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July 2, 2019 - July 8, 2020
I was far more concerned about two other, more concrete hazards: first, that through a series of reckless, poorly conceived experiments, scientists would prematurely implement CRISPR without proper oversight or consideration of the risks, and second, that by virtue of being so effective and easy to use, CRISPR might be abused or employed for nefarious purposes.
I strongly believe that scientists working in this field have a responsibility to conduct their research openly, to educate the public about their work, and to engage in collective discussions about the possible risks, benefits, and ramifications of their experiments before conducting any that might cross the Rubicon, so to speak. In the case of CRISPR, it seemed clear that public discussion was falling far behind the breakneck pace of scientific research.
I found myself thinking about analogies to nuclear weapons, a field in which science advanced in secrecy and without adequate discussions about how researchers’ findings should be used.
Oppenheimer said: “It is my judgment in these things that when you see something that is technically sweet, you go ahead and do it and you argue about what to do about it only after you have had your technical success. That is the way it was with the atomic bomb. I do not think anybody opposed making it; there were some debates about what to do with it after it was made.”
it seemed likely that rushing ahead with the research could still cause harm—by undermining society’s trust in this new form of biotechnology, if nothing else.
I sought answers in another pivotal moment in the history of biotechnology,
the birth of recombinant DNA. And in this case, scientists had moved proactively—and, ultimately, successfully—to prevent their work from inadvertently causing harm.
at the time, Berg and other scientists recognized that experimenting with modified genetic material could have myriad, unpredictable, and potentially dangerous consequences.
Because of these concerns, Berg and his team of researchers held off on attempting the experiment.
Before his research went any further, he wanted to enlist his fellow scientists to run a thorough cost-benefit analysis.
The concerns raised at this meeting led scientists to request that the National Academy of Sciences establish a committee to formally investigate the new technology.
“Berg letter,”
It was one of the first times that scientists had voluntarily refrained from conducting a whole class of experiments in the absence of any regulatory or governmental sanctions.
Instead of leading to an uproar and crippling restrictions, as some scientists had feared, this transparency ultimately gave rise to a consensus that allowed research to proceed with popular support.
technologies that should be subject to democratically articulated imaginations of the futures we want, not the opposite. Science and technology often claim to be servants of society; they should take that promise seriously. Imagining what is right and appropriate for our world—and what threatens its moral foundations—is a task for democracy, not for science.”
absolutely agree that society as a whole—rather than scientists individually or even as a group—should decide how any given technology is used. But there’s a wrinkle here, which is that society cannot make decisions about technologies it doesn’t understand, and certainly not about those it knows nothing about. It’s up to scientists to bring these breakthroughs to the public’s attention, as Berg and his colleagues did,
I would need to leave the comfort of my lab and help spread the word about the implications of our research. Only that way could CRISPR be fully understood by the people whose lives it would soon affect. Only that way, I hoped, could its worst excesses be averted.
The meeting, which we held on January 24, 2015,
Even more interesting than these presentations, in my opinion, were the group’s open-table deliberations about the future of gene editing. These conversations were enthusiastic and creative, covering topics I had previously grappled with only on my own.
use of gene editing specifically in the human germline should be the focus of our white paper.
It was clear that germline editing was the one area where few had ventured and where public discussion was most urgent.
As long as it could be proven safe and effective, this cohort argued, and as long as its benefits clearly outweighed its risks, how could we hold this mode of therapy to a higher standard than any other medical treatment? Ultimately, though, we realized that this wasn’t
our decision to make. It was not up to us, the seventeen people in the room, to determine what the public should think about germline editing.
our responsibility was twofold. First, we had to make the public aware that germline editing was an emerging societal issue that should be confronted, studied, discussed, and debated. Second, we had to urge the scientific community—those individuals who were familiar with the technology, and who were aggressively...
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On March 19, 2015, the article was published online with the title “A Prudent Path Forward for Genomic Engineering and Germline Gene Modification.”
four specific recommendations.
