Questionable concoctions?
Scientists are whipping up new foods in the laboratory that may be both beneficial and harmful.
Image: Joseph Tart
Picture a herd of 30,000 pigs bred from fertilized eggs injected with human genetic material. They look and smell like normal pigs. If you needed an emergency transfusion, you would no doubt be grateful for clean, disease-free blood from these transgenic pigs. And, if you desperately needed a kidney, you might be thrilled to receive one from a pig.
Alvin Young--
Most people have a gut feeling they don't like the idea of bioengineered foods.
Photo: USDA
But what about a thick, juicy transgenic pork chop? The meat would be leaner than traditional pork, and sales could help pig producers of the future cover high research costs. Ready for dinner? If you answered, "no way," you're not alone, says Alvin Young, director of the U.S. Department of Agriculture's Agricultural Biotechnology Office.
High on the Hog?
Biotech pigs produce leaner meat, but consumers prefer the taste of the fattier roasts.
Photo: Terry D. Etherton
Whenever he talks to college students, Young routinely gauges public response to transgenic research. Three-fourths of the students who take part in Young's informal surveys tend to be enthusiastic about the possibility of life-saving medical products from pigs. Ask them about transgenic meat, though, and 85-90% of the students quickly turn up their noses. "Most just have a gut feeling that they don't like the idea," Young muses. "Could they get over it? I think they could." In his meetings with students, Young addresses the most critical question currently facing food biotechnologists: will consumers actually buy genetically engineered foods?
The world may soon learn the answer to that question. Calgene, Inc. of Davis, California, will begin selling a genetically engineered tomato this year. Dubbed the "Flavr Savr," Calgene's invention will be the first "whole" biotech food on the market. Because a section of its genetic code has essentially been spliced, flipped, and reinserted, the Flavr Savr stays fresh up to 10 days longer than conventionally grown varieties, says Carolyn Hayworth, Calgene's manager of investor and public relations.
In May this year, a final decision by the FDA gave Calgene the go-ahead to market Flavr Savr, ending the tomato's long, arduous journey from the lab bench to the marketplace. Along the way, the company has repeatedly been at the center of heated public debate about bioengineered foods. Clearing so many hurdles has clearly taken a toll on the company: for the six-month period ending 31 December 1993, Calgene posted a whopping net loss of $21,192,000, compared to a net loss of $11,104,000 for the second half of 1992.
Research at companies like Calgene promises fresher, hardier, more disease-resistant foods, according to Edward N. Brandt Jr., director of the Center for Health Policy at the University of Oklahoma Health Sciences Center. "You also have the possibility of additional nutrient fortification of foods," adds Brandt, chair of the FDA's Food Advisory Committee, which reviewed Calgene's safety data.
The potential benefits of bioengineered foods have been touted by such respected authorities as the World Health Organization and the American Dietetic Association. Indeed, researcher Thomas J. Hoban IV of North Carolina State University notes that biotechnology "has the potential to improve agricultural productivity and enhance the food supply."
Biotechnology critics disagree, charging that companies like Calgene are more concerned with making money than feeding Americans. The Pure Food Campaign insists that products such as bovine growth hormone only add to the nation's food surplus, while subjecting consumers to unnecessary health risks. Foods like the Flavr Savr, which is expected to cost about $1 more per pound compared to conventionally grown tomatoes, won't help feed the world's hungry, says Ronnie Cummins, the group's U.S. national director. "We have not heard of a single [bioengineered] food product that's designed for anything other than to enhance the profits of the company," Cummins charges.
Joan Gussow--
Technological rabbits have big, noxious droppings.
Photo: Alan Gussow
More moderate groups such as the Environmental Defense Fund, meanwhile, are pushing for tougher regulatory control and labeling of biofoods. Joan Gussow, professor of nutrition and education at the Teachers College of Columbia, worries about the environmental consequences of bioengineering. Scientists generally agree, for instance, that "super-resistant" insects will evolve in response to genetically engineered crops containing
Bacillus thuringiensis
, a natural soil bacterium that generates an insect-fighting protein. Some believe, however, that insect resistance to such crops can be controlled.
Others aren't so sure. "Everybody behaves as if magically, science will find a way," says Gussow, author of
Chicken Little, Tomato Sauce, and Agriculture
. "My answer to that is that technological rabbits have big, noxious droppings. We're always hoping that the next technology will clean up the mess we made with the last one. I think biotech is being viewed as the solution to the problems we created with high-tech agriculture."
