China spins real life Frankensteinian gene-editing tale

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Any discussion of Frankenstein in the context of genetic-editing quickly risks running into the realm of paranoia. Still, there are plenty of reasons to exercise caution at the vanguard of bio-tech today.

On November 26, news headlines around the world declared: “China gives birth to the world’s first genetically edited babies with AIDS immunity.”

He Jiankui, an associate professor at Southern University of Science and Technology, had just revealed the remarkable birth of his creations. In a process only one step longer than IVF, he had used CRISPR/Cas9 technology to locate and modify the gene in question—CCR5.

The CCR5 gene works as a signpost for the HIV virus, showing it where it can invade human immune cells. If a human has no CCR5 gene, the HIV virus can neither locate nor destroy cells. This is how two newborns now come to have “AIDS immunity.”

It is the kind of technological advance you would think everyone would celebrate. After all, AIDS has been an exasperating disease for experts and medical practitioners. There is still no straightforward way to stop it. But while the matter quickly caught the attention of experts, scholars, and practitioners, it quickly snowballed into accusation, criticism, and strong condemnation.

Scientists stand united

More than 100 scientists signed a “Joint Statement by Scientists” in opposition to the research. The statement said, “The biomedical ethics review for this so-called research was practically meaningless. Directly experimenting on people can only be described as madness.”

Since then, 140 AIDS researchers have also issued a statement expressing their united objection. China’s Technology Daily posed four issues about the “gene-edited babies,” and dxy.com, an online physicians’ community, issued a series of “ethical questions.”

On November 27, US biologist and Nobel Laureate Professor David Baltimore told the Second International Summit on Human Genome Editing at Hong Kong University that the birth of gene-edited babies was an unfortunate turn of events.

Most responses to the research contain two key questions: First, does the research violate ethics? Second, does further pursuit of this technology trigger unpredictable risks?

Southern University of Science and Technology is officially “unaware” and “unsupportive” of Associate Professor He’s  research. According to [state broadcaster] China Central Television, the Shenzhen Medical Ethics Committee initiated an investigation into the ethical implications for Shenzhen and the Shenzhen Harmonicare Women’s and Children’s Hospital (the hospital involved).

The gene-edited babies story continues to cause a furor. Contrary to current condemnation, when People’s Daily reported earlier research carried out at Sun Yat-sen University that compared HIV carriers’ and the general public’s awareness of and attitudes toward gene-editing, more than 60% expressed support.

A survey of 2,537 US adults by the Pew Research Center showed that 60% of Americans supported gene-editing of unborn babies to reduce the risk of major illness.

It is clear that current criticism has gone beyond the medical ethics field. It has spread to government and scientists who are concerned about unstable factors, sensitivities, and techniques that have traditionally been treated with extreme caution. It is this fanfare that has brought the case back for treatment.

Gene-editing angst

Gene-editing technology is hardly new, having been tested in the lab for decades already. So given the speed of human scientific and technological development, why do we still not have sci-fi style genetic realities? The main reason is that we want to avoid opening Pandora’s box and risking widespread human tragedy. But why are we so cautious and anxious about this?

As we understand it, gene-editing is a technology that mutates DNA, allowing us to change, add or delete genetic material at specific points of a genome. Scientists have devised several methods for editing genomes. The latest baby case used the CRISPR/Cas9 method.

Other methods include:

  • Homologous recombination, developed in the late 1970s. This involves the exchange of genetic information between two similar DNA strands. This method has been shown to be inefficient and have a low degree of accuracy.
  • Zinc finger nuclease (ZFN), developed in the 1990s. Researchers began using ZFN to increase the specificity of gene-editing and reduce off-target results. This method has a higher success rate, but is hard and time-consuming to carry out.
  • Transcriptional activator-like effector nucleases (TALENs), developed in 2009. TALENs are capable of binding specific DNA sequences by targeting them. For those who understand it, TALENs has clear advantages over ZFN.
  • CRISPR, which discovers, excises, and replaces specific parts of DNA through a specially programmed enzyme called Cas9. This technology can change the color of mice skin, and produce mosquitoes unable to transmit malaria and insect-resistant crops. This method is efficient, accurate, inexpensive, easy to use, and extremely powerful.

Gene-editing is of enormous significance in the prevention and treatment of human disease. At the moment, most research is conducted on cells and animals. Scientists expend considerable energy determining if gene-editing is safe, effective and applicable to people.

CRISPR/Cas9 technology is a huge step toward offering treatment solutions for human disease, but there are many ethical, social, and legal concerns. Mutations to the human genetic makeup are hard to predict, so studies have been published that call for the wholesale prohibition of human gene-editing technology.

In an article on “Human Germline Genome Editing” in the American Journal of Human Genetics, a survey conducted by the National Academy of Sciences, the National Academy of Medicine, the Chinese Academy of Sciences, the Japanese Gene Therapy Society, and the International Stem Cell Research Institute, reports that most respondents believe basic research may be carried out on gene editing, but at least in the short term, clinical applications should be avoided.

This should be until we are sure that gene-editing methods such as CRISPR/Cas9 will not change human embryonic genes for good, will not alter off-target genes, and will not lead to modified genes being passed down from generation to generation.

Bringing gene-editing into the clinic will change the human gene pool. “Once the modified gene sequence is introduced into the human population, genetic changes will be difficult to reverse,” said Professor Baltimore. And it is likely to move swiftly into the market, used to enhance human characteristics such as height or intelligence.

As a result, many national and industry experts are against the editing of human embryonic genes. According to the National Institutes of Health official website, a 2014 study showed that 29 of the 39 countries under review banned the editing of human reproductive genes. In April 2015, the Chinese National Institute of Health issued a statement reaffirming that it would not provide any funding for genetic editing of human embryos due to ethical and safety concerns.

Crossing red lines

The statement says editing human genes was a red line that should not be crossed, and that there was no reliable medical evidence to prove it was ethical to use CRISPR/Cas9 on embryos. The UK government has approved the editing of human embryos in the lab, but only if they are destroyed after seven days.

Furthermore, Sun Yat-sen University scientists announced that they would continue to carry out gene-editing on three-nuclear fertilized human eggs (fertilized eggs that cannot develop normally) using CRISPR/Cas9 technology. Although the university has said it will not allow embryos to develop, their actions have triggered heated discussion.

Gene-editing and allowing these two babies to be born clearly breaks the principles that scientists and the industry have maintained between themselves. This has given rise to the concern that has accompanied these two babies into the world, turning it into panic and distress. If safety and ethical issues are not satisfactorily addressed, gene-edited babies will not convince the public of the need for such medical experimentation. As for the future of these two babies, who knows?

Perhaps as they grow up, this technology will gain more stable prospects. We do need to recognize that gene-editing is a technology for future use, but we need to recognize what is missing in the case in question today.

As for customizing babies wholesale, Zhang Feng, a pioneer in CRISPR/Cas9 gene-editing technology said in an interview with Atlantic Monthly: “We’re still a ways from that. Designer babies and so forth, I think those are even further out. We don’t even understand biology enough to even contemplate what those things would be. We can’t even treat a single mutation that causes sickle-cell disease right now.”

So, while labelling the science as like something from “Frankenstein” makes it slightly horrifying, in the field of genetic editing, being cautious is not a bad thing.

Translated by Heather Mowbray. This article originally appeared in our Chinese-language sister website.