Two research groups have found a way to change the genetic make-up of pigs which brings on transplant rejection. Dick Ahlstrom, Science Editor, reports.
Separate research groups in the UK and US have moved us closer towards the day when pig organs could be used for transplant in humans. Ethical and safety issues remain to be addressed but such a development could eliminate the worldwide shortage of donor organs and prevent unnecessary deaths.
The two groups have found a way to change the genetic make-up of pigs, knocking out a gene that brings on rejection of an organ after transplant in a human. This should make it easier to use pig tissues in humans, known as xenotransplantation.
The first announcement came on Wednesday when PPL Therapeutics Plc of Edinburgh announced the birth on December 25th of five cloned "knock-out" piglets. Marking the holiday season, the company named them Noel, Angel, Star, Joy and Mary.
The second announcement is published this morning in the journal Science by researchers at the University of Missouri-Columbia and Immerge BioTherapeutics Inc of Charlestown, Maryland. Their piglets were born on September 21st and also have this key gene knocked out.
There is potential for huge rewards for any research team that can overcome the technical hurdles and enable the use of animal tissues in human treatments. PPL estimates the world market is worth more than $5 billion (€5.5 billion) for solid organs and $6 billion (€6.6 billion) for cellular therapies for diabetes, Parkinson's and Alzheimer's diseases.
The first use of the technology could come in as little as four years when insulin-producing islet cells from knock-out pigs will be transplanted into diabetics who lack working islet cells. If successful, this would bring about a revolution in medical treatments and would reduce, if not eliminate, waiting lists for organ donations.
The US and UK teams have brought this eventuality forward because they found a way to protect transplant tissues from the body's powerful immune system. Our immune systems defend us from bacteria and viruses, "foreign" invaders which are recognised as non-self and immediately attacked by specialised cells and antibodies. The body mounts a particularly powerful attack against non-self tissues, causing "hyperacute rejection" of the foreign tissues and their destruction within minutes.
This rapid rejection occurs when human antibodies attach to sugar molecules on the surface of the transplanted pig organ's cells. The two research groups found a way to prevent this happening by stopping the surface sugar from forming.
They identified a key gene associated with the surface sugar, 1,3 galactosyl transferase, and then used genetic technologies to knock it out of the genetic blueprint. This in itself would not have been enough, however, to produce these special piglets.
The pig cells were modified in a test tube and their nuclei were then transferred into emptied-out egg cells. Both research teams employed the same cloning process, nuclear cell transfer, originally used to make Dolly the cloned sheep. This delivered piglets that carried the knock-out modification and a greatly reduced risk of immune system attack.
Pigs are the preferred species for xenotransplantation on scientific and ethical grounds. Many of their organs are quite similar to human organs and with cloning there is a limitless supply.
Difficulties remain, however.There are concerns about the transfer of latent pig viruses into humans with unknown consequences. Nor is there hard evidence that animal organs will work as expected after transplant.
The companies behind the piglets were nonetheless delighted. "With one of the major technical hurdles and scientific risks overcome, the promise of xenotransplantation is now a reality, with the potential to revolutionise the transplant industry," said Dr Alan Colman, research director at PPL.
"Based on the success reported today, we can now proceed with pig strains chosen solely for their advantages in xenotransplantation rather than their large-scale availability," said Dr Robert Hawley, of Immerge BioTherapeutics Inc. His company chose miniature swine for its research because their smaller organ size more closely matches human organs.