The attempts of modern scientists to create animals with human organs were preceded by many years of research, and just about these plans will begin to be implemented. However, opponents of such experiments are concerned about the ethical side of the issue, notes the BBC Earth columnist.
In the science fiction novel by H. G. Wells, "The Island of Dr. Moreau," the protagonist Edward Prandick, who was thrown onto the coast of the island as a result of a shipwreck, stumbles upon a woman and two men squatting near a fallen tree in a forest clearing.
All three are completely naked except for the rags wrapped around their thighs.
Prendick draws attention to their "fat faces", which "lacked a chin, their foreheads protruded forward, and their heads were covered with sparse bristly hair." He notes: "Never before have I met such bestial creatures."
When Prendick approaches the natives, they try to talk to him, but their speech sounds very fast and indistinct; they shake their heads and sway from side to side, carrying, as it seemed to the hero, "some incredible nonsense."
Despite the partially hidden nudity and seemingly human appearance of the savages, Prendick catches in them an undeniable "resemblance to pigs", and their behavior seems to be "marked by the seal of something animal."
One night, accidentally entering the operating room of Dr. Moreau, Prendick finds out what the matter is: the scientist turns animals into people, changing their body and brain in his own image and likeness.
However, despite all efforts, the doctor does not manage to rid his creations of the manifestations of their basic instincts.
The unstable society he created is soon consumed by anarchy, which leads to the death of Moreau.
120 years have passed since the novel first saw the light of day, and today's headlines may give the impression that we are dangerously close to Wells's dystopian perspective.
"Frankenstein scientists are working to create a chimera, which is a cross between a man and an animal," screamed one of the headlines in the British Daily Mail in May 2016.
"Science seeks to break down the barrier between humans and the animal kingdom," said a Washington Times article published two months later. The author of the article argued that intelligent animals would soon break free from the laboratories.
The reason for the excitement was the plans of scientists to implant human stem cells into animal embryos in order to grow individual human organs for transplantation in patients in need of transplantation.
This technology is expected to shorten the waiting time in line for surgery and reduce the risk of organ transplant rejection.
These bold and ambiguous plans were preceded by more than three decades of scientific research. The experiments have helped scientists unravel some of the fundamental mysteries, investigate the nature of interspecies differences, and figure out how a cluster of cells in a mother's womb becomes a living organism.
Given the prospects for financing such projects, humanity is rapidly approaching an important milestone in this area.
"This area of knowledge is evolving very quickly," said researcher Janet Rossant at the University of Toronto, who pioneered the study of chimeras. "Our understanding of biology will reach a new level."
But only on condition that we first resolve a number of difficult ethical problems associated with our idea of what it means to be human.
For many millennia, chimeras were only characters in myths and legends.
The biological term is borrowed from ancient Greek mythology: Homer described the chimera as a strange creature with the head and neck of a lion, the body of a goat, and a serpentine tail. According to legend, this immortal fire-breathing creature was found in the country of Lycia, located in Asia Minor (a peninsula in western Asia, part of the territory of modern Turkey - Ed.).
The scientific definition of a chimera is less colorful. This term is used to describe any organism made up of genetically dissimilar cells.
Chimerism occurs in nature, particularly as a result of the fusion of twin embryos soon after conception, and can lead to startling results.
Take, for example, bilateral (bilateral) gynandromorphs, in which one side of the body has the characteristics of a male and the other is female. Such creatures are essentially the result of the merger of two fraternal twins.
If the coloration of individuals of different sexes is very different, as is the case with many species of birds and insects, the result can be very unusual and impressive.
For example, in the red cardinal, bilateral gynandromorphism results in a bright red plumage of the "male" side and gray plumage of the "female".
However, much more often cells of different embryos mix in random combinations, leading to more subtle changes in the whole organism.
Such chimeras look and behave exactly like other individuals of the given species.
There is a chance that you yourself are a chimera, since scientific studies show that at least 8% of non-identical twins absorb cells from their siblings during embryonic development.
Despite the fact that creatures like those described in Greek myths do not exist in nature, this does not prevent scientists from trying to create their own chimeras in the laboratory.
Janet Rossant was one of the first scientists to do this.
In 1980, while working at the Canadian Brock University, she published in the journal Science the results of an experiment in which a chimera was grown from the genetic material of two different types of mice: a laboratory albino mouse, a subspecies of the house mouse (Mus musculus), and wild Ryukyu mouse (Mus caroli), which lives in several Asian countries.
Previous attempts to breed interspecies hybrid creatures have often failed. The embryos either did not attach to the wall of the uterus at all, or turned out to be underdeveloped, and then the case most often ended in miscarriage.
The Rossant method consisted of a complex surgical procedure approximately four days after conception.
