To a Friend
|
Email this Page To a Friend |
|
U.S. Food and
Drug Administration
FDA Consumer magazine
January-February 2001
Table of Contents
By Carol Lewis
Potatoes with built-in insecticide. Rice with extra vitamin A. Decaf coffee beans fresh off the tree. Just when Americans have begun to digest the idea of custom-built crops, along comes another major advance in biotechnology that could make an even bigger splash onto the dinner plate: genetically engineered fish.
Using the same type of gene transfer techniques that give plants new, more desirable traits, scientists have created a genetically engineered variety of Atlantic salmon that grows to market weight in about 18 months, compared to the 24 to 30 months that it normally takes for a fish to reach that size. For fish farmers, raising these so-called transgenic fish could be faster and cheaper because it takes less feed and about half the time to produce a crop they can send to market.
Transgenic animals are just another class of products developed through biotechnology that, it is hoped, will give renewed energy to the decades-old Green Revolution. Transgenic technology promises more and better crops and food animals to feed a continuously growing world population. Genetically engineered plant crops, such as corn and soybeans, have been on the market for several years. Now, genetically engineered animals may soon begin to make their way through the regulatory net, and ultimately to the dinner table--possibly starting with fast-growing fish that the sponsor promises will begin a "Blue Revolution."
The potential benefits of transgenic animals, however, do not stop at food production. Scientists created the first transgenic animals to advance basic biomedical research, genetically modifying lab rats, mice, rabbits, and monkeys to give them characteristics that mimic human diseases. These research resources, for example, rapidly advanced the understanding of oncogenes--genes that have gone awry and are responsible for causing cancers. Moreover, researchers now seek ways to genetically modify the organs of animals, such as pigs, for possible transplantation into humans.
And finally, transgenics can turn animals, such as cows, sheep and goats, into pharmaceutical factories that produce in their milk protein-based drugs such as alpha antitrypsin, a protein that can be used to treat cystic fibrosis.
Despite these benefits, genetic engineering of animals has met with some of the same resistance already aimed at designer crops. Critics cite ecological concerns, ethical objections and food-safety issues.
But no matter how transgenics is applied, the Food and Drug Administration will play a key role in regulating the products resulting from this rapidly emerging genetic technology. This means that any drug or biologic created through transgenic techniques will need to undergo the same FDA scrutiny as any other treatment that a company wants to market, including clinical trials that demonstrate safety and effectiveness. And while it's still too soon to tell how quickly foods derived from transgenic animals will move to the market, FDA has already begun to focus on how it will ensure that they meet the same safety standards as traditional foods.
Making a transgenic animal is deceptively simple, especially when compared to traditional breeding approaches. In traditional breeding, when farmers or breeders want to introduce some new characteristic into a type of animal, they must find an individual animal that carries the desired trait. They then mate the individual to try to create a new line of animals sharing the genes that express the desired quality.
With genetic engineering, scientists possess the tools to isolate and manipulate single genes in the laboratory. In recent years, researchers have learned to insert single genes into the fertilized eggs of animals in such a way that the new gene is turned on in the resulting adult. (See "Creating A New Variety Of Fish".)
First the scientist isolates the gene that conveys a particular trait of interest-disease resistance or faster growth, for example. Then a molecular vehicle is created that will carry the gene into the nucleus of the cell and permanently integrate it into the chromosome. The entire construct--the transplanted gene, called a transgene, and its transport vehicle--might be physically injected into a fertilized egg using a glass needle viewed under a microscope. Other approaches use disabled viruses to inject the construct into the cell. If the egg survives and begins to grow and divide, then the potential embryo is implanted into a surrogate mother. Of the offspring that make it to birth, only a very small number will carry the new gene integrated in such a way that it actually functions.
But when it works, the result is a new individual of a variety of animal with a characteristic never before seen. The individual animal can then be multiplied by conventional breeding. The resulting animal may be enormously valuable. Inserting a single gene into an animal, that then manufactures a rare protein in its milk, could produce a drug that is worth many millions of dollars an ounce. The Genzyme Transgenics Corporation of Cambridge, Mass., for example, has created a goat that carries the gene for antithrombin III, a blood protein that can prevent blood clotting in people. The company purifies the protein out of the goat's milk.
