Biologists are moving rapidly to make practical use of new methods for transferring genes between species of higher animals, methods that some expect will create new breeds of livestock containing human genes.
But as the scientists proceed toward what they see as desirable ends, they confront opponents who charge that their work is inhumane and that it violates the "biological integrity of species."
Last month, author-activist Jeremy Rifkin, leader of a private group opposed to genetic engineering, filed suit in U.S. District Court here asking that the Agriculture Department be stopped from doing such research. While the suit is pending, USDA scientists directly involved will not discuss the matter, but others around the country who are pursuing similar ends express chagrin and dismay.
They contend that although their methods are new, their goals are not so different from those of conventional animal breeders. They say the concept of species integrity is almost meaningless in scientific terms.
"This whole area is so new that most people outside the field don't know how to judge it," said Finnie Murray, a reproductive biologist doing gene-transfer experiments on pigs and sheep at Ohio University. "The problem is that these people just don't have a strong grasp of what species are and how genes are moving around in nature anyway."
Biologists say that many people outside agriculture are unaware of the vast amount of genetic change in various species already achieved through conventional selective breeding. For example, breeders have produced 1,000-pound pigs, four times normal size. Most biologists agree that this degree of natural genetic change is more extensive than anyone is contemplating for gene transfer. The advantage of the new methods is that many generations of breeding can be bypassed in a single step.
Many biologists also object to the assertion that there is something wrong with using human genes.
"I just despise this attitude that scientists are doing something immoral by putting human genes in animals," said John Fulkerson, a biologist who coordinates biotechnology research for the Agriculture Department. "In no sense are we imparting humanism to a cow."
The genes, Fulkerson noted, are human only in the sense that they have the same molecular structure as human genes. They are laboratory-made copies that, depending on circumstances, either have been placed in bacteria and reproduced as the bacteria multiply or have been synthesized from off-the-shelf chemicals.
Murray said he believes that if the public understood the biology it would welcome gene-transfer research as an ethically sound and promising avenue to more efficient food production. In some cases, the research also is aimed at producing medically useful substances.
Interest in this new form of genetic engineering was sparked two years ago when a research team implanted rat genes for growth hormone in mouse embryos that then grew faster than normal, some attaining twice normal size.
Then less than a year ago, the same group repeated the experiment using human genes. Again, the result was giant mice. In both cases, the genes became a permanent fixture of the animals' genetic makeup and were inherited normally by their offspring. The new strains of giant mice have perpetuated themselves through several generations.
Although the procedures were first developed in mice, the methods used are basically the same for all mammals. In many cases the goal is similar, too: the production of larger, faster-growing meat animals.
Mice first received foreign genes because more is known about their genetics and embryonic development than about any other species. Next well-known are those of human beings. The obvious choice was to put human genes into mice.
The gene for growth hormone was selected because it was one of a fairly small group that already had been isolated and because its effect, if it worked, might be dramatic.
Biologists felt that gene transfer was plausible because the genetic code is the same for all forms of life. Also, genes for a given substance are similar from one species to the next and, therefore, they direct the manufacture of similar products. The molecular structure of cow insulin, for example, is so close to that of human insulin that diabetics can use it.
Genes are the basic units of heredity. Each is a large molecule shaped like a long chain, made of smaller linked molecules. A sequence of many genes -- a chain of chains -- makes up a chromosome. The chemical of which genes and chromosomes are made is DNA, or deoxyribonucleic acid. Each human cell contains 46 chromosomes, which together contain an estimated 50,000 genes.
Four kinds of molecules make up a gene. The sequence in which they are linked determines the message they give to the cell, much as the sequence of letters determines a word.
The mouse experiments were done by a team led by Ralph L. Brinster of the University of Pennsylvania and Richard D. Palmiter of the University of Washington in Seattle.
They did not implant the gene alone. Like many genes, the growth gene usually operates while linked to a piece of DNA. Gene regulators are not necessarily choosy about which gene they switch on and off. Brinster and Palmiter chose a regulator that normally responds to excess zinc atoms in a cell by switching on a gene that makes a protein that can capture the potentially toxic zinc atom.
