At the AAAS Annual Convention this weekend in Austin, Pablo Ross of the University of California announced in a presentation “Towards Xenogeneic Generation of Human Organs” that he had managed to produce a sheep embryo containing a small amount of human cells. Following this event, there was a rash of media headlines about the birth of the first “human-sheep” chimera. In early 2017, Ross and his colleagues had already successfully introduced human stem cells into a pig embryo, producing a chimeric embryo with 1 in 100,000 cells being human. The announcement made in Austin goes further, as the team were talking about one human cell in 10,000 in the sheep chimera embryo.
The CRISPR technology which has been used has enabled them to produce embryos that do not develop a certain organ (for example the pancreas), which allows the introduction of a human stem cell to replace the organ. It’s worth noting that there are reservations about this experiment, since the embryo was only allowed to develop for 28 days (including 21 in the sheep). It would be necessary to extend this period to observe the replacement organ (potentially transplantable to a human) developing fully.
These experiments as we know take place in the context of immunology research whose aim is to improve the compatibility of organs in the transplant process and prevent rejections. In an interview with The Guardian, Rd. Ross says, ” Even today the best matched organs, except if they come from identical twins, don’t last very long because with time the immune system continuously is attacking them[1] ”
When you know the number of people who die every year from organ transplant failure resulting from immune-compatibility problems, you can see the need for this kind of research. So, for the Organ Donation and Transplant Day that it organized in 2015 , the European Directorate for the Quality of Medicines and Health Care released some statistics that conveyed the urgency of the situation: 39 343 patients received transplants in 2015, of which 62% were kidney transplants, 24% livers and 7% hearts. But 18 people waiting for a transplant died every day (6702 patients on waiting lists died in 2015).
From those statistics alone, the research being carried out by Pablo Ross and all those working on chimeras seems all the more necessary. But, that notwithstanding, there are sure to be some questions about the extent of these experiments, because you could well imagine the possibility of other organs being involved in the experiment. In the Guardian article cited above, Dr. Hiromitsu Nakauchi of Stanford University says, “The contribution of human cells so far is very small. It’s nothing like a pig with a human face or human brain. We have published several papers showing we can target the region, so we can avoid human cells differentiating in to the human brain or human gonads.”
Here we enter the fantastical realm of the myth of the chimera that goes back to ancient times. In Grimal’s Dictionary of Greek and Roman Mythology there is the following definition: ” The chimera is a mythical animal, part goat and part lion. Sometimes it said to have a snake’s hindquarters and a lion’s head. Sometimes it has a snake’s tail on a goat’s body, sometimes several heads, one a goat and one a lion. It breathes fire. It is the issue of the union of Typhoon and the ‘Viper’ Echidna. It was raised by the King of Caria, Amisodares and lives in Patera. The king of Lycia, Iobates, ordered Bellerophon to kill it because it was causing havoc in his lands; with the help of the winged horse Pegasus, Bellerophon succeeded; it is said that he had tipped his spear with a piece of lead. In the heat of the flames breathed out by the chimera, the lead melted and killed the beast. [2]” The concept of the chimera, before being transposed to the scientific field, had come down the centuries to refer to hybrid animals[3] . In his “History of Animals” Aristotle had put them in a separate category amounting to not including them in “nature” – impossible to classify, because they were unable to reproduce. In the Middle Ages there were stories of many imaginary beings such as the Unicorn, the Dragon or the Centaur. Linnaeus and Buffon were to take an interest in hybrid beings, the latter going so far as to describe the mule as a “monster composed of two natures” and planned an experimental mating programme between a tame zebra and a horse. But it was strictly speaking at the end of the 19th century that the first chimeras resulting from scientific experiments were to appear in the work of Hans Driesch, in 1891, with his famous experiment: he agitated sea urchin eggs in order to separate them into nucleic and non-nucleic fragments. Each hemi-blastomer produced a complete embryo. The opposite experience is possible: it is feasible to combine two sea urchin embryos in order to obtain a complete pluteus. That was the birth of experimental embryology, and the beginning of scientists creating chimeras. We can distinguish three main types:
- Chimeras by aggregation, obtained through inter-species transplants
- Chimeras by injection, obtained by the injection of foreign cells into the blastocell cavity of an embryo.
- Transplants
So-called natural chimeras can be added to this classification.
We would include in that the human-sheep chimera which, even though it is completely new, is the result of long developments from the very early history of experimental embryology, which is itself part of the oldest history of natural history and the way in which man conceives of nature. In this context, the “Chimera” is a supernatural being, a magnet for our fascinated imaginations. Literature will gravitate to this theme. And based on Ross’s recent experience, we realise that the aim in these stories is always the same: “to conceive and create an imaginary body made of organs that do not come together in nature with the ultimate goal of prolonging life”. Added to this is a fundamental debate about whether life is preformed or whether it is the result of epigenesis … But we would need another editorial to develop this theme.
We will finish by quoting Professor Jean Bernard: “We must not forget the chimeras that we create in humans. Jean Dausset will remember that when we published the first work on bone marrow transplants, we entitled it: “A doubly chimeric undertaking: bone marrow transplant?” And a year or two ago, I had a private conversation with a girl who had been saved from advanced leukaemia by a marrow transplant. She was very troubled, and she said to me: if I understand this correctly, what my heart now pumps into my arteries is my brother’s blood. And it’s true: you know that after a bone marrow transplant, the bone marrow of the donor remains permanently in the recipient. That is also a chimera.[4] ”
[1] “Even today the best matched organs, except if they come from identical twins, don’t last very long because with time the immune system continuously is attacking them,” “Breakthrough as scientists grow sheep embryos containing human cells”, Nicola Davis, in The Guardian
[2] P. Grimal. Dictionary of Greek and Roman Mythology, PUF 1951
[3] In “Conditions de possibilité, réalisations et significations des chimères biologiques,” https://fr.scribd.com/document/49599993/Memoire-Jean-Paul-Oury-Chimeres Jean-Paul Oury
[4] Jean Bernard, in “Soi et non soi, Discussion sur le Soi des chimères”
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