Animal research

Randall Prather: How decades of animal research led to this month’s heart transplant |

Just three months ago, surgeons successfully attached a kidney from a genetically modified pig to a human recipient.

Since then, new successes have continued to accumulate. In December, the kidney procedure was successfully repeated.

Then, earlier this month, we celebrated another huge leap forward in such xenotransplantation: surgeons successfully transplanted a pig’s heart into a human patient who lives in the Baltimore area.

For this achievement, congratulations are in order.

The success of these procedures relied on the incredible skill of surgeons and medical professionals, and it also took decades of behind-the-scenes research to lay the groundwork for genetic engineering in pigs.

It was a continuum of work that I was part of in a lab in Missouri for more than two decades and now offers hope to the more than 100,000 people waiting for organ transplants.

But there was also a time when that initial research was derided as, pardon the pun, the pork barrel expense.

In 2001, I and a team of collaborators at the University of Missouri, and Robert Hawley of Immerge Biotherapeutics in Boston, first patented the technology to create so-called “knockout pigs.”

Simply put, our research has shown how to remove – or knock out – a molecule on the surface of a pig cell.

These “knockouts” affect genes that control a variety of traits.

To develop the potential of the technology, we started with projects that might seem silly to some.

Through our genetic engineering research, we have shown that it is possible to develop bioluminescence in pigs, essentially by causing them to emit a low level of light.

This development was a vital proof of concept (and these “green” pigs remain essential for scientists by providing easily traceable cells, for example to study the use of stem cells to repair organ damage).

We have shown that pigs can be produced from genetically modified cells, such as the process used to clone the sheep Dolly.

Then comes a steady drumbeat of progress that benefits both human and animal health.

For example, we succeeded in disrupting the gene that makes pigs susceptible to porcine reproductive and respiratory syndrome virus.

These pigs are now resistant to a deadly virus that kills thousands of animals every year and costs pork producers in North America and Europe around $6 million a day.

Taken collectively, all of these milestones were part of the slow process that helped us discover how knockout pigs and gene editing could help people.

By developing these and other enabling technologies, we have been able to create pigs that help us study a range of diseases, including cystic fibrosis, retinitis pigmentosa and cancer.

Fast forward to 2022; Revivicor was able to use knockout pig technology licensed from the University of Missouri (one of 10 genetic modifications included by Revivicor) to develop a heart and kidney that are resistant to hyperacute rejection.

This is essential because hyperacute rejection occurs when the body’s defenses attack a foreign organ.

It follows in minutes without that specific knockout.

It is clear that we are now taking the first steps towards a new era of human health and well-being.

I mentioned that there are over 100,000 people on transplant lists, the vast majority of whom are waiting for a kidney.

These patients have the option of undergoing dialysis while waiting.

For those who need a heart, the options are more limited.

Basically, there are two ways out of any transplant list: either you receive an organ or you die.

It was reported that the Baltimore patient was faced with that choice, and receiving a pig’s heart was the last (and best) option.

This is the unique hope offered by xenotransplantation, based on decades of fundamental discoveries and the enabling technologies that make genetic engineering in pigs possible.

There’s a direct line between glowing pigs and saving lives – it just takes scientists time to find out what’s possible.

Randall Prather is Distinguished Professor of Animal Science at the University of Missouri and Director of the National Swine Resource and Research Center.