a debate that takes shape

As part of the BorderLine cycle, co-production Mission Agrobiosciences-INRAE ​​and Quai des Savoirs

The announcement caused surprise. In early January 2022, a team of American surgeons from the Maryland School of Medicine successfully transplanted a genetically modified pig heart into a patient, David Bennett, who unfortunately died two months later. Qualified as a technological feat, however, this operation, known as “xenograft” (forged from the Greek xenos, “foreigner”) raises a host of questions: what are the biological, moral, ethical or even legal boundaries that these inter- species ? Should limits be set on their expansion? What humanity do they draw? A transplant doctor, a philosopher and a sociologist discussed the subject with the public on December 15, 2022 at the Toulouse Museum, during a new BorderLine meeting co-organized by the Mission Agrobiosciences-INRAE ​​and the Quai des Savoirs. Couldn’t attend? In this article, find the recurring words of the debate, and some snapshots taken on the spot.

GRAFT

From xenograft to autograft: what answers to the shortage of organs?

Olivier Bastien, former director of organ and tissue removal and transplants at the Biomedicine Agency, sets the tone: ” All developed countries lack organs. “Let’s just take France, where “ 500 patients die every year while waiting for a transplant “. It is that the latter, explains the doctor-anesthesiologist ” can treat diseases that cannot be treated otherwise “. In fact, in the current context of insufficient organ donations, xenografts, which could involve the heart, the kidney or the cornea, raise many hopes. First attempts are also documented from the beginning of the 20th century, with in particular the transplant of a kidney from a pig and another from a goat in two women. A time when ” there was no real ethical reflection, and where we did not know the problem of rejection “recalls Olivier Bastien. A difficulty that is still difficult to overcome today, and all the more so in the case of xenografts where it is an interspecies transplantation, which will increase rejection: the human body having innate defenses, the proteins ” foreign » are eliminated from the first minutes. But let’s continue. After one ” quiet period Between the end of the 1960s and the beginning of the 2000s, research on xenografts experienced a resurgence with the discovery of Crisper-Cas9 [1]« a technology that allows animals to be genetically modified to limit large releases “. And today ? As the operation in January 2022 demonstrated, ” we reach the goal “says the doctor. However, for the philosopher Jean-Michel Besnier, former member of the CNRS Ethics Committee and the INRA and IFREMER Ethics and Precautionary Committee (Comepra), “ xenograft has no future “. In its viewfinder, among the paths opened by the development of induced pluripotent stem cells (IPS) [2], the possibility of creating, in vitro, organs made from cells specific to a given individual and which resolves de facto the delicate question of rejection. Its name: autograft. Since then, ” why not imagine that we have organic twins that would allow us to tap into this organ bank? ” But Olivier Bastien to recall the time scale and this urgency: ” If you need a heart transplant, it’s tomorrow, not a year from now. IPS, you won’t have time to make it. While with a breeding of genetically modified pigs, you now have a drug. »

ANIMAL

From the medicinal animal to the sentient being

As we have seen, the xenograft induces the use of genetically modified animals. A sensitive question, which carries its share of paradoxes: “ Almost simultaneously, we become aware that the animal is “sentient” [3] and we want to clone pigs with all our might “, points out Jean-Michel Besnier. Olivier Bastien nuance. Clone with all your might, really? ” Needs for cloning and grafting, this does not even represent a thousandth of pig farming in France “. In the audience, a person reacts: As long as we don’t ban eating meat, it’s difficult to outlaw the use of pigs to heal people “. Another picks up, pointing out the conditions “ unworthy in which the pigs used for therapeutic purposes are reared. Judge: birth by caesarean section, therefore without contact with the mother, then total absence of social life. Not to mention the fact that ” even in the most efficient laboratories, 90% of genetically modified animals die before they reach adulthood “, informs Olivier Bastien. But, continues the philosopher, what animal advocates say is that if you mistreat animals, there’s no reason why you shouldn’t mistreat humans. There is a potential dehumanization in the use of animals for experimentation. (…) Do we need, for example, animal quotas for scientists? Let’s listen to Fabien Milianovic, sociologist at Sup-Biotech, who was invited as a key witness. For him, these questions actually testify to a shift in our representation grids, which is also largely documented by the work of Catherine Rémy [4]. Until recently, the ” dualistic reasoning [5] » inherited from Descartes indeed allowed us to use the animals as we saw fit since we « judged radically different from humans “. But things changed from the 1960s, and especially with the European directive on animal experimentation of 2010, where the ” we switch to a gradualist model, recognizing a certain proximity of humans with other animals such as primates. From this proximity is thus born a stricter framework for animal experimentation. Result ? ” We can’t do anything “Slices Olivier Bastien.

