Why pig heart transplant is a milestone
The first successful transplant of a pig’s heart into a human in the United States offers hope to hundreds of thousands of patients awaiting organs. It certainly is a watershed moment in medicine and marks the culmination of years of research.
This could help solve the chronic shortage of organs and help change lives worldwide. The long waiting lists and the slim possibility of getting a suitable organ make transplants a tricky proposition. According to organdonor.gov, about 110,000 Americans are waiting for an organ transplant, and 17 people die every day without getting one.
“If we could use genetically engineered pig organs, they'd never have to wait, they could get an organ as they needed it. Plus, we wouldn't have to fly all over the country at night-time to recover organs to put them into recipients," Dr Christine Lau, chair of the Department of Surgery at the University of Maryland School of Medicine, told the BBC.
What the pig heart recipient said before the heart transplant
The patient, David Bennett, a 57-year-old Maryland handyman, knew there was no guarantee the experiment would work but he was dying, ineligible for a human heart transplant and had no other option, his son told The Associated Press.
"It was either die or do this transplant. I want to live. I know it's a shot in the dark, but it's my last choice,'' Bennett said a day before the surgery, according to a statement provided by the University of Maryland School of Medicine.
What the heart transplant patient's son said
Pig heart valves also have been used successfully for decades in humans, and Bennett's son said his father had received one about a decade ago.
As for the heart transplant, "He realizes the magnitude of what was done and he really realizes the importance of it," David Bennett Jr. said. "He could not live, or he could last a day, or he could last a couple of days. I mean, we're in the unknown at this point."
What the doctor who conducted the heart surgery said
Dr Bartley Griffith, who performed the surgery, said the patient's condition - heart failure and an irregular heartbeat - made him ineligible for a human heart transplant or a heart pump. Griffith had transplanted pig hearts into about 50 baboons over five years, before offering the option to Bennett.
What’s organ transplantation?
Organ transplantation is a surgical procedure where an organ is removed from a person’s body (donor) and fixed in the body of another person (recipient). It’s a life-saving operation for the recipients whose organ has failed, as it provides a lease of life.
Organs that can be transplanted include the liver, kidney, pancreas, heart, heart valves, lungs, intestine, corneas, middle ear, skin, bone, bone marrow and connective tissue.
Kidneys are most transplanted, while the least common organ transplants are the intestines. Every hospital has its criteria for evaluation for transplants, and they are matched for several characteristics, including blood type and size of the organ.
How the transplant was done
Patients' bodies reject animal organs
Prior attempts at such transplants - or xenotransplantation - have failed, largely because patients' bodies rapidly rejected the animal organ. Notably, in 1984, Baby Fae, a dying infant, lived 21 days with a baboon heart.
What is xenotransplantation?
Xenotransplantation is the process of grafting — or transplanting — organs or tissues between members of different species. It's alternatively called “xenografting”.
There had been experiments in which human skin cells were grown outside the body on a layer of nonhuman cells — and then used in humans for skin reconstruction. These can also be considered a “xenotransplantation product”.
For xenotransplantation to work, the “product” or organs must be “alive”, and circulation and return of patients’ blood must occur through live non-human cells.
What made the difference in this heart transplant?
The Maryland surgeons used a heart from a pig that had undergone gene-editing to remove (or "knockout") a sugar in its cells that's responsible for that hyper-fast organ rejection. Several biotech companies are developing pig organs for human transplant. The one used for Friday's operation came from Revivicor, a subsidiary of United Therapeutics.
Over the years, scientists have turned from primates to pigs, tinkering with their genes.
Just last September, researchers in New York performed an experiment suggesting these kinds of pigs might offer promise for animal-to-human transplants. Doctors temporarily attached a pig's kidney to a deceased human body and watched it begin to work.
Why a pig’s heart is preferred for human transplant?
It’s not an ordinary pig’s heart straight from the farm. Rather, it is a product of the latest advances in genetic engineering, explained The New Scientist.
The technique of genetically modifying pigs — known as “GalSafe pigs” — has been going on for years, with the end point of making pigs-to-humans organ transplant safe and effective.
In the mid-2010s, scientists found that the “knockout” (or alteration) of alpha gal, a sugar molecule on the surface of cells, and could help minimise allergic reactions to pork and reduce the risk of organ rejection in transplant patients.
This made transplants from the pigs less likely to be rejected by primate recipients. In the past, cells of pig pancreas had been successfully transplanted into people with diabetes.
Scientists at the US firm Revivicor, a subsidiary of biotech United Therapeutics, are pioneering this technique.
What are the experiments with other animal parts?
Over the years, only a few attempts at human xenografting had been reported in scientific journals. The US FDA has approved genetic modification in pigs for biomedicine, but does not currently approve any human solid organ xenograft projects.
