How One Rogue Scientist Could Sink Global Gene Therapy Progress

Amid a global uproar denouncing a Chinese scientist’s work to deliver gene-edited twin babies, worries emerge that other valuable future research in the area could be put on hold, effectively crippling industry experts and researchers.

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Could startling revelations from one Chinese researcher hamper overall gene therapy research?

The likelihood of one bad apple crippling the global progress of overall gene editing technology has never been higher.

Amid controversial claims that Chinese researcher He Jiankui created the world's first gene-edited babies, there has been overwhelming condemnation and criticism of the so far unverified work, which knocked out the HIV infection-related CCR5 gene at the fertilized embryo stage before womb implantation. (Also see "Deny, Denounce, Debate: China Gene-Edited Babies Awaken Genie In The Bottle" - Pink Sheet, 27 Nov, 2018.)

He's claim surfaced a day before the opening of the Second International Summit on Human Genome Editing in Hong Kong, three years after the first summit during which there has been much advancement in the fast-growing space.

The negative response has been such that a small group of researchers has started worrying that the sudden downpour of cold water could dampen the nascent hope of using gene-altering technology to treat life-threatening and rare diseases.

The worry seems legitimate, given that over 100 scientists and biologists attending the summit released a statement voicing grave concerns and calling for an international moratorium on such embryonic gene editing.

The statement, circulated during the Nov. 27-29 summit, organized by the non-profit Center for Genomics and Society (CGS) and Human Genetics Alert, expressed civil society’s dismay and outrage at He’s claims, and asked summit organizers to call on governments and the United Nations to establish a legally enforceable moratorium on any further such experiments.

"[He's] procedure was irresponsible...its flaws include inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures" - closing statement of 2nd International Summit on Human Genome Editing

Wide Condemnation 

“The horrifying history of eugenics in the 20th century should show the disastrous consequences of going down this path,” said David King, CEO of Human Genetics Alert. “It should act immediately to prohibit such experiments, and ensure that He Jiankui is prosecuted as a warning to others.”

Meanwhile, the Hong Kong summit organizers, led by the US National Academy of Science, released its own closing statement condemning He’s “deeply disturbing” experiment, and called for an independent investigation, but the organizers restrained from calling for an international moratorium.

“We recommend an independent assessment to verify this claim and to ascertain whether the claimed DNA modifications have occurred,” said the Nov. 29 statement. Even if verified, “the procedure was irresponsible“ the statement went on, pointing to flaws including “inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures.”

There was also harsh criticism from other corners of the globe. The director of the University of Oxford's Oxford Uehiro Centre for Practical Ethics dubbed He's work "monstrous", and Dr Eric Topol, founder and director of the Scripps Research Translational Institute in the US, said in a New York Times opinion piece that the research was "a misguided, reckless use of powerful gene-altering tools". 

"There are still too many risks, too many unknowns, about tinkering with our heritable genetic blue-prints," including potential changes to other parts of the genome that could induce diseases. "The risk of unintended editing is considerable" and the ability to discern these changes is still rudimentary," Topol noted. 

A group of more than 100 Chinese scientists also turned to China's social media service Weibo to denounce the work as a "huge blow" to the standing of Chinese research in the biomedical field.

China Official Responses

Amid the outrage and controversy from other researchers, the Chinese government has also condemned the gene editing experiment as “a severe violation of law and ethics regulations”, and called for a halt to further such experiments.

“The reported case by the media has severely violated national laws and ethical principles, and related regulators and local officials are investigating it; we’ll punish any illegal or unethical behaviors,” Deputy Commissioner of the National Health Commission Zeng Yixin said.

China’s Ministry of Science and Technology (MOST) has requested a halt to the research activities of these involved in the experiments.

The gene editing of human embryos with a purpose of pregnancy and giving birth is prohibited in China, pointed out Xu Nanping, Deputy Minister of MOST. The gene-edited baby experiment violated national regulations and an ethical bottom line, is shocking and unacceptable, and should not be tolerated, the official added.

Even He's employer, the China Southern University of Science and Technology, was stunned by the news and acknowledged that its management or the faculty of biology department He works for were not notified of the study.

While He presented his case during the Hong Kong summit on Nov. 28, he has since apologized, but said he is proud of using the technology to relieve the suffering of HIV-affected people in China.

"There is a lot of potential for using gene editing to alleviate disease suffering, and providing a productive path forward is the best way to ensure that patients' hopes will get realized" - Feng Zhang, Broad Institute

Throwing Baby Out With Bath Water?

But some observers are more pragmatic, and worried that valuable and well-conducted research into the use of gene-editing technology in life-threatening and rare conditions could suffer by an all-out cookie cutter ban on such work, effectively throwing the baby out with the bath water.

Feng Zhang, one of the pioneers of the CRISPR-cas9 gene-editing technology and director of the Broad Institute of Harvard University and the Massachusetts Institute of Technology, said gene editing could benefit patients of genetic diseases, which include muscular dystrophy, inherited retinal diseases and Fanconi anemia among others.

Zhang previously had called for an international moratorium on embryo gene editing, but said this shouldn’t stop research on the treatment of patients suffering from certain conditions.

"Rather than focusing on criticizing what has happened, we should learn the lessons that it has taught us," Feng wrote in an email, quoted by US National Public Radio. "There is a lot of potential for using gene editing to alleviate disease suffering, and providing a productive path forward is the best way to ensure that patients' hopes will get realized.”

Fellow Researcher Voices Hope

“There are two different gene therapy development strategies - gene replacement therapy and gene altering therapy,” said Wu Xiaobing of Ruixi Gene Therapy Research Institute, a Beijing-based firm developing treatments for rare diseases including mucopolysaccharidosis and spinal muscular atrophy (SMA).

“Currently, gene therapy developers are limited to use human cells, not embryos,” she noted. “Gene editing technology has a large potential in gene therapy development, and we are also preparing in terms of accumulating technology know-how.”

The company has purchased an SMA-induced mouse model from Jackson Labs and is conducting systematic analysis on using gene therapy to treat rare conditions that mostly affect babies.

(With contributions from Ian Haydock in Tokyo.)

From the editors of PharmAsia News.