While all over the world talk about the dangers of genetic editing, China is actively engaged in it. In the race for the technology of editing the human genome, the winner will be the one who not only actively invests in science, but is also the least willing to limit himself.
“We were furious with this extremely irresponsible misconduct, which clearly violated the normative and medical ethics of China and countries around the world,” - this is how authoritative Chinese scientists assessed the risky experiment of their compatriot biophysicist He Jiankui.
In 2018, He announced that he had mutated the genomes of two embryonic twin girls, ostensibly to protect them from HIV. The news of this dangerous experience has riveted the world's attention. For the first time, the scientist crossed the line that genetics all over the world publicly and tacitly agreed not to cross. As a result, the Southern University of Science and Technology in Shenzhen disowned his experiments and fired the scientist, and the Ministry of Health of Guangdong Province decided to investigate.
But the scandal is on the wane: "Chinese Doctor Frankenstein" seems to have escaped with indicative condemnation from colleagues. Meanwhile, new reports about the development of Chinese science sound no less alarming.
Brain erectus
In the same southern China, just over a thousand kilometers west of He's laboratory, a group of biologists raised macaques with a human variant of a gene that affects brain development. Transgenic monkeys turned out to be smarter than ordinary ones - their short-term memory improved.
And this experience is fraught with no less serious consequences. In the current research climate, the focus will shift even more to the modification of monkeys: genetic experiments with primates will multiply, and from there will come the lion's share of knowledge about the interaction of genes.
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The key question is what kind of experiments they will be and where they will be carried out.
Scientists wondered whether it was ethical to add human DNA into the monkey genome back in 2010. An article about this was published in the journal Nature Reviews Genetics and caused serious discussion. The temptation was great: it was possible to take a genetic sequence unique to our species, raise an animal with this sequence and see how its behavior will change. Nine years ago, the authors of the article reasoned: if a way has been found to study how and which genes make us human, is it necessary?
Today, the Zoological Institute of the Chinese Academy of Sciences creates transgenic monkeys using various methods of genetic engineering. Fresh work - five individuals raised with the human gene MCPH1 inserted into their DNA. This gene affects the intrauterine development of the fetal brain, it is also called "microcephalin", but its role is not well understood. In terms of brain size and typical behavior, transgenic animals did not differ from ordinary animals, but their short-term memory and reaction speed in some tasks turned out to be better.
It is likely that the human gene MCPH1 influenced the development of the macaque brain. Their neurons matured more slowly, the myelin sheath on the nerve fibers appeared later, and the expression of synaptic genes was delayed. The authors of the experiment write: "We hypothesize that the delay in neural maturation in transgenic monkeys could increase their time window for neural network plasticity, similar to neoteny in human brain development." That's why macaques performed better on tests - their brains were slightly more plastic, they could learn faster. It seems the authors have found a tool that can be used to influence cognitive abilities.
Conditions for a genetic breakthrough
For the search for "unique" human genes to bear even more impressive results, three conditions are needed. China has them.
First condition: there must be a lot of monkeys. The Zoological Institute of the Chinese Academy of Sciences manages the monkey farm. Over two thousand individuals live there, many carry transgenes. It takes 4-5 years to raise a monkey, keeping it more expensive than the same mice, but in recent years, with the support of the government, similar farms have also appeared in Kunming, Shenzhen, Hangzhou, Suzhou and Guangzhou. The population of macaques for research purposes in the country is constantly growing and has reached many tens of thousands.
The second condition is political will, the intention to purposefully use monkeys to study the brain. Non-human monkeys serve as models for various diseases, including neurodegenerative diseases, autism, depression, schizophrenia. China even exports animals to other countries. The number of laboratory macaques in the United States is comparable, but up to 43% of them are used in the United States to study HIV / AIDS, and in addition, the American Congress recently insisted on reducing the amount of experimental work with them. China is becoming the world center for primate research and will increase its monkey resource.
The China Brain Project (CBP) is a science initiative on which the government has a strong stake. Similar initiatives have been launched in the US and the EU since 2013, but the Chinese one stands out for its focus on working with non-human primates. Experiments on them are spelled out in the priorities of the SVR.
