The first successful transfer of a gene from one animal species to another--from rabbits to mice and then to their offspring--has been achieved by biologists.
The gene is one that directs the manufacture of part of hemoglobin, the oxygen-carrying part of blood.
The achievement is a history-making first that can be expected to speed the already swift progress of genetic engineering--in this case, engineering to transfer some traits of one creature to another, first in animals but then, possibly, in man.
The technique could be used either to transfer a gene from a different species to create genetically unique animals, or to transfer some desired trait within the same species.
The biologist who headed the effort, Dr. Thomas E. Wagner of Ohio University, is already working with a Denver firm called Genetic Engineering Inc. to learn to produce what he calls "three-parent cattle." These would be cattle with added genes from an otherwise unrelated bull or cow to confer some valued quality, such as faster growth or more milk production.
But the same method may be applied some day in humans, say, to give a gene to produce insulin to an infant whose family has a strong tendency to diabetes. Or a gene to produce normal blood cells in a family strongly susceptible to a debilitating disease such as sickle cell anemia.
In short, some human diseases or terrible genetic defects might be prevented by introducing a missing or substitute gene.
Wagner and his co-workers performed their experiments in part in Athens, Ohio, at their university, and partly in collaboration with the Jackson Laboratory in Bar Harbor, Maine. A collaborator there would not allow his name to be used until a scientific paper appears in print.
The scientists first obtained segments of the genetic material, or DNA, that makes up the rabbit gene that produces beta-globin, one of two molecules in rabbit hemoglobin.
They then flushed egg cells from the oviducts of female mice just hours after the females mated.
They then injected the rabbit DNA into these egg cells, directly into the male pronuclei, that is, the male mouse sperm that had already entered the female egg cells and begun to swell. This is the step just before the sperm combine with female genetic material to give future offspring what would ordinarily be a two-parent heritage.
The scientists injected 312 mouse eggs in this way and kept them growing in the laboratory for four to five days. Then they transferred the 211 of them that survived into foster mouse mothers.
These females had 46 offspring. Five contained rabbit hemoglobin protein in their red blood cells.
A male and female of these partly rabbit-blooded mice were mated. This mother had eight offspring; at least five also possessed the new rabbit gene and the hemoglobin protein it produces.
In short, Wagner said in an interview, "we have demonstrated not only that we can introduce a gene into a species but that when the animal becomes mature it not only contains the new genetic material but is making the desired product. And that its offspring are producing the same product, this new protein of rabbit origin."
A large part of the "trick" that makes this possible, he said, is injecting the foreign DNA into the egg cells at the right moment.
For the past eight years, he explained, he has worked on "the very early process of fertilization from the male, or sperm, point of view--what happens to the sperm cell when it enters the egg."
What happens is that the sperm's searching head penetrates the egg wall, then quickly swells into what is called the pronucleus.
"This," Wagner said, "is the one time in an animal's entire life history when it is normal for it to accept foreign genetic material. It is a privileged time, a time when by definition the egg must be in a vulnerable state to allow the integration of foreign DNA.
"We're essentially tricking the egg into believing the rabbit DNA is part of the male's DNA that it must accept anyway."
Other scientists have also been trying to transfer genes from one species to another. Dr. Beatrice Mintz of the Institute for Cancer Research in Philadelphia has reported implanting a herpes virus gene at least into the fertilized egg of a female mouse.
But the Wagner achievement is a "first" and "quite important," said Dr. Elizabeth Russell, a well-known Jackson Laboratory scientist.
As to applications, Wagner forecast uses in animal breeding within 10 to 20 years, "with major implications for the animal industry." Today it takes generations to improve the genetic qualities of animals by selective breeding.
But in the future, he said, one might, for example, want cattle that grow as well on grass or hay as they do on more refined and expensive feed--"as well as goats or sheep or buffalo grow on such roughage." So "you might transfer this trait alone of a buffalo to a cow, and leave all the rest of the buffalo behind."
Such hybrid animals would be of huge value, he said, in the many parts of the world where nothing grows well except grass and other forage, "and animals are the only way of converting grass to useable protein."
Ohio University has signed an exclusive licensing agreement with Genetic Engineering Inc. to work toward such uses.
Medical uses are probably further away, Wagner said. It may take long observation before anyone is sure the new genes are doing only what they're supposed to do and not causing new harm.
But another great dividend, he pointed out, should be knowledge.
Work like this will give biologists a tool to look into one of nature's greatest mysteries: how genes act or "express themselves" inside cells, and how and when they are "turned on" during an embryo's wondrous development.