A Rough Trip for Flavr Savr
Conventional tomatoes are so fragile that they must be shipped green. After reaching supermarkets, they're zapped with ethylene gas, the natural ripening agent in tomatoes. To make hardier tomatoes, Calgene developed an ingenious process involving a half-dozen basic steps.
First, researchers isolate or clone the polygalacturonase (PG) gene, which causes tomatoes to soften and rot. Next, they flip the PG gene into an "antisense" position. The PG gene must then be combined with a marker gene that works like the crosshairs on a rifle, targeting a section of the tomato genome. (In the case of the Flavr Savr, Calgene's marker is the kanamycin-resistant gene, which helps
E. coli
bacteria fight off the deadly effects of antibiotics.) Thus marked, the reversed PG gene is introduced into agrobacterium and placed in a petri dish with tomato leaves. After the leaves are infected with agrobacterium, they form new plants containing the reversed PG gene.
Calgene's safety data were scrutinized by the FDA in April. FDA Food Biotechnology Coordinator James H. Maryanski said that the Flavr Savr appears to be safe. A final ruling in May approved the tomato's usage.
Questions have been raised, however, about the kanamycin-resistant gene. Some fear this marker gene could possibly find its way into nearby soil microbes or even into the human digestive tract, resulting in a dangerous resistance to antibiotics. Such a scenario is unlikely because the marker gene is rapidly degraded, Maryanski says. Yet, he concedes, "there is a very low probability" that the marker gene could somehow turn up in the wrong place.
Critics also worry about three 28-day toxicity studies in which rats were gavaged, or force-fed tomatoes. In the second and third of these studies, gastric erosion was noted in some animals, but Calgene says those symptoms had nothing to do with the Flavr Savr. "These erosions were minute, pinpoint-sized erosions," explains Calgene's Hayworth. "They occurred in rats that were fed water only, as well as rats that were fed conventional tomatoes only."
As a result of the Flavr Savr controversy, current FDA approval procedures and food labeling laws are once again claiming the limelight. Unlike food additives, most whole foods don't require FDA approval, Maryanski explains. Consequently, genetically engineered tomatoes aren't subject to premarket review, and they don't need to be labeled. (In fact, Calgene approached the FDA voluntarily, to make sure its product would comply with all consumer safety standards.)
"If the gene you're using is a tomato gene that's been introduced into corn, and that protein has been safely consumed in the past, then we're not going to treat those as new food additives," Maryanski says. That's because such products would be classified by the FDA as "GRAS," or "generally recognized as safe," he adds.
Exceptions to the FDA's current regulatory system include bioengineered foods containing potential toxins or common allergens. For example, if a new, frost-resistant tomato contains DNA from a fish, that product would have to be labeled because the FDA recognizes that many consumers are allergic to fish.
At the Environmental Defense Fund, Senior Attorney D. Douglas Hopkins says labeling, premarket testing, and registration of bioengineered foods are essential to protect all consumers from potential allergens. "Genetically engineered foods are, for the most part, added proteins," he says. "Food allergens are virtually all proteins, and food allergies--many of them serious--afflict between 2.5 million and 5 million Americans."
Jim Altemus--
Instead of labeling foods, companies should educate consumers.
Photo: Monsanto
Do consumers really want more labels? Jim Altemus, manager of plant science communications for biotech giant Monsanto of St. Louis, Missouri, says additional labeling would only confuse consumers. Instead of labeling, he says, companies like Monsanto must take responsibility for educating consumers. "The general public says they don't want labeling," Altemus says. "When you ask them what they want on their food containers, they're the first ones to say, 'Don't put more six-point type on containers in language I can't understand.'"
But a 1992 study by Hoban suggested that consumer attitudes about labels are less clearcut. In his survey of 1228 adults, Hoban asked about the importance of different types of information on labels. "Over 80 percent of respondents rated each type of food label information as 'very important,'" his report concludes. "These results support the idea that people want more information on a variety of topics, including biotechnology."
Hoban cautions, however, that the labeling issue is by no means black and white. For instance, respondents generally seemed to want labels on whole foods such as genetically engineered tomatoes. Yet, some admitted that labels on complex processed foods such as ketchup might be confusing and unnecessary.
Milk Wars
Calgene's high-tech tomato may have set off a few sparks, but recombinant bovine growth hormone continues to fuel a raging public debate. Also known as bovine somatotropin (BST), the hormone prompts cows to produce 10-12% more milk. BST entered the market in February of this year. Since then, millions of BST injections have been sold, reports Gary Barton, Monsanto's director of environmental communications.
