called "Why We Hate Gene Patents." "We're learning that many diseases are caused not by the action of single genes, but by the interplay among multiple genes," Ms. Caulfield said. She noted that just before she wrote her article, "scientists announced that they had decoded the genetic structures of one of the most virulent forms of malaria and that it may involve interactions among as many as 500 genes."
Even more important than patent laws are safety issues raised by the consortium's findings. Evidence of a networked genome shatters the scientific basis for virtually every official risk assessment of today?s commercial biotech products, from genetically engineered crops to pharmaceuticals. "The real worry for us has always been that the commercial agenda for biotech may be premature, based on what we have long known was an incomplete understanding of genetics," said Professor Heinemann, who writes and teaches extensively on biosafety issues. "Because gene patents and the genetic engineering process itself are both defined in terms of genes acting independently," he said, "regulators may be unaware of the potential impacts arising from these network effects." Yet to date, every attempt to challenge safety claims for biotech products has been categorically dismissed, or derided as unscientific. A 2004 round table on the safety of biotech food, sponsored by the Pew Initiative on Food and Biotechnology, provided a typical example: "Both theory and experience confirm the extraordinary predictability and safety of gene-splicing technology and its products," said Dr. Henry I. Miller, a fellow at the Hoover Institution who represented the pro-biotech position. Dr. Miller was the founding director of the Office of Biotechnology at the Food and Drug Administration, and presided over the approval of the first biotech food in 1992.
Now that the consortium's findings have cast the validity of that theory into question, it may be time for the biotech industry to re-examine the more subtle effects of its products, and to share what it knows about them with regulators and other scientists. This is not the first time it has been asked to do so. A 2004 editorial in the journal Nature Genetics beseeched academic and corporate researchers to start releasing their proprietary data to reviewers, so it might receive the kind of scrutiny required of credible science. According to Professor Heinemann, many biotech companies already conduct detailed genetic studies of their products that profile the expression of proteins and other elements. But they are not required to report most of this data to regulators, so they do not. Thus vast stores of important research information sit idle. "Something that is front and center in the biosafety community in New Zealand now is whether companies should be required to submit their gene-profiling data for hazard identification," Professor Heinemann said. With no such reporting requirements, companies and regulators alike will continue to "blind themselves to network effects," he said. The Nature Genetics editorial, titled "Good Citizenship, or Good Business?," presented its argument as a choice for the industry to make. Given the significance of these new findings, it is a distinction without a difference.
Denise Caruso is executive director of the Hybrid Vigor Institute, which studies collaborative problem-solving. E-mail: firstname.lastname@example.org.
AN INTERVIEW WITH DR. CHARLES BENBROOK ON GENETIC ENGINEERING - Bioneers - March 5, 2006 - By Arty Mangan
[EXCERPT: "So they have no control over where in that cell or where in that plant's genome the new genetic material gets lodged and expressed. Because they don't have control over that, they have absolutely no basis to predict how that trans-gene, the new genetic material, is going to behave in the future as that plant deals with stresses in its environment, whether it's drought, too much water, pest pressures, imbalances in the soil, or any other source of stress. They just don't know how it's going to behave."]
Dr. Charles Benbrook (http://www.organic-center.org/about.staff.php?action=detail&bios_id=43) is a consultant on agricultural policy, science and regulatory issues. He was formerly an agricultural staff expert on the Council for Environmental Quality at The White House at the end of the Carter Administration, Executive Director of the Subcommittee of the House Committee on Agriculture, and Executive Director of the Board on Agriculture of the National Academy of Sciences. Dr. Benbrook was interviewed by Arty Mangan of Bioneers (http://www.bioneers.org/).
Arty Mangan: Has anything changed in terms of the regulatory requirements for approval of genetically engineered (GE) crops today compared to when they were first introduced?
Charles Benbrook: In general, I think it is harder to get a new GE food approved today than it was ten years ago. But the regulatory programs in any part of the world, including Europe, certainly aren't founded in really solid, rigorous, conservative, precautionary science. There are still many leaps of faith embedded in the review and approval processes.
Arty Mangan: The biotech industry talks about the precision of genetic engineering. How precise is the technology?
Charles Benbrook: Anyone that's been involved in the discussion about genetically engineered crops has heard proponents claim that this is the most precise technology ever developed for the transformation of crops. For the most part, this claim is made and not challenged. It is true that the molecular biologists that create a trans-gene do know precisely what that trans-gene is composed of, because they make it. They pieced it together. In the regulatory submissions, for example, there will be a diagram of the trans-gene, exactly what genetic material is in different places, how they put it together, and what the function of the different parts of the trans-gene are. So that's the front end of the process. They do have precise control over that. Whereas in conventional breeding, when a plant breeder crosses two plants, they really don't have precise control or knowledge of how those genes combine in the next generation of a plant.
So it's true that in terms of knowing exactly what gene you're trying to move into the plant, it is more precise. But it's not more precise. In fact it's fundamentally more imprecise, in that the techniques that are used to move the trans-gene into the crop are no more precise than a shotgun. They shoot into the cells thousands of particles that have the trans-gene coating and hope that one penetrates into the inside of the cell and gets picked up and stably expressed. They hope that it's only one, and that it gets expressed properly. But they have no way of knowing whether it does, and in fact they do know that it's likely that more than one of those particles actually leads to some expression, and some may lead to some partial expression.
So they have no control over where in that cell or where in that plant's genome the new genetic material gets lodged and expressed. Because they don't have control over that, they have absolutely no basis to predict how that trans-gene, the new genetic material, is going to behave in the future as that plant deals with stresses in its environment, whether it's drought, too much water, pest pressures, imbalances in the soil, or any other source of stress. They just don't know how it's going to behave. They don't know how stable that expression is going to be, or whether the third generation of the plant is going to behave just like other generations. They don't know whether the promoter gene, which has been moved into the plant to turn on the new piece of genetic material, will influence some other biosynthetic pathway that's in the plant, turning on some natural process of the plant when it shouldn't be turned on, or turning it off too soon. There are all sorts of things that they don't know.