We asked experts from the scientific and bioethics communities to create forums that would allow interested members of the public to access reliable information about new gene-editing technologies, their potential risks and rewards, and their associated ethical, social, and legal implications. We called on researchers to continue testing and developing the CRISPR technology in cultured human cells and in nonhuman animal models so that its safety profile could be better understood in advance of any clinical applications. We called for an international meeting to ensure that all the relevant
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article, published in the journal Protein and Cell, described experiments in Junjiu Huang’s lab at Sun Yat-sen University in Guangzhou, China. Huang and his colleagues had injected CRISPR into eighty-six human embryos. The target in this study was the gene responsible for producing beta-globin, a part of the hemoglobin protein that carries oxygen through the body. People with defects in the beta-globin gene develop the debilitating blood disorder known as beta-thalassemia.
the results of Huang’s experiments were mixed. Upon examining the beta-globin genes of the tested embryos, the researchers found that a mere four of the eighty-six embryos contained the intended mutations, a gene-editing efficiency of just 5 percent.
Huang had taken care to ensure that no CRISPR babies could be born as a result of his experiments by using triploid human embryos. So named because they contain three sets of twenty-three chromosomes
By using triploid embryos that were destined for disposal, however, Huang and his colleagues could neatly sidestep the inevitable objections that they were destroying potential human lives.
It quickly became apparent that many others in the scientific community shared my concern about Huang’s experiments,
Nature and Science had both rejected Huang’s manuscript,
The response to Huang’s article from many scientific and governmental agencies was swift, and unanimous.
“the Administration believes that altering the human germline for clinical purposes is a line that should not be crossed at this time.”
genome editing as one of the six weapons of mass destruction and proliferation that nation-states might try to develop, at great risk to America.
“Biological and chemical materials and technologies, almost always dual use, move easily in the globalized economy,” wrote the report’s authors, dual use being a term of art for technologies that can be used for both peace and war.
the responses to the first tests of CRISPR in human embryos were far from unanimously negative.
“to intentionally refrain from engaging in life-saving research is to be morally responsible for the foreseeable, avoidable deaths of those who could have benefitted. Research into gene-editing is not an option, it is a moral necessity.”
the audience about the science of gene editing, discuss the societal implications of this new technological power, and address issues of equity, race, and disability rights. This wide spectrum of topics could be grouped into three basic categories: safety considerations, ethical considerations, and regulatory considerations.
by the end of the meeting, which took place in the first few days of December 2015, I found that I had as many questions as I had had when we’d started, if not more. But I also had a deeper appreciation for the rationale of people on opposing sides of the debate, many of whom argued passionately for their points of view and helped me to refine my own thinking on the issue of germline editing.
impossible to fit all of these conversations and viewpoints into a single book, let alone a single chapter, so I will confine myself to one perspective: my own.
It’s almost certain that germline editing will eventually be safe enough to use in the clinic. Microsurgery on egg cells and embryos, such as fertilization by sperm injection and biopsy sample removal for preimplantation genetic diagnosis (PGD), has already become routine in fertility clinics.
challenge—how to make this gene-editing system precise enough to alter only the target gene and only exactly as intended—will soon be overcome.
It seems obvious that we should reject any procedure that might trigger DNA editing at unintended sites, as sometimes occurs with CRISPR and other gene-editing technologies. But the truth is that our entire lives are spent at risk of such random genetic changes, and the threat from them is arguably far greater than any that CRISPR would pose.
Every time our cells duplicate their DNA during cell division, somewhere between two and ten novel DNA mutations creep into the genome. Every person experiences roughly one million mutations throughout the body per second,
rapidly proliferating organ like the intestinal epithelium, nearly every single letter of the genome will have been mutated at least once in at least one cell by the time an individual turns sixty.
Any mutations that CRISPR might make—intentional or not—would almost certainly pale in comparison to the genetic storm that rages inside each of us from birth to death. As one writer put it, “Genetic editing would be a droplet in the maelstrom of naturally churning genomes.”
Another option that might become possible in the future is to avoid off-target mutations entirely by editing primordial egg and sperm cells instead of fertilized embryos.
we must consider not just whether the technology can work accurately, but also whether the effects of accurate edits will be the ones we intend.