Growth and lactation in mammals are regulated by a natural hormone originating in the pituitary gland. In the mid-1980s, researchers learned that a synthetic version of bovine growth hormone also stimulates lactation, partly by generating a secondary hormone, insulinlike growth factor-I (IGF-I). Today, Monsanto makes BST by inserting a gene from cows into
E. coli
bacteria, which multiplies in fermentation tanks.
How safe is BST? In the 24 August 1990 issue of
Science
, researchers representing the FDA's Center for Veterinary Medicine concluded that "the use of recombinant bovine growth hormone (rbGH) in dairy cattle presents no increased health risk to consumers." According to authors Judith C. Juskevich and C. Greg Guyer, BST doesn't appear to be biologically active in humans. To prove their point, the authors cited research from the 1950s in which injections of bovine growth hormone "were not effective" as treatment for children suffering from dwarfism--apparently because animal growth hormone doesn't bind with growth hormone receptors in human tissue. They also described short-term oral toxicity tests using rats.
After an exhaustive nine-year evaluation, the FDA finally ruled in November 1993 that the meat and milk from BST-injected cows is safe. "There is virtually no difference in milk from treated and untreated cows," FDA Commissioner David A. Kessler told
The New York Times
. "It's not possible using current scientific techniques to tell them apart." In fact, the FDA in February warned dairy distributors to avoid labeling products as "free" of BST, since untreated cows generate growth hormone, too.
Researchers like Bill von Meyer, president of Fairview Industries, a genetics and chemistry research company in Middleton, Wisconsin, remain unconvinced of BST's safety. Von Meyer, who reviewed Monsanto's safety data after being contacted by a concerned dairy farmer, says rodent toxicity tests were much too brief and didn't involve enough animals. Another scientist, Samuel S. Epstein, a professor of occupational and environmental medicine at the University of Illinois at Chicago, has suggested a link between IGF-I--the secondary hormone stimulated by BST use--and breast cancer in humans. In a February 14 letter to Kessler, Epstein warned that "IGF-I induces malignant transformation of normal human breast epithelial cells." Infants are particularly susceptible to cellular changes caused by IGF-I, according to Epstein, who also serves as chair of the Cancer Prevention Coalition.
After Epstein went public with his letter at a February meeting of the American Association for the Advancement of Science, Kessler received a rebuttal letter from Dennis M. Bier, a professor of pediatrics and director of the Children's Nutrition Research Center at Baylor College of Medicine. "I am aware of no substantive evidence in the world's scientific literature that IGF-I causes malignant transformation of normal human breast epithelial cells," Bier told Kessler. In response, Epstein cited Harris and colleagues in the 13 August 1992
New England Journal of Medicine
: "It now appears highly likely that a series of growth factors are responsible, at least in part, for the evolution of normal breast epithelia to breast cancer. These factors include IGF-1."
Still, Monsanto and the FDA say Epstein's fears are unfounded. "The consumption of dietary IGF-I plays no role in either inducing or promoting any human disease, nor does it cause malignant transformations of normal human breast cells," the FDA announced in a March 16 news release.
The Pure Food Campaign and some farmers say cows injected with BST are more likely to develop mastitis, causing pus to form in udders. "That raises questions about extra antibiotic use," says Bruce Krug, coordinator for the New York Farmers' Union. Barton says, however, that mastitis tends to occur in all highly productive cows. "[Mastitis] is controlled by good management," Barton says. "The better your farming operation, the less mastitis you have."
Noting that U.S. milk production already exceeds the demand for it, Krug says BST may force small dairy farmers out of business. Sheldon Krimsky, chair of the Department of Urban and Environmental Policy at Tufts University, agrees with Krug. "It's been demonstrated by economic analysis that [BST] is likely to displace small farmers," says Krimsky, who serves on the board of directors for the Council for Responsible Genetics.
But Monsanto says BST can give large as well as small farming operations an economic boost. "The efficient producers are going to benefit," Barton says. "It's $5.50 [per injection], so whether you have 100 or 1000 cows, your cost is proportional to the size of your herd."
And consumers may actually support BST use. In a January 1994 survey for the Grocery Manufacturers of America, Hoban concluded that "the use of BST in milk production will have no real impact on projected future consumption of milk."
Even so, some researchers fear that the BST controversy could adversely affect public opinion about other genetically engineered foods. "I don't like to see people judging the whole potential of biotechnology based on the example of BST," says Peggy G. Lemaux, an associate cooperative extension specialist at the University of California, Berkeley.
Peggy G. Lemaux--
Due to conventional plant breeding, modern crops don't look anything like their wild relatives.