Is this new part of the genome that the biotechnologist has moved in, exempt from the laws of evolution from then on? It's kind of ridiculous to think that it would be. But that's really what the industry and the die-hard proponents of biotechnology are asking us to believe, that somehow once they move these trans-genes in - despite the fact that they don't understand how many copies there are, they don't understand how stable they'll be, they don't understand how stresses are going to effect them - that they're not going to be influenced by the laws of evolution. It's an irresponsible leap of faith that has been underwritten by our universities, our government, by the companies and by people that know better.
This is what drives a lot of people crazy. The scope of the fraud, if you will - I know that's a harsh word - the scope of the fraud that's being sold to the American public about this technology is almost unprecedented.
The biotechnology industry says, "Well, if one of these genetically engineered plants kind of goes crazy, it's probably not going to be fit and it won't survive. It won't last in the environment. Nature will select out against it." For somebody that works for a public institution to make that point, it really borders on libelous. It's such a violation of the public trust for scientists who understand this stuff to be so divorced from fairness in talking about the technical issues to an audience of non-scientists. It's really scandalous, in my opinion.
Arty Mangan: The comparisons that the biotech industry makes to promote genetic engineering for the most part are within the context of industrial agriculture. Shouldn't the comparisons be between the potential of sustainable agriculture and genetic engineering? If they compare the promise of biotech to the worst of the industrial agricultural system--that's an easier case to make.
Charles Benbrook: I think you're right. If conventional agriculture and the problems of conventional agriculture are the benchmark against which biotechnology is judged, it will be easier to sell biotech because biotech can solve some of the problems created by conventional agriculture. But what about just avoiding the problems altogether by really simple things, like management and cultural practices? You know, you hear these people say that we've got a big problem with vitamin A. We've got to use genetic engineering to create golden rice that has elevated vitamin A content. There are millions and millions of people in the world that don't get enough vitamin A. But what about growing some squash? Growing some crops that are already high in vitamin A? What about diversifying diets a little bit?
We're worried about how we are going to feed nine billion people, ten billion people in a world that's going to continue to develop economically. If everybody just ate a little bit less meat, we'll be fine. We don't have to give up meat. If North America and Europe would eat a third less meat, and all of that farmland devoted today to growing livestock feed that's converted at about six pounds of plant biomass to one pound of animal product, if that land were redirected to rice and wheat and tomatoes and peas and nutritionally dense foods, we could eliminate world hunger.
There are so many presumptions that go unchallenged with the way these people frame the dialogue that it's no wonder the public is confused and really doesn't know what to believe. It's very difficult for the public to cut through all the conflicting messages to find what's important, but that's unfortunately the state of the debate.
What finally attracted me to work in the area of organic agriculture is that it's the only thing that's got some integrity left. It's a viable and promising alternative. Even though probably not all farmers are going to be using fully organic systems, the more people that are farming organically, the more we're going to learn about the biology of farming, and the better conventional agriculture is going to get. I think that the success now of really good large-scale organic farmers is starting to change the practices of a lot of conventional farmers. That may be where the really big environmental consumer benefits are. If ten percent of agriculture becomes organic, that could influence sixty percent of conventional agriculture to change pretty dramatically, and that's a much bigger part of the food supply; it's a much bigger part of the land base. I think that it's important for the organic community to highlight more in these public discussions the fact that organic farmers are pioneers in understanding the biology of farming systems, and how to grow healthy plants and healthy animals without a lot of chemicals and drugs and things that raise risks. That's important. Even though we don't have enough organic apples to feed all the kids in schools in America, it's still important that we try to expand that, because I think it'll change conventional agriculture as well.
Copyright 2005 Collective Heritage Institute
Super Organics - Forget Frankenfruit - the new-and-improved flavor of gene science is Earth-friendly and all-natural. Welcome to the golden age of smart breeding - Richard Manning - http://www.wired.com/wired/archive/12.05/food.html?tw=wn_tophead_4
Once upon a technologically optimistic time, the founders of a swaggering biotech startup called Calgene bet the farm on a tomato. It wasn't just any old tomato. It was the Flavr Savr, a genetically engineered fruit designed to solve a problem of modernity.
Back when we all lived in villages, getting fresh, flavorful tomatoes was simple. Local farmers would deliver them, bright red and bursting with flavor, to nearby markets. Then cities and suburbs pushed out the farmers, and we began demanding our favorite produce year-round. Many of our tomatoes today are grown in another hemisphere, picked green, and only turn red en route to the local Safeway. Harvesting tomatoes this way, before they've received their full dose of nutrients from the vine, can make for some pretty bland fare. But how else could they endure the long trip without spoiling?
Flavr Savr was meant to be an alternative, a tomato that would ripen on the vine and remain firm in transit. Calgene scientists inserted into the fruit's genome a gene that retarded the tendency to spoil. The gene-jiggering worked - at least in terms of longer shelf life.
Then came the backlash. Critics of genetically modified food dubbed the Flavr Savr "Frankenfood." Sparked by the Flavr Savr's appearance before the US Food and Drug Administration, biotech watchdog Jeremy Rifkin set up the Pure Food Campaign, stalling FDA approval for three years and raising a ruckus that spread to Europe. When the tomato finally emerged, it demonstrated that there was no accounting for taste at Calgene. Flavr Savr wasn't just oddly spelled; it was a misnomer. Even worse, the fruit was a bust in the fields. It was highly susceptible to disease and provided low yields. Calgene spent more than $200 million to make a better tomato, only to find itself awash in red ink. Eventually, it was swallowed by Monsanto.
But the quest for a longer-lasting tomato didn't end there. As the Flavr Savr was stumbling (Monsanto eventually abandoned it), Israeli scientist Nachum Kedar was quietly bringing a natural version to market. By crossbreeding beefsteak tomatoes, Kedar had arrived at a savory, high-yield fruit that would ripen on the vine and remain firm in transit. He found a marketing partner, which licensed the tomato and flooded the US market without any PR problems. The vine-ripened hybrid, now grown and sold worldwide under several brand names, owes its existence to Kedar's knowledge of the tomato genome. He didn't use genetic engineering. His fruit emerged from a process that's both more sophisticated and far less controversial.
