Chinese researchers recently presented a paper that left the scientific community speechless; created a “chimeric” baby macaque from the stem cells of two genetically different embryos. According to theirs paperpublished in a prestigious magazine cellthis is the first time a chimeric primate has been born with ” a high proportion » cell from a donor, and this experience could have significant consequences.
What is a chimera?
The term chimera refers to an organism that contains cells from two different organisms. Unlike the vast majority of normally built individuals, a chimera therefore represents a double genetic inheritance, with two different DNAs coexisting within the same organism.
This situation can occur naturally through certain processes that occur during fetal development, particularly when two embryos fuse during the early stages of growth. This is, for example, the case with certain species of marmosets (see This item research).
But more often than not, chimeras are Artificial, that is, created in a laboratory using genetic engineering techniques. In order to achieve this, researchers start from embryonic stem cellswhich can differentiate into a bunch of different cells.
The goal of this approach is to study complex biological processes that play a decisive role in the development of organisms. For example, we can use stem cells that carry very specific genetic mutations to study how they affect an individual’s physiology and health.
Record chimerism rate
The monkey studied by Chinese researchers also belongs to this last category. To give birth to him, they started by collecting recipient eggs from female crayfish macaques before fertilizing them in vitro.
They drew at the same time stem cells from donor embryos about a week old. They are then genetically modified to become fluorescent. This step makes it possible to distinguish between the cells that develop from the fertilized egg and those that develop from those stem cells in the future chimera.
After this manipulation, they injected these stem cells 74 recipient embryos. The strongest ones were then implanted in 40 surrogate mothers, with different results. Transplants were difficult to take hold; pregnancy started in only 12 of these women. In the end, only one of them ended up giving birth.
After birth, the researchers analyzed several tissues of the baby macaques, including the brain, heart and lungs. The goal was to determine chimerism rate, that is, the proportion of cells originating from the stem cells of the donor embryo. To achieve this, simply check for the presence of the aforementioned green fluorescent marker.
And the result was quite spectacular. In 26 tested fabrics, the rate of chimerism varied between 21% and 92%, with an average of 67%—hence the greenish hue of the little monkey. This is the highest result ever achieved in primates. In comparable studies, this rate was generally between 0.1% and 4.5%.
A real experimental success…
The advantage of working with primates is that they are genetically very close to humans – significantly more than traditional models of developmental biology, such as mice. By studying monkey physiology, we can therefore often draw very relevant conclusions about human biology.
Chimeric primates allowgo even further in this business. They could enable researchers to conduct extremely sophisticated studies on serious diseases, stem cell-based treatments, organ transplants, how certain drugs work, etc.
Until now, these chimerism rates of a few percent have made these chimeric primates of little relevance in the context of basic research. But now this rate above 50% could pave the way for new, much more advanced work. From a strictly experimental point of view, it is therefore a great success and an interesting step forward for the medical sector that must be welcomed.
…and always the same ethical questions
But not everything is rosy. Even if this work scrupulously adheres to Chinese ethical rules, it did not fail to raise many difficult questions about the limits of animal experimentation.
This is all the more true when dealing with primates (which includes humans) and especially with developmental biology, as is the case here. This rather exploratory work often has extremely serious consequences for the health of guinea pigs. This chimeric macaque, for example, must be euthanized after only ten days. He was suffering from hypothermia and was breathing hard.
More and more alternative techniques are beginning to emerge to avoid the need for conscious guinea pigs. In particular, we can cite the research of organoids, and small artificial cellular structures that reproduce the functioning of certain tissues. But currently there is still no experimental platform that could reproduce all the nuances of the functioning of the whole organism, which is unfortunately necessary for the most advanced work in biology.
Therefore, we hope that work of this type will pave the way for the development of sufficiently advanced substitutes to advance medicine, while limiting the use of experiments beyond the first stages of development.
The text of the study is available here.