Genetically Altered Organisms: When the Old Becomes the New
Carlson, Elof Axel
THERE HAS been much discussion in magazines, newspapers, and the nightly news about genetically modified organisms. Why did French farmers attack a McDonald's fast food restaurant that used...
...Regulate...
...Despite such risks, many people will choose organic foods over commercial preparations that use chemical preservatives...
...That feat was like introducing a chromosome of a chimpanzee into a human...
...That does not matter...
...We did not ban bridge building when the Tacoma Narrows bridge collapsed...
...All of us harbor genes from other organisms...
...While such decisions may not have health consequences, they do raise the concern that unprofitable breeds and varieties will disappear...
...Presumably the warning labels and the instructions to patients will be effective, and there will be little or no accidental use of thalidomide by women in early pregnancy...
...Are they induced by chemicals...
...Regulation can work...
...Values often change...
...Gene therapy is subject to very demanding regulations by health agencies and hospital policies...
...It also required a knowledge of genetic tools as they developed in the first half of the twentieth century, including the ability to induce mutations...
...Others object that the altered genes may disturb the ecosystem in some unknown way...
...The FDA established most of its regulations long before modern technology introduced means to move genes chemically from one species into another...
...60 DISSENT / Winter 2001 GENETICALLY ALTERED ORGANISMS Fear of lawsuits is a powerful motivator for companies that answer to their stockholders...
...As far as future toxicity and carcinogenicity, these are very difficult to test for any product introduced as a preservative, taste enhancer, extender of shelf life, or natural pesticide...
...This risk already exists in nature for those genes currently in their own species, and lateral transfers of them to unrelated life forms (such as from a cereal grain plant to a tree) are exceptionally rare...
...Other genetic pesticides could be used and field tested...
...It was only after the thalidomide disaster that Germany, England, and other countries with thalidomide babies established regulatory commissions with the clout that regulators had in the United States...
...Society is so complex today that it is difficult to conceive of runaway disasters that cannot be checked...
...Much more ominous was the "negative eugenics" movement, whose adherents believed that the species needed culling...
...Virtually the entire world reacted to the cloning of Dolly the sheep in 1997 as if the "brave new world" had bounded out of a work of fiction into our laps...
...We learn from mistakes, establish or improve regulatory agencies to monitor new technologies, use legal action to make mistakes costly...
...ELOF AXEL CARLSON is a professor in the department of biochemistry and cell biology at the State University of New York, Stony Brook...
...We welcome this as a public necessity despite the enormous costs of such testing because we do not want another thalidomide disaster...
...Debate...
...A sizable segment of the public expects the genetic modification of humans for medical purposes to lead to abuses and unintended consequences...
...Of course, but they will not be repeated, or they will lead to lawsuits and more regulations to prevent their recurrence...
...Age-corrected studies over a century of monitoring have actually shown a decrease of stomach cancers, an increase of respiratory cancers, and virtually no change in all other cancers...
...Before molecular technology, in the 1940s, scientists could cross cognate species (such as the fruit flies Drosophila melanogaster and Drosophila simulans) and by difficult genetic crosses get one of the chromosomes of D. simulans into a D. melanogaster descendant and study the effects of the foreign genes that were introduced...
...And for most people this seems wrong...
...It may also be difficult to regulate the decisions by farmers on whether to use one highly profitable genetically modified crop or to continue to use less profitable varieties that already exist...
...Many perfectly natural products like wheat or peanuts can be infected by mold and produce natural carcinogens such as aflatoxins...
...Parents may then choose elective abortion or use in vitro fertilization and return to the uterus only embryos that lack the gene mutations associated with their risk...
...It is not the introduction of genes from one species into another that is new, it is the conscious ability to do this by scientific means...
...It is a theme replayed in hundreds of novels, films, and video dramas that use Aldous Huxley's Brave New World as their model...
...When new technologies are introduced, governments have to oblige competing interests...
...As a generation or more of people eat such foods without harm, a new generation of users will consider it as natural as riding to work in an automobile instead of on a horse...
...For the most part, genetically modified organisms will not change the diversity of the living world...
...It overlooked human error in operating the reactors and faulty design (the Chernobyl reactor would never have been approved in the United States...
...No one today can market a drug for prescription unless that product has been carefully tested and the evidence of its safety and effectiveness reviewed by a government agency...