Welcome to the world of smart breeding.
The tale of the Flavr Savr is a near-perfect illustration of the plight of genetically modified organisms. A decade ago, GMOs were hailed as technological miracles that would save farmers money, lower food prices, and reduce the environmental damage unintentionally caused by the Green Revolution - a movement that increased yields but fostered reliance on chemical fertilizers, pesticides, and wanton irrigation. Gene jocks said they could give us even greater abundance and curb environmental damage by inserting a snip or two of DNA from another species into the genomes of various crops, a process known as transgenics.
In some cases, GMOs have fulfilled their promise. They've allowed US farmers to be more productive without as much topical pesticide and fertilizer [???]. Our grocery stores are stuffed with cheaply produced food - up to 70 percent of all packaged goods contain GM ingredients, mainly corn and soybean. GM has worked even better with inedible crops. Take cotton. Bugs love it, which is why Southern folk music is full of tunes about the boll weevil. This means huge doses of pesticides. The world's largest cotton producer, China, used to track the human body count during spraying season. Then in 1996, Monsanto introduced BT cotton - a GMO that employs a gene from the bacterium Bacillus thuringiensis to make a powerful pesticide in the plant. BT cotton cuts pesticide spraying in half; the farmers survive.
But while producers have embraced GMOs, consumers have had a tougher time understanding the benefits. Environmentalists and foodies decry GMOs as unnatural creations bound to destroy traditional plants and harm our bodies. Europe has all but outlawed transgenic crops, prompting a global trade war that's costing US farmers billions in lost exports. In March, voters in Mendocino County, California, banned GMO farming within county lines.
Opponents have found an ally in crop scientists who condemn the conglomerates behind transgenics, especially Monsanto. The company owns scores of patents covering its GM seeds and the entire development process that creates them. This gives Monsanto a virtual monopoly on GM seeds for mainline crops and stifles outside innovation. No one can gene-jockey without a tithe to the life sciences giant.
Which brings us back to smart breeding. Researchers are beginning to understand plants so precisely that they no longer need transgenics to achieve traits like drought resistance, durability, or increased nutritional value. Over the past decade, scientists have discovered that our crops are chock-full of dormant characteristics. Rather than inserting, say, a bacteria gene to ward off pests, it's often possible to simply turn on a plant's innate ability.
The result: Smart breeding holds the promise of remaking agriculture through methods that are largely uncontroversial and unpatentable. Think about the crossbreeding and hybridization that farmers have been doing for hundreds of years, relying on instinct, trial and error, and luck to bring us things like tangelos, giant pumpkins, and burpless cucumbers. Now replace those fuzzy factors with precise information about the role each gene plays in a plant's makeup. Today, scientists can tease out desired traits on the fly - something that used to take a decade or more to accomplish.
Even better, they can develop plants that were never thought possible without the help of transgenics. Look closely at the edge of food science and you'll see the beginnings of fruits and vegetables that are both natural and supernatural. Call them Superorganics - nutritious, delicious, safe, abundant crops that require less pesticide, fertilizer, and irrigation - a new generation of food that will please the consumer, the producer, the activist, and the FDA.
Nearly every crop in the world has a corresponding gene bank consisting of the seeds of thousands of wild and domesticated relatives. Until recently, gene banks were like libraries with millions of dusty books but no card catalogs. Advances in genomics and information technology - from processing power to databases and storage - have given crop scientists the ability to not only create card catalogs detailing the myriad traits expressed in individual varieties, but the techniques to turn them on universally.
One of the smart breeder's most valuable tools is the DNA marker. It's a tag that sticks to a particular region of a chromosome, allowing researchers to zero-in on the genes responsible for a given trait - a muted orange hue or the ability to withstand sea spray. With markers, much of the early-stage breeding can be done in a lab, saving the time and money required to grow several generations in a field. Once breeders have marked a trait, they use traditional breeding tactics like tissue culturing - growing a snip of plant in a nutrient-rich medium until it's strong enough to survive on its own. One form of culturing, embryo rescue, allows breeders to cross distant relatives that wouldn't normally produce a viable offspring. This is important because rare, wild varieties often demonstrate highly desirable characteristics. After fertilization, a breeder extracts the premature embryo and fosters it in the lab. Another technique - anther culture - enables breeders to develop a complete plant from a single male cell.
The science behind some of these techniques makes transgenics look unsophisticated. But the sell is simple: Smart breeding is the best of transgenics crossed with the best of organics. It can feed the world, heal the earth, and put an end to the Big Ag monopoly.
Take it from Robert Goodman, the former head scientist at Calgene who now works with the McKnight Foundation, overseeing a $50 million program that funds genomics research in the developing world. "The public argument about genetically modified organisms, I think, will soon be a thing of the past," he says. "The science has moved on."
In the mid-'80s, a grad student in plant breeding at Cornell University was handed a task that none of her peers would take. Her name: Susan McCouch. Her loser assignment: Create a map of the 40,000 genes spread across the rice genome. In 1988, the completion of that work would be heralded as a scientific breakthrough. Sixteen years later, it's beginning to shake corporate control of science.
A genome map is a detailed outline of an organism's underlying structure. Until McCouch came along, rice - the most important food for most of the world's poor - was an orphan crop for research. Big Ag was interested only in the Western staples, wheat and corn. But good maps enlighten - geologists once looked at maps of South America and Africa and figured out that the edges of the two continents fit together, giving rise to the idea of plate tectonics. McCouch's map was just as revealing. Researchers compared it to the genomes of wheat and corn and realized that all three crops, along with other cereal grasses - more than two-thirds of humanity's food - have remarkably similar makeups. The volumes of research into corn and wheat could suddenly be used to better understand developing world essentials like rice, teff, millet, and sorghum. If scientists could find a gene in one, they'd be able to locate it in the others.