But even though the medical applications of transgenics remain intriguing, the animal health and food production applications seem to be generating most of the new excitement and considerable concern.
Taking their lead from the scientists who created new genetically engineered crops that, for example, resist insects without the need for pesticide spraying, researchers involved in the production of food animals began to think about how they could use genetic modifications to improve the production or quality of their products.
Typically, says John Matheson, a senior review scientist in FDA's Center for Veterinary Medicine (CVM), "Researchers start with the protein they want to add and work backwards." It's the protein that the transplanted gene encodes that actually gives the animal a new trait.
The best example so far of the transgenic strategy in food animals, and its success, is the faster-growing salmon. The science behind the so-called supersalmon was discovered by accident 20 years ago when Choy Hew, PhD, then a researcher at Memorial University of Newfoundland in Canada, accidentally froze a tank filled with a particular species of flounder. When the tank was thawed out, the flounder were still alive. Initially, no one knew how they survived. This species, it turns out, has a gene that produces a protein that works like the antifreeze in a car's radiator. This antifreeze protein is found in many types of polar fish that must survive extremely cold conditions.
Researchers isolated and copied the part of the flounder DNA that works like a genetic switch to turn on the production of the antifreeze protein. Normally, this genetic switch is only turned on when the fish is exposed to cold.
Hew and his colleagues then attached the flounder's genetic on-switch to a previously isolated gene from Chinook salmon that produces a growth-stimulating hormone. Using transgenic techniques, they inserted the new combination--the flounder on-switch with the salmon growth hormone gene--into fertilized salmon eggs. In the resulting salmon, the flounder's genetic switch appears to stay turned on, producing a continuous supply of salmon growth hormone that then accelerates the fish's development. While the resulting fish do not seem to reach a mature size that is larger than conventional salmon, they grow much faster.
Breeding transgenic varieties is an effective way to create an animal with a new characteristic, but large mammals-cows, pigs and goats-don't multiply as plentifully or as rapidly as fish. Several research teams have turned to cloning--as in Dolly, the sheep--as a way to expand the herd of transgenic animals. This approach combines two cutting-edge techniques. First, a transgenic animal with the desired characteristics is created. Then, cloning techniques are used to create replicas of the transgenic animal. Using a transgenic approach just makes it easier to get the desired genetic characteristics in the animal, which is then cloned to produce a core breeding herd.
Useful as it may be, animal biotechnology won't go forward without objections. For all the promise that industry sees in the dawning era of genetically engineered animals, others-including animal rights activists, environmentalists, and consumers-see problems.
The concern about genetically engineered foods, says Carol Tucker Foreman, director of the Food Policy Institute at the Consumer Federation of America (CFA) in Washington, D.C., "is in marked contrast to the public acceptance of genetically engineered drugs. When faced with serious illness, most people are willing to take risks to combat a disease." Food is different, she says, since it is so basic, both physically and emotionally. "It's not surprising that consumers are extremely averse to any food-related risk, especially if the risk is perceived as imposed by someone else, beyond individual control and without any countervailing benefit." Consumers, she says, are concerned mostly about such potential health problems as allergic reactions and antibiotic resistance.
But FDA Commissioner Jane E. Henney, MD, points out that foods produced using bioengineering processes are evaluated to make sure they are not more likely to cause allergies. "Under the law and FDA's biotech food policy," she says, "companies must tell consumers on the food label when a product includes a gene from one of the common allergy-causing foods, unless it can show that the protein produced by the added gene does not make the food cause allergies."
But Art Jaeger believes, "It's not just about dangerous foods--it's also a matter of consumer choice." The assistant director for CFA and advocate for mandatory labeling says consumers need to know when a food is genetically altered because many have religious or cultural convictions that would preclude them from selecting foods produced through transgenic technology. Jaeger says that his organization wants tougher regulations and feels that all information on the safety of biotechnology applications should be made publicly available.