Photo: Jack Dykinga
Pigs as Bioreactors
"It looks like a pig, smells like a pig, and in fact it tastes like pork. But biochemically, it's something very different," says Norman Steele, research leader for the USDA's Nonruminant Animal Nutrition Lab, describing pigs injected with bovine growth hormone. The pigs are just one example of current efforts to create transgenic livestock.
Compared to conventional pork, meat from pigs containing bovine growth hormone may provide more protein and less fat, USDA researcher Vernon G. Pursel wrote in the 16 June 1989 issue of
Science
. Other possible benefits of transgenic livestock include increased wool production by sheep and improved disease resistance among chickens.
Pursel has reported, however, that bovine growth hormone-transgenic pigs tend to suffer a litany of health ailments, including gastric ulcers, arthritis, and a shortened lifespan. Such detrimental effects may seem too high a price tag for sweeter pork chops. But what if transgenic pigs served as a "factory" for more valuable products? In the May 1993 issue of the
Journal of Animal Science
, Pursel and C.E. Rexroad, Jr. noted the potential of transgenics as bioreactors for rare medical products.
Genetically engineered pigs could someday produce human hemoglobin, interferon for chemotherapy, or even organs for transplant into humans. But that dream is far from reality. "The problem with the transgenic approach at the present time is that it can't be regulated adequately enough to prevent detrimental effects," Pursel explains. "Many of the genes that would be useful remain unknown. The genes that are well known aren't well regulated enough."
In addition to transgenic research, researchers at the USDA and several corporations, such as Upjohn, Eli Lilly, and American Cyanamid, are investigating the use of porcine somatotropin (PST). Pigs injected daily with PST for at least 30 days pack on as much as 300 grams of muscle protein per day, Steele reports. The result, he says, is leaner, juicier pork chops. Unfortunately, Steele notes, PST must be injected daily. For a large pig producer, he says, daily injections would be far too costly and time consuming.
But consumers might be willing to cover the cost of PST injections. In a study of 120 families, Ken J. Prusa and colleagues at Iowa State University concluded that "leanness of meat was important to 98 percent of the consumers, and 83 percent indicated that they would pay more for leaner pork if available." Families were asked to taste test ham roasts and loin roasts from PST-treated pigs as well as control pigs. Overall, Prusa wrote in the May-June 1993 issue of the
Journal of Food Science
, PST loin and ham roasts were as acceptable as meat. However, consumers said the control ham roasts were juicier, more tender, and more flavorful than the PST-generated roasts.
Natural Pesticides and Herbicides
As the public grows increasingly concerned about the use of chemical pesticides and herbicides, companies like Monsanto are developing crops with natural defense mechanisms. Among the strategies now being investigated is the use of
Bacillus thuringiensis,
or Bt, in potatoes, cotton, corn, and other crops. A natural soil bacterium, Bt fights off insects by producing a special protein.
Already, Bt crops have shown great promise for reducing chemical pesticide use. In a 1993 issue of
Plant Molecular Biology,
Jeff Wyman and colleagues described a technique for enhancing Russet Burbank potatoes with a
cryIIIA
gene, which encodes for Bt protein. Such transgenic plants effectively kill juvenile Colorado potato beetles and force adult beetles to stop feeding, Wyman reports.
He readily admits, however, that insect resistance to Bt crops is "almost inevitable." To prevent widespread problems, resistant beetle populations should be diluted with nonresistant specimens, Wyman says. Mixing transgenic and conventional seeds also helps slow the evolution of super-resistant pests, he adds.
The good news, says researcher Fred Gould of North Carolina State University, is that pests seem to develop resistance to single groups of Bt toxins. Consequently, "as insects become resistant to one Bt toxin, that toxin could be successfully replaced by a different Bt toxin," Gould wrote in the September 1992
Proceedings of the National Academy of Sciences.
Monsanto is also developing soybeans, corn, and other crops that won't die when they're sprayed with Roundup, a weed killer classified by the EPA as noncarcinogenic. Made by Monsanto, Roundup effectively kills weeds, but it also kills surrounding crops by interfering with photosynthesis, explains Jim Altemus, manager of plant science communications at Monsanto.
Critics charge that Monsanto's research will encourage increased use of Roundup. "We hope it does," Altemus says. Unlike many herbicides, he notes, Roundup doesn't cause cancer or harm wildlife.