By extension, characteristics of one crop should be present in related plants. If a certain variety of wheat is naturally adept at defeating a certain pest, then rice should be, too; scientists would just need to switch on that ability. McCouch started her project as a way to unlock the door to the rice library; it turned out she cut a master key.
Still at Cornell, McCouch is now learning how crossbreeding domesticated rice with wild ancestors can achieve super-abilities that neither parent possesses. "We're finding things like genes in low-yielding wild ancestors, which if you move them into cultivated varieties can increase the yields of the best cultivar," McCouch says. "Or genes of tomatoes that come out of a wild background - they make a red fruit redder. We also have ways to make larger seeds, which can yield bigger fruit." Generations of unscientific plant breeding have inadvertently eliminated countless valuable genes and weakened the natural defenses of our crops. McCouch is recovering the complexity and magic.
Food scientists around the world are picking up on her work. In China, researcher Deng Qiyun, inspired by McCouch's papers, used molecular markers while crossbreeding a wild relative of rice with his country's best hybrid to achieve a 30 percent jump in yield - an increase well beyond anything gained during the Green Revolution. Who will feed China? Deng will. In India, the poorest of the poor can't afford irrigated land, so they grow unproductive varieties of dryland rice. By some estimates, Indian rice production must double by 2025 to meet the needs of an exploding population. One researcher in Bangalore is showing the way. H. E. Shashidhar has cataloged the genes of the dryland varieties and used DNA markers to guide the breeding toward a high-yield super-rice. In West Africa, smart breeders have created Nerica, a bountiful rice that combines the best traits of Asian and African parents. Nerica spreads profusely in early stages to smother weeds. It's disease-resistant, drought-tolerant, and contains up to 31 percent more protein than either parent.
This is not exclusively a matter of crafting new rice varieties in the developing world. Irwin Goldman, a horticulture professor at University of Wisconsin-Madison, cites McCouch's work as critical to the progress he's made with carrots, onions, and beets. For example, he has spawned a striped beet through some sophisticated genome tweaking - and in the process revealed methods to improve the appearance and taste of all sorts of vegetables.
Beet genes make two pigments of a class of chemicals called betalain. When both are present, the beet is red. Switch off one gene, as happens in natural mutations, and the beet is gold. Switch it on and off at different stages and the beet becomes striped. Creating a striped beet is not hugely important by itself - striped heirloom varieties date back to 19th-century Italy. What's significant is that Goldman pinpointed the genes responsible for the trait and figured out how to turn them on.
This type of smart breeding may one day lead to something as useful as a high-yield rice that's naturally rich in beta-carotene, which our bodies convert to vitamin A. For years, genetic engineers have been trying to introduce so-called golden rice to Asia, where vitamin A deficiency causes millions of people to go blind every year. Creating the GM version wasn't easy - it required the insertion of two daffodil genes - but it wasn't nearly as difficult as getting it to the people. As with the Flavr Savr, golden rice drew the ire of the Frankenfood crowd while running afoul of some 70 patents. A natural counterpart wouldn't encounter such problems. Far-fetched? Maybe, considering that there's no known naturally occurring rice containing beta-carotene. [this is contradicted by Syngenta] Then again, we never thought carrots had vitamin E - until Goldman found some.
By scouring the carrot gene bank, Goldman discovered several exotic varieties of carrots (ranging in color from yellow to orange, red, and purple) that make vitamin E. Capitalizing on that native ability is a matter of tagging the relevant genes and crossbreeding the wild relatives with ordinary, everyday carrots. Gene bank searches are also revealing a whole host of antioxidants, sulfur compounds, and tannins - chemicals that bring sharp color and strong tastes - that have been stripped out of our lowest-common-denominator crops over the centuries. Many of these qualities not only fight cancer and increase the nutritional value of our vegetables, but also make them taste better while helping plants fight disease. We now have the ability to bring these traits back.
And we can do it quickly. It often takes seed companies several years to establish a new variety. To recover their investment, they release seeds that don't usually pass on the parents' traits, forcing farmers to buy new seed every year. Smart breeding, by contrast, is faster and cheaper because much of it can be done in the lab - reducing the time and expense of growing countless varieties in the field. Goldman's work is funded by university dollars, which allows him to give away the spoils. He links up with local organics growers, farmers' markets, and the expanding counter-agribusiness food movement and hands out open-pollinated seeds - ag's version of open source.
Richard Jefferson is an iconoclastic American bluegrass musician living in Australia. He's also a brash biotechnologist intent on wrestling control of our crops away from Big Agriculture. As head of Cambia (the Center for the Application of Molecular Biology to International Agriculture), a plant science think tank in Canberra, he's sowing the seeds of a revolt, citing the open source ethos of Linus Torvalds and Richard Stallman as inspiration. "In the case of almost every single enabling technology, the corporations have acquired it from the public sector," he says. "They have the morals of stoats."
If McCouch and Goldman are making an end run around GMO by improving on methods that predate genetic engineering, Jefferson is taking a direct approach. All three scientists use an expanded knowledge of plant genomes to create new crop varieties. But where McCouch and Goldman do gene bank searches and study genome maps to figure out which plants to bring together, Jefferson digs into the genome itself and moves things around. He doesn't insert anything - he calls transgenics "hammer and tong science; as dull as dishwater" - but he's not above tinkering. His big idea: manipulate plants to teach ourselves more about them.
Jefferson made a name for himself as a grad student in 1985 when he discovered GUS, a clever little reporter gene that causes a glow when it's linked to any active gene. He distributed GUS to thousands of university and nonprofit labs at no cost - but charged the Monsantos of the world millions. He used the money to establish Cambia, which invents technologies to help developing world scientists create food varieties without violating GMO patents.
