Dr He Jiankui, a Chinese researcher, speaks during the Human Genome Editing Conference in Hong Kong, Wednesday, Nov. 28, 2018. Photo / AP
Dr He Jiankui, a Chinese researcher, speaks during the Human Genome Editing Conference in Hong Kong, Wednesday, Nov. 28, 2018. Photo / AP
Hong Kong scientists have warned of far-reaching effects on humans and consequences that will not be seen for several generations after a Chinese scientist claimed he had created the world's first gene-edited babies.
Dr He Jiankui's experiment to alter the DNA of twin babies - also known as germ line gene editing - means the changes in those genes could be passed on and inherited by the next generations.
"By doing this, He is changing the human gene pool, we may not be able to see the impact of this until several generations later," said Dennis Lo Yuk-ming, chairman of Chinese University's Department of Chemical Pathology.
"Academically, there is no consensus we should be doing this and the technology is not fully there yet - so to do it now, it's very irresponsible," Lo said on Thursday, the last day of an international genome summit in Hong Kong.
It was expected scientists and experts would produce a formal statement on gene editing, including what is acceptable and how trials can be regulated.
He, who earlier sparked international debate after revealing his unprecedented trial, defended his research at the summit on Wednesday and revealed there was another potential pregnancy of a gene-edited embryo.
He used the gene-editing tool CRISPR, a method that makes it easier and more accurate to alter genes that has emerged in recent years. He hoped the modification would make the twins, Lulu and Nana, resistant to HIV infection.
However, such technology has not matured, which could result in genes that were not the target of the experiment also being modified.
"There may be 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, in a set of essays and articles published posthumously, predicted that genetic engineering would lead to a race of "superhumans", by editing traits of intelligence and instincts of aggression. He worried this capability would end up concentrated in the hands of the wealthy and powerful.
He Jiankui, a Chinese researcher, speaks during the Human Genome Editing Conference in Hong Kong yesterday. Photo / AP
Another expert, Derrick Au Kit-sing, director of CUHK's centre for bioethics, said He's experiment had happened "far too early".
"Even as this research is done on animals, we have no idea what long-term effects it will have - let alone know if it's safe to do on humans," Au said.
"The whole scientific and medical community believes this happened too early, we simply have no idea what future risks there may be," he said.
He's research, announced on Monday, drew swift global condemnation, with China's Ministry of Science and Technology investigating whether he had broken the law. Critics said He's research was not medically necessary as the risk of HIV could be reduced or prevented with other methods or treatment.
Au also questioned whether it was ethical for He's test subjects to be recruited by an HIV/Aids advocacy group.
"It is seemingly ethically problematic to find these so-called volunteers to do this experiment, because these are people of a more vulnerable group, they could be easily manipulated and affected," Au said, adding that he questioned whether the couples really understood the experiment and knew the risks.
Hong Kong law prohibits work on embryos that allow it to develop beyond 12 days, according to the Council on Human Reproductive Technology.
Gene modification resulting in a live birth is banned in a number of countries, including China, for safety and ethical concerns.
He's clinical trial with the seven couples was put on hold after the controversy broke, but he said he would continue to monitor the twins until they were 18 years of age.
What is gene editing? Who's doing it? And is it right?
The scientific community is largely aghast at the claim that a woman in China gave birth to the world's first genetically edited babies earlier this month, born from embryos modified to make the twins resistant to HIV infection.
The announcement was made on Monday by Chinese scientist He Jiankui on the eve of the Second International Summit on Human Genome Editing, held in Hong Kong, where the world's leading thinkers in the field have converged to discuss the technology and its ethics.
Using techniques such as CRISPR-Cas9, scientists now have the power to not just engineer the expression of a certain gene, but to target multiple genes along a DNA strand. Photo / 123RF
His claim has deepened the sense of urgency surrounding the debate on the morality of gene editing, one that has already intensified in recent years with the rapid advance of technology.
These advances are largely due to the discovery of a powerful gene editing tool known as CRISPR-Cas9, whose gene editing applications were first identified by University of California, Berkeley biochemist Jennifer Doudna and Emmanuelle Charpentier, director of the Max Planck Institute for Infection Biology in Berlin.