Fantastic Possibilities
From disease-resistant chickens to potatoes that don't bruise thanks to moth DNA, the U.S. government clearly supports the development of bioengineered foods. For the fiscal year 1994, the government will spend about $211 million on biofood research, Young reports. Most of the work is being directed by the USDA. Big business is also investing heavily in bioengineered foods. For the calendar year 1993, for instance, biotech company DNA Plant Technology of Cinnaminson, New Jersey, spent $13.4 million on research and development. Calgene's R&D costs came to $2.6 million for the same period.
For Young, biotechnology represents a solution to the problem of an overcrowded planet. "As the population continues to increase, we will see a doubling of food requirements, probably by 2020 or 2030," he says. "The options available to us are either to take more land for agriculture or figure out how to increase the productivity of the land we have." Biotech, Young says, can help U.S. farmers achieve the goal of sustainable agriculture, which doesn't leave fields barren.
To support more efficient, productive farming, researchers are engineering crops to resist cold weather, drought, pests, disease, and spoilage, as well as plants that can fix their own nitrogen in soil, reducing the need for chemical fertilizers. Lemaux and Yuechun Wan, for instance, are growing barley that fights barley yellow dwarf virus. Every year, this virus wipes out 3% of the nation's barley crop, explains Lemaux. Supported by the Plant Gene Expression Center (a joint venture of the USDA's Agricultural Research Service, UC-Berkeley, and the California Agricultural Experiment Station), Lemaux's research may also provide a model for improving the viral resistance of wheat and oats.
You say potato . . .
Crops engineered with natural defense mechanisms may lead to a reduced need for pesticides.
Photo: Agriculture Research Magazine
Since the advent of biotechnology, two key developments have set the stage for genetic engineering of foods. First, Lemaux explains, researchers learned to clone plants from tissue culture. Second, they refined a way to introduce DNA into cells by using agrobacterium as a carrier. In the past, unfortunately, researchers have found it difficult to insert desirable genetic material into cereal crops because agrobacterium isn't an effective carrier for those types of foods. But Lemaux and Wan successfully introduced a viral-resistant gene into barley by using a "gene gun" to fire genetic material into plant embryos.
The Pure Food Campaign opposes such technology and instead advocates labor-intensive organic farming. Young contends, however, that large-scale organic farming simply wouldn't be practical as a way to feed all the people in the United States. And Lemaux points out that conventional plant breeding has already dramatically altered the nation's crops. "If you look at the progenitors of our modern-day crops, there probably isn't a product in the grocery store that looks anything like its wild relatives," she notes. According to Young, biotechnology should actually help increase the biodiversity of U.S. crops.
Even so, efforts to develop viral-resistant crops are prompting some scientists to ask difficult environmental questions. Specifically, if pest-resistant plants can encourage the evolution of super pests, could viral-resistant crops promote extra-potent viruses?
In the 11 March 1994 issue of
Science
, Ann E. Greene and Richard F. Allison of Michigan State University proposed a mechanism by which viruses might recombine with the genetic material of transgenic plants. "As transgenically expressed viral mRNA is available to recombine with replication viruses," the authors wrote, "RNA recombination should be considered when analyzing the risks posed by virus-resistant transgenic plants."
A rebuttal to Greene and Allison's paper appeared in the same issue of
Science.
"We believe that it is unlikely that recombinants between transgene RNA and viral genomic RNA will occur at frequencies greater than they already are occurring by recombinations between virus genomic RNAs in natural conventional and subliminal infections," wrote Bryce W. Falk and George Bruening of the University of California at Davis. "The potential benefits of engineered resistance genes far outweigh the vanishingly small risk of creating new and harmful viruses."
As researchers continue to ponder the environmental consequences of bioengineering, Jane Rissler of the Union of Concerned Scientists says the FDA must revamp its review process to include tough premarket testing and labeling of genetically engineered foods. "They ought to be devoting their resources to developing a food policy that really does protect consumers," she says.
Defined under the direction of former Vice President Dan Quayle, the FDA's current regulatory system isn't fair to consumers or to companies like Calgene, according to Marsha Cohen, a law professor at Hastings College of the Law, University of California. Throughout the FDA's lengthy review of the Flavr Savr tomato, Cohen says, "Calgene didn't know where all the hoops were" because policies were unclear.
For now, though, the FDA will evaluate new biofoods on a case-by-case basis, Maryanski says. And researchers like Lemaux will keep focusing on the potential benefits of better barley and other genetically engineered crops. "There are really some fantastic things that can be done with biotechnology, but [the science] needs a lifetime to develop," Lemaux says. "It shouldn't develop in an unbounded way, but it should develop."
Ginger Pinholster
Ginger Pinholster is a freelance writer in Wilmington, Delaware.