"Changing the stock of human genes": concerns raised by the babies of Chinese scientists published on the gene

Hong Kong scientists have warned of far-reaching effects on humans and consequences that will not be felt for several generations after a Chinese scientist claimed that he had created the first babies in the world with modified genes.

The experience of Dr. He Jiankui aimed at altering the DNA of twin babies – also known as germline gene editing – means that modifications of these genes could be inherited and transmitted by the next generations.

"By doing this, it modifies the stock of human genes, we may not be able to see the impact for generations to come," said Dennis Lo Yuk-ming, chairman of the department of chemical pathology of the 39, Chinese university.

"From an academic point of view, there is no consensus on the fact that we should be doing this and the technology is not yet complete, so do it now, that's all." is very irresponsible, "said Lo on Thursday, the last day of an international genome summit in Hong Kong.

Scientists and experts were expected to produce an official statement on gene editing, including what is acceptable and how to regulate testing.

He, who had previously sparked international debate after the revelation of his unprecedented lawsuit, defended his research at Wednesday's summit and revealed that there was another potential pregnancy for a gene-modified embryo.

He used the CRISPR gene editing tool, a method that makes it possible to modify genes more easily and with greater precision, appeared in recent years. He hoped that this modification would make the twins, Lulu and Nana, resistant to HIV infection.

However, this technology has not yet matured, which could result in modification of genes that were not the target of the experiment.

"This could have unintended consequences – for example, if it affected other genes related to cell reproduction, it could lead to cancer," Lo said.

The late physicist Stephen Hawking predicted, in a series of posthumously published essays and articles, that genetic engineering would lead to a race of "superhumans", altering traits of intelligence and instincts of aggression. He feared that this ability would end up in the hands of the rich and powerful.

Another expert, Derrick Au Kit-sing, director of CUHK's Center for Bioethics, said his experience was "far too early".

"Even though this research is done on animals, we have no idea of ​​its long-term effects – let alone know if this can be done safe for humans," said Au.

"The whole scientific and medical community feels that this has happened too early, we simply have no idea of ​​the risks for the future," he said.

His research, announced Monday, was quickly condemned worldwide. The Chinese Ministry of Science and Technology has investigated whether it broke the law. Critics said his research was not medically necessary because the risk of contracting HIV could be reduced or prevented by other methods or treatments.

Au also asked if it was ethical that he test subjects were recruited by an HIV / AIDS advocacy group.

"It is seemingly ethically problematic to find these so-called volunteers to do this experiment because they are people belonging to a more vulnerable group, they could be easily manipulated and affected," Au said, adding that he wondered if the couples really understood the experiment and knew the risks.

The Hong Kong law prohibits work on embryos that allow it to grow beyond 12 days, according to the Council on Human Reproductive Technology.

Genetic modification leading to a live birth is prohibited in a number of countries, including China, for reasons of safety and ethics.

His clinical trial with the seven couples was put on hold after the controversy, but he said he would continue to monitor the twins until the age of 18.

What is gene editing? Who did it? And is it true?

The scientific community is largely shocked by the claim that a woman in China gave birth to the first genetically modified babies in the world earlier this month, born from modified embryos to make the twins resistant to HIV.

The announcement was made Monday by Chinese scientist He Jiankui on the eve of the Second International Summit on the Human Genome Publishing, which was held in Hong Kong, where the world's leading thinkers in the field have converged to discuss technology and its ethics.

His statement reinforced the sense of urgency surrounding the debate on the morality of gene editing, a debate that has already intensified in recent years with the rapid progress of technology.

These advances are due in large part to the discovery of a powerful gene editing tool called CRISPR-Cas9, whose gene editing applications were first identified by Jennifer Doudna, biochemist at Berkeley; and Emmanuelle Charpentier, director of the Max Planck Institute for Infection Biology in Berlin.

While technologies enabling scientists to modify DNA strands have been in development since the 1970s, the CRISPR-Cas9 discovery has accelerated scientists' ability to improve cultures, control infections and eliminate hereditary diseases. This also opens the door to radical changes in human DNA – it's this technology that would have been used by He to prevent newborn twins from inheriting infection from the hepatitis C virus. HIV.

What is gene editing?