Transgenic researchers treat the genome like software, as if it contained binary code. If they want an organism to express a trait, they insert a gene. But the genome is more complicated than software. While software code has two possible values in each position (1 and 0), DNA has four (A,C,T, and G). What's more, a genome is constantly interacting with itself in ways that suggest what complexity theorists call emergent behavior. An organism's traits are often less a reaction to one gene and more a result of the relationship between many. This makes the expression of DNA fairly mysterious.
Jefferson is out to master this squishy science with a practice he calls transgenomics. You are different from your siblings because your parents' genes were unzipped during reproduction and the 23 chromosomes on each half rejoined in a unique pattern. The same thing happens in plants. Jefferson has modified native genes to act as universal switches that turn a plant's latent genes on and off. Simply put, he's rigging the reproductive shuffle.
In a process he calls HARTs - homologous allelic recombination techniques - Jefferson manipulates genomes (no insertions allowed) to force plants to mimic other crops. "We're taking inspiration from one plant and asking another plant to make that change in itself," he says. One example Jefferson likes to talk about is sentinel corn - a plant-sized version of the GUS gene that would turn red when it needs water. It may not sound like much, but by the time a traditional corn plant wilts, it's usually too late. More efficient irrigation would mean the difference between profit and loss - or nourishment and starvation.
Jefferson's greatest hope to challenge Big Ag comes in what's known as apomixis - plant cloning. He wants to teach all sorts of crops to clone themselves the way dandelions and blackberries do naturally. When a plant's seeds produce genetically identical offspring, there's no need to buy hybrid seeds every year. Jefferson and rival scientists claim to have several paths to apomixis - but the race is competitive and no one's offering details. The real problem, says Jefferson, is not developing the methods, but releasing them into a world of patents. "I am not a technological optimist who thinks that if you put a technology out there, everything is going to be fine," he says. "How you put it out there matters as much or more than what it is."
His solution is to create an open source movement for biotechnology. In his vision, charitable foundations, which have paid for most of the world's public-interest crop science, would fund platform technologies and provide free licenses to public and private scientists. Commercial end products would be encouraged, but the basic technology, the OS, would remain in public hands. To get the whole thing started, Jefferson is offering up Cambia's portfolio of patents.
It's tempting to reach for the Linux versus Microsoft analogy to describe Cambia's plan to unlock some of the astounding technologies that remain dormant in labs and greenhouses. It's powerful, but also decentralized, networked, and accessible - democratic. It's like Monsanto's mainframe giving way to biotech's equivalent of the PC.
Agriculture is one of the most ill-conceived human endeavors. We plow down stable communities of hundreds of species of plants to get single-row crops. We replace entire ecosystems with pesticides, fertilizers, precious fresh water, and tractor emissions. Then, after every harvest, we start all over again. Organic agriculture breaks this cycle. But it's just a Band-Aid on the wound.
Add the knowledge and tools of biotechnology, though, and we are on the verge of something enormous. Plant genomes carry age-old records that reveal the complex manner by which nature manages itself. Researchers around the world - McCouch, Goldman, and Jefferson are a few examples - are learning to not only read those records but re-create them.
Which is not to say success is automatic. This new era of food won't arrive with a technological big bang. But that's a good thing. Single events are too easy to control and monopolize. A steady trickle of innovation will buy time to get the marketing right. Public perception is as complex as the genome, and just as important to master. The science is taking hold. If the business side can clearly communicate what superorganics are - and what they are not - these new foods will not only change the way we eat, they'll change the way we relate to the planet.
How Smart Breeding Works
The mission: Develop rice that's resistant to bacterial blight and will thrive around the globe.
SEARCH Food scientists scour the rice gene bank, consisting of 84,000 seed types, in search of varieties with blight immunity.
INSERT MARKER Scientists extract DNA from selected varieties and tag the blight-immunity gene - previously identified by researchers - with a chemical dye.
CROSSBREED A network of researchers around the world cross disease-resistant varieties with thousands of local versions. With some plants, this means merely putting two varieties in a room. Self-pollinating rice requires manual pollen insertion.
ANALYZE The offspring are analyzed to detect the presence of the immunity gene. Those containing the gene are planted in a field.
TEST Mature plants are exposed to bacterial blight to confirm resistance. Those that don't die, and maintain desired traits from the local variety, are distributed. Unless
REPEAT Sometimes, the process reveals several genes responsible for a trait. Three genes confer resistance to different blight strains. In such cases, breeders repeat the crossbreeding until all genes are turned on.
END RESULT A rice plant with broad resistance to bacterial blight that will thrive in local conditions.
Richard Manning (email@example.com) is the author of Against the Grain: How Agriculture Has Hijacked Civilization.
THE FOLLOWING TWO DISCUSSIONS ON THE ROLE OF DNA WITHIN LIVING, CELLULAR SYSTEMS BOTH REPRESENT A USEFUL CONTRIBUTION AS INFORMATIVE, ACCESSIBLE TEXTS IN THE UNDERSTANDING OF THAT ROLE AS WELL AS AUTHORITATIVE CRITIQUES ON THE CLAIMS MADE FOR DNA'S CENTRALITY THAT UNDERPIN THE THINKING OF PROTAGONISTS OF GM CROPS AND FOOD.
Unravelling the DNA Myth - Barry Commoner
(Barry Commoner has a long and rich history in environmental science and social activism. After gaining his PhD in biology from Harvard University in the US, he spent 34 years at Washington University in St Louis, Missouri, There he explored viral function and led cellular research with implications for cancer diagnosis. In the 1950s, Commoner was heavily involved in the debates on nuclear weapons, and in the 1960s, he became involved in other environmental issues including pollution and energy sources. In 1980, Commoner set up and headed the Center for the Biology of Natural Systems at Queens College, New York. He now directs the Critical Genetics Project there (www.criticalgenetics.org), which aims to look at new ways of understanding the roles of the living cells molecular constituents, such as DNA, RNA and protein, in the biology of inheritance. Barry Commoner is the author of nine books and has served on numerous advisory and editorial boards. He can be reached by email at firstname.lastname@example.org .)