And then there are environmental concerns. Purdue University animal scientist Bill Muir and biologist Rick Howard conducted a study funded by USDA on genetically engineered fish, which led them to warn of possible risks from transgenic fish escaping into nature. They worry that transgenic fish escaping from aquaculture facilities into the wild, for example, could damage native populations, even to the point of extinction. But Elliot Entis, president of A/F Protein, Inc., an international biotechnology firm based in Waltham, Mass., feels that environmental concerns can be addressed by producing transgenic fish in closed aquaculture systems (controlled, artificial environments) or by producing all female, sterile fish.
FDA, in cooperation with other federal agencies, will evaluate these proposed environmental safety measures prior to any approval.
At a time when genetically engineered plant crops have spurred protests in the United States, the use of biotechnology in food-animal production is likely to attract an even larger set of critics because both transgenics and cloning deal with animals.
People for the Ethical Treatment of Animals (PETA), a large animal rights organization headquartered in Norfolk, Va., for example, feels that people shouldn't be tinkering with animals like Frankenstein and is very much opposed to intensive animal agriculture.
In general, CVM's Matheson says that for animal safety, the goal of regulating products of animal biotechnology is to ensure healthful surroundings, proper medical treatment, discovery of any special management measures needed, and freedom from pain and suffering.
FDA already has the legal authority to regulate most products derived from transgenic animals, whether they are used as drugs, as human food, or as animal feed. Therefore, only guidances or regulations that cover specific aspects of animal biotechnology may need to be added-not whole new statutory frameworks for regulating the products. These guidances will likely address such issues as safety of the target animal and protection of the environment.
Most of the gene-based modifications of animals for food production fall under CVM regulation as new animal drugs. The genetically modified growth hormone for the fish, for example, will be regulated the same way the agency regulates bovine somatotropin, the genetically engineered bovine growth hormone that makes cows produce more milk. Transgenics simply provides another means to add growth hormone to an animal.
"When I speak to folks about the regulation of animal genetic engineering," says Matheson, "the first reaction is often surprise that genetically engineered animals could possibly be viewed as containing new animal drugs." People are surprised, he says, because their experience with animal drugs is limited to products they buy for their pets.
With transgenic salmon, the inserted growth hormone trait is inherited by subsequent generations. With cows, the drug is periodically injected into each one. Either way, products regulated as new animal drugs in the United States are subject to rigorous premarket requirements to determine effectiveness and ensure food, animal and environmental safety.
"One of the good things about regulating transgenics as animal drugs," says CVM director Stephen F. Sundlof, DVM, PhD, "is that we can make sure that the environmental controls and other safety measures are built right into the process." This process includes target animal safety, safety to the environment, and safety for consumers to eat foods derived from genetically engineered animals.
CVM intends to use various approaches, including a contract with the National Academy of Sciences, to identify further environmental safety issues associated with investigation and commercial use of transgenic animals. To do this, the agency will cooperate closely with other federal and state agencies that have related authorities, such as the Fish and Wildlife Service and the National Marine Fisheries Service, in the case of transgenic Atlantic salmon.
The agency already is gearing up for the major debates it expects regarding transgenic animals--debates likely to mirror the discussions now underway for bioengineered crops. At this time, no transgenic animals have been approved to enter the human food supply, but a few individual transgenic animals have been allowed to be rendered and used in animal feed.
While it's true that new compounds to combat specific diseases or to optimize the nutritional value of food products can also be created by conventional means, researchers believe that transgenics technology can help make it possible to produce them more quickly, in larger quantities, and ultimately, at lower cost to consumers.
"After over 10 years of examining products on a case-by-case basis," says Matheson, "I can say that the guidance and regulatory structure for animal biotechnology is starting to evolve. I hope we can learn from our experiences with plant biotechnology to make the road a little smoother."
Carol Lewis is a staff writer for FDA Consumer.
Breeders can now use the tools of biotechnology to introduce new characteristics into animals. For example, researchers have figured out how to give a type of salmon a gene that directs the production of a growth hormone, causing the fish to grow to full size in substantially less time. Here is an outline of the steps needed to introduce the new growth hormone gene into the salmon.
--C.L.
Table of Contents
| How to Subscribe |
Back Issues | Editorial Questions
FDA/Office of Public Affairs
Web page created by tg 2000-DEC-15.