Thursday, September 8, 2016

Chinese researchers have genetically modified a human embryo—and many scientists think they’ve gone too far

Chinese researchers have genetically modified a human embryoand many scientists think they’ve gone too far

A team of scientists in China dropped a bombshell earlier this month, and almost nobody noticed.

Researchers led by Junjiu Huang of Yat-sen University in Guangzhoupublished the world’s first scientific paper on altering the DNA of human embryos.

The pioneering research is controversial, though it was conducted on damaged embryos that could not have developed into a human. Many scientists contend that newly developed genetic-engineering methods need to be studied further in animals before running the risk of unpredictable human mutations and scarier developments in human evolution such as eugenic programs.

How could such a monumental paper go unnoticed? It was published on April 11 in the little-known online journal Protein and Cell, after being rejected by the more prestigious journals Science and Nature—partly on the grounds that the research was unethical, according to a report by Nature’s news division, which operates independent of the scientific journal. And that rejection highlights a major divide in the world of advanced genetic research: Scientists have discovered a powerful new tool, but they are also very concerned about where it may lead.

CRISPR: A fresh technique

The idea behind genetic medicine is fairly simple, even if the details are complex. Copies of a unique genetic code—in the form of DNA—are present in almost every human cell. People suffering from genetic disorders possess mutated genes—that is, misplaced letters in their DNA. The idea, then, is to heal genetic disorders by fixing the gene itself.

In the last few years, researchers have developed a powerful new method of snipping out defective DNA strands and replacing them with healthy one. The breakthrough tool—touted by MIT Technology Review as perhaps the biggest biotech discovery of the century—that enabled Huang’s team to conduct its research is called CRISPR (that stands forClustered Regularly Interspaced Short Palindromic Repeats, if you were wondering).

CRISPR was developed by observing the age-old battle between bacteria and viruses. In 2005, researchers discovered that bacteria use CRISPR genetic sequences as a biological weapon to remember, detect and dismember enemy viruses, honing in on specific sections of viral DNA and cutting them out.

Soon after this discovery, scientists were able to modify CRISPR to target genetic sequences in other living cells. This gave them the precision scissors that they had been looking for to target specific genes. It opened the door to fixing the mutated genes that cause hereditary disorders in both a very targeted way—honing in on specific DNA sequences—but also on a very broad scale, applied to every cell within an organism. CRISPR, combined with a few specialized proteins, essentially promises to be a find-and-replace tool for fixing damaged genetic material.

Here’s a video from MIT that goes into a little more detail:

Incidentally, some of the early CRISPR research was done by Rodolphe Barrangou, a scientist working for the yogurt company Danisco, whotold the science writer Carl Zimmer that many dairy companies use CRISPR sequences in their bacterial cultures. “If you’ve eaten yogurt or cheese, chances are you’ve eaten CRISPR-ized cells,” he told Zimmer.

Mixed results

Huang’s team didn’t experiment with viable human embryos. Instead they used some of the abnormal, non-viable embryos that are inevitably created as part of in-vitro fertilization therapy, such as when two sperms insert their DNA into a single egg.

The team injected 86 embryos with engineered CRISPR sequences that targeted genes responsible for the blood disorder β-thalassaemia. About 71 of the embryos survived the 48-hour period needed for CRISPR to work. Fifty-four of the embryos could be genetically tested. Only 28 had the defective sequence removed, and an even tinier fraction of those ended up with the “pasted-in” healthy genetic sequence.

More worryingly, in some cases the CRISPR technique unintentionally caused mutations in other parts of the genome.

“If you want to do it in normal embryos, you need to be close to 100%,”Huang told Nature. “That’s why we stopped. We still think it’s too immature.” (Huang was not immediately available for comment when Quartz tried to reach him via email.)

Don’t edit human DNA

A group of prominent geneticists published a paper in Science last month—including Jennifer Doudna, a University of California Berkeley professor who last year collected a $3 million Breakthrough Prize, bankrolled by Facebook founder Mark Zuckerberg and other tech billionaires, for her pioneering work on CRISPR—that urged scientists to refrain from testing the technique on human embryos.

The paper concluded that “the potential safety and efficacy issues arising from the use of this technology must be thoroughly investigated and understood before any attempts at human engineering are sanctioned, if ever, for clinical testing.”

Fifteen western European countries currently prohibit genetically modifying the germ line (which includes sperms, eggs, and embryos), and a major US health research committee has said (pdf, p.101) it “will not entertain proposals for germ-line alterations.”

The Science authors recommended that steps be taken to “[s]trongly discourage, even in those countries with lax jurisdictions where it might be permitted, any attempts at germ-line genome modification for clinical application in humans.”

A slippery slope?

Proponents of genetic engineering tend to talk about the potential benefits, such as eradicating hereditary diseases like hemophilia or sickle-cell anemia not just in a single patient, but in all of his or her descendants as well. Opponents talk about the dangers of genetic fixes gone wrong, or at the extreme end of the spectrum, the dystopian prospect of wealthy parents ordering up genetically perfect “designer babies.”

“Even unambiguously therapeutic interventions could start us down a path towards non-therapeutic genetic enhancement,” a group of scientists wrote in Nature in March. They told their colleagues around the world: “Don’t edit the human germ line.”

But it may be too late. According to an anonymous researcher cited by Nature, at least four groups in China are working on genetically modifying human embryos. The MIT Technology Review reported last month that research groups at Harvard Medical School and at least one other center in Boston are looking into so-called human germ-line engineering, along with other scientists in China and the UK.

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