By this time, the fertilized egg had already turned into a blastocyst - a clot of inner cell mass surrounded by a protective layer called trophoblast, which would later become the placenta.
Rossant and colleague William Frels injected an internal cell mass taken from a Ryukyu mouse blastocyst into a laboratory mouse egg.
Since the trophoblast in the blastocyst of the host mouse was not damaged during the operation, the DNA of the forming placenta still corresponded to that of the mother. As a result, the embryo successfully adhered to the uterine wall.
Scientists had only to wait 18 days, observing the course of pregnancy.
The experiment was strikingly successful: of the 48 newborn mice, 38 were chimeras, containing the genetic material of both types of mice.
“We have shown that crossing the interspecies barrier is possible,” says Rossant. Chimerism was clearly manifested in the color of the mice: alternating spots of white and reddish hair.
Even in terms of temperament, these chimeras were markedly different from the parent individuals.
“We got a very strange mixture of characters,” says Rossant. "Ryukyu mice are very restless: so that they don't run away, you have to put them on the bottom of the bucket, and you should take them with tongs, after putting on leather gloves."
Lab mice are much quieter. “The behavior of our chimeras was something in between,” notes the researcher.
According to Rossant, at today's level of development of neuroscience, such experiments can help research the behavior of different species.
“You could compare the behavioral differences with which parts of the chimera's brain contain two different types of cells,” she says. "I find this area of research very interesting."
In her early work, Rossant used her chimeras to study how organisms develop in the womb.
The study of genes was still just beginning, and the clear differences between the two species helped to trace how cells are distributed throughout the body of a chimera.
Thanks to this, scientists have found out from which elements of the inner cell mass certain organs are formed.
Scientists can also use this approach to study the role of certain genes. For this, a genetic mutation can be artificially created in one of the embryos, while the other will be used as a control one.
By studying the chimera thus obtained, researchers will be able to determine which specific body functions are affected by certain genes.
The Rossant method was soon adopted by other scientists around the world. In one of the experiments, it was possible to create a chimera from goat and sheep cells.
The appearance of the animal was very unusual: its skin looked like a patchwork quilt, interspersed with sheep's wool and coarse hair, typical of a goat.
Time magazine described the chimera as “a zoo keeper's trick: a goat in an angora sweater.
Rossant has also consulted on a number of endangered species conservation projects: the idea was to implant embryos into the uterus of domestic animals.
"I don't know how successful these initiatives were, but the idea is still alive today," she says.
Now the Rossant method is planned to be applied within the framework of a project that could theoretically open a new page in regenerative medicine.
Over the past two decades, scientists have been trying to learn how to grow new organs in the laboratory from stem cells that can turn into tissue cells of any type.
It is believed that this strategy has enormous potential for the development of transplantology.
“The problem is that while stem cells are very similar to embryonic cells, they are not exactly the same,” says Juan Carlos Ispisua Belmonte of the J. Salk Institute for Biological Research in La Jolla, California.
So far, stem cells remain unsuitable for transplantation.
Ispisua Belmonte and a number of other researchers believe that the solution should be found in farms. The goal of scientists is to create chimera animals for growing the necessary organs.
"Embryogenesis is widespread in nature, and 99% of its results are positive," says the scientist. "We don't yet know how to recreate it in the laboratory, but animals do it very well, so why not make nature work for us?"
Unlike the chimera of a goat and a sheep, in which cells of two different species were randomly distributed throughout the body, in these chimeras foreign tissues must be concentrated in specific organs.
Through genetic manipulations, researchers expect to "knock out" certain organs from the host's body, place human cells in the vacant space and force them to form the corresponding organs, but already human, of the required size and shape.
"The animal will become an incubator," says Pablo Juan Ross of the University of California, Davis.
It is already known that in theory this is possible. In 2010, Hiromitsu Nakauchi of Stanford University School of Medicine and colleagues used a similar technique to grow a rat pancreas in a mouse.
Now the most suitable "incubators" for human organs are pigs, whose anatomical structure is very close to that of humans.
If this plan works, it will help solve many of the existing problems in transplantation.
“On average, the waiting list for a kidney transplant now takes about three years,” explains Ross. At the same time, it would be possible to grow the required organ to order in a pig's body in just five months.
“This is another advantage of using pigs as carriers: they grow very quickly,” explains the scientist.
Interspecific chimeras can find application in pharmacology.
Often, when testing new types of drugs on animals, the results are successful, but when people use the same drugs, unexpected and undesirable consequences arise. “The result is a waste of time and money,” Ispisua Belmonte stresses.
Let us imagine the prospects of the proposed method using the example of a new drug for liver diseases.
“If we placed human cells inside a pig's liver, then within the first year of work on the creation of a drug, we could determine whether it is potentially toxic to the human body,” the researcher notes.
