Thursday, 10 February 2022 05:32

Could animal-to-human transplantation fill the EU’s organ shortage void?

After the first successful animal-to-human organ transplant, hopes are high that this could offer a way to tackle the chronic global organ shortage. While it is slowly becoming a reality in the US, the EU is close on its heels.

Demand for organ transplantation is drastically outstripping supply both in the EU and worldwide, leading to an ever-growing number of patients on waiting lists.

According to Emanuele Cozzi, the president of the European Committee on organ transplantation at the Council of Europe, patients’ need exceeds the available supply of all types of organs.

However, the most critical shortage is in kidneys. Based on Eurotransplant data, by the end of 2021 almost 10,000 patients in Austria, Belgium, Croatia, Germany, Hungary, Luxembourg, Netherlands, and Slovenia were waiting for kidney transplants. However, fewer than 3,000 kidneys were transplanted that year in the countries mentioned.

As for the EU as a whole, Cozzi estimated that there could be as many as 30-40,000 patients waiting for kidneys.

While many patients with terminal organ failure are able to be kept alive thanks to dialysis, a mechanical way to support life, this only applies in certain cases.

“But we don’t have dialysis for the heart. We don’t have dialysis for the liver, we don’t have dialysis for lungs,” Cozzi pointed out, adding that there are also very few artificial organs, such as artificial hearts.

Animal to human transplantation

In the context of “tremendous shortage of organs and absence of mechanical organs” as well as “tremendously slow” proceeding of genetically engineered organs from regenerative medicine, animal to human transplantation, known as xenotransplantation, has been heralded as a solution to save patients’ lives.

“At this moment in Italy, we have approximately 5,000 people waiting for a kidney. If I don’t have 5,000 human kidneys and I can provide 5,000 pig kidneys, that is great,” Cozzi said, adding that the ultimate objective is to provide an organ to everybody.

While the concept may sound like science fiction, in early January 2022, news broke that a team of US scientists had made history with the first-ever successful heart transplant from a genetically-modified pig.

Moreover, the US is also running a programme focused on kidney transplantation from pigs to humans, as well as a clinical trial underway using pig’s skin on severely burned patients.

And it appears that the EU is hot on its heels.

Organ transplantation in 2021

While there are currently no clinical trials of animal to human transplantation in Europe, preclinical studies, during which pig organs were transplanted to a primate, have shown “very promising results […] for quite a few years,” according to Cozzi.

“There is data generated in preclinical studies that have shown that the genetically engineered pig organs can sustain the life of baboons,” Cozzi said, adding that Europe “definitely has the know-how and experts.”

Asked when we can expect something similar to happen in the EU, Cozzi was cautiously optimistic.

“It’s difficult to say, but it may be maybe sometime during this year, why not?” he suggested.

No EU legal basis

According to a Commission spokesperson, as it stands, there is no EU legal framework for organ transplantation from animals to humans. This means that the legalities of xenotransplantation fall to individual member states.

However, research involving animals in genome editing studies is required to comply with the EU directive on the protection of animals used for scientific purposes, as well the various directives and regulations on the contained use, deliberate release and transboundary movement of genetically modified organisms (GMOs).

As per the 2018 European Court of Justice ruling, gene-edited organisms fall, in principle, within the scope of the GMO Directive and are therefore subject to the obligations laid down by that directive.

Many open questions remain

While the US data is “very encouraging,” it reflects only a few cases, Cozzi emphasised, stressing that more research data must be generated to help answer a number of open questions related to safety and efficacy to explore before expanding human trials.

Only once the data is generated, can the application “be broadened in a stepwise manner, in a limited number of first-class centres with expertise in xenotransplantation”.

“It may just turn out that we can save lives. And then, at that point, we really do have the green light to go ahead and do hundreds or thousands of patients. Now, it is a start, but it is very promising,” Cozzi said.

One way in which xenotransplantation could prove a particularly attractive option is on price.

This is because, even when factoring in the need to grow animals in a pathogen-free environment, this would still be cheaper than other options such as dialysis, according to Cozzi.

“That will cost but if you consider the cost of dialysis, this is going to be very cheap,” he said, pointing out that “from one pig, in theory, you can get heart, you can kidney, you can possibly get lungs”.

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And pandora said, what’s in that box?

However, venturing into this new realm of possibilities has also opened a plethora of questions, not least of which include ethical considerations.

For example, xenotransplantation has caused a considerable amount of consternation among animal welfare campaign groups, who point out that the EU has outlined the goal of phasing out the use of animals in science.

As such, Luisa Bastos, animals in science programme leader at Eurogroup for Animals, told EURACTIV that she would expect instead to see a “growing investment on disease prevention, in the improvement of the still ineffective system of organs donations, and on furthering the technologies that are already providing solutions for some transplantation needs.”

For example, while there is no technology or method yet that allows for the production of a whole synthetically produced heart for transplantation, Bastos cited examples such as biomimicry using synthetic materials and also growing tissues from the patients’ own stem cells.

She also highlighted a number of animal welfare threats linked to genetic modification, the effects of which she said can also be “difficult to predict”.

These include pain, suffering and distress, as well as a concern that animals will be increasingly viewed as “biological tools rather than sentient animals with intrinsic value”.

“Animals should not be regarded and used as a resource for ‘spare parts’ for humans,” she said, highlighting a range of other options including organ donation and lab-grown artificial organs or tissues, such as the bladder.

In response to this criticism, Cozzi pointed out that, in the US, 50 million pigs are used for food per year. He hoped that it will be possible to “use a few 100 or a few 1,000 pigs to meet clinical requirements,” suggesting that, from an ethical and emotional standpoint “people will accept that we use a pig not only as a source of food but also as a source of organs”.

He added that as many as two-thirds of the heart valves used for transplants already come from pigs or cows.

“So that would be a broader application of something we use ready, which is the pig organs for tissue for clinical needs,” Cozzi concluded.

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