Genes are sequences encoded in DNA strands; they determine the characteristics of an organism, its development and, in some cases, the diseases that it will contract. Scientists have the ability to modify a DNA sequence, or gene, within a living cell, to "modify" the gene and alter its expression in the body. With gene editing, scientists can exchange the basic DNA components of a disease-producing gene for a new genetic code that does not produce the disease.

The term "genome" is a broader term that refers to the entire DNA sequence of an organism or the complete roadmap of an organism. Using techniques such as CRISPR-Cas9, scientists now have the power not only to design the expression of a given gene, but also to target multiple genes along a single strand. DNA, thus creating more impact on the genome.

What is CRISPR-Cas9?

CRISPR-Cas9 is a molecular system that acts as a very precise pair of scissors, locating the right place on a strand of DNA to cut a gene and insert its replacement. This is a tool that has been borrowed from an immune system present in bacteria, where CRISPR molecules have stored the genetic code of past infections in order to defend against them. When they are exploited by scientists, CRISPR molecules can match and find DNA sequences, while Cas9, its associated enzyme, binds and cuts DNA.

Other gene editing techniques using enzymes to target DNA existed before 2012 and are still used, such as zinc finger nucleases (ZFNs) and transcriptional effector type effectors. (TALEN), but are considered less precise and more expensive. laboratories to be used in relation to CRISPR-Cas9.

How advanced is genome modification technology today?

The CRISPR technique has already been used to modify plants and animals. Earlier this year, researchers at Imperial College London used this technology to find a key capable of destroying the world's population of mosquitoes, while those at the University of Edinburgh produced pigs resistant to viruses. There are many agricultural applications, from non-browned mushrooms created by a professor at Pennsylvania State University in 2016 to tomato plants with fewer branches in excess, developed by scientists at the Cold Spring Harbor Laboratory in New York. The products of these advances are, at this stage, limited to laboratories.

The use of CRISPR and similar technologies to combat human diseases is one of the most compelling potential applications, capturing research funding and the attention of scientists. The great ease of use of CRISPR means that laboratories around the world use it to study how gene editing can eliminate HIV-related hemophilia diseases. Chinese scientists were the first to experiment with injecting CRISPR-modified genes to cells, directly into humans. They used this technique to eliminate a gene that prevents the immune system from attacking cancer cells as part of a clinical trial conducted in 2016 with a patient with cancer. of lung at Sichuan University in Chengdu. Last year, a California-based private company tried for the first time to allow proteins to modify genes directly in the body, as opposed to modifying cells and then injecting them, in order to stop the genes responsible for Hunter syndrome. This procedure was not based on CRISPR, but on ZFNs.

The leading edge of genome editing technology is the modification of the human embryo. While this technology evokes the fears of "designer babies" whose DNA has been altered to improve appearance or intelligence, the scientific world has focused its experiments on embryonic experiments on the prevention of hereditary diseases. The first known experiments of embryo modification were published by Chinese researchers at Sun Yat-sen University of Guangzhou in 2015, just three years after the discovery of CRISPR-Cas9 technology. The first embryos were published with CRISPR in the United States last year by a researcher from Oregon Health and Science University, who managed to suppress the genes associated with hereditary diseases.

These exercises were purely experimental until he claimed that he had implanted in a female embryo modified by a gene intended for twins.

Why is genetic modification controversial?

When scientists modify the human embryo, they create changes that can affect the genetic makeup of future generations. Unlike changes to developed human cells, which will only affect the person treated with these cells, changes to sperm, eggs, or embryos can be inherited. Scientific organizations around the world have stated that such an important impact should be carefully considered and deliberated with the public before its use.

In regard to the current controversy around Him, another ethical consideration is health. Because technology is so new, the effects that the editing process can have on DNA and the resulting human life are unknown. Scientists around the world are asking if he has carefully studied the future health of babies before using this new technology.

The birth of twins strikes at the heart of the concerns of "designer babies" often expressed about genome editing. However, physical attributes and personality are usually related to several genes. Thus, although the human genome may be modified, it would be difficult to select such effects. For the moment, science has oriented its experiments towards the elimination of diseases and not towards the selection of desirable characteristics.

– Morning of South China