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 wasnt so long ago that Scottish scientists stunned the world with Dolly,  the fatherless sheep cloned directly from her mothers 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.  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.  And it, 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 industrys assurances that genetically engineered soybeans have been altered only by the presence of the alien gene, the plants own genetic system has been unwittingly altered as well, with potentially dangerous consequence.  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 organisms genome its total complement of genes should fully account for its characteristic assemblage of inherited traits.  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 cells 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 industrys widely advertised claim that its methods of genetically modifying food crops are "specific, precise, and predictable"  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? Cricks 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. Cricks second hypothesis neatly links the gene to the protein. This "sequence hypothesis" states that the genes 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 persons 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.
Cricks 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."  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, Cricks 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."  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.  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 Watsons "ultimate description of life" than the genes alone can tell us.
Scientists and journalists somehow failed to notice what had happened. The projects 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."  Properly understood, this modest, if esoteric, account fulfills Cricks 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 genes 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. 
Alternative splicing thus has a devastating impact on Cricks 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).  The discovery of alternative splicing also nullifies the exclusiveness of the genes hold on the molecular process of inheritance. The genes 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.
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.  The shortfall in the human gene count could and indeed should have been predicted. It is difficult to avoid the conclusion troublesome as it is that the projects 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 would tell us who we are. 
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 theorys ubiquitous icon. In their original description of the discovery of DNA, Watson and Crick commented that the helixs 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 lifes magic molecular key. 
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 fertilised egg, the genome is replicated many billions of times, its precise sequence of three billion nucleotides retained with extraordinary fidelity.  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 tube, 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 synthesised DNA. 
Thus, in the living cell the genes nucleotide code can be replicated faithfully only because an array of specialised proteins intervenes to prevent most of the errors which DNA by itself is prone to make and to repair the few remaining ones. In this sense, genetic information arises not from DNA alone but through its essential collaboration with protein enzymes a contradiction of the Central Dogmas precept that inheritance is uniquely governed by the self-replication of the DNA double helix.
Another important divergent observation that in order to generate the inherited trait, the newly made protein, a strung-out ribbon of a molecule, must be folded up into a precisely organised ball-like structure. The biochemical events that give rise to genetic traits for example, enzyme action that synthesises a particular eye-colour 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 a special type of "chaperone" protein properly folds them. 
By the mid 1980s, long before the $3 billion Human Genome Project was funded, and long before genetically modified (GM) crops began to appear in our fields, a series of protein-based processes had already intruded on the DNA genes 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-to- protein process. By any reasonable measure, these results contradict the Central Dogmas 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 credibility of the Human Genome Project is not the only casualty of the scientific communitys 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 multi-billion 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 maize 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.
That the industry is guided by the Central Dogma was made explicit by Ralph Hardy, president of the US National Agricultural Biotechnology Council and formerly director of life sciences at DuPont, a major producer of GM seeds. In 1999, in Senate testimony, he succinctly described the industrys guiding theory this way: "DNA (top management molecules) directs RNA formation (middle management molecules) directs protein formation (worker molecules)."  The outcome of transferring a bacterial gene into a maize 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 version of the Central Dogma is the scientific foundation upon which each year billions of transgenic plants of soybeans, maize, 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 plants 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 plants protein-mediated systems. Higher plants, such as maize, soybeans, and cotton, are known to possess proteins that repair DNA miscoding;  proteins that alternatively splice messenger RNA and thereby produce a multiplicity of different proteins from a single gene;  and proteins that chaperone the proper folding of other, nascent proteins.  But the plant systems evolutionary history is very different from the bacterial genes. As a result, in the transgenic plant the harmonious interdependence of the alien gene and the new hosts 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. 
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 plants genome has itself been unwittingly altered. Monsanto 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."  A year later, Belgian researchers discovered that a segment of the plants own DNA had been scrambled. The abnormal DNA was large enough to produce a new protein, a potentially harmful protein. 
One way that such mystery DNA might arise is suggested by a recent study showing that in some plants carrying a bacterial gene, the plants enzymes that correct DNA replication errors rearrange the alien genes nucleotide sequence.  The consequences of such changes cannot be foreseen. The likelihood in GM 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 US. The degree to which such disruptions do occur in GM 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. 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 GM crops now being grown represent a massive uncontrolled experiment whose outcome is inherently unpredictable. The results could be catastrophic.
Cricks Central Dogma has played a powerful role in creating both the Human Genome Project and the unregulated spread of GM 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 genes 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.  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 cells 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 recognise how little we truly understand about the secrets of the cell, the fundamental unit of life.
Why, then, has the Central Dogma continued to stand? To some degree the 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 offence, 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 centred 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 commercialised 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 GM 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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Reference for this article: Unravelling the DNA myth, Seedling, July 2003, GRAIN
Copyright notice: Copyright © 2002 by Harpers Magazine. All rights reserved. Reproduced (and shortened) from the February issue by special permission.
Website link: http://www.grain.org/seedling/seed-03-07-2-en.cfm
Seedling is the quarterly magazine of GRAIN.
The DNA Era - Richard C. Lewontin, Gene Watch vol 16, no. 4, July 2003
(Richard C. Lewontin is an evolutionary geneticist, philosopher of science, and social critic. An early pioneer in the development of molecular population genetics, his works include Biology as Ideology, The Triple Helix: Gene, Organism, and Environment, and Not in Our Genes, co-authored with Steven Rose and Leon Kamin. He is Alexander Agassiz Research Professor at Harvard University, and regularly writes for the New York Review of Books.)
No one who reads the newspapers or scientific journals can have missed the fact that this is the 50th anniversary of the publication of the correct three-dimensional structure of DNA. That structure, a double helix of two chains of nucleotides, has become a popular icon and the very phrase, double helix has been spoken and written so often as to become part of ordinary discourse.
