The breakthrough will be where more is allowed
Why does China need questionable experiments with the human genome
Denis Tulinov, Forbes, 06/18/2019
For links to sources, see the original article – VM.
While the world is talking about the dangers associated with 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 less willing to limit himself than others. "We were furious at this extremely irresponsible offense, which clearly violated the regulatory and medical ethics of China and countries around the world," – this is how authoritative Chinese scientists assessed the risky experiment of their fellow biophysicist He Jiankui.
In 2018, He announced that he had introduced a mutation into the genome of two twin girls at the embryonic stage, allegedly protecting them from HIV. The news about this dangerous experience attracted the attention of the whole world. For the first time, the scientist crossed the line that geneticists all over the world openly and tacitly agreed not to cross. As a result, the Southern University of Science and Technology in Shenzhen disowned his experiments and dismissed the scientist, and the Ministry of Health of Guangdong Province decided to investigate.
But the scandal is on the decline: "Chinese Doctor Frankenstein", it seems, got off with a demonstrative condemnation from colleagues. Meanwhile, new reports about the development of Chinese science sound no less alarming.
The brain is erect
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 the lion's share of knowledge about the interaction of genes will come from there.
The key question is what kind of experiments they will be and where they will be conducted.
Scientists have been thinking about whether it is ethical to introduce human DNA into the monkey genome, back in 2010. An article about this was published in the journal Nature Reviews Genetics and caused a serious discussion. The temptation was great: there was an opportunity to take a genetic sequence unique to our species, raise an animal with this sequence and see how its behavior would change. Nine years ago, the authors of the article reasoned: if a way is 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 MCPH1 gene embedded in DNA. This gene affects the intrauterine development of the fetal brain, it is also called "microcephalin", but its role has not been really studied. In terms of brain size and typical behavior, transgenic animals did not differ from ordinary ones, but their short-term memory and reaction speed in some tasks turned out to be better.
Probably, the human MCPH1 gene still 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 started belatedly. The authors of the experiment write: "We suggest that the delay in neural maturation in transgenic monkeys could increase their time window of neural network plasticity, similar to neoteny in human brain development." That's why macaques did better on tests – their brains were a little more plastic, they could learn faster. It seems that the authors have found a tool that can be used to influence cognitive abilities.
Conditions for a genetic breakthrough
In order for the search for "unique" human genes to bear even more impressive fruits, three conditions are needed. China has them.
The first condition: there must be a lot of monkeys. The Zoological Institute of the Chinese Academy of Sciences manages, among other things, a monkey farm. There are over two thousand individuals living there, many of them carrying transgenes. It takes 4-5 years to raise a monkey, keeping costs more 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 of 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 States to study HIV/AIDS, and in addition, the US Congress recently insisted on reducing the amount of experimental work with them. China is becoming a global center for primate research and will increase its monkey resource.
China Brain Project (CBP) is a scientific initiative on which the government is making a serious bet. Similar initiatives have been launched in the USA and the EU since 2013, but the Chinese one stands out with an emphasis on working with non-human primates. Experiments on them are spelled out in the priorities of the SVR.
The third condition for a breakthrough in human gene research is the training of the right specialists. China is intensively preparing them. This is evident from the dynamics of Chinese universities' participation in iGEM (International Genetically Engineered Machine), the main international competition in synthetic biology and genetic engineering. If in 2012 29 Chinese teams (out of 250 participants from all over the world) submitted applications, then in 2016 there were already 63 (out of 299), in 2017 - 83 (out of 312), in 2018 - 103 (out of 343), and at iGEM–2019 already 117 Chinese teams (out of 376) showed up. For comparison, the statistics of the USA, the closest competitor: 94, 76, 73, 79, 65. The others are behind by a large margin.
Human defect
The main attempts of the unique genetic engineering experiments of 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 specifically for genetic testing. And it's not for nothing that their article was published only in a Chinese magazine, and He has no publication at all.
Chinese research with the replacement and editing of human genes will accumulate. Humans have a lot of genes. If you introduce them to monkeys two and three at a time, studying the effects of combinations, then the field of activity is not plowed. And it is not enough to introduce a human transgen: then it is necessary to remove the corresponding monkey gene, which the authors did not do (but they will certainly do it on the next turn).
Thus, scientists of this particular country in the future can gain valuable knowledge – in particular, how specific DNA changes affect the mind and psyche.
What can be done with such knowledge, taking into account the technical possibility to edit human DNA at the embryo stage? The practice of intervention in the germ line will come into the world in small steps, starting with the correction of very rare and otherwise irremediable defects. It all depends on how successful it will be.
A fork looms ahead: either some side effects will appear quickly 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. That's what research is for.
Another fork: from correcting defects and further through reducing the risks of getting sick to designing new human properties. The color of the eyes or skin is not interested, these are trifles. It's about the brain. There will definitely be something to "fix" in it.
DNA Boundaries
It is expected that a third child with a blocked He gene will be born in August 2019. Judging by the sharp reaction of scientists and doctors to He's antics and by the dominant tone of their comments, standards for the coming years will be tightened rather than vice versa, and experiments on editing human DNA will begin to restrain even in China.
An international group of scientists made an open letter to the world community in the journal Nature with a proposal to introduce a moratorium on clinical editing of human germ line DNA (sperm, eggs, embryos). The WHO expert commission did not stand aside either, which also has its own position: "It is currently irresponsible to use clinical editing of the human germ line genome."
Nevertheless, it is obvious that the technology of genome editing will develop, and faster and faster. 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 of this race. A huge colony of monkeys has been raised here for research, they are making a serious bet on genetic engineering and launching a project to study the brain, based on transgenic and gene–editing technologies plus non-human primates as models.
The USA has a higher potential in neuroscience, there are no fewer monkeys at its disposal, but their BRAIN Initiative is not aimed directly at 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 junction with neuroscience. However, Rospotrebnadzor in the near future intends to submit to the State Duma a bill on the protection of the genetic data of its citizens. Before any study of human DNA, the bill requires a 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 citizens of the country. This could theoretically mean that genome researchers would be responsible for experiments that potentially threaten human health.
However, China is not going to introduce another restriction, which is recommended by Rospotrebnadzor. Anyone who commits any manipulation of human DNA, the Russian bill will give the status of a personal data operator. In fact, the document will oblige research centers to create separate systems for the protection of genetic personal data. It's expensive and long. The introduction of such a norm, if it does not stop promising genetic research in Russia, then it will certainly slow down a lot.
The article was prepared with the participation of the Laba.media resource
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