Dna: The Secret of Life

by Watson, James

  Monsanto was never able to reverse this unfortunate momentum. In April 2000, the company effected a merger but its partner, the pharmaceutical giant Pharmacia & Upjohn, was primarily interested in acquiring Monsanto's drug division, Searle. The agricultural business, later spun off as an independent entity, still exists today under the name Monsanto. Gone, however, are the company's pioneering bravado and aura of invincibility.

  The GM foods debate has conflated two distinct sets of issues. First, there have been the purely scientific questions of whether GM foods pose a threat to our health or to the environment. Second, there are economic and political questions centered on the practices of aggressive multinational companies and the effects of globalization. Much of the rhetoric has focused on agribusiness, Monsanto in particular. Having seemed throughout the 1990s to view the technology as little more than a means of dominating the world food supply, the company may indeed have harbored unwholesome dreams of becoming the Microsoft of the food industry, but since its stunning reversal of fortunes, this aspect of the controversy has been rendered largely baseless. It is not likely that another company with as much to lose will stumble into the same minefield. A meaningful evaluation of GM food should be based on scientific considerations, not political or economic ones. Let us therefore review some of the common claims.

  It ain't natural. Virtually no human being, save the very few remaining genuine hunter-gatherers, eats a strictly "natural" diet. Pace Prince Charles, who famously declared in 1998 that "this kind of genetic modification takes mankind into realms that belong to God," our ancestors have in fact been fiddling in these realms for eons.

  Early plant breeders often crossed different species, bringing into existence entirely new ones with no direct counterparts in nature. Wheat, for example, is the product of a whole series of crosses. Einkorn wheat, a naturally occurring progenitor, crossed with a species of goat grass, produced emmer wheat. And the bread wheat we know was produced by a subsequent crossing of emmer with yet another goat grass. Our wheat is thus a combination – perhaps one nature would have never devised – of the characteristics of all these ancestors.

  Furthermore, crossing plants in this way results in the wholesale generation of genetic novelty: every gene is affected, often with unforeseeable effects. Biotechnology, by contrast, allows us to be much more precise in introducing new genetic material into a plant species, one gene at a time. It is the difference between traditional agriculture's genetic sledgehammer and biotech's genetic tweezers.

  It will result in allergens and toxins in our food. Again, the great advantage of today's transgenic technologies is the precision they allow us in determining how we change the plant. Aware that certain substances tend to provoke allergic reactions, we can accordingly avoid them. But this concern persists, stemming to some degree from an oft-told tale about the addition of a Brazil nut protein to soybeans. It was a well-intentioned undertaking: the West African diet is often deficient in methionine, an amino acid abundant in a protein produced by Brazil nuts. It seemed a sensible solution to insert the gene for the protein into West Africa's soybean, but then someone remembered that there is a common allergic reaction to Brazil nut proteins that can have serious consequences, and so the project was shelved. Obviously the scientists involved had no intention of unleashing a new food that would promptly send thousands of people into anaphylactic shock; they halted the project once the serious drawbacks were appreciated. But for most commentators it was an instance of molecular engineers playing with fire, heedless of the consequences. In principle, genetic engineering can actually reduce the instance of allergens in food: perhaps the Brazil nut itself will one day be available free of the protein that was deemed unsafe to import into the soybean.

  It is indiscriminate, and will result in harm to nontarget species. In 1999 a now-famous study showed that monarch butterfly caterpillars feeding on leaves heavily dusted with pollen from Bt corn were prone to perish. This was scarcely surprising: Bt pollen contains the Bt gene, and therefore the Bt toxin, and the toxin is intentionally lethal to insects. But everyone loves butterflies, and so environmentalists opposed to GM foods had found an icon. Would the monarch, they wondered, be but the first of many inadvertent victims of GM technology? Upon examination, the experimental conditions under which the caterpillars were tested were found to be so extreme – the levels of the Bt pollen so high – as to tell us virtually nothing of practical value about the likely mortality of caterpillar populations in nature. Indeed, further study has suggested that the impact of Bt plants on the monarch (and other nontarget insects) is trivial. But even if it were not, we should ask how it might compare with the effects of the traditional non-GM alternative: pesticides. As we have seen, in the absence of GM methods, these substances must be applied liberally if we are to have agriculture that is as productive as modern society requires. Whereas the toxin built into Bt plants affects only those insects that actually feed off the plant tissue (and to some lesser degree, insects exposed to Bt pollen), pesticides unambiguously affect all insects exposed, pest and non-pest alike. The monarch butterfly, were it capable of weighing in on the debate, would assuredly cast its vote in favor of Bt corn.

