You could breed animals for intelligence
Growing human organs in animals : "It is very unlikely that we will create a pig with a human brain"
Mr. Nakauchi, take a pig embryo that cannot form a heart and inject human stem cells into it. A human heart grows in the animal, ready for the transplant. You showed that this recipe could work in 2010 when you cultivated a pancreas from rat cells in mouse embryos. You are now experimenting with human stem cells in sheep embryos. Similarly successful?
No. If we inject human stem cells into sheep embryos, after about three weeks we will find, at best, one human cell out of 8000 sheep cells. Unfortunately we are still losing a lot of human cells.
Can better results be expected if the sheep embryo is unable to form an organ due to a genetic defect?
We hope so, but we have not yet done the experiment in sheep. What is certain is that in order to get to human organs, we must increase the contribution of human cells to the animal's embryo.
Is it better to inject the stem cells into the embryo at an early stage or later, in the more developed fetus?
We try both, but it is much easier to inject the cells into the early embryo in the Petri dish than later into the sheep's uterus.
[More information on xenotransplantation:
* The first pig hearts could be transplanted to patients in Germany
* Monkey lives with a pig heart for more than half a year
* 62 virus genes deleted from the genome of pig cells]
The idea is to grow human organs in pigs because their organs are so similar to humans. Why are you experimenting with sheep now?
We probably worked with pigs earlier than many others, but ten years ago we weren't allowed to use human stem cells in pig embryos. So I went to Stanford where I could. But there I initially worked with specialists in sheep development. We are now allowed to experiment with pigs in Japan too.
What do you think of the concern that human cells not only create the desired organ, but also contribute to the brain and “humanize” it?
We are still at the very beginning. We cannot yet grow many human cells in one animal. So it is very unlikely that we will create a pig with a human brain or human germ cells. We also stop developing all of these chimeras after two to four weeks. So we proceed very carefully and try to keep the brain free of human cells.
Can you do that?
In fact, it's relatively easy. A suicide gene can be built into human cells, which is always switched on when the genes necessary for brain differentiation become active. Human cells that want to develop into brain cells then die.
If human cells cannot survive in pigs or sheep because the genetic distance is too great, would you consider the possibility of growing human organs in monkeys?
In theory it is possible. In fact, I'm pretty sure that human organs can be grown in chimpanzees or macaques because the genetic distance is less than that of pigs. But I would only do it if we can establish a system that prevents human cells from getting into the monkey's brain.
That brings back memories of films like “Planet of the Apes”, in which the animals then acquire human intelligence.
This is a misunderstanding. In a chimera, the genome is not changed, only genetically different cells are mixed, in this case human and monkey cells. That doesn't affect the next generation. In addition, we want to work primarily with sheep or pig embryos and gain experience of how human cells behave in them. Only if really necessary could one experiment with non-human primates.
According to reports Spanish researchers working with Juan Carlos Izpisúa Belmonte have already made such chimeras from human and monkey cells. In China.
This is a rather unusual system in which Belmonte remains in the USA and the Spanish colleagues carry out the tests in China. Like some kind of smuggling. That could have a negative effect. These experiments raise ethical and societal concerns and should be performed step by step on small animals and then on larger animals, slowly and carefully.
Do you think the public would ever accept growing human organs in monkeys? There are calls for human rights to be given to monkeys.
The difficulty lies in how to define being human. This is a philosophical question with no definitive answer. If brain death is recognized as a sign of a person's death, then being human is defined by the brain. So as long as the brain of a chimera is free of human cells, it is not human. But I emphasize: the goal is not to create human-ape chimeras, but to grow organs.
In order to get an organ from the pig, the patient has to live long enough until the stem cells are grown and then the pig has grown with its organ. How long does it take?
It takes about a month to grow the patient's stem cells. Then it takes about six to ten months for the pig to grow up.
Pigs grow quickly. For example, if such a heart has been implanted in a child, won't it continue to grow as quickly? Too fast?
The heart first grows in a pig, but it is a human heart. After the transplant, it should continue to grow as it does in humans.
Even if the organs are made up of human cells, there will still be some animal cells in them - how can you get rid of them to prevent rejection?
The immune system will take care of that. Or we equip the pig cells with a suicide gene that can be switched on with a drug. This could be injected shortly before the transplant, so that the pig cells die.
What organ might be the first to mature in an animal from human cells and transplant into a human?
The pancreas. But we also work on the liver, lungs, thymus and blood vessels. However, most of the research we're still on mice and rats. We take it step by step.
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