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In addition to a mythological being made up of parts of different species, a
chimera
is, according to the RAE, an illusion, a dream, "that which is proposed to the imagination as possible or true, not being so".
In science, organisms created in the laboratory with cells of two different species are also known by this term.
And the advances made in this field in recent years make this meaning take on more and more prominence, paving the way for Regenerative Medicine and knowledge of human biology.
The last significant achievement has a Spanish stamp.
Juan Carlos Izpisúa's team -from the Salk Institute of La Jolla (USA) and the San Antonio de Murcia Catholic University- has developed, for the first time, chimeras of humans and monkeys.
Specifically, the researchers have created
embryos with macaque and human cells
, some of which have survived up to 20 days.
The experiment has been carried out in a laboratory in China with expertise in developing primate embryos outside the body.
The objective of the research, Izpisúa emphasizes through email,
is not the creation of a new hybrid species
.
In fact, the embryos have not been implanted in any organism and their development has stopped without having completed three weeks of gestation.
The aim of the experiment, he continues, is to provide greater insight into the still largely unknown early stages of development and, in the longer term, to advance the possibility that human organs can be 'manufactured' in an animal organism.
"For obvious reasons, it
is almost impossible to study early human embryonic development naturally
. Therefore, the creation of chimeric models in vitro allows us to advance our understanding of the possible errors that occur in the early stages of embryogenesis", details the Castilian-La Mancha researcher, who acknowledges that the research raises important ethical questions.
One of the objectives of experimental biology is "the development of models that allow studying diseases and biology under conditions 'in vivo'", adds the researcher.
On the other hand, he stresses, these models could also be useful as a
platform for evaluating the efficacy and safety of drugs
and, ultimately, for advancing regenerative and transplant medicine.
"Every year, tens of thousands of patients die on the waiting list for a transplant. The ability to generate human tissues or cells in a host species will advance the field of xenotransplantation and alleviate the lack of organs for transplantation that we now suffer" , Izpisúa points out.
The scientist remarks that the work has been possible thanks to the fact that Weizhi Ji's team, from the Kunming University of Science and Technology in Yunnan (China), and an essential part of the research, generated technology last year that made it possible to monkey embryos survived and grew outside the body.
Method
To carry out the research, the scientists started from macaque blasts that, six days after their creation,
injected 25 human cells
.
Specifically, the infused cells were a type of stem cells, developed a few years ago in Izpisúa's laboratory, with the ability to differentiate in addition to any embryonic cell, in other extra-embryonic structures, such as the placenta.
They have used this cell type to create the chimeras, which scientists call
"extended" induced pluripotential stem cells (iPS)
, in order to have the maximum differentiation capacities in the monkey embryo.
After one day, human cells were detected in 132 embryos.
According to the data of the work, which is published in the journal
Cell,
the survival of the embryos began to suffer from the tenth day.
By the 19th day, three chimeras were still alive
.
Either way, the researchers note that the percentage of human cells present in the embryos remained high throughout the follow-up time.
In this sense, the scientists were able to identify various communication pathways between human and monkey cells (after analyzing the transcriptomes), they verified that
human cell lines had integrated into the tissue
and certified that development was maintained despite genetic diversity. , they point out in the scientific journal.
In 2017, the Izpisúa team carried out the first experiment to create
chimeras with human and pig cells
, although the bet did not have very good results.
Instead, they did successfully develop rat and mouse chimeric embryos.
The main problems of that research with pigs, Izpisúa points out, were due to the fact that, evolutionarily, pigs and humans have a large number of differences.
The greater closeness between macaques and humans, he adds, will probably improve the generation of chimeras in the medium term.
In this regard, Izpisúa emphasizes that the objective is to use the data generated in this study with macaques to
reinvigorate research with pigs
and take them back as a model for the development of organs for transplantation.
"What is possible today was impossible yesterday"
In their work, the researchers acknowledge that these kinds of advances raise
important bioethical questions
.
"Our work is aimed at achieving a benefit for human health and
ethical considerations are, for us, of the utmost importance,
" says the researcher, who recalls that the research has been reviewed by both those responsible for bioethics from the institutions involved and by outside experts.
Either way, Izpisúa emphasizes that "what is possible today was impossible yesterday", which is why he calls for
close collaboration
between scientists, authorities and experts in bioethics to keep action protocols and guides updated.
In an accompanying article in
Cell
, bioethicists
Henry T. Greely
, from Stanford University, and
Nita A. Farahany
, from Duke University, both in the United States, emphasize that these types of findings " it raises new ethical challenges that society will have to discuss ".