The fact that genes were composed of DNA had already been established nine years before the publication of Watson and Cricks paper on its structure, and the chemical, as opposed to the spatial, configuration of DNA was also well known before 1953. Yet, despite the obvious importance of DNA in understanding the molecular details of both heredity and development, it was not until after the publication of the proposed double helical structure that DNA started increasingly to occupy the interest of biologists and finally became the focus of the study of genetics and development. 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 sodisturbing is that every biologist knows they are false.
First, DNA is not self replicating. It is manufactured out of small molecular bits and pieces by an elaborate cell machinery made up of proteins. If DNA is put in the presence of all the pieces that will be assembled into new DNA, but without the protein machinery, nothing happens. What actually happens is that the already present DNA is copied by the cellular machinery so that new DNA strands are replicas of the old ones. The process is analogous to the production of copies of a document by an office copying machine, a process that would never be described as self-replication. In fact, many errors are made in the DNA copying process; there is protein proofreading machinery devoted to comparing the newly manufactured strands to the old ones and correcting the errors. An office copier that made such mistakes would soon be discarded.
Second, DNA does not make anything, certainly not proteins. New proteins are made by a protein synthesis machinery that is itself made up of proteins. The role of the DNA is to provide a specification of the serial order of amino acids that are to be strung together by the synthetic machinery. But this string of amino acids is not yet a protein. To become a protein with physiological and structural functions, it must be folded into a three dimensional configuration that is partly a function of the amino acid sequence, but is also determined by the cellular environment and by special processing proteins that, among other things, may cut out parts of the amino acid chain and splice what remains back together again.
The other function of DNA is to provide a set of on-off switches that are responsive to cellular conditions so that different cells at different times will produce different proteins. When the conditions of the cell set a switch associated with a particular gene to the on position, then the protein manufacturing machinery of the cell will read that gene. Otherwise the cell will ignore it.
In this mechanical description of the relation of DNA to the rest of the cellular machinery there is no master molecule, no secret of life. The DNA is an archive of information about amino acid sequences to which the synthetic machinery of the cell needs to refer when a new protein molecule is to be produced. When and where in the organism that information is read depends on the physiological state of the cells. An organism cannot develop without its DNA, but it cannot develop without its already existing protein machinery (unless it is a parasite like a virus that has no synthetic power of its own but gets a free ride on its hosts protein machinery).
The unjustified claim for special autonomous powers of DNA is the prelude to the next step in building a picture of a DNA-dominated world. This picture is simply the molecular version of a biological determinism that has dominated explanations of the properties of organisms, and especially of humans, since the nineteenth century. Differences in temperament, talents, social status, wealth, and power were all said to reside in the blood. The physical manifestations of these claimed hereditary differences could be seen by criminal and racial anthropologists in the shapes of noses and heads and the color of skins. With the rise of Mendelian genetics, genes were substituted for blood in the explanations, but they remained, for the fifty years of genetics, merely formal entities with no concrete description beyond the fact that they were some bit of a chromosome. The discovery that DNA is the material of the gene, and the subsequent determination of the correspondence between nucleotide sequences of genes and amino acid sequences of proteins, then provided a concrete molecular basis for a total scheme of explanation of the organism. The fact that organisms are built primarily of proteins and that DNA carries the archive of information for the amino acid sequence of the proteins gave an immense weight to the conclusion that the organism as a whole is coded in its DNA. A manifestation of this view is the claim made, at a symposium in commemoration of the 100th anniversary of the death of Darwin, by a founder of the molecular biology of the gene: that if he were given the DNA sequence of an organism and a large enough computer, he could compute the organism. One is reminded of Archimedes claim that, given a long enough lever and a place to stand, he could move the earth. But while Archimedes may have at least been right in principle, the molecular biologist was not. An organism cannot be computed from its DNA because the organism does not compute itself from its own DNA.
It is a basic principle of biology, known to all biologists but ignored by most of them as inconvenient, that the development of an organism is the unique consequence of its genes and the temporal sequence of environments in which it developed. The current fascination of developmental genetics is with the way in which information from different genes enters into the formation of the major features of an organism. How does the front end of the animal become differentiated from the back end? Why does the egg of a horse develop into an animal with four legs while the egg of a bird produces an organism with two legs and two wings, and the egg of a butterfly results in an animal with six legs and two sets of wings? This concentration on the major differences and similarities between different species has resulted in a genetically determinist view of development that ignores the actual variation among individuals. There is an immense experimental literature in plants and animals showing that individuals of the same genetic constitution differ widely from each other in physical characteristics if they develop in different environments. Moreover, the relative ranking in some physical trait of individuals of different genotypes changes from environment to environment. Thus, a genetic type that is the fastest growing at one temperature may be the slowest at another. But even genes and environment together do not determine the organism. All symmetrical organisms show a fluctuating asymmetry between their two sides and the variation between left and right sides is often as great as the difference between individuals. For example, the fingerprint pattern on the left and right hands of a human individual are not identical; on some fingers, they may be extremely dissimilar. This variation is the manifestation of random growth differences that arise from small differences in the local tissue and cell conditions in different parts of the body, and from the fact that there is random variation in the number of copies of particular molecules in different cells. A consequence is that two individuals with identical genes and identical environments will not develop identically. If we want to understand human variation, we need to ask far more subtle and complex questions than is the rule in DNA-dominated biology.
The other side of the movement of DNA to the center of attention in biology has been the development of tools for the automated reading of DNA sequences, for the laboratory replication and alteration of DNA sequences and for the insertion of pieces of DNA into an organisms genome. Taken together, these techniques provide the power to manipulate an organisms DNA to order. The three obvious implications of this power are in the detection and possible treatment of diseases, the use of organisms as productive machines for the manufacture of specific biological molecules, and the breeding of agricultural species with novel properties.
