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Blue pupil: what will the world be like if human genes are transformed?
a few years ago, a new genetic modification technology was invented abroad, and it has been widely used in China, but it is only used in animals and plants (whether somatic cells or sex cells) or human somatic cells at home and abroad. Due to ethical issues and the explicit prohibition of laws in some countries, no one has ever modified the genes of human sex cells.

This situation was broken by Huang Junjie, an associate professor of biology at Sun Yat-sen University in China, and his collaborators on April 18th. They reported for the first time in the world that human sex cells were genetically modified to obtain early embryos. A stone stirs up a thousand waves, and the concerns caused by this study have been fermenting recently.

why does this technological progress cause great ethical controversy? Once gene technology is applied to sex cells, not only the "personal tailor" of genes may appear, but also it can affect many generations and even human evolution. "Mr. Sai" will publish many articles on this, and different opinions are welcome to contribute. In the first article published today, Wang Chengzhi, an assistant researcher at the Institute of Biophysics of the Chinese Academy of Sciences, believes that this technological progress has opened a Pandora's Box, and the consequences may be unpredictable.

Wang Chengzhi (Assistant Research Fellow, Institute of Biophysics, Chinese Academy of Sciences)

On April 18th, the research team led by Huang Jun, an associate professor of biology at Sun Yat-sen University was in Protein &; Cell magazine published a paper, which reported the research progress of transforming human embryos by gene editing technology for the first time in the world. In this study, the research team modified the HBB gene (encoding hemoglobin) in human trinuclear fertilized eggs. A stone has stirred up a thousand waves, and the international scientific community has made a rapid and different response to this research, and the ethical concerns caused by this research are also constantly fermenting.

Hereditary diseases: endless defects

In the paper published by Huang Jun on the research group, they modified the HBB gene encoding globin in fertilized eggs, and the mutation of this gene will lead to a common genetic disease-β thalassemia.

This disease can lead to severe anemia, dysplasia, bone changes and even neonatal death. There are many similar genetic diseases, and a large part of them are familial. These diseases afflict the whole family from generation to generation, as if their ancestors had some kind of insoluble curse.

before the 2th century, people's understanding of these diseases was very superficial, and there was almost no countermeasures. To make matters worse, the custom of consanguineous marriage was very popular in the east and west of ancient times. In the 16th century, Charles II, the illustrious heir of the Habsburg dynasty in Spain, suffered from various genetic diseases due to long-term consanguineous marriage of his family, especially because of physical defects and no children, which eventually led to the rapid decline of the Habsburg dynasty. In ancient China, consanguineous marriages often occurred. A famous example is that Emperor Wu of the Han Dynasty and his empress Chen Ajiao were cousins.

Obviously, inbreeding leads to the inheritance and accumulation of genetic defect genes in the family, while intermarriage between people with different genetic backgrounds will "dilute" the genetic defect genes. However, even if only one parent has a chromosome containing a genetic defect gene, the possibility of his offspring inheriting the gene is still as high as half. Obviously, if we want to completely eliminate a genetic disease in a family, we must ensure that all babies born do not carry the diseased gene, and the fertilization process in vivo is random under physiological conditions.

In p>214, Peking University Qiaojie, Xie Xiaoliang and Tang Fufu cooperated to help a couple with genetic diseases to select embryos without pathogenic genes and known mutations in vitro by using polar single cell sequencing technology, thus completely freeing their babies from the "family curse". This is a "milestone" breakthrough in the history of genetic diseases, which makes human beings end the pathogenic genes of their families at the individual level for the first time.

The difference between this work and Huang Jun's team work is that it is only a process of artificially selecting fertilized embryos, and it does not touch the ethical red line of artificially modifying embryo genes. And this red line is no less than the dividing line between human beings and the "creator". Beyond it, human beings may enter another world that transforms their own species.

genetic modification: the hand of "God"

People have probably never stopped thinking about where they came from and why they are human, because different cultures can find a similar story: one (or more) super-powerful "God" created all species, including people. Other similar stories can be found in these fairy tales with different cultural backgrounds. For example, some "gods" can transform existing species. For example, Athena transformed Medusa's long hair into a poisonous snake in ancient Greek mythology, and there is even a legend in Japanese mythology that evil spirits bewitch a man to plant his lover's head and get a face tree. It can be seen that human imagination has been able to transform creatures across borders.

in fact, human beings' desire to transform species has always existed and been practiced. Today, animals and plants that are closely related to human beings, from potted plants in the office to pets at home, to various animal husbandry as food, are almost all transformed by human beings through various breeding methods (mainly through hybridization), and the principles behind all this were not recognized by human beings until the last century.