...Even the forty-year ban of thalidomide has been overruled, and the drug reintroduced as an allegedly effective agent for leprosy, tuberculosis, certain types of cancer, and possibly other diseases...
...This does not mean that every new technology should be let loose in a laissez-faire world...
...To the anthropologist or geneticist, organisms, including humans, are constantly being altered...
...One major objection could be the unexplored psychological difficulties for the cell donor and the children when an adult relates to his or her cloned twins...
...within a decade or two after the mapping of the human genome, there will be many potential disorders that can be treated with gene replacement therapy...
...we celebrated the bumper crops generated by hybrid corn...
...The nuclear power industry failed miserably because it deluded itself with the safety predictions of its engineers...
...The results were transforming for agriculture...
...Whether there should be such regulations is a matter for governments to debate...
...When recombinant DNA technology was first introduced a generation ago, similar fears were raised...
...We all know that the respiratory cancers are almost entirely a consequence of tobacco smoking...
...That's plain old evolution whether carried out in prehistoric times largely by natural selection or in more recent times (about fifteen thousand years or so to the present) by a variety of conscious and unconscious means of selection...
...They are grotesquely artificial compared to their progenitors, if their progenitors even exist today...
...Their sequences can be determined...
...Most people realize that if commercially valuable animals and plants can be altered by molecular technology, so too can humans...
...But there is no evidence that the hundreds of chemical additives introduced into our foods have increased the frequency of cancers in the population...
...But some industries did not manage to convince the public of their safety...
...Doing so gives the public little protection against those who would delude themselves or put quick financial success ahead of the common welfare...
...It could be a big disappointment if most clonal twins turn out to be different from their co-twin parent, lacking the motivation for success, say, that the parent somehow acquired and could not pass on...
...Are the protesters right...
...In that well-known case some eight thousand children, mostly German and English, were born deformed, many with missing or deformed arms and legs, when their mothers used thalidomide to minimize morning sickness in early pregnancy...
...Different types of modified plants can be grown instead and field tested for safety...
...Monarch butterflies have eaten toxic pollen, for example, but it is unlikely that their flight paths will be so fully blanketed with harmful crops that the species will become extinct...
...The technology is assisted DISSENT / Winter 2001 n 57 GENETICALLY ALTERED ORGANISMS by tools for sequencing genes, for multiplying those genes, and for determining the functions of genes...
...Barring natural or human selection, the frequency of a gene remains constant from generation to generation...
...Other scientists lobbied for laws restricting immigration to keep out those alleged to be carriers of defective germ plasm...
...These include • allergies to protein products (allergens) of introduced genes • modified crop plants with genetically produced pesticides endangering beneficial insects (for example, monarch butterflies on their migratory paths) • transfers of genes from modified crops to plants in the surrounding ecosystem by pollination of related species or by aphids and other organisms that may carry cells or partially shredded chromosomes in their mouths and introduce them to a totally different species (a process called the lateral transfer of genes) • replacing many varieties of a crop with a single variety that later proves vulnerable to a new pathogen • losing genetic varieties of animal breeds through loss of commercial value • long-range, unanticipated toxic or carcinogenic effects from eating genetically modified foods • exploitation of farmers in developing nations by selling seeds that produce sterile crops and force a dependency on the supplier Many of these, although possible, are unlikely to be a major worry...
...When better varieties come along, the old ones are no longer planted...
...A combination of fancy biochemistry and computers can spin out data on what sequences of DNA are genic and what sequences are background noise—relic genes of the past and repetitive DNA—that serves no known function (the bulk of DNA fits that last category...
...It would require a lot of generous acceptance by a partner whose own cell would not be used...
...Science accelerates overnight what normally occurs at a glacial pace...
...there are no known mutations unique to physical or chemical mutagens...
...Similarly if a protein product is an allergen to a significant number of people, other genes can be used to produce products that do not provoke such allergies...
...Anyone with a good memory knows that virtually every new technology has encountered initial resistance and within a decade or less settles into the ordinary...
...If you had chicken pox as a child, some of that virus DNA ended up in the chromosomes of your nerve cells and the proteins from those genes became embedded in your peripheral nerve fibers...
...Once the therapy works, demand will increase, though this may turn out to be a temporary approach...