“Baby Fae”, a child born with a malformed heart, survived for a short period of time with a baboon heart.
Initially, there were concerns that virus genes naturally found in pig DNA could cross to humans. These concerns, however, have faded after humans with diabetes had successful transplants of pig pancreas cells.
Previous research using primates as recipients of whole pig organs showed no such problems.
FDA approves genetically-modified line of pigs
On December 14, 2020, the US Food and Drug Administration granted approval for a genetically-modified line of pigs. It marks the first time a GM animal has been given the regulatory go-signal for both therapeutic development and food consumption.
The alteration knocks out alpha-gal, a sugar molecule on the surface of cells, and could help minimize allergic reactions to pork and reduce the risk of organ rejection in transplant patients.
Cardiac Xenotransplantation Program
Dr Muhammad Mohiuddin, Professor of Surgery at the University of Maryland School of Medicine, established the Cardiac Xenotransplantation Program with Dr. Bartley Griffith, who performed the transplant.
The doctors are currently closely monitoring the recipient to check for signs of rejection. To control rejection, the recipient is also taking immune-suppressing medications. He was coping well with the new heart, doctors reported.
10 genes knocked out
The ‘donor’ pig had six human genes inserted into its genome. Altogether 10 genes were modified in the pig heart, explained Dr Muhammad Mohiuddin, considered one of the world’s foremost experts on transplanting animal organs. “Four genes were ‘knocked out’ — three of them are responsible for producing antibodies that cause rejection. Another gene responsible for controlling growth of pigs and its organs, was also knocked out,” he said.
What are the risks?
There are both short-term and long-term risks associated with organ transplant – including procedure, function and psychological problems.
Viruses are among the most common causes of infection after organ transplantation. The recipient is susceptible to a broad array of viral pathogens. Some may be transmitted with the graft received from the donor, while others may result from exposure.
Simultaneous infections with multiple viral or viral and non-viral pathogens are common. The risk depends on the intensity of exposure, virulence of the virus and intensity of immune suppression used to prevent graft rejection.
Donating an organ can also expose a healthy person to the risk of and recovery from surgery.
Immediate, surgery-related risks of organ donation include pain, infection, hernia, bleeding, blood clots, wound complications and, in rare cases, death.
Heart surgeries, and its history
Until 1896, it was generally thought that the heart could not be operated on.
However, that changed when Ludwig Rehn in Germany sutured an actively bleeding wound in the right ventricle of a patient who had been stabbed. The patient recovered, and cardiac surgery was born.
In 1925, Henry Souttar, at the Middlesex Hospital, operated successfully on a young woman with mitral valve disease – the first successful operation anywhere in the world, on a patient’s heart valve.
The technology which led to the development of cardiopulmonary bypass, the heart-lung machine, was first developed in the 1930s when early experiments were carried out on cats by John H Gibbon in the USA.
In 1939, the first successful heart surgery was conducted to fix a hole in the heart or PDA (patent ductus arteriosus), a heart problem that can manifest soon after birth and means that oxygen-rich blood from the aorta mixes with oxygen-poor blood from the pulmonary artery.
The procedure involves closing the open PDA with stitches or ligatures, and was first carried out in Boston by a surgical trainee, Robert Gross, without the permission of his chief of surgery and when his chief was away on holiday.
In 1960, the US surgeon Albert Starr implanted a mechanical valve that he had invented into a 52-year-old man who lived for another 10 years.
During this time, there were major developments in technology to help cardiac surgery. There were also a range of improvements in drug therapy and safer anaesthesia.
In 1967, the era of coronary artery surgery was initiated by Rene Favaloro in Brazil. By developing coronary artery bypass surgery, which diverts blood around narrowed or clogged sections of major arteries, he changed the way we treat coronary disease.
In December, 1967, the first heart transplant was performed by Christiaan Barnard in South Africa.
If the 1980s saw major refinements in cardiac surgery, the 1990s brought a transformational change with the development of ‘interventional cardiology’. This meant that some of the procedures which were previously only done by surgeons were now starting to be carried out by cardiologists in catheter laboratories.
Heart-related problems do not always require surgery. Sometimes they can be addressed with lifestyle changes, medications, or nonsurgical procedures.
Coronary angioplasty is a minimally invasive procedure in which a stent is inserted into a narrowed or blocked coronary artery to hold it open. Nonetheless, surgery is often needed to address problems such as heart failure, plaque buildup that partially or totally blocks blood flow in a coronary artery, faulty heart valves, dilated or diseased major blood vessels and abnormal heart rhythms.
How human to human heart transplants are done
While it's too soon to know if the operation really will work, it marks a step in the decades-long quest to one day use animal organs for life-saving transplants. Bennett was breathing on his own. The next few weeks will be critical as Bennett recovers from the surgery and doctors carefully monitor how his heart is faring.