How pigs will save thousands of human lives through organ transplants – New York Post

Dr. Robert Montgomery made history last September when he became the first surgeon to successfully transplant a pig kidney into a living person. Its a victory thats especially sweet for the 62-year-old doctor, whos only alive today because of a transplant.

Montgomery was born with a heart condition that killed both his father and older brother, both of whom died young (his brother at 35, his dad at 52). He finally got a heart transplant in 2018, after years of waiting because he wasnt sick enough to make the organ donor list.

So he knows all too well what the waiting is like as a patient, Montgomery, head of the NYU Langone Transplant Institute, told The Post. The uncertainty of not knowing if youre going to get an organ. Im very aware of the people who dont make it across the finish line.

Although his patient was clinically brain-dead before the operation, the transplanted kidney remained functional for 54 hours, long enough to detect any immediate rejection. Its a promising sign that xenotransplantation the medical term for implanting other species organs and tissues into humans may soon become the norm.

Montgomerys groundbreaking surgery was just the beginning of the huge strides in xenotransplantation over recent months. On Jan. 7, David Bennett, a 57-year-old man with end-stage heart disease, received a genetically modified pig heart at the University of Maryland Medical Center.

Though he wasnt considered an ideal candidate he had a criminal history, as well as a history of ignoring advice from his doctors Bennett, who remains (as of this writing) alive with his pig heart, became the public face of the thousands of patients who need an organ and are out of options.

I want to live, he said in an interview prior to the surgery. I know its a shot in the dark, but its my last choice.

In the US alone, there are over 106,000 people on the transplant waiting list, and around 17 die every day without getting a desperately needed kidney, heart or lung, according to the American Transplant Foundation. Human organ donors are on the rise 12,588 in 2020, up by almost a thousand from the previous year but its not nearly enough to meet the demand. In many cases, the best hope for a transplant is somebody elses tragedy. For a patient to live, somebody else must die.

This continues to be the single greatest unmet need in transplantation, said Montgomery. Its a supply and demand problem. And its only getting worse every year.

But that may change thanks to xenotransplantations recent watershed moments. Just a few decades ago, pig organ transplants were still the stuff of science fiction, the kind of technology that only existed in Margaret Atwood novels.

From the outside, I can see why itd look like this happened out of nowhere, said Montgomery. But weve been laying the groundwork for these innovations for years.

The pig organs used in both surgeries came from Revivicor, a Virginia-based biotechnology firm thats been working to produce genetically modified pigs since 2003. (Theyre a spin-off from another company, PPL Therapeutics, that cloned Dolly the sheep in the 90s.)

And theyre far from alone. The biotech eGenesis, another startup looking to harvest pig organs for transplants, raised $100 million in 2019 to clinically test their xenotransplant organs.(The companys staff wears t-shirts bearing the company slogan This pig might save your bacon.)

Even Smithfield Foods, which packages and sells pork products like bacon, hot dogs, and sausages, opened a bioscience branch in 2017 with an $80 million grant from the US Department of Defense to start raising hogs specifically for organ transplants.

Its become a bit of a race to see who can get there first, says Montgomery.

Its not just the advances in science determining if xenotransplants become commonplace. It also matters if the public is ready for this type of thing, Montgomery said.

In a 1998 survey, just 42 percent of people said theyd be OK with a pig organ transplant, while 96 percent preferred a human organ. That number has slightly increased in recent years, according to a 2018 Pew survey. Now 57 percent, or six-in-ten Americans, think genetically engineering animals for transplant organs is acceptable, while 41 percent still arent convinced.

We shouldnt be dependent on this paradigm that another human being has to die for somebody else to live.

It doesnt help that the history of xenotransplantation is filled with surreal and even macabre tales. Jean-Baptiste Denis, a 17th-century physician to the French king Louis XIV, preferred the blood of animals in transfusions because he believed they were less inclined towards debauchery. During the 1920s, a doctor named John Brinkley became briefly infamous for transplanting goat testicles into human scrotums to cure impotence. (Unsurprisingly, many of his patients died from infection.)

Human-to-human organ transplants became a reality in the mid-20th century beginning in 1954 with the first successful kidney transplant and almost immediately, organ shortage was an issue. Monkeys and chimpanzees were the first animals considered for transplants, if only because theyre genetically closest to humans.

During the 60s, several transplant surgeries were attempted using chimp kidneys, but only one patient survived for nine months which was enough for Thomas Starzl, the pioneering transplant surgeon, to call it a real beacon of hope.

The most famous xenotransplant of the last century was Baby Fae, an infant born with a lethal heart defect who received a baboon heart in 1984. She died just days after the transplant, and public reaction was more shock than awe. The Washington Post warned of medical adventurism, and the Journal of Medical Ethics dismissed it as a beastly business.