Since the regulator responds to zinc, the researchers theorized that they should be able to control the growth hormone gene's activity by varying the amount of zinc in the animals' diet. Feed zinc and the regulator should make its attached gene go into action. Withhold zinc and the regulator should keep the gene switched off.
Once they had the gene-regulator combinations prepared, the researchers obtained fertilized mouse eggs. One by one, the eggs were put under a microscope and injected, using an extremely fine needle to squirt the gene and its regulator into the egg's nucleus.
The one-celled embryos then were implanted in the uterus of a surrogate mouse mother. Most failed to develop, but of those that did, a small fraction had the gene. The amount of zinc in regular mouse feed turned out to be enough to switch the gene on and the mice grew to varying sizes above normal.
"It's important to remember," Palmiter said, "that these mice are normal in every respect except that they're big. They have perfectly normal proportions and are in good health."
Many agricultural researchers find the prospect of similarly engineered meat animals attractive. A giant steer or a giant hog appeals to some, but more significant is that such animals probably would grow faster, reaching conventional market weights in less time.
Much the same procedure is being tried at several research centers, although not all are working with growth hormone.
Murray, at Ohio University in Athens, for example, said he is planning next spring to give dairy goats genes that may increase their milk production. If that works, he will adapt the method to dairy cattle. Murray also plans to try growth hormone on sheep, then beef cattle.
Palmiter is working on pigs and growth hormone and also hopes to produce pigs with a gene for the human blood factor that hemophiliacs lack. Those with hemophilia now must make do with limited quantities of expensive blood factor extracted from human blood. If pigs could be given the gene, they could be bled periodically and the factor extracted. When the pigs reached market weight, Palmiter said, they would be perfectly good meat animals.
Duane Kraemer at Texas A&M said he hopes to produce a breed of cattle that can make several kinds of interferon, the anti-virus substance. Cattle are vulnerable to many viral diseases and, Kraemer asked, "what could be inhumane about producing livestock that resist disease?"
Australian researchers, looking to increase wool production, plan to give sheep a gene for the wool ingredient of which the animals have the least amount: an amino acid called cysteine, which forms part of the protein called keratin of which wool is made.
Despite all the activity, no one has yet reported success in altering the heredity of any animal larger than a mouse. Most researchers expect this to come fairly soon, perhaps next year.
The obstacle that worries the researchers most is Rifkin and his lawsuit. Rifkin, a philosopher and not a scientist, contends that nature has established barriers between species -- "mating walls," he calls them -- and that it is "morally reprehensible" for scientists to move genes across that barrier.
"I admit that I have a biased perspective on this," Rifkin said, "but I think there should be a public debate so that society can make up its own mind."
Biologists challenge Rifkin's premise that genetic barriers separate species. "It makes no sense biologically to say that," Palmiter said.
The concept of "species" is a vague one in biology. There is no agreed-upon definition.
Breeders of plants and animals commonly cross genetically different kinds of individuals to produce new combinations. Sometimes they even create new species. Wheat and rye, for example, are not even members of the same genus but they have been crossed to produce a new grain called triticale.
Palmiter and others point out that there are many instances in which natural processes have pirated genes from one species and implanted them in another. This is believed to be the mechanism that gave rise to viruses, which consist of a small bundle of genes in a protein coat. It has been shown that the genes in many viruses are the same as those possessed by certain species of animals or plants.
Biologists think that viruses are, in effect, escaped genes. Certain kinds of viruses have the ability to infect a cell and splice their genes permanently into the cell's chromosomes. If the cells happen to be in the gonads, which produce sperm and eggs, the genes that have escaped from another species will become a permanent part of the infected species' genetic legacy.
"Mother Nature has done more to commingle the genes of species than we can ever do," said Fulkerson.
Rifkin's opposition, Fulkerson said, is reminiscent of the objections voiced at the turn of the century when Luther Burbank pioneered the modern science of plant breeding by artificially crossing different varieties to produce scores of new hybrids.