Pig-to-human heart transplant.

Ardillaun

On January 7, a 57 year old man with terminal cardiac failure underwent a nine hour operation at the University of Maryland School of Medicine and received a cardiac transplant from a pig. Three innovations made this historic procedure possible:

1. Genetic modification. Ten genes were changed in the pig: three were removed that would have caused a rapid, antibody-mediated rejection of the foreign organ; one was removed that would have made the heart too big; and six human genes were added to reduce inflammation, rejection and blood coagulation.

2. A perfusion solution to keep the porcine heart in optimal condition between operations. Apparently, this product contains cocaine which caused a regulatory headache for the researchers.

3. A powerful drug, KPL-404, that suppresses the body’s immunological reaction (in particular, CD-40) to the foreign organ.

The potential significance is enormous - many thousands die every year awaiting organ transplantation form human donors and demand will only increase - but there’s an army of potential problems ahead. One expert called the patient ‘courageous’ which is not something you want to hear.

On the medical side, rejection and infection are the two big immediate dangers. Rejection comes in three basic types - hyperacute, acute and chronic. The hyperacute stage seems to have been successfully navigated but the body has a myriad of responses to foreign antigens that are not fully understood.

An infection is made more likely because of the immunosuppressive medication the patient is on. This could be any extrinsic infectious agent or might have travelled in the transplanted organ itself. Longer term, one has to wonder how a heart from a quadruped will perform pumping blood all the way up to the head in a biped. Not a major worry right now.

There are ethical issues. If the patient dies in the next few weeks the decision to go ahead will be questioned; this is an experimental treatment and I’d say the surgical team are not getting much sleep at the moment. Some people may have concerns about any animal transplants to humans. There are also those may be put off specifically by a pig donor for religious reasons.

The patient was denied a human transplant partly because of his poor compliance with treatment recommendations in the past, including management of hypertension. One aspect of the story dominating coverage at the moment is that he did time for a serious assault and the family of the victim are asking why a such a person deserves incredibly expensive care. Doctors would say they treat anybody regardless of their past.

https://www.dicardiology.com/videos/video-details-first-pig-heart-transplant-surgery-human

Unfortunately, this is not the first time a surgeon has attempted such an operation. In 1997 an Indian surgeon had a go without the gene modification and other mod cons. The patient died and he was jailed.

https://timesofindia.indiatimes.com/home/science/in-1997-this-indian-doctor-tried-pig-heart-transplant-was-jailed/articleshow/67111349.cms

Ardillaun

On September 20, 2023, a second patient received a genetically altered pig heart transplant. The patient, a 58 yer old male with terminal heart disease who was too sick for a human transplant, seems to have few illusions about his prospects:

Before undergoing the transplant, Mr. Faucette said he recognized that it would be a miracle if he was able to leave the hospital and go home, and another miracle if he lived for months or a year longer. “Realistically, this is in the early-stage learning process,” he said of the procedure.

https://www.nytimes.com/2023/09/22/health/pig-heart-transplant-faucette.html?smid=nytcore-ios-share&referringSource=articleShare

Ardillaun

I should add that David Bennett, the first recipient of a genetically modified pig heart, died two months after his transplant.

Victor

"1. Genetic modification. Ten genes were changed in the pig: three were removed that would have caused a rapid, antibody-mediated rejection of the foreign organ; one was removed that would have made the heart too big; and six human genes were added to reduce inflammation, rejection and blood coagulation."

At what point can that much genetic modification take place? Are we talking about when the pig was still a single cell? Does that mean pigs customised for individual human patients or for human patients generally?

Ardillaun

https://www.boards.ie/discussion/comment/121161804#Comment_121161804

As I understand it, and I would welcome any correction, the technology used is somatic cell nuclear transfer, basically the same as the one that created Dolly the sheep. The change happens in a single cell. A somatic fibroblast nucleus with modified genes is placed in an ovum whose own nucleus has been removed. Organs from this genetically modified pig are meant for any human.

https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.122.059191

Ardillaun

Some more background on the previous case.

https://www.nejm.org/doi/full/10.1056/NEJMoa2201422?query=recirc_curatedRelated_article

Ardillaun

Mr. Faucette has made it to one month:

https://edition.cnn.com/2023/10/20/health/pig-heart-transplant-maryland-update/index.html

Ardillaun

Lawrence Faucette has just died.

https://edition.cnn.com/lawrence-faucette-second-pig-heart-transplant-dies/index.html

Ardillaun

OK, news about a different organ this time. On March 16, Rick Slayman, a 62 year old man with terminal kidney failure and multiple other serious medical problems received a pig kidney in Boston. The pig donor was genetically altered in a similar way to the pigs used in the two Maryland heart transplants above but was a different type of pig. Recently, a pig kidney transplanted into a brain-dead human patient survived for a month. So far, Mr. Slayman is apparently doing well. Incredibly, he may be discharged ‘soon’.

https://www.cnn.com/2024/03/21/health/pig-kidney-transplant-living-person/index.html

World’s First Genetically-Edited Pig Kidney Transplant into Living Recipient Performed at Massachusetts General Hospital

70 years ago at the same hospital, MGH, the first human-to-human kidney transplant occurred, between identical twins.

Ardillaun

I really don’t know why the hospital won’t provide updates. Mr. Slayman is in some ways the medical equivalent of an astronaut - the world knows he is a hero in grave danger and is rooting for him. However, unlike an astronaut, a successful outcome could have profound consequence for the health of millions in short order. Anybody who is overweight should be paying attention to this story but we don’t know what is happening.

kowloonkev

I would hazard a guess that most of the world are not rooting for him.

Ardillaun

Some good news for this thread at last. Richard Slayman, who received a pig kidney last month, was discharged from hospital yesterday. Obviously, it’s early days yet but what a moment for science and medicine. Let’s hope this brave man enjoys the future he deserves.

https://www.bostonherald.com/2024/04/03/the-massachusetts-man-who-received-a-pig-kidney-transplant-discharged-from-mgh-one-of-the-happiest-moments-of-my-life/

Ardillaun

While in hospital the patient had an episode of acute cellular rejection which looks like it has been treated:

[URL unfurl="true"]https://www.statnews.com/2024/04/08/xenotransplantation-pig-kidney-rejection-richard-slayman/[/URL]

Ardillaun

Here is another approach to the same problem:

https://www.sciencenews.org/article/grow-human-kidney-pig-embryo