13 October 2020

How do you feel about medical chimeras?

Pig's heart

Polina Loseva, N+1

There has been talk of growing organs for humans inside other animals for a long time. In most countries, however, such experiments are either prohibited or at least not approved – that is, they do not receive funding. American scientists, however, do not lower their hands: they regularly ask fellow citizens if their attitude to chimeric animals has changed. Are you ready to get a liver grown inside a pig?

The recipe for chimera looks like this: you take cells from one organism, turn them into stem cells and plant them in the embryo of another species. And if the recipient embryo carries a mutation, because of which it does not develop any organ (for example, liver or pancreas), then this organ will grow almost exclusively from donor cells. That is, you will get, for example, a mouse with rat kidneys or a pig with a human liver.

This is how the problem of donor organs can be solved: instead of building long chains to transfer, for example, kidneys from one person to another, simply grow "spare" human kidneys in other animals.

However, the human in chimeras may be more than planned. By injecting human cells into the embryo of another species, we cannot be sure that they will remain only inside the kidneys or liver. Most likely, they will also settle in other organs – for example, recently in a chimeric mouse, human cells have populated a variety of tissues, including the retina of the eye. And this means that some part of the nervous system of such an animal will turn out to be human. And despite the fact that so far the maximum proportion of human cells in chimeras is no more than four percent, it is difficult to predict how they will behave there. It is even more difficult to determine what level of chimerism can be considered safe and after what proportion of human cells we can talk about the appearance of human "qualities" in animals.

Therefore, experiments with chimeric animals today are in a semi-legal status. In the USA, a moratorium was imposed on them back in 2014. The experiments themselves did not end, but their funding stopped, which slowed down further study of the issue and refinement of the technique. In Europe, it is forbidden to grow embryos with human cells for longer than 14 days – it is believed that after that day the nervous system begins to form. In Russia, there does not seem to be a separate legislative ban on chimeric embryos, but there is a ban on violating the integrity of a human embryo for medical purposes. This means that it is probably possible to set up an experiment, but most likely no one will allow to raise a pig with human organs – in general, everything is about the same as with editing the genome of embryos: it is not formally prohibited, but anyone who tries to take a risk is likely to be stopped.

Last year it became clear that this area would not stand still any longer. With an interval of a couple of days, there were reports of chimeric embryos in Japan and China. In Japan, by July 2019, the creation of a chimera from a human and a mouse was approved, which will be planted in the uterus of mice and will be grown there for a little longer than 14 days.

In China, they went further: there, a group of European and American scientists, who escaped from prohibitions and lack of funding to the east, managed to get a chimera from a man and a monkey. However, it did not come to the birth of chimeric animals again – the pregnancy of monkeys was interrupted. But it turned out to be enough to show that such experiments are possible, and most importantly, that there are countries that are ready to conduct them at home.

In order to keep up with their Eastern colleagues, American scientists decided to convince their government of the need for change. They conducted an online survey of 430 people on how they feel about chimeric embryos and how ready they are to become a cell donor for a human pig or accept a donor organ grown inside such a hybrid. The survey results are published in the journal Stem Cell Reports (Crane et al., The American Public Is Ready to Accept Human-Animal Chimera Research).

Question 1.
Here are the three stages of creating chimeras:
1) an analog of embryonic cells is obtained from adult human cells and injected into a pig embryo, creating a chimera
2) a pig is born with a human organ
3) the organ is transplanted to a person.
Which operations are ethically unacceptable?

The American survey did not come out of thin air: it was created based on Japanese, which was conducted in 2016 (Sawai et al., Public attitudes in Japan towards human–animal chimeric embryo research using human induced pluripotent stem cells). Modern Americans turned out to be even more determined than the Japanese four years ago.

chimera1.jpg

This is how the opinions of Americans about some experiments with chimeras were distributed. A drawing from the article by Crane et al.

chimera2.png

The difference between ordinary people and scientists. Figure from the article by Sawai et al.

Question 2.
It is possible that when creating a chimeric embryo, human cells will get inside different pig tissues. What do you think, in which pig organs is the presence of individual human cells acceptable? Specify all the options acceptable to you.

The Americans were also more resolute in relation to individual organs. Like the Japanese, they were more often ready to imagine a chimeric skin or liver, and less often – germ cells or brain. But the proportion of those for whom it was theoretically acceptable was 10-20 percent higher.

chimera3.jpg

What Americans and Japanese think about the permissibility of chimeric organs. A drawing from the article by Crane et al.

It is difficult to say what is the reason for such a spread – whether it is cultural differences or just the fact that four years have passed and people have become calmer about biotechnology. The authors of the American survey considered that people are sufficiently ready to lift the moratorium on experiments with chimeric embryos. It is possible that one day a wave of biotechnological determination will reach Of Russia.

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