Dr Muhammad M Mohiuddin spent years as a xenotransplantation expert trying to figure out how to make a pig's heart survive in a human body.

In the early 1990s when Dr Muhammad Mansoor Mohiuddin was practising to become a heart transplant surgeon he received a piece of advice that changed the way he wanted to help his patients. 

Mohiuddin was born and raised in Karachi, Pakistan. After completing his medical studies at the city’s famed Dow Medical College, he earned a fellowship to study at the University of Pennsylvania Medical Center in Philadelphia. 

One day his mentor Dr Verdi J DiSesa, a well-known cardiac transplant surgeon, asked Mohiuddin if he wanted to make a difference for patients who slowly die in hospital beds, waiting for heart transplants.

There are never enough human donors around to save the thousands of patients on the waiting list. In the US alone, more than 110,000 people are waiting for donor organs including kidneys and hearts. 

DiSesa said that if Mohiuddin could figure out how to graft an animal organ into a human - known as xenotransplantation - and ensure that the organ worked, he could help tens of thousands of people instead of just a few. 

And so for the next 30 years, Mohiuddin experimented with different cocktails of drugs and therapies on baboons to find a way to make an animal organ survive in a human. 

His efforts finally paid off on January 7, when his team at the University of Maryland School of Medicine successfully transplanted the heart of a genetically modified pig into a man suffering from a severe heart ailment. 

“It was my dream, which came true. It’s something I didn’t imagine doing in my lifetime,” Mohiuddin, who is the director of the Cardiac Xenotransplantation Programme at the university, tells TRT World. 

The 57-year-old patient David Bennett, who received the pig’s heart, is recovering. He might need to stay at the hospital for at least two months before he’ll be able to return to his normal life, says Mohiuddin. 

There were two stages to the landmark surgery. Mohiuddin took the heart out of the pig and kept it in a specially designed preservation container. His colleague Bartley Griffith then surgically implanted it into the patient. 

Years of work 

This surgical procedure was the last leg of a long process that spans decades. Previous attempts to graft a baboon or pig organ didn’t work because a human body would reject it within days - sometimes within minutes. 

It’s due to the strong immune response. Even in normal human-to-human organ transplants, doctors use strong immunosuppressant drugs to reduce the rejection rate. 

Over the years, scientific advancements such as the CRISPR CAS9 gene-editing technology reduced barriers. By editing the genes of a pig, its organs can be made to resemble those of humans. 

(Pig has emerged as an animal of choice for donor organs because it’s easy to breed and the size of its organs is similar to that of humans) 

The genetically modified pig used in Bennett's surgery had 10 edited genes. It’s the same type of pig that Mohiuddin uses for his research.

Still, a major hurdle was how to tame the human body’s immune response to accept the animal organ. The available immunosuppressant drugs would reduce immunity to such low levels that an organ recipient became susceptible to diseases and infections.

Then in 2014, Mohiuddin experimented with a new drug called KPL-404, which used a specific antibody to increase the chances of a pig organ’s survival in humans. 

The combination of gene-editing tools, KPL-404, and the special solution made by a Swedish company to help preserve the pig’s heart made Bennett’s successful transplant possible, says Mohiuddin. 

Still a long way to go 

Even though a heart from a genetically modified pig has been successfully attached to a baboon’s body with the help of the drug Mohiuddin developed, it wasn’t tested on a human before.

The US health regulator, the Food and Drug Administration (FDA), requires that any medicine or medical procedure has to go through strict trials and tests before they are applied on people. 

The transplant could be performed on David Bennett only after the FDA authorised an emergency use. 

“Bennett was a very sick patient. He would have died within a couple of days if we hadn't given him some sort of support,” says Mohiuddin. 

Bennet was surviving with the aid of a heart-lung machine, his own heart had grown twice in size and he had received multiple CPRs before the transplant was carried out. 

Mohiuddin praised the FDA staff for considering Bennett's case on an emergency basis. 

“We filed the request on December 20 and received approval on New Year’s eve. They kept working with us throughout the Christmas holidays.” 

The transplant process still has to undergo clinical trials before it becomes widely available. There are concerns about some porcine viruses that can jump to humans, he says. 

Mohiuddin, who is also the president-elect of the International Xenotransplantation Association, says there’s a strong need to control and regulate animal-to-human organ transplants. 

“Obviously if the surgical process on Bennett succeeds then we will be under tremendous public pressure to help more people. I am already receiving emails from patients who are ready to receive pig hearts.” 

Mohiuddin says he’s satisfied with what he has achieved in the 30 years of his xenotransplant work. But he still has a long way to go. 

“I want to see this become a normal routine procedure. I will try to do my best to convince the FDA that it should not be only Mr Bennett but everyone who is eligible must be given a chance.” 

Source: TRT World