A technician prepares a DNA sample at a GangaGen Inc. laboratory in Bengaluru, India. 9Photographer: Samyukta Lakshmi/Bloomberg)

Brave New World of Editing Human DNA Starts in China

(Bloomberg) -- Researchers expressed surprise at the report Nov. 26 of the birth of the world’s first gene-edited babies -- twin girls. It’s no surprise that the scientist making the claim was from China. As part of its effort to dominate scientific spheres including biotechnology, the country has taken the lead in testing uses of Crispr, a tool newly available to researchers enabling them to alter DNA codes simply and inexpensively. Chinese scientists were the first to test Crispr in monkey embryos, in non-viable human embryos, in adult humans -- and now this. The announcement of the first designer babies has renewed debate over whether China’s regulatory system is sufficiently grappling with the ethical considerations and medical risks of Crispr.

1. What’s the controversy?

This is the first reported case in which genes were manipulated in embryos that were then used to produce babies. Altering the genes of an embryo changes DNA in every cell, including the eggs or sperm, of a resulting person who had no say in the matter, and those alterations will be passed on to progeny. That muddies the principle that participants in clinical research must give their informed consent. This is important because editing with Crispr is experimental in humans and entails risks. The technique works by making cuts in DNA. Sometimes these may be unintended, and bring unknown effects.

2. Anything else?

Some researchers expressed outrage that these risks were taken for what they consider an insufficient purpose. The Chinese investigator, He Jiankui, says his goal was to produce babies immune to HIV, the virus that causes AIDS. He says he altered a gene in the embryos that makes a protein called the CCR5 receptor, which HIV uses to enter cells. Critics point out that HIV infection is relatively uncommon in China, there are other ways to prevent it, and it’s treatable. Even if the gene-editing worked, the twins won’t be invulnerable to HIV, which can also get into cells via a receptor called CXCR4. What’s more, studies suggest that CCR5 deficiencies increase vulnerability to West Nile virus and influenza. Reports by the U.S. National Academies of Sciences, Engineering and Medicine in 2017 and the U.K.’s Nuffield Council on Bioethics in 2018 concluded that human trials of editing reproductive, or germline, cells should be used only to fill unmet medical needs and benefit those whose genes are altered.

3. Was the gene-editing trial approved?

That’s not clear. The researcher says he had approval from the medical ethics committee at Harmonicare Hospital in Shenzhen. The company that owns the hospital said in a filing that it believed signatures on an application to the committee had been forged and that it was investigating.

4. What are the relevant rules in China?

Under guidelines issued by the National Health and Family Planning Commission in 2003, gene editing of embryos isn’t banned, but the use of genetically modified eggs, sperm or embryos for reproduction is prohibited. These are not laws, and are enforced through the commission’s ability to withdraw the licenses of fertility clinics.

5. What are the rules elsewhere?

Twenty-nine of the 47 member states of the Council of Europe -- including France, Denmark, Switzerland and Spain -- have ratified the 1997 Oveido Convention, which prohibits modification of germline genes. In the U.S., Congress has banned the Food and Drug Administration from considering such trials. A 2002 Australian law calls for imprisonment for 15 years for anyone who purposely makes heritable alterations in a human cell.

6. Does lax regulation account for China’s lead?

Certainly not all of it. China wants to be a leader in the defining technologies of the 21st century and has poured billions into funding research. As a participant chosen for its prestigious Thousand Talents scheme -- a plan to lure back talented Chinese from overseas -- He would have received at least a starting bonus of about $143,000 for his research, with the possibility of additional research grants of roughly $700,000. He also founded a startup called Direct Genomics that makes DNA-sequencing equipment, which also received government funding, according to its website. According to the database clinicaltrials.gov, China has 12 human trials involving the Crispr method. One of these is active, with eight in the recruiting stage. In the U.S., there are six Crispr-related trials, four of which are recruiting and none of which are active.

7. How is China responding?

The country’s biotech companies and universities have worked hard to counter suspicions that their endeavors are rife with fraud and minimally supervised experimentation. The Genetics Society of China and the Chinese Society for Cell Biology were quick to condemn the gene-editing work, calling it a serious ethical violation. A group of 122 Chinese research scientists on Monday published a letter that called the project unfair to the vast majority of Chinese scholars who work conscientiously and respect ethical boundaries. The Chinese Union of Life Science Societies, an umbrella of 22 national-level associations, said that it strongly opposed research that violated the spirit of science and ethics, and that He’s case had “severely disturbed the order of scientific research and seriously damaged China’s international reputation in the life science field.”

The Reference Shelf

  • A QuickTake explainer on Crispr.
  • A paper by the U.K. Nuffield Council on Bioethics on China’s regulations on germline gene editing.
  • A piece in Nature describes the ethical debates around Crispr.

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