The third prerequisite for a breakthrough in human gene research is training the right people. China prepares them intensively. This can be seen in the dynamics of the participation of Chinese universities in the iGEM (International Genetically Engineered Machine), the main international competition in synthetic biology and genetic engineering. If in 2012 29 Chinese teams applied (out of 250 participants from all over the world), then in 2016 there were already 63 (out of 299), in 2017 - 83 (out of 312), in 2018 - 103 (out of 343), and 117 Chinese teams (out of 376) have already entered iGEM-2019. For comparison, the statistics of the United States, the closest competitor: 94, 76, 73, 79, 65. Others are behind by a wide margin.
Human defect
The main attempts at unique genetic engineering experiments in recent years have come from China. Like He Jiankui, scientists from Kunming crossed the line by creating macaques with human DNA not for clinical (that is, vital for humans), but for genetic testing. And it is not without reason that their article was published only in a Chinese magazine, while He has no publication at all.
Chinese research into human gene replacement and editing will continue to accumulate. A person has many genes. If you introduce them to monkeys in two and three, studying the effects of combinations, then the field of activity is unplowed. And it's not enough to introduce a human transgene: then you really need to delete the corresponding monkey gene, which the authors did not do (but they will certainly do it at the next round).
Thus, scientists of this particular country in the future can obtain valuable knowledge - in particular, how specific changes in DNA affect the mind and psyche.
What can be done with such knowledge, taking into account the technical possibility of editing human DNA at the embryo stage? The practice of interfering with the germ line will come into the world in small steps, starting with the correction of very rare and otherwise irreparable defects. It all depends on how successful it is.
A fork looms ahead: either some side effects will quickly appear and the topic will be closed for a long time, or at first everything will go smoothly, and possible "bugs" will affect, for example, only after two or three generations. Or will there be no bugs at all? Short answer: we don't know. This is what research is for.
Another fork: from correcting defects and then, through reducing the risk of getting sick, to designing new human properties. The color of the eyes or skin is not interesting, these are trifles. It's about the brain. There is definitely something to "fix" in it.
DNA boundaries
The third child with the blocked He gene is expected to be born in August 2019. Judging by the sharp reaction of scientists and doctors to He's trick and the dominant tone of their comments, the standards for the coming years are more likely to tighten than vice versa, and experiments on editing human DNA will begin to be held back even in China.
An international group of scientists appeared in the journal Nature with an open letter to the world community with a proposal to introduce a moratorium on the clinical editing of the DNA of the human germ line (sperm, eggs, embryos). The WHO expert commission also did not stand aside, which also has its own position: "At present, it is irresponsible to apply clinical editing of the human germ line genome."
Nevertheless, it is obvious that genome editing technology will develop, and more and more rapidly. And the winner in this race is the one who not only actively invests in science from a financial point of view, but is also less willing to limit himself than others.
China can be considered one of the favorites in this race. They have raised a huge colony of monkeys for research, are betting heavily on genetic engineering, and are launching a brain research project based on transgenic and gene-editing technologies, plus non-human primates as models.
The United States has a higher potential in neuroscience, there are no less monkeys at its disposal, but their BRAIN Initiative does not directly target the genetic modification of monkeys, and experiments of this kind are likely to experience more restrictions there.
Russia also has a good potential for the development of genetic research, including at the interface with neuroscience. However, Rospotrebnadzor in the near future intends to submit to the State Duma for consideration a bill on the protection of the genetic data of its citizens. Before any human DNA test, the bill requires written permission from a citizen.
The same measure is being introduced by China, which also intends to include healthy human genes and embryos among the inalienable rights of its citizens. This could theoretically mean that genome researchers will be held responsible for experiments that potentially threaten human health.
However, the PRC is not going to introduce another restriction recommended by Rospotrebnadzor. Anyone who performs any manipulation with human DNA, the Russian bill will give the status of a personal data operator. In fact, the document will oblige scientific centers to create separate systems for protecting genetic personal data. It is expensive and time consuming. The introduction of such a norm, if it does not stop promising genetic research in Russia, will certainly greatly slow down.
The article was prepared with the participation of the resource Laba.media
Author: Denis Tulinov