U.K. Firm Creates Pig Clones That Lack Rejection-Causing Gene for Transplants
By GAUTAM NAIK
Staff Reporter of THE WALL STREET JOURNAL
LONDON -- The British company that helped clone Dolly the sheep said it has created five pig clones whose organs may be able to avert an immune rejection were they transplanted to humans.
The move by PPL Therapeutics PLC is seen as a significant step toward making animal-to-human organ transplants a reality and meeting a huge clinical need: More than 75,000 Americans and thousands of Europeans are in need of transplants, and many will die because the supply of human organs is severely limited.
While scientists have long sought ways to transplant animal organs into humans -- a technique called xenotransplantation -- they haven't been able to overcome the longstanding problem of immune rejection by the human body. Now, PPL says it has created five "knockout" pigs that lack the gene chiefly responsible for triggering a massive immune response in the human body during transplantation. PPL says its technique deactivates, or knocks out, the relevant gene.
"There are still lots of questions" about the viability of animal-to-human transplantation, said Alan Colman, research director of PPL, a company that vaulted to prominence after helping to clone Dolly in the mid-1990s. "But the immune rejection has been the principal hurdle."
The news caused PPL's shares to soar 23 pence,or 44%, to 76 pence on the London Stock Exchange.
PPL's work hasn't been reviewed or confirmed by other scientists. While the Scottish company may have created a big splash by moving quickly to announce its achievement, rival scientists are involved in similar experiments. For instance, a team of Swiss drug maker Novartis AG and biotechnology concern BioTransplant Inc. of Boston has been working on cloning a miniature pig that would be genetically altered to eliminate features of porcine organs that cause the human body to reject them.
PPL's experiment is, in many ways, the main result sought by the company's scientists in developing the cloning methods that led to Dolly. In this case, however, the researchers went several steps further: They first took skin cells from a pig fetus, isolated a specific gene and altered it so it essentially stopped working. The gene then was reintroduced to the original cells, where it substituted for the same functioning gene already present in a small number of those cells. Finally, PPL transferred the genetic information from these cells to unfertilized pig eggs -- the cloning operation -- and transferred those eggs back to a foster mother. The resulting pigs were born with inactivated genes. The hope is that their organs therefore are less likely to trigger an immune rejection when transplanted into humans.
PPL still has lots of work to do. Each cell has two copies of each gene. Thus far, PPL has deactivated only one of the copies in the five pigs it created, all of which are female. It is awaiting the birth of several male pigs that would have the second gene deactivated. By mating the two groups of pigs, the company expects to create a small number of animals that have both copies of each "knockout" gene deactivated.
Even if the immune-rejection problem is surmounted, it isn't clear whether a pig's heart, say, would automatically -- and efficiently -- do the job of a human one. Other transplants could be trickier. Pig kidneys, for example, produce hormones that may not be compatible with hormones produced by human kidneys. Pigs also harbor certain viruses that could be deadly to humans.
PPL said the first application of its advance will be to test insulin-producing cells for the treatment of diabetes from the knockout pigs first in primates and later in humans. Clinical trials involving humans aren't expected to begin for at least four years.
The latest experiments were carried out by PPL's U.S. unit in Blacksburg, Va., and partly funded by the U.S. government. The five pigs were born on Christmas day and named Noel, Angel, Star, Joy and Mary. |