At first, pig organs seemed more promising. Pig organs are anatomically similar to human organs, says Michael K. Gusmano, a professor of health policy at Lehigh University. Humans and pigs also share 98 percent of the same genes. But pig organs were still attacked by human immune systems as foreign invaders. In 1997, two Indian surgeons attempted a pig heart and lung transplant on a 32-year-old patient, and when he died, the surgeons were jailed for homicide, with the media describing it as the plot of a horror movie.

But then something changed. Researchers learned how to humanize pig hearts, said Bruno Reichart, a retired transplant surgeon and CEO of XTransplant, a company attempting to commercialize pig-to-human heart transplants. More scientifically, they found a way to cut out the alpha-gal, a sugar molecule in pig cells that triggers the human immune system.

The gene-editing tool CRISPR developed in 2012, which went on to win a Nobel Prize in chemistry in 2020 was used to alter genes that caused a pigs heart to grow too large, enough to sustain a 600-pound pig.

We introduced enzymes that would find and cut specific points in a pigs DNA and then change it to DNA that we prefer, said Harvard geneticist and eGenesis co-founder George Church. We edited pig genes to make them more like human genes.

In 2015, a baboon was kept alive with a pig heart for 945 days, still a record. Reichart, who was involved in many of the baboon experiments, also helped develop an experimental nutrient solution that successfully preserved porcine hearts out of the body for hours, he told The Post. That is more difficult when compared to human organs: you must perfuse porcine hearts with a cold solution containing nutrients, hormones and oxygen.

Everything changed in late 2020, when the FDA approved the one-time emergency use of an organ from a genetically modified GalSafe pig, produced by Revivicor. It opened the floodgates for what The Atlantic described in 2017 as Big Pork the companies looking to cash in on the pig organ transplant boom.

As companies now race to be the first with a medical breakthrough that will save lives and also generate billions in profits, theres concern about whether some will cut corners to get there quicker.

Thats always a worry, says Gusmano. Thats why it is important for the industry to be carefully regulated, including surprise inspections. As with all medical drugs and devices, we cannot have a market with goods that people trust and are willing to use without appropriate regulation and oversight.

Not everybody believes the burgeoning pig organ industry will have the best interests of the public in mind. Wired magazine recently called xenotransplantation a capatalist myth, adding that our medical systems will always serve the most privileged at the expense of the least.

Not so, said Church, who points out that the cost of a heart transplant in the US is around $1.66 million, according to the most recent estimates, while pig transplants, judging solely on the cost of the pig heart transplants for baboons, are a comparative steal at just $500,000.

Engineered organs could reduce costs in all sorts of ways, he said.

The future of xenotransplantation is either cause for eager anticipation or cautious optimism, depending on who you ask.

Martine Rothblatt, the CEO of United Therapeutics the company that owns Revivicor, which provided organs for all the recent xenotransplant breakthroughs didnt mince words in a 2015 TED Talk. Just like we keep cars and planes and buildings going forever with an unlimited supply of building and machine parts, why cant we create an unlimited supply of transplantable organs to keep people living indefinitely?

Others arent as fast to claim that pig organs will become the new standard.

Hearts will be possible, says Reichart. Kidneys will need more consistent preclinical results. Lungs and livers are more difficult.

Church, however, thinks the sky is the limit. Blood cells, stem cells, eyes, skin, thymus, pancreas, bones, tendons, nerves, veins, gastrointestinal components, he said, listing all the human parts that are or may soon be replaceable with pig tissue.

While heart and kidney transplants get all the attention, less flashy surgeries are happening every year, moving us closer to a world where pigs are becoming a one-stop-shop for human replacements. Genetically engineered pigs have already been used for everything from skin replacements for burn wounds to corneas to restore sight.

Montgomery tries to be pragmatic when discussing the future of pig organ transplants, but his enthusiasm and optimism are apparent. I think its going to be in our lifetime, he said. And I say that as somebody in his early 60s. As long as there arent any major setbacks, I think Ill be doing routine xenotransplants in the next ten years.

For Montgomery, it isnt enough that deserving patients get access to organ transplants. We can have an unlimited supply, he says. The goal is to transplant people who previously werent thought of as good transplant candidates. There are 800,000 people with end-stage kidney disease, and only around 90,000 of them are on the list to get an organ transplant.

All sorts of factors determine who does and doesnt qualify for a donor organ, like age, medical history, and survivability odds. Some recent studies have even found that Black, Hispanic and low-income patients are less likely to get on a transplant list than white and wealthy patients.

But with an on-demand reserve of pig organs, waiting lists would become obsolete. We shouldnt be dependent on this paradigm that another human being has to die for somebody else to live, Montgomery said. We have to have something thats more sustainable.

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How pigs will save thousands of human lives through organ transplants - New York Post