On pigs, monkeys and humans. "Human-animal chimeras have been used in various biomedical studies for several years." - Zeme un valsts
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On pigs, monkeys and humans. "Human-animal chimeras have been used in various biomedical studies for several years."

 

Biologists have for the first time grown a human-monkey chimera: the organisms developed for 19 days. This study raises many ethical questions.

Meduza, 17 April


Chimeras are organisms that contain cells from at least two different individuals, i.e., with two distinct sets of DNA. In certain cases, chimeras form, so to speak, naturally; this happens, for example, if a foetus absorbs its twin during pregnancy. We are talking about cases where fertilisation results in so-called dizygotic twins, i.e., twins that have originated from two egg cells. In the early stages of pregnancy, one of the twins may die, and some of the deceased twin's cells may be absorbed by the surviving foetus, which will therefore contain cells from two different individuals. These people, of course, may not even know themselves that they are chimeras. Several years ago, the case of Karen Keegan was discussed in the news. She needed a kidney transplant, and for this reason, both she and her family members underwent genetic testing to determine potential compatibility. Surprisingly, the test results showed that Karen could not be the mother of her own children. However, doctors very soon discovered that Karen is a chimera: the DNA in her blood cells differs from the DNA in the rest of the cells in her body. A person can also become a chimera after a bone marrow transplant. In the case of a bone marrow transplant, the patient's bone marrow is replaced by a donor's bone marrow. Bone marrow contains stem cells that transform into red blood cells, or erythrocytes, which means that the patient's erythrocytes will be genetically identical to the donor's erythrocytes. For a certain period, any person who has received a blood transfusion becomes a chimera, although in the case of a bone marrow transplant, at least some of the erythrocytes will be genetically identical to the donor's erythrocytes for the rest of the person's life. A very common phenomenon is so-called microchimerism – when there is only a small proportion of another individual's cells in a person's body. The most common example of microchimerism is pregnancy. During pregnancy, a small portion of foetal cells usually enters the woman's bloodstream and then travels through the body to various organs. Studies show that microchimerism is observable in almost every pregnancy for at least a certain period, but in individual cases, foetal cells can remain in a woman's body for the rest of her life. Any person who has received an organ transplant can also be considered a chimera, because in such a case, their body also contains the cells of another individual.

In all the examples mentioned, we are talking about chimerism within a single species, because the cells of another individual present in the chimera come from an organism of the same species, but for several years now, biomedical research has made quite extensive use of chimeras whose bodies contain cells originating from individuals of at least two different species – either two different animals (for example, rats and mice), or a human and an animal, as is the case reported by Meduza. Human-animal chimeras have been used in various biomedical studies for several years. For example, in several studies, human stem cells have been transplanted into mice to investigate how they change. There have also been studies in which human tumour cells were introduced into mice to develop cancer treatment methods for humans. Significantly, in most cases, the human-animal chimeras used in studies are created by introducing human cells at a later stage of development – into an animal foetus, a newborn, or an already adult animal. For this reason, the donor (in this case, human) cells are only present in those tissues where they are introduced. By contrast, if stem cells are introduced much earlier – at the embryonic stage of development – the cells should potentially also form in other tissues of the chimera. However, studies have shown that achieving such a result is only possible by using the latest breakthroughs in stem cell and gene-editing technologies. Thanks to these technologies, there is a real possibility of creating chimeras with a greater presence of human cells, and using larger animals, such as pigs and sheep. But this, in turn, provides an opportunity not only to obtain better models for disease research but also to create organs that could be transplanted into humans. The same group of researchers from the Salk Institute that just created the first human-monkey chimera came to the attention of the mass media four years ago, thanks to an experiment in which the first human-pig chimera was created. The pig was chosen because its size would make it possible to obtain transplantable organs for humans, but the experiment proved unsuccessful: a very small number of human cells formed in the chimera's body – only one human cell for every 100,000 pig cells. Scientists considered the main cause of the failure to be that pigs and humans are, after all, very distant species. Moreover, instead of the predicted one year, the creation of such a chimera took four years and more than 1,500 pig embryos. This led to moving on to monkeys.

Thus, the recently published Salk Institute study does not raise significantly new ethical questions that had not already been asked in 2017, when the human-pig chimera was created. There are people who point out that these types of experiments are unnatural, and by conducting them, we are interfering with the natural order of things. This objection in itself is not particularly strong, as such an accusation could, in fact, be applied to any medical technology. Organ transplantation is not natural, but it would be natural to die from pancreatic cancer. Much more serious, it seems, are the concerns about our inability to predict what kind of living being might emerge in the case of such experiments. Namely, if this creature's cells and organs are so very similar to human cells and organs, then how will this creature differ from a human in a moral sense? But if there is no significant moral difference, then the possibility of using chimera organs for transplantation no longer seems so, to put it mildly, attractive. But this, in turn, leads to the question of our treatment of animals that are not human. Let us assume that the cognitive abilities of the created chimeras do not differ significantly from the abilities of non-chimeras, namely, that both the pig-human and monkey-human chimeras do not differ in terms of cognitive abilities from ordinary pigs and monkeys. In such a case, could we justify the creation of chimeras for experiments and for obtaining transplantable organs? If we look at how we currently treat, for example, pigs, then we would likely have to admit that there are no real objections that can be raised against the creation of human-pig chimeras either. Conversely, if we object to chimeras, then most likely we would also have to review our attitude towards the use of pigs for food. Human attitudes towards animals do tend to be rather strange, so for those who find our treatment of pigs acceptable, I suggest imagining a dog instead of a pig. Here, some might object that the slaughtering and eating of pigs is not at all comparable to the use of chimeras for obtaining transplantable organs, because the former is, after all, a matter of trivial gastronomic choice, whereas the latter is about saving a human life. In a sense, of course, this is true: the shortage of organs is a significant problem. For example, in Europe, an average of 18 people die every day while waiting in line for a transplantable organ. The opportunity to grow organs using chimeras could save these lives. However, these lives could also be saved by a higher number of donated organs. In this regard, some countries fare better than others. For example, in 2018, there were 48.3 donors per million in Spain who donated their organs to others after death, whereas in Latvia, it was only 12.6. Sometimes, when trying to justify the use of animals to save human lives, the analogy of a lifeboat is used: imagine that there are two people and, for example, a dog in a lifeboat. The boat is struggling to stay afloat, and it is clear that not all the beings in the boat will be able to be saved, so someone must go overboard. In such a case, it seems, the lesser evil would be to leave the dog overboard so that the humans could be saved. In exactly the same way, we can breed animals to obtain transplantable organs from them. However, it seems the main problem with this argument is that these animals are not in our boat.

Article from the June 2021 issue of Rīgas Laiks magazine

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