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Germline engineering could lead to designer babies and superstrength

Using CRISPR-Cas9 to edit genes is controversial but exciting

In the past month momentum has mounted around a technology called CRISP​R-Cas9, often described as a "search and replace" tool for DNA. The reason? It's possible that scientists are now looking into using the revolutionary technique to permanently edit the genome of human eggs, sperm and embryos, a process called germline engineering.

This is the new frontier of genetic engineering, in which modifications made to reproductive cells—the germline—would be passed down to subsequent generations. Scientists aren't sure what the effects of that might be yet.


"Every time you make a sperm or an egg cell, you're scrambling the genomes you inherited from your mom and dad, so who the hell knows what could happen," said David Al​bertini, who researches fertility treatments and regenerative medicine at the University of Kansas Medical Center. "You might have effects that show up not in the first generation, but in the second, third, or fourth one."

Scientists are advising caution as the technology advances. However, human germline engineering may be moving faster than expected. Last month, repo​rts surfaced claiming that scientists from China, the United Kingdom and at least a couple biotech companies in Boston are working on editing human germlines.

"This is about fundamentally changing human nature."

The possibilities of human germline engineering—which could enable the precise editing of disease-causing genes and also give rise to highly-customized designer babies—could certainly trigger public hysteria, said Arthu​r Caplan, head of medical ethics at New York University's Langone Medical Center.

He speculates that public response to the technology might parallel the panic that arose around cloning with the birth of Dolly th​e sheep in the mid 1990s. "People went batshit crazy about Dolly," he said. "I think germline engineering has the potential to be like that. This is about fundamentally changing human nature."

Caplan thinks the scientific community will respond skeptically to the human germline studies that are rumored to be coming out soon. "The papers are supposed to be coming out in journals that are not first-rate, by people who are not well-established at CRISPR or other gene-splicing techniques," he said. "I think there will be a lot of criticism that this is not a report coming from reliable, A-team sources."


But the public is a different story, said Caplan. "My hunch is that the public would feel very negatively about human germline engineering—negatively enough that there might a push towards getting Congress to pass laws prohibiting it."

CRISPR-Cas9, often shortened to just CRISPR, hijacks a process that bacteria use to recognize and splice DNA sequences in invading viruses.

In 2012, a group of scientists led by researchers at the University of California, Berkeley report​ed that they could program the bacterial system to identify any DNA sequence and edit the genes at that specific site.

Since then, scientists have published around 600​ papers investigating the technology in a wide variety of applications, including modifying non-reproductive and reproductive cells in animals, and non-reproductive cells in adult humans.

Last w​inter, Chinese scientists used CRISPR to edit genes related to metabolism, immune cell development and sex determination in monkey embryos.

Clinical trials for treatments involving CRISPR-Cas9 in non-reproductive cells are not that far off, according to Jenn​ifer Doudna, a professor at Berkeley and one of inventors of the technique. "I think we'll start to see clinical trials for adult patients within maybe two or three years," she said.

For human germline engineering, the timeline becomes much murkier because there are still unanswered questions about how often the technology misfires and what its risks are. "We have to better understand the technology before our society, regulatory agencies, clinicians and scientific community can make an informed decision about how to proceed," said Doudna.


Experimentally, however, human germline engineering is already possible. "Certainly in terms of the scientific capabilities and the ease of using the technology, it's there," Doudna told Motherboard. "We're confident, based on all the data that's out there, that this is a technology that could work in the human germline."

"You could make a mutation that has one effect that's desirable but it might have several other effects that are undesirable—and they might not show up for 20 years."

In humans, CRISPR could conceivably be used to remove a disease-causing mutation permanently from a germline, so that resulting offspring would not suffer from the disease and also wouldn't have to worry about passing the mutation onto their offspring, explained Doudna. But beyond repairing genetic defects, germline engineering can also be used to augment genetic traits—meaning it could theoretically lead to superhumans and designer babies.

​George​ Church, a prominent geneticist at Harvard Medical School, has identified certain gene variants, for example, that could lead to cha​racteristics like extra-strong bones, insensitivity to pain, or low body odor.

Doudna doesn't think those modifications will happen anytime soon. "We don't understand the genome well enough," she said. "What about unintended consequences? You could make a mutation that has one effect that's desirable but it might have several other effects that are undesirable—and they might not show up for 20 years."


In anticipation of public backlash, two independent teams of the field's leading scientists published editorials in Nat​ure and Sci​ence last month asking researchers to take heed moving forward.

"It is thought that studies involving the use of genome-editing tools to modify the DNA of human embryos will be published shortly," wrote the authors of the Nature piece. "In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable." The scientists go on to explicitly recommend a moratorium on human germline modification.

The authors of the Science piece stopped short of calling for a moratorium, focusing instead on the need to outline a "prudent path" for the application of genome engineering technologies.

"It's important to appreciate that this technology is widely available, it's straightforward to employ, and it mostly works," said Doudna, who helped author the Science article. She does not expect that it will be possible to police people who want to use CRISPR to modify human germ cells.

"I don't think any of us can really impose regulations that would stop any private entity or people in certain other countries from doing things with the technology," she said. "Our best strategy for dealing with this kind of thing is just to build as much consensus in the scientific community as we can."


Any clinical trials of gene therapies that would directly affect human offspring should certainly await careful testing in animals and adult humans first, said Church. In addition to his work at Harvard, Church is the co-founder of a life sciences company called eGe​nesis, which is using CRISPR to edit th​e genomes of live animals such as pigs and cattle.

For now, editing human germ cells with CRISPR does not necessarily offer therapeutic advantages over existing technologies, Church said. He points out that there are many other ways to treat genetic diseases already—according to the Journal of Gene Medicine, there have been over 2,000​ clinical trials looking at gene therapies on non-reproductive cells to treat a host of diseases. "Of those, only a couple involve gene editing. None of them involve CRISPR," he said.

Parents who are concerned about heritable genetic disorders, for instance, can already genetically profile embryos produced through in vitro fertilization, to ensure that the embryo that gets implanted in the uterus does not carry a disease-causing mutation.

"For a lot of disease prevention you could use embryo selection instead of embryo engineering," said Caplan. "It's not like we have to go immediately to CRISPR style techniques."

In the short term, gene-editing the human germline would really only treat diseases that can be traced to a single gene mutation, such as sickle cell anemia, cystic fibrosis and Huntington's disease, according to Kansas's Albertini. "For things like point mutations, this technology could be very cool," he said. "But that's only a fraction of the story of why we get diseases." Most genetic diseases involve a much more complicated interaction between multiple mutations and environmental factors.

Doudna and Caplan are now calling for an international consortium of scientists and other stakeholders to start formally discussing human germline engineering. They both expressed that the meeting, which might be convened through the National Academy of Sciences, should take place before the end of 2015.

Doudna hopes an international meeting will allow the scientific community to get out in front of the conversation and develop some specific guidelines around the application of CRISPR. "I certainly hope that those papers that are rumored to be floating around get published at some point, which they probably will," she said. "As a community we just have to be prepared for a lot of questions, and we have to be ready to address them."

Goodbye, Meatbags is a series on Motherboard about the waning relevance of the human physical form. Follow along here.