The Human Genome Project has been largely justified by the promise that it will now be possible to locate genes that cause human disease by comparing the DNA sequences of affected and unaffected individuals. Once the nucleotide difference has been established, that difference can be used as a diagnostic criterion, as a predictor of a future onset of the disease, and as a basis for a cure by gene replacement therapy. It is undoubtedly true that some fraction of human ill health is a consequence of deleterious mutations. However, while family studies can strongly suggest that a disease is being inherited as a single Mendelian gene difference, the determination that it is a consequence of mutation of a particular gene is not a trivial problem. A blind search for a genetic difference that is common to all affected individuals is impractical given that, on the average, any two humans differ from each other at 3 million nucleotide sites. On the other hand, if the biochemistry of the disease is sufficiently well understood, it may be that a few candidate genes can be singled out for investigation. Alternatively, studies of the pattern of inheritance may show that the disorder is inherited coordinately with an associated gene of known location in the genome, greatly narrowing down the search for the DNA variation implicated in the disease.
As in all other species, for any given gene, human mutations with deleterious effects almost always occur in low frequency. Hence specific genetic diseases are rare. Even in the aggregate, genes do not account for most of human ill health. Given the cost and expenditure of energy that would be required to locate, diagnose and genetically repair any single disease, there is no realistic prospect of such genetic fixes as a general approach for this class of diseases. There are exceptions, such as sickle cell anemia and conditions associated with other abnormal hemoglobins, in which a non-negligible fraction of a population may be affected, so that these might be considered as candidates for gene therapy. But for most disease that represents a substantial fraction of ill health and for which some evidence of genetic influence has been found, the relation between disease and DNA is much more complex and ambiguous. Claims for the discovery of genes for schizophrenia and bipolar syndrome have repeatedly been made and retracted. It is generally accepted that cancer is a consequence of mutations in a variety of genes related to the control of cell division, but even in the strongest individual case, the breast cancer-inducing BRCA1 mutations, only about 5% of such cancers are linked to these specific mutations.
Up to the present we do not have a single case of a successful cure for a disease by means of gene therapy. All successful interventions, whether in genetically simple disorders like phenylketonuria or in complex cases like diabetes, have been at the level of biochemistry and were in place well before anything was known about DNA. Of course, a successful gene therapy for some disease may be produced in the future, but the claim that the manipulation of DNA is the path to general health is unfounded. In fact, on a world scale, most ill-health and premature death is caused by a combination of infectious disease and undernourishment factors which genetic manipulation will never solve.
The second implication, 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 Lillys standard treatment is dangerous no longer have an easily obtainable alternative supply. The most widely known and contentious application of DNA technology to production is in agriculture. The introduction of DNA sequences derived from widely divergent species into agricultural varieties has resulted in a struggle of immense proportions in both North America and Europe. The proximate purpose of the creation of varieties with DNA introduced from other kinds of organisms is to produce agricultural crops with novel features that cannot be obtained by the usual methods of selection because the relevant genes are not present in the agricultural species. The benefits to farmers, consumers and commercial seed producers vary considerably from case to case, although in every case the ultimate goal of the commercial breeder is increased profit and the protection of their property rights. There are four cases to be distinguished. First there is the introduction of pest and disease resistance, as in the introduction of the BT protein from Bacillus thuringiensis into maize. This is intended to reduce the labor, chemicals and machinery needed by the farmer for pest control. Some of the cost reduction is lost in the higher price of the commercial seed, but saving labor is important to farmers. Second, there is creation of varieties that are resistant to herbicides used to control weeds. The best-known examples are the Roundup Ready varieties produced by Monsanto, designed to coerce farmers into purchasing Monsantos general herbicide (Roundup) as well as their seed. The supposed advantage to the farmer is a reduction in machinery and labor involved in tillage, but again the cost saving is reduced by the increased price of seed. The third case is the pure protection of property rights of the seed producers with no benefit to farmers or consumers. The most infamous example is the attempted introduction of Terminator technology by the Delta Pine and Land Company, which was later purchased by Monsanto. Terminator seed varieties will germinate and produce sterile crops, thus forcing farmers to purchase commercial seed anew every year. (It should be noted that this technology, of no advantage to farmers or consumers, was produced in cooperation with the U.S. Department of Agriculture). The fourth case is the introduction into mass produced field crops of DNA coding for particular compounds normally only produced by specialty species. This technology has the potential to destroy much of the economy of Third World countries that are dependent on the export of agriculturally produced commodities. An example is the transfer into rape seed, a widely grown crop in North America, of the DNA coding for palmitic acid oils that are used in industrial processes. Normally these oils are extracted from oil palm seed grown in Southeast Asia.
While much of the opposition to transgenic agriculture has been based on the unnaturalness of the process, this objection misses the point. No agricultural variety is natural,but is the product of centuries of gradual, cumulative genetic modification from its wild ancestors to produce varieties that are utterly different from the ancestral forms. Moreover, crosses between different species have been a standard method of plant breeding for more than a century. The real issue is that DNA technology provides a powerful tool for the control of agricultural production by monopolistic producers of the inputs into agriculture with no ultimate advantage either to farmers or consumers and with the possibility of destroying entire national agricultural economies. All of the elements that characterize the era of DNA have in common an underlying simplistic view of living organisms. By concentrating in practice and in theory on the properties and functions of a single molecule, biologists, both in their professional work and in their public statements, reduce the extraordinary complexity of life processes to the structure and metabolism of DNA. This emphasis ignores the intricate and multiple ways in which organisms are built and function. The intricacy is a consequence of the structural and metabolic functions of proteins and the interactions of those proteins with each other, with other molecules, and with the environment in the course of development.
Moreover, for human life, no account at all is taken of the role of social and economic processes in determining health and life activities and molding the processes of industrial and agricultural production. We cannot understand our size, shape and internal functioning except by a detailed understanding of the extremely complex web of interactions among the various molecules which form the body in concert with influences exerted by our environments. We cannot understand the origin and development of our mental states except by an understanding of the map of nervous connections and how that map is influenced by experience. We cannot understand why agricultural technology develops in particular directions if we do not understand the social, political and economic interactions that drive technological innovation. The bottom line is that life in all its manifestations is complex and messy and cannot be understood or influenced by concentrating attention on a particular molecule of rather restricted function.
Gene Watch is published by the Council for Responsible Genetics - http://www.gene-watch.org
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