Today, two basic knowledge about biological traits have almost become common sense: all biological traits are determined by genes; The essence of gene is deoxyribonucleic acid (DNA) sequence. When man has spied into the mystery of creation, the inevitable thing is about to happen: man wants to transform himself.

Human beings want to transform themselves, as can be seen from the increasingly popular plastic surgery hospitals, but human beings have never transformed themselves at the genetic level. Since the door of "double helix structure" was opened, human beings have been more and more free to manipulate DNA. Tools such as restriction endonucleases, ligases and modified enzymes are constantly being discovered and modified, and scientists can splice DNA fragments in test tubes like Lego bricks at will; Polymerase chain reaction, DNA synthesis technology and DNA sequencing technology enable scientists to read and create new DNA sequences; The discovery of homologous recombination in cells allows scientists to edit the DNA in cells: first, prokaryotes such as Escherichia coli, then lower eukaryotes such as yeast were conquered, and then a series of model organisms such as fruit flies, zebrafish and mice were also "taken down" by scientists one by one.

In p>213, the advent of CRISPR-Cas9 technology made genetic modification an extremely low-cost and extremely simple thing to operate, and any student with a basic molecular biology background could learn and operate it in a short time. At this point, the "hand of God" seems to be in the hands of human beings: we have the ability to transform the genes in human cells and even change the genes of embryos to get the individuals we want.

with a beautiful imagination, technology can make everything sound beautiful. The scientific community has also become enthusiastic about gene modification (known as gene editing in the industry), and good news has come one after another: scientists have successfully removed the viral DNA from the latent cell model of HIV, scientists have successfully knocked out the oncogene of cancer cells, scientists have successfully modified genetic defects in human stem cells ... Scientists seem to have been omnipotent, except for gently pushing the last door open.

mutant: Pandora's box?

The movie X-Men imagines that various mutants have appeared in human beings due to genetic evolution, and the conflict between mutants and ordinary people has brought the world into various disasters. With the maturity of gene editing technology, genes can be artificially "evolved", which may make imaginary plots in some movies become reality.

Imagine that if the genes of human embryos can be edited at will, first of all, many genetic diseases can be completely eradicated, but human beings will not be satisfied with this, because they still want to obtain "better" genes. For example, some parents may want their children to have genes such as "smarter", "healthier" and "more beautiful". Once genetic technology is applied to embryos, there may be a "personal tailor" of genes. Just as plastic surgery technology was originally used in medicine to repair serious defects or deformities caused by diseases or trauma, it inevitably became a way of self-customization. Like the same beautiful face in Korean beauty contests, who knows if it will reappear at the genetic level?

If genetic modification is only about artificial selection or even creating "better" genes to pass on to future generations, the world is just more homogeneous individuals. But if this Pandora's Box is opened, the consequences may be unpredictable.

We can't forget that there are always some crazy people in human beings. When they master certain resources, they will trample on human nature. During World War II, Hitler lectured his subordinates and said, "We should take this approach to hundreds of millions of stupid Slavs: transform the best of them according to our requirements and isolate the rest in their own pigsty." Even if human civilization enters the 21st century after a bitter world war, extreme religious forces are still rampant in many places. Imagine what the world would be like if some of them mastered gene editing technology and applied it to human beings.

science and ethics: where will mankind go

Bernard Shaw, an Irish playwright, once famously said, "There are two tragedies in life, one is that you can't get what you want, and the other is that you get what you want." Scientists have spent a lot of energy to develop gene editing technology to the present height. When the desire of generations of scientists to eliminate human genetic diseases has seen a glimmer of light, does human beings push the door into the forbidden area outside the "paradise" or think twice before acting? This will determine the future of mankind.

Science is pure, just as Faraday compared science to a newborn baby. But the baby will eventually grow up. The terrible thing is that once he grows up, he will no longer listen to his parents. It may become a saint or a devil. Just as human beings created wealth, now wealth is also controlling human beings. If science cannot be tied to the ethical red line, it may become a runaway wild horse.

In p>1996, Dolly's cloned sheep was born, which indicated that human beings could start to copy higher organisms. In 21, craig venter, a "scientific madman", synthesized the artificial creature "Synthia" for the first time, which indicated that human beings could create new species. Now, we are standing in the forbidden area of transforming human beings-our own species, and ethics has never been so important. Nowadays, most countries have passed laws prohibiting human cloning. Maybe it's time for our legislators to face the problem squarely.