Both professors acknowledge that in this research the scientists themselves point out the ethical and social implications of their work, as well as that they followed the existing rules, guidelines and supervision.
However, they allude to certain ethical aspects derived specifically from research on chimeric blastocysts, such as those related to animal welfare, obtaining the human cells that have been used or the mixture of human and non-human tissues itself.
Regarding the latter, they indicate that "a strong position against such a mixture could spell the end of many long-standing research, as well as some clinical practices related to heart valves."
They also note that "
public discourse and deliberation about human and non-human primate research is crucial
. Surprising the public with unexpected, and often disconcerting research, can have serious consequences for that research and for those researchers, but also for the public confidence in science in general ".
The long-term goal of the work is not to obtain embryos or fetuses from chimeras that can be implanted in vivo or, of course, born creatures, the bioethicists grant, and
"it is not entirely clear if these results are or will be possible
.
"
However, "
those future experiments are now at least plausible
. We must start thinking about that possibility," they conclude.
The need to initiate a social debate on these scientific investigations is a dimension of the study also highlighted by
Cian Lynch
, from the Laboratory of Cellular Plasticity and Disease of the Institute for Biomedical Research (IRB Barcelona).
This scientist, a researcher in the field of chimeras and who is not involved in the work, considers that the study published today by
Cell
"has two equally remarkable aspects: an advance in biomedical research and an ethical dimension to consider", even though note that "many years of science, balanced by careful consideration and ethical guidelines, remain before this extraordinary biomedical solution can be used in patients."
Lynch notes that "
interspecies chimeras
, using human embryonic stem cells in monkey embryos, offer the potential to solve the two main problems underlying our organ transplant crisis [insufficient organ numbers and risk of immune rejection]."
Despite the commendation of the objective, the path to achieve it is thorny, so "extreme ethical care must be taken into account in said experimentation, and the work of Izpisúa-Belmonte gives high priority to this aspect, describing in detail the guidelines Ethics and the discussion that preceded his experiments. "
From a technical point of view, Lynch observes that the resulting efficiency with these chimeras, like that found with other evolutionarily more distant animals such as mice or pigs, "remains low, however, the data are promising in the sense of that greater efficiency appears possible in the future. "
For
Bernhard Payer, an expert in embryogenesis
and group leader at the Center for Genomic Regulation (CRG) in Barcelona, the research "could shed light on the molecular mechanisms involved in interspecies differences."
Studying these keys would allow, therefore, to increase the efficiency in the development of chimeras in the future and "if the conditions of culture in vitro are improved to the point of achieving a greater advance of the embryos in their development, the system could potentially be used for the first phases of organogenesis ", points out the researcher, who describes the work as" important advance ".
Less favorable is the opinion of this work by
Alfonso Martínez Arias
, recently incorporated as ICREA professor in the Department of Experimental and Health Sciences at Pompeu Fabra University, after decades at the University of Cambridge.
"From a scientific point of view, the work is very poor and it is very difficult to see data that justifies what the researchers say;
there are very few images of chimera embryos and those that do exist are indecipherable
. Given the headline, it would have been nice to see more technical level ", he writes to this medium.
"It contributes nothing but noise. The experiment is unnecessary, because there are others underway in the field of chimeras, using mainly pigs, which are quite advanced and are more promising. The authors justify their experiment in that they have already made an attempt mixing human cells with pig embryos and it did not work for them. As they did not repeat it it is difficult to know the reasons.
I think they should have persevered with the pig or the sheep
, which have much less ethical problems. "
Martínez Arias reflects that "an important point in Science is not doing something that only a researcher can do, but something that can be extended to other researchers. It is difficult to see how this work can be repeated independently, with ease, which will complicate its verification (including the results that are reported) since not only must be settled with ethical issues, but the colonies of primates that are needed are not something normal or easy to establish. In any case, the French researcher P. Savatier published a Similar experiment, but more rigorous, last year reaching the conclusion that these chimeras do not work, which is the conclusion that one draws by reading the article in detail. It is worrying that this work is going to raise such a stir, especially given its low technical level, and that creating an alarm creates problems for more sensible studies of chimeras that are already underway. "
And he concludes that "aside from all this, the work with
organoids
is making great strides and will surely provide solutions to certain medical problems that the authors cite as their objective, thus solving the use of animals that, in this case, is totally unnecessary. ".
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