HUMANITY

Human identity disrupted by hybridization with animals or technology

What inter-species barriers cross xenografts? Jean-Michel Besnier observes that ” the term xenograft carries in itself the negation of the border: one associates the foreigner with the transplant and, consequently, one assumes that one has established a continuity which is culturally disturbing “. He adds that through cross-species transplantation, ” it is assumed that there may be a permeability between the world of animals and that of humans. “There is not, because” when it comes to producing a pig’s heart that can be transplanted, aren’t we humanizing the pig or animalizing the human? “Remains that for Olivier Bastien, “ hybridization already takes place every day, with heart valves from pigs, or their skin that is used to cover burns “. Be that as it may, analyzes Jean-Michel Besnier, ” the decision that prevails is that of prioritizing biological survival over human, spiritual life “. Raising the question of xenografts also means questioning biotechnology and in particular other alternatives to transplantation, such as the artificial heart. ” Limits are also ontologicalabounds Jean-Michel Besnier. With biotechnologies, we are forced to ask ourselves the question of the identity of the human being, which is increasingly approached as a process whose genome has to be edited. “. The living, it would only be the algorithm? It is in any case, from the 1970s, the worried questioning of the Nobel Prize for medicine François Jacob [6]. A time when the idea was born transgressive but common today “that medicine would be none other than the art of repairing bodies, no longer sick, but well” Out of order “. And to conclude that with today’s transhumanist tendencies, ” two alternatives are considered: to genomize the human, or to cyborguize it ».

DON

Solidarity in question

In France, the allograft, between human individuals, is based on donation: unless explicitly opposed to it, everyone is presumed to be a donor of their organs. But with the xenograft, it is a fundamental value of our societies that is undermined: “ The question of the gift arises in an increasingly individualistic society, in which the notion of solidarity is no longer obvious. The regular announcements made about advances in medicine and technology may have a chilling effect on solidarity. Crispr-Cas9 indeed gave the impression that we would be able to do without this proactive approach », worries Jean-Michel Besnier. The former president of the National Consultative Ethics Committee, Didier Sicard, even saw in it a ” rupture in the unity of the human species: what do we do with the other within it, if this other is an animal? “. More measured, Fabien Milanovic concedes that “ we are certainly in an increasingly individualistic society, where solidarity is disintegrating, but is this not to the benefit of new solidarities? Consider, for example, the multiple movements that work for the attribution of rights to animals or to natural entities such as rivers and rivers.

ASIA

Let’s not let the industry manage the problem

In some Asian countries, such as China, Japan or South Korea, it is impossible to remove organs from deceased donors. The xenograft is therefore presented there as a means of overcoming the shortage of grafts thus induced, informs Olivier Bastien, who also reports that these countries have made it a ” national priority “. It is because the ethical questions that are current in our latitudes arise differently there. Jean-Michel Besnier explains: “ In our imaginations, the basic unit of life is the organ; in China, it’s the fabric. This is the reason why there is no bioethics in this country, but also why transplants are not experienced in the same way. “. The other side of the coin, deplores the one who relaunched research on xenografts in France, Olivier Bastien, is that ” we are way behind asia “. Result, ” the Chinese are today capable of producing 1000 genetically modified pigs per year: if tomorrow they can produce transplants, which countries will oppose it? (…) This raises the question of medical tourism, offering wealthy individuals the possibility of going for a transplant in China. The professor is convinced: instead of letting the industry manage the problem, we need to take it ».

ETHICS

Develop questions collectively

What limits should be set for work on xenografts, and more generally for the expansion of human bodies? Nothing is simple because, warns Jean-Michel Besnier ” there are not on one side the scientists who would be in a headlong rush of progress and, on the other, the philosophers who would brake with four irons “. Pragmatic, Olivier Bastien prefers to rely on the texts: ” The body is protected; you can’t commodify it or hybridize it. The legal and ethical framework prohibits doing anything and France is one of the strictest countries in this area “. Its rules are very simple, anything that is not allowed is forbidden “. Same story on the side of Fabien Milanovic, according to whom ” things are certainly doable, but what is desirable? » Ceci, « it must be defined with all the people concerned. Especially since a host of questions, all more sensitive than the others, remain unanswered: Do surviving patients with pig hearts have the right to reproduce? asks Olivier Bastien, for example. ” Through xenograftsanalyse Fabien Milanovic, Finally, the question of democratic practice in the sciences arises: who has the authority and the legitimacy, not only to ask questions, but also to regulate? “This being all the more burning that until now, ” the subject was not really discussed “, testifies Olivier Bastien who sees” for the first time a general public debate on the issue ».

Par Laura Martin-Meyer

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