Rossant agrees that the method has great potential, but emphasizes that scientists still have serious work to be done: “I give credit to the courage of those who dared to work on this task. It is feasible, but I must admit that researchers will have to face very serious difficulties along the way."
Many of them are technical in nature.
From the point of view of evolution, a person differs from a pig much more than a rat from a mouse.
Scientists know from experience that in such cases, the likelihood of rejection of donor cells by the host's body increases significantly.
“It is necessary to create special conditions for human cells to survive and divide [in a pig],” says Ispisua Belmonte.
This will require finding a "primary", flawlessly pure source of human stem cells that can transform into any tissue.
It may also be necessary to genetically modify the host's organism to reduce the likelihood of rejection of foreign cells.
However, so far the main obstacle holding back research is ethical considerations.
In 2015, the US Department of Health's National Institutes of Health instituted a moratorium on funding experiments to create chimeras in humans and animals.
True, it was subsequently announced that the ban could be lifted - provided that each such experiment will be subjected to additional evaluation before funding is provided.
Meanwhile, Ispisua Belmonte received a $ 2.5 million grant proposal on the condition that he uses monkey cells instead of human cells to create the chimera.
The greatest concern is the hypothetical probability that human stem cells will reach the pig's brain, leading to the creation of a creature with some of the abilities and behaviors inherent in humans.
“I think this scenario should be considered and discussed in detail in research,” says Rossant. After all, her chimeras did show the temperamental traits of both types of mice. To create a human consciousness trapped in an animal body is a nightmarish plot worthy of Wells's pen.
Researchers are quick to emphasize that certain precautions can be taken. “By injecting cells at a certain stage in the development of the embryo, we may be able to avoid this risk,” says Belmonte.
Another possible way out is to program stem cells at the genetic level to self-destruct under certain conditions in order to avoid their introduction into the nervous tissue.
But these decisions are not convincing enough for Stuart Newman, a cytobiologist at New York College of Medicine, who has been worried about the potential consequences of such experiments since the creation of the goat-sheep chimera in the 1980s.
Newman’s concern is not so much the modern plans of scientists as a future in which chimeras could gradually acquire more and more human characteristics.
“The more human you can bring into these hybrids, the more interesting they become, both scientifically and medically,” he says.
“Now someone can swear that they will never create chimeras in human likeness, but after all, the latent desire still remains. There is something in the topic itself that encourages scientists to move further and further in this direction."
Let's say scientists have created a chimera to research a new drug for Alzheimer's. Researchers are initially given permission to create a creature with a brain that is, say, 20% human. But over time, they may come to the conclusion that in order to fully understand the effects of the drug, it is necessary to increase the proportion of the human brain to 30 or 40 percent.
In addition, Newman said, in order to receive funding, the researcher often has to declare increasingly ambitious research goals: "It's not that scientists are trying to create monsters … Research is a natural, evolving process, and it will not stop by itself."
Equally important, such experiments can dull our sense of humanity, Newman continues: “The transformation of our culture allows us to transcend these boundaries. In this case, a person is seen as just a material object."
Knowing about the existence of human chimeras, we may not become so much doubt about the manipulation of human genes in order to create children "to order."
And Newman is not alone in his fears.
John Evans, a sociologist at the University of California, San Diego, points out that the very discussion of human-animal hybrids has focused on cognitive abilities.
In this context, we can conclude that such chimeras can not be treated like people if they do not have human rational thinking or speech.
But this kind of logic can lead us down the slippery slope of discussions about how to deal with members of our own species.
“If society begins to view a person as a set of abilities, it will begin to treat its own members with a smaller set of these abilities as second-class people,” warns Evans.
Ispisua Belmonte believes that many of these concerns, especially those that are reflected in the sensational headlines, are so far unfounded.
“The media and regulators think we will start growing important human organs in pigs almost tomorrow. This is science fiction speculation. We are still at the very beginning of our journey."
And, as the journal Nature writes, the debate about the ethics of such research should not involve emotions.
The concept of interspecies chimerism may seem disgusting to some, but the suffering of people with incurable diseases is no less terrible. You cannot solve moral and ethical problems only on the basis of instinctive reactions.
Whatever the final decision, it should be borne in mind that its potential consequences are not limited to the scientific field.
“The way we talk about a person in this discussion can inadvertently change the way we view ourselves,” writes Evans.
After all, it is the question of what defines a person that lies at the heart of Wells' novel. After returning from the island of Dr. Moreau, Pendrick retires in the English province far from large cities, preferring to human communication to observe the starry sky.
Having witnessed the violent violation of the natural interspecific barrier, he can no longer look at people without noticing the animal nature in them: “It seemed to me that even I myself was not a rational human being, but a poor sick animal tormented by some strange disease that makes him to wander alone like a lost sheep."