...It paid heavily in public trust and rightly so...
...It is a theme that goes back to Mary Wollstonecraft Shelley's image of Dr...
...We did not ban cruise liners when the Titanic sank...
...Throughout this change from family farming to agribusiness, hardly a protest was heard...
...In the more distant future parents at risk will be easily identified through the human genome project, which will make detecting mutant genes as easy as using a dictionary...
...They would welcome crops that grow in regions of low annual rainfall, or in brackish water, or that require less costly fertilizers and less hard human labor to bring to market...
...Today genes can be routinely transferred from one species to another by injecting them into cells or infecting cells with them by using an altered virus or synthetic vector...
...Will there be some failures...
...A baby is likely to be infected with herpes virus...
...The mutagens are used to increase the frequency with which they occur...
...Genes can be isolated and chemically cloned...
...It is unlikely that an epidemic or ecological catastrophe can result from these field-tested genetically altered plants or animals...
...This includes concerns about the egoism of the parent who provided the nucleus and about generational conflict if the parent-twin is frustrated by the child-twin's profoundly different generational values...
...We have consumed our culls, kept our rejects from breeding, and bred our best specimens for what appealed to us...
...Why then, now, do we suddenly feel an unease about the direction agribusiness is taking us...
...They see these as unnatural— although most do not object to the unnatural use of synthetic fertilizers, pesticides, and herbicides to improve crop yields...
...At present most parents in most of the world take what nature or fate provides because they are unaware that they have reproductive options...
...If these new, genetically modified organisms are not already on the market, they are within the reach of today's technologies...
...Frankenstein and his uncontrolled monster...
...Monitor...
...Although the United States is reasonably well protected by this legal action (as the tobacco and firearms industries are now realizing), this may not be true in countries where the power of individuals to file class action lawsuits does not exist...
...Some regulations concerning environmental protection already apply to the testing and release of genetically modified plants...
...58 n DISSENT / Winter 2001 GENETICALLY ALTERED ORGANISMS There are potential problems with genetically modified organisms...
...DISSENT / Winter 2001 61...
...Shifts in gene frequency are another cause of worry...
...Those who violate these guidelines pay a heavy price professionally in the lawsuits that the neglectful institution will face when things go wrong...
...Because genetic modification has so many applications, no single agency currently exists for their regulation...
...Is all this as legitimate as the fear of nuclear energy or the fear of another thalidomide disaster...
...We continue to import animals and plants from around the world despite dozens, out of many thousands, of imported species that have become pests, weeds, and nuisances...
...Hybrid corn, rust-resistant wheat, cattle designed for dairy or the butcher's block, and a steady output of varieties were developed at the nation's agricultural field stations by Ph.D.s who knew what they were doing...
...Very different was the experience in the United States...
...We welcomed the efficiency of modern farms...
...The cloning issue is complicated by the reality that we already have natural clones—identical or monozygotic twins...
...It was a hope that appealed to, but was finally rejected by, intelligent people in the first third of the twentieth century...
...The problem is as old as agriculture itself...
...They also don't object to mating members of the same species to introduce genes (for example using strains of wheat from China and strains of wheat from North America...
...Not a single catastrophe has resulted from that technology...
...As recently as the 1950s there were epidemics of Claviceps pupureum, which can lead to ergotism in infected rye (with effects similar to that of an LSD overdose...
...What do we mean by genetically altered organisms...
...Few people and almost no government programs have consciously selected humans for those behavioral attributes...
...The compromise that seems to work best is regulation...
...We did not stop building dams when the Baldwin Hills dam burst...
...Thalidomide was designed and promoted by its German manufacturer as an over-the-counter sedative and it had not been adequately tested for safety or effectiveness...
...It is unlikely that genes from a modified crop will be transferred by insects (for example, aphids) into other crops or into the natural ecosystem...
...There are two separate issues here—that of replacing some genes for genetic therapy and that of cloning individuals from a body cell (the fancy word is somatic, a cell that is not a reproductive cell...
...no known epidemics leading to species extinction or near extinction have arisen from them, at least not in historical times...
...He believed there were genes for intelligence, eminence, and special talents in the arts, sciences, and humanities...
...Among the sequences of DNA known to be genic, computers can quickly identify cognate sequences from data bases and their functions can be assigned...