While technologies allowing scientists to edit strands of DNA have been in development since the 1970s, the discovery of CRISPR-Cas9 has accelerated the abilities of scientists to enhance crops, control infection, and eliminate hereditary diseases. It also opens the door to radical changes to human DNA – it was this technology that was purportedly used by He to prevent the newborn twins inheriting HIV infection.
Genes are sequences coded into strands of DNA; they determine an organism's traits, development, and, in some cases, which diseases they will get. Scientists have the ability to change a DNA sequence, or gene, within a living cell, "editing" the gene and changing how it is expressed in the organism. With gene editing, scientists can swap out the DNA building blocks of a disease-producing gene for new genetic code that doesn't produce the disease.
"Genome" is a broader term that refers to an organism's entire DNA sequence, or the entire road map for an organism. Using techniques such as CRISPR-Cas9, scientists now have the power to not just engineer the expression of a certain gene, but to target multiple genes along a DNA strand, thus creating more impact on the genome.
What is CRISPR-Cas9?
CRISPR-Cas9 is a molecular system that acts as a pair of very precise scissors, pinpointing the right spot on a strand of DNA to cut out a gene and insert its replacement. It is a tool that was borrowed from an immune system found in bacteria, where CRISPR molecules stored genetic code from past infections in order to defend against them. When harnessed by scientists, CRISPR molecules can match and find DNA sequences, while Cas9, its accompanying enzyme, binds and cuts DNA.
Other gene editing techniques that use enzymes to target DNA existed prior to 2012 and are still in use, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), but these are considered less precise and more expensive for laboratories to use as compared to CRISPR-Cas9.
The CRISPR technique has already been used to change plants and animals. Earlier this year, researchers at Imperial College London used the technology to find a key that could wipe out the world's mosquito population, while those at the University of Edinburgh produced virus-resistant pigs. There are numerous agricultural applications, from mushrooms that do not brown, created by a Pennsylvania State University professor in 2016, to tomato plants with fewer excess branches, developed by scientists from Cold Spring Harbour Laboratory in New York. The products of these advances, at this point, are limited to laboratories.
The use of CRISPR and similar technologies to counter human disease is one of the most compelling potential applications capturing research funding and scientists' attention. The wide ease of use of CRISPR means that labs around the world are using it to look at how gene editing can eliminate diseases from haemophilia to HIV. Chinese scientists were the first to experiment with injecting cells with CRISPR-modified genes directly into humans. They used the technique to remove a gene that stops the body's immune system attacking cancer cells, in a 2016 clinical trial with a lung cancer patient at Chengdu's Sichuan University. Last year a private company in California made the first attempt to allow proteins to edit genes directly within the body, as opposed to modifying cells and then injecting them, in a bid to stop genes that produce Hunter syndrome. That procedure relied not on CRISPR, but ZFNs.
t the very forefront of genome editing technology is the modification of the human embryo. While this technology evokes fears of "designer babies" with DNA altered to enhance looks or intelligence, the scientific world has focused embryonic experiments on hereditary disease prevention. The first known embryo editing experiments were published by Chinese researchers at Sun Yat-sen University in Guangzhou in 2015, just three years after the discovery of the CRISPR-Cas9 technology. The first embryos were edited with CRISPR in the United States last year by a researcher at Oregon Health and Science University, who successfully removed the genes associated with inherited diseases.
These exercises were purely experimental until He's assertion that he had implanted the gene-edited embryo for twins into a woman.
When scientists edit the human embryo they are creating changes that have the potential to impact the genetic composition of future generations. Unlike edits that are made to developed human cells, which will only affect a person treated with those cells, edits made to sperm, eggs cells or embryos can be inherited. Scientific bodies globally have said that such a weighty impact needs to be carefully considered and deliberated with the public before it is used.
When it comes to the current controversy surrounding He, another ethical consideration is health. Because the technology is so new, the effects that the editing process may have on the DNA and the resulting human life are unknown. Scientists around the world are asking if He carefully considered the future health of the babies before using this new technology.
The birth of the twins strikes at the heart of the "designer babies" concerns that are often voiced around genome editing. However, physical and personality attributes are usually linked to multiple genes, so while the human genome may be edited, selecting for such effects would be complicated to pull off. For now, science has steered its experimentation towards the elimination of disease, not the selection of desirable traits.