  It will lead to an environmental meltdown with the rise of "superweeds." The worry here is that genes for herbicide resistance (like those in Roundup Ready plants) will migrate out of the crop genome into that of the weed population through interspecies hybridization. This is not inconceivable, but it is unlikely to occur on a wide scale for the following reason: interspecies hybrids tend to be feeble creations, not well equipped for survival. This is especially true when one of the species is a domesticated variety bred to thrive only when mollycoddled by a farmer. But let us suppose, for argument's sake, that the resistance gene does enter the weed population and is sustained there. It would not actually be the end of the world, or even of agriculture, but rather an instance of something that has occurred frequently in the history of farming: resistance arising in pest species in response to attempts to eradicate them. The most famous example is the evolution of resistance to DDT in pest insects. In applying a pesticide, a farmer is exerting strong natural selection in favor of resistance, and evolution, we know, is a subtle and able foe: resistance arises readily. The result is that the scientists have to go back to the drawing board and come up with a new pesticide or herbicide, one to which the target species is not resistant; the whole evolutionary cycle will then run its course before culminating once more in the evolution of resistance in the target species. The acquisition of resistance, therefore, is the potential undoing of virtually all attempts to control pests; it is by no means peculiar to GM strategies. It's simply the bell that signals the next round, and summons human ingenuity to invent anew.

  Despite her concern about the impact of multinational corporations on farmers in countries like India, Suman Sahai of the New Delhi-based Gene Campaign has pointed out that the GM food controversy is a feature of societies for which food is not a life-and-death issue. In India, where people literally starve to death, as Sahai points out, up to 60 percent of fruit grown in hill regions rots before it reaches market. Just imagine the potential good of a technology that delays ripening, like the one used to create the Flavr-Savr tomato. The most important role of GM foods may lie in the salvation they offer developing regions, where surging birthrates and the pressure to produce on the limited available arable land lead to an overuse of pesticides and herbicides with devastating effects upon both the environment and the farmers applying them; where nutritional deficiencies are a way of life and, too often, of death; and where the destruction of one crop by a pest can be a literal death sentence for farmers and their families.

  As we have seen, the invention of recombinant DNA methods in the early 1970s resulted in a round of controversy and soul-searching centered on the Asilomar conference. Now it is happening all over again. At the time of Asilomar, it may at least be said, we were facing several major unknowns: we could not then say for certain
that manipulating the genetic makeup of the human gut bacterium, E. coli, would not result in new strains of disease-causing bacteria. But our quest to understand and our pursuit of potential for good proceeded, however haltingly. In the case of the present controversy, anxieties persist despite our much greater understanding of what we are actually doing. While a considerable proportion of Asilomar's participants urged caution, today one would be hard-pressed to find a scientist opposed in principle to GM foods. Recognizing the power of GM technologies to benefit both our species and the natural world, even the renowned environmentalist E. O. Wilson has endorsed them: "Where genetically engineered crop strains prove nutritionally and environmentally safe upon careful research and regulation . . . they should be employed."

  The opposition to GM foods is largely a sociopolitical movement whose arguments, though couched in the language of science, are typically unscientific. Indeed, some of the anti-GM pseudoscience propagated by the media – whether in the interests of sensationalism or out of misguided but well-intentioned concern – would be actually amusing were it not evident that such gibberish is in fact an effective weapon in the propaganda war. Monsanto's Rob Horsch has had his fair share of run-ins with protesters:

  I was once accused of bribing farmers by an activist at a press conference in Washington, D.C. I asked what they meant. The activist answered that by giving farmers a better performing product at a cheaper price those farmers profited from using our products. I just looked at them with my mouth hanging open.

  Let me be utterly plain in stating my belief that it is nothing less than an absurdity to deprive ourselves of the benefits of GM foods by demonizing them; and, with the need for them so great in the developing world, it is nothing less than a crime to be governed by the irrational suppositions of Prince Charles and others.

  In fact, a few years from now, when the West inevitably regains its senses and throws off the shackles of Luddite paranoia, it may find itself seriously lagging in agricultural technology. Food production in Europe and the United States will come to be more expensive and less efficient than elsewhere in the world. Meanwhile, countries like China, which can ill afford to entertain illogical misgivings, will forge ahead. The Chinese attitude is entirely pragmatic: With 23 percent of the world's population but only 7 percent of its arable land, China needs the increased yields and added nutritional value of GM crops if it is to feed its population.

  On reflection, we erred too much on the side of caution at Asilomar, quailing before unquantified (indeed, unquantifiable) concerns about unknown and unforeseeable perils. But after a needless and costly delay, we resumed our pursuit of science's highest moral obligation: to apply what is known for the greatest possible benefit of humankind. In the current controversy, as our society delays in sanctimonious ignorance, we would do well to remember how much is at stake: the health of hungry people and the preservation of our most precious legacy, the environment.

  In July 2000 anti-GM-food protesters vandalized a field of experimental corn at Cold Spring Harbor Lab. In fact there were no GM plants in the field; all the vandals managed to destroy was two years' hard work on the part of two young scientists at the lab. But the story is instructive all the same. At a time in which the destruction of GM crops has become positively fashionable in parts of Europe, when even the pursuit of knowledge on that continent and this one can come under attack, those in the vanguard of the cause might do well to ask themselves: what are we fighting for?

