PPL Therapeutics Plans to Cull Sheep

PPL Therapeutics, which in 1996 made world news with the cloning of Dolly the sheep, announced in July that a downturn in its fortunes would lead it to cull most of its flock of 3,000 genetically modified sheep.

PPL Therapeutics produced the first transgenic sheep in 1991. The sheep are genetically modified to express recombinant Alpha-1 Antitrypsin (AAT) in their milk. AAT was to be used to treat lung disorders, but in June drug company Bayer announced that it was ending its three year partnership with PPL Therapeutics on trials of AAT.

PPL Therapeutics does plan to keep some of the sheep for possible future breeding programs.

Source:

Thousands of sheep face cull after drugs trial shelved. Ananova, July 15, 2003.

Dolly firm to cull its sheep. The BBC, July 15, 2003.

Genetically Modified, Cloned Pigs Could Provide Organs for Humans

PPL Therapeutics announced this week that on Christmas Day five genetically modified and cloned Pigs were born that bring the possibility of Xenotransplantation — transplanting organs from animals to human beings — one step closer.

The pigs are genetically modified to make it more likely that an organ transplanted to human beings would not be rejected by the human immune system. Researchers knocked out a gene in the pigs that produces an enzyme that adds a sugar to the surface of the cells. This sugar would be identified immediately by the human immune system which result in an attack and the rejection of the organ.

Which does not mean that organs from these genetically modified pigs are ready to be transplanted into humans. In fact, another gene that performs a similar function would have to be knocked out as well as several human genes added in order for there to be a reasonable chance at transplanted organs not being rejected.

Still, PPL Therapeutics vice-president David Ayares told New Scientist that he hopes human trials could begin within five years. Pigs, by the way, would be ideal for heart transplants since the heart in this particular species of pig is roughly the same size as the human heart.

Since the pigs were cloned, PPL Therapeutics would have the ability to quickly ramp up production of replacement organs should their technology eventually succeed in human trials.

Of course, the animal rights community is opposed to this, with the Campaign for Responsible Transplantation once again raising the red flag about possible pig viruses being passed on to human beings. CRT has spent the last couple of years arguing that the possibility of cross-infection of porcine endogenous retrovirus should lead to an outright ban of xenotransplantation with pigs.

In 1997, researchers proved that, at least in laboratory conditions, PERV could jump from pig cells to human cells. PPL Therapeutics and other companies hoping to market this technology will likely have to create pigs that are free from PERV. The PERV virus has been completely sequenced and patented, however. Another company, Immerge, has bred pigs which it says are genetically modified so they cannot pass along PERV to human beings.

Which is largely irrelevant to the animal rights activists, for whom the argument is largely a smokescreen. Wired, for example, cites an earlier interview with CRT’s Alix Fano in which Fano said,

Every animal has hundreds of retroviruses, and there’s no way you can breed them out. And there could be other viruses lurking in these pigs, not to mention parasites, bacteria, fungi and latent infections of all kind.

Of course if medical technologies are required to meet a criteria of eliminating unknown fears and possibilities, then a lot more has to go out the window than just xenotransplantation. For example, pig heart valves are currently used in valve replacement surgery — and with no reports of cross contamination of pig viruses, parasites, etc. to my knowledge.

Ironically, Dr. Jay Fishman, who sequenced the PERV disease, presented a paper in May 2000 noting that organs transplanted from animals to humans might actually turn out to be safer because common human diseases that cause organ failure would likely not grow in organs transplanted from another species. Wired quotes Fishman as writing in that paper,

Due to the species differences between the host (human) and donor (non-human species), the risk of infection of the transplanted organ … may actually be decreased. This incudes common pathogens such a cytomegalovirus, Epstein-Barr virus, … herpes, hepatitis B and C, and possibly human immunodeficiency viruses.

Sources:

Cloned pigs as organ donors?. Kristen Philipkoski, Wired, January 3, 2002.

Knock-out pig clones advance transplant hopes. Emma Young, New Scientist, January 3, 2002.

Animal transplants: a step closer?. The BBC, January 3, 2002.

New pig clones born. The BBC, January 2, 2002.

Dolly Researchers Turn Skin Cells into Stem Cells

Researchers who helped clone Dolly the Sheep have turned what they learned there into an incredible breakthrough. Researchers at the U.S. subsidiary of PPL Therapeutics last week announced they had managed to turn cells from the skin of cows into stem cells. They were then able to turn the stem cells into functioning heart cells.

This has a number of important implications for human research. Stem cells of the sort announced by the researchers are typically found only in fetuses. Those stem cells can become literally any other type of cell if given the correct signals.

As organisms grow and age, however, the stem cells become differentiated and able to transform into fewer and fewer different types of tissue. This is necessary to control development of the organism.

For this reason, research involving stem cells in human beings has to date required the controversial use of fetal tissue. Experimental treatment for |Parkinson|’s disease, for example, uses fetal tissue in an attempt to spur growth of neurons in the brain.

Because of the ongoing controversy over abortion, use of fetal tissue has proven to be a political minefield (Great Britain is the only government in the world that currently allows government funding for such projects), and there are other limitations. Taking adult cells, such as from the skin, and turning back the clock, so to speak, to transform them into undifferentiated stem cells has been one of the ultimate goals of genetic research.

Dr. Ron James, managing director of PPL Therapeutics, told the BBC, “The results of this experiment give us confidence that the method we are developing as a source of stem cells is working and I believe it will be equally applicable to humans.”

If that proves to be true, which is an enormous if, it could revolutionize medical treatments leading to such science fiction-like scenarios as growing replacement for defective hearts and other organs.

Source:

Tissue transplant advance. The BBC, February 23, 2001.