...That technology splices a gene from one organism into a piece of DNA (a virus or similar small object) and then uses that altered object to bring the imported gene to a desired chromosome, often of another species...
...Untoward events have happened...
...It is not clear that those regulations apply to such novel genetic possibilities as the modification of crops to do better in hostile environments, or for use as natural pesticides or herbicides, or to produce special features that farmers and distributors seek—longer shelf life, prevention of bruising, flavor enhancement, and attractiveness to the consumer...
...As much as 10 percent of humanity was believed to fall into hereditary degenerate classes...
...Are they natural...
...Why did French farmers attack a McDonald's fast food restaurant that used genetically modified vegetables (with introduced genes to generate pesticides) and modified beef (with introduced genes that release growth hormones to speed development and increase the size of cattle...
...Humans can, and do, alter gene frequency by creating breeds of animals and plants for a variety of needs for hobbyists, horticulturists, and farmers—and for eugenicists, too...
...But developing countries with hungry mouths to feed happily accept genetically modified rice that provides better nutrition and any genetically modified crop plants that resist a host of infectious diseases...
...Human biological products produced by animals or pharmaceuticals produced by animals and plants, including vaccines through food crops, will be regulated by the FDA with the same tough standards it uses for conventional drugs...
...There is no consistency in what people, individually or as groups, find objectionable...
...Years later, the original virus, latent in the cells, may flare up and produce a cold sore...
...The middle classes of the world are better informed and already use a variety of options now available, including DISSENT / Winter 2001 n 59 GENETICALLY ALTERED ORGANISMS treatments for infertility and prenatal diagnosis for birth defects...
...The industry also had a shameful record of harassing critics and hiding its true costs and government subsidies...
...that degenerate groups arose and had to be contained or eliminated...
...Ironically "negative eugenics" is a very ineffective means of changing gene frequency in populations...
...More affluent people like less monotonous diets and can afford to pay for a rich variety...
...In the near future a few genetic disorders may be treatable by gene therapy...
...Elsewhere, some object to the new forms of genetic modification on the grounds that introduced genes may lead to unpredictable human health problems...
...Why does the Prince of Wales promote organic foods and decry genetic modification as "playing God...
...When Francis Galton first conceived of "positive eugenics" in 1883, he urged the best and the brightest to have more than the average number of children...
...Without intense human effort, few of our domesticated animals or plants would survive in the wild...
...There are more likely to be losses of species and changes in the ecosystem from population growth, booming economies, and the advance of developing nations into affluence...
...Critics will probably sift through the options and accept some and reject others...
...Many parents may choose that option...
...Fears, Legitimate and Illegitimate As in all new technologies, there is a learning curve for safety and public acceptance...
...It is the new that brings uncertainty...
...No doubt much that is possible with molecular technology can and does occur at a tremendously less frequent rate through rare biological events...
...It's your decades-old infection flaring up...
...The tools to achieve these molecular transfers of genes have been widely used since the introduction of what has been called recombinant DNA technology in the 1980s...
...Yet the mutations produced by any of these agents (called mutagens) are difficult or impossible to distinguish from naturally occurring mutations...
...The demand for genetically modified organisms is more likely to increase than to decrease the foods people eat around the world...
...Objections to scientific cloning must avoid claims that would also apply to natural born twins...
...Nor is it likely that some totalitarian state would seek to clone armies as somehow more efficient than citizens shaped by highly skilled drill sergeants...
...Bans should only be enforced if a danger is demonstrable and the threatened harm is serious enough (for example, sickness, death, ecological damage...
...The aflatoxins are potent carcinogens, especially for liver cancer...
...The first is in the works...
...Did they have their origin from exposure to ionizing radiation (like the first commercial production of penicillin as an antibiotic...
...Some scientists, especially physicians, favored compulsory sterilization laws for what were called "the unfit...
...Far more difficult to regulate are the improbable or unpredictable consequences of using genetically modified organisms...
...The public wants protection from harm, and the manufacturers want protection from unreasonable restrictions, especially laws that ban their products...
...Mutations can be directed, even designed, to alter gene function in novel ways...
...There are repositories at some universities for different varieties of plant seeds no longer being used commercially, but it might be helpful if the Department of Agriculture provided funding for a few stock centers for storage of seeds (or frozen tissues) of such abandoned varieties...