  CHAPTER SEVEN

  THE HUMAN GENOME:

  LIFE'S SCREENPLAY

  The human body is bewilderingly complex. Traditionally biologists have focused on one small part and tried to understand it in detail. This basic approach did not change with the advent of molecular biology. Scientists for the most part still specialize on one gene or on the genes involved in one biochemical pathway. But the parts of any machine do not operate independently. If I were to study the carburetor of my car engine, even in exquisite detail, I would still have no idea about the overall function of the engine, much less the entire car. To understand what an engine is for, and how it works, I'd need to study the whole thing – I'd need to place the carburetor in context, as one functioning part among many. The same is true of genes. To understand the genetic processes underpinning life, we need more than a detailed knowledge of particular genes or pathways; we need to place that knowledge in the context of the entire system – the genome.

  The genome is the entire set of genetic instructions in the nucleus of every cell. (In fact, each cell contains two genomes, one derived from each parent: the two copies of each chromosome we inherit furnish us with two copies of each gene, and therefore two copies of the genome.) Genome sizes vary from species to species. From measurements of the amount of DNA in a single cell, we have been able to estimate that the human genome – half the DNA contents of a single nucleus – contains some 3.1 billion base pairs: 3,100,000,000 As, Ts, Gs, and Cs (see Plate 38).

  Genes figure in our every success and woe, even the ultimate one: they are implicated to some extent in all causes of mortality except accidents. In the most obvious cases, diseases like cystic fibrosis and Tay-Sachs are caused directly by mutations. But there are many other genes whose work is just as deadly, if more oblique, influencing our susceptibility to common killers like cancer and heart disease, both of which may run in families. Even our response to infectious diseases like measles and the common cold has a genetic component since the immune system is governed by our DNA. And aging is largely a genetic phenomenon as well: the effects we associate with getting older are to some extent a reflection of the lifelong accumulation of mutations in our genes. Thus, if we are to understand fully, and ultimately come to grips with, these life-or-death genetic factors, we must have a complete inventory of all the genetic players in the human body.

  Above all, the human genome contains the key to our humanity. The freshly fertilized egg of a human and that of a chimpanzee are, superficially at least, indistinguishable, but one contains the human genome and the other the chimp genome. In each, it is the DNA that oversees the extraordinary transformation from a relatively simple single cell to the stunningly complex adult of the species, comprised, in the human instance, of 100 trillion cells. But only the chimp genome can make a chimp, and only the human genome a human. The human genome is the great set of assembly instructions that governs the development of every one of us. Human nature itself is inscribed in that book.

  Understanding what is at stake, one might imagine that to champion a project seeking to sequence all the human genome's DNA would be no more controversial than sticking up for Mom and apple pie. Who in his right mind would object? In the mid-1980s, however, when the possibility of sequencing the genome was first discussed, this was viewed by some as a decidedly dubious idea. To others it simply seemed too preposterously ambitious. It was like suggesting to a Victorian balloonist that we attempt to put a man on the moon.

  It was a telescope, of all things, that inadvertently helped inaugurate the Human Genome Project (HGP). In the early 1980s, astronomers at the University of California proposed to build the biggest, most powerful telescope in the world, with a projected cost of some $75 million. When the Max Hoffman Foundation pledged $36 million, a grateful UC agreed to name the project for its generous benefactor. Unfortunately, this way of saying thank-you complicated the business of raising the remaining money. Other potential donors were reluctant to put up funds for a telescope already named for someone else, so the project stalled. Eventually, a second, much wealthier California philanthropy, the W. M. Keck Foundation, stepped in with a pledge to underwrite the entire project. UC was happy to accept, Hoffman or no. (The new Keck telescope, on the summit of Mauna Kea in Hawaii, would be fully operational by May 1993.) Unprepared to play second fiddle to Keck, the Hoffman Foundation withdrew its pledge, and UC administrators sensed a $36 million opportunity. In particular, Robert Sinsheimer, chancellor of UC Santa Cruz, realized that the Hoffman money could bank
roll a major project that would "put Santa Cruz on the map."

  Sinsheimer, a biologist by training, was keen to see his field enter the major leagues of big-money sciences. Physicists had their pricey supercolliders, astronomers their $75 million telescopes and satellites; why shouldn't biologists have their own high-profile, big-money project? So he suggested that Santa Cruz build an institute dedicated to sequencing the human genome; in May 1985, a conference convened at Santa Cruz to discuss Sinsheimer's idea. Overall it was deemed too ambitious and the participants agreed that the initial emphasis should instead be on exploring particular regions of the genome that were of medical importance. In the end, the discussion was moot because the Hoffman money did not actually make its way into the University of California's coffers. However, the Santa Cruz meeting had sown the seed.