...The virus introduces some or all of its DNA into the mucosal cells of the baby's mouth...
...If they don't exist, or if they lack sufficient authority, critics should pressure their legislators to provide tough testing standards...
...Our food preferences keep changing...
...In middle age you may suddenly erupt with a case of shingles...
...In general, Europeans fear genetically modified foods...
...The transition from the family farm to agribusiness was gradual, a year-by-year seamless shifting away from the horse and mule of the mid-nineteenth century to the tractors, combines, seed producers, cattle auctions, and other means of mass production of foods for a population that kept doubling and thumbing its nose at Malthus...
...Farmers who could afford it sent their children to the state agricultural schools that proliferated after the Civil War...
...the Rasmussen report, prepared for the U.S...
...Either the traits are environmentally caused (for example, paupers, vagrants, recidivist criminals), and thus of no genetic significance, or their frequency would not be changed, even over centuries or millennia, by sterilization of those with known genetic disorders (for example, single-gene and polygenic birth defects) because most of the affected children arise from healthy parents...
...It is far better to regulate an industry than to ban it...
...Fortunately, scientists set up very strict safety regulations that worked...
...Corporate responsibility" didn't work...
...government by engineers on the safety of nuclear reactors, predicted one failure for every ten thousand years of operation, and hardly a decade elapsed before reactors at Three Mile Island and Chernobyl proved the report wrong...
...How Should Society Respond...
...Some of those chemicals are potent poisons and so caus56 DISSENT / Winter 2001 GENETICALLY ALTERED ORGANISMS tic we would do well to keep our distance from them (alkylating agents including mustard gas...
...The applications of that knowledge are limitless and include the following: • use of normal genes for gene therapy in those human genetic disorders whose tissues are targeted to receive sufficient numbers of normal genes to provide normal function • introduction of genes serving as natural pesticides into species lacking those pesticides • introduction of genes that provide resistance to herbicides • introduction of genes for the production of vitamins, amino acids, and other food supplements in crop plants that do not provide these in adequate amounts • introduction of pharmaceuticals for human disorders, the gene products manufactured by genetically altered sheep, cows, pigs, or other animals • introduction of genes to produce vaccines and anti-tumor agents • genetic design of pigs and other animals whose organs can be used in human transplants without fear of rejection • alteration of crop plants so that they thrive in the weather patterns of different countries or regions of a country • cloning of desired animals for commercial production on a larger scale (perpetuating record-breaking chickens, sheep, pigs, cattle, and so on...
...We may worry about how mutations arise...
...There is scarcely a food we eat (beef, poultry, vegetables, cereal grains) or natural cloth we wear (wool, cotton, silk, linen) that is not the product of deliberate human cultivation and selection...
...We probably consume in our familiar foods hundreds of such agents in small doses and most of these have never been tested because they have been around for many generations...
...In all likelihood, this would not be a widely used option...
...Cloning The movement against genetically modified organisms draws on many fears...
...No one knows if the decrease in stomach cancer is a bonanza from refrigeration, from less use of smoked fish and meats, or from a shift to other ways of preserving or preparing food...
...Is there a more effective way than that...
...We think of genetically altered organisms primarily as products of the technologies of the twentieth century, when selection, which once depended only on a good eye and patience— with Luther Burbank as the exemplar—became a science of complex crosses to get genes from one strain into another...
...Warnings of peripheral neuritis and severe constipation among the elderly who used it were ignored...
...The New Technology Modern technology uses some old natural standbys to achieve genetic change...
...Modifications produced by recombinant DNA technology had to go through a stringent process of production and testing either through self-imposed regulation by a new industry or through rules established by government agencies when this new technology first appeared and the industry requested such surveillance...
...But the major concern today is focused on molecular technology, which can shift genes from one organism to different species...
...The Food and Drug Administration (FDA), through the heroic work of Frances Kelsey, acted effectively, and very few thalidomide babies were born in the United States...
...That required a knowledge of Mendel's laws of heredity (how genes are passed from parent to offspring) and later the mathematics of gene distribution in multigenerational crosses and in populations...
...Today's dinner table may display beef produced almost entirely by artificial insemination, a technology introduced long before the molecular basis of heredity was worked out...
Vol. 48 • January 2001 • No. 1
