The biologists have done it again. Not so long ago it was cloning and embryonic stem cells that challenged moral imagination. These days all eyes are on a powerful new technique for engineering or “editing” DNA. Relatively easy to learn and to use, CRISPR has forced scientists, ethicists and policymakers to reconsider one of the few seeming red lines in experimental biology: the difference between genetically modifying an individual’s somatic cells and engineering the germline that will be transmitted to future generations. Instead of genetic engineering for one person why not eliminate that disease trait from all of her or his descendants? This week, the U.S. National Academy of Sciences, the Chinese Academy of Sciences, and the U.K. Royal Society are trying to find ways to redraw that red line. And redraw it in a way that allows the technology to help and not to hurt humanity. Perhaps the hardest but most critical part of the ethical challenge: doing that in a way that doesn’t go down a dark path of “improvements” to the human race. Compared to previous strategies, the technique known as CRISPR (clustered interspaced short palindromic repeats) is faster, more reliable and cheaper than previous methods for modifying the base pairs of genes. CRISPR is made up of scissors in the form of an enzyme that cuts DNA strands and an RNA guide that knows where to make the cut, so the traits expressed by the gene are changed. Already, labs are applying gene editing in pluripotent stem cells. Older methods are being used to help the human immune system’s T cells resist HIV, which might be done better with CRISPR. Gene editing trials are also in the offing for diseases like leukemia. It looks very much like these genies are out of the bottle. Since the 1960s, technical limitations, the prospect of unintended consequences, and the “eugenic” implications of deliberate alterations of future generations weighed heavily against germline engineering. Many countries, including many in Europe, have laws that forbid human germline modification. The National Institutes of Health won’t pay for such research but there’s no law against using private funds. China also doesn’t prohibit it. But over the past 20 years, advances in laboratory techniques, genetic screening for disease traits, and the prospective fruits of the Human Genome Project have smudged the red line. Gradually, the public health benefits of changing the human germline have gained as much emphasis as the risks. Some observers have noted that, aside from the efficiencies that could be realized with germline engineering, the ethical distinction between germline and somatic cell modification may already be moot, since even somatic cell modifications can “leak” into effects on gametes. The emergence of CRISPR has made it impossible to delay more definitive guidance. Even apart from risks and benefits, are we prepared to modify our genetic heritage with all the implications for humanity’s relationship to the rest of the natural world? Following a wave of publicity about CRISPR, last spring a number of scientists and researchers called for a voluntary moratorium on its use. Their proposal was reminiscent of the Asilomar moratorium on recombinant DNA research in 1975. Asilomar is commonly (but not universally) thought to have been an effective response on the part of the scientific community to public fears about biohazards. But the world of life sciences research is far different now than it was 40 years ago, when the community was much smaller and more intimate. Sophisticated experimental biology is now a globalized affair. Funding pressures, the virtually instantaneous availability of experimental procedures and results, and the fact that researchers may have limited face-to-face contact make self-policing far more challenging than it once was. Indeed, within weeks of the calls for a moratorium, a Chinese team performed a modification of non-viable embryos, a proof-of-concept experiment that fell smack into the ethical grey zone and further shook confidence in the prospects for an effective moratorium. With events moving so quickly, the summit organized by the U.S. National Academies, along with its British and Chinese counterparts, will need to face a few key ethical issues. How can technical risks, like “off target” effects that change an important gene instead of the one intended, be avoided? Are there any diseases that could justify attempts to diffuse genetic changes in a human population? And who is to make such monumental decisions on behalf of unborn generations? Recommendations from the Academies aren’t law but they can establish guiding principles for legitimate scientific practices. Ten years ago a National Academy of Sciences committee that I co-chaired set rules for doing human embryonic stem cell research that were voluntarily adopted in many parts of the world. When it comes to the ethics of science, the scientific community needs to lead but also needs to listen to non-scientists. Especially in the case of the human germline, one principle worth defending is that between therapy and enhancement. Even if population-wide disease prevention is sometimes acceptable, attempts to otherwise “improve” the human race should be banned. Other principles will apply mainly to agricultural research. Genetically modified plants and animals are the focus of a parallel National Academies study on the ecological risks of gene drive experiments that might someday lead to deliberate changes of non-human populations in the wild. New techniques like CRISPR will make the recently approved fast growing salmon look old fashioned. The experiments that are both the most promising and the most risky are that those that involve rapidly propagating species like insects, like eliminating the ability of mosquitoes to carry the malaria parasite. And accidents are always possible so best biosafety practices will have to be reviewed and strengthened, including perhaps inbred biological barriers like the “suicide genes” that will cause modified organisms to die if they escape the lab. One thing is clear: CRISPR and its descendants will have lives beyond the laboratory. Jonathan D. Moreno is the David and Lyn Silfen University Professor at the University of Pennsylvania where he teaches bioethics and the history of science. He is the author of “The Body Politic: The Battle Over Science in America.”
This week, the U.S. National Academy of Sciences, the Chinese Academy of Sciences, and the U.K. Royal Society are trying to find ways to redraw that red line. And redraw it in a way that allows the technology to help and not to hurt humanity. Perhaps the hardest but most critical part of the ethical challenge: doing that in a way that doesn’t go down a dark path of “improvements” to the human race.
Compared to previous strategies, the technique known as CRISPR (clustered interspaced short palindromic repeats) is faster, more reliable and cheaper than previous methods for modifying the base pairs of genes. CRISPR is made up of scissors in the form of an enzyme that cuts DNA strands and an RNA guide that knows where to make the cut, so the traits expressed by the gene are changed. Already, labs are applying gene editing in pluripotent stem cells. Older methods are being used to help the human immune system’s T cells resist HIV, which might be done better with CRISPR. Gene editing trials are also in the offing for diseases like leukemia. It looks very much like these genies are out of the bottle.
Since the 1960s, technical limitations, the prospect of unintended consequences, and the “eugenic” implications of deliberate alterations of future generations weighed heavily against germline engineering. Many countries, including many in Europe, have laws that forbid human germline modification. The National Institutes of Health won’t pay for such research but there’s no law against using private funds. China also doesn’t prohibit it.
But over the past 20 years, advances in laboratory techniques, genetic screening for disease traits, and the prospective fruits of the Human Genome Project have smudged the red line. Gradually, the public health benefits of changing the human germline have gained as much emphasis as the risks. Some observers have noted that, aside from the efficiencies that could be realized with germline engineering, the ethical distinction between germline and somatic cell modification may already be moot, since even somatic cell modifications can “leak” into effects on gametes. The emergence of CRISPR has made it impossible to delay more definitive guidance.
Even apart from risks and benefits, are we prepared to modify our genetic heritage with all the implications for humanity’s relationship to the rest of the natural world? Following a wave of publicity about CRISPR, last spring a number of scientists and researchers called for a voluntary moratorium on its use. Their proposal was reminiscent of the Asilomar moratorium on recombinant DNA research in 1975. Asilomar is commonly (but not universally) thought to have been an effective response on the part of the scientific community to public fears about biohazards.
But the world of life sciences research is far different now than it was 40 years ago, when the community was much smaller and more intimate. Sophisticated experimental biology is now a globalized affair. Funding pressures, the virtually instantaneous availability of experimental procedures and results, and the fact that researchers may have limited face-to-face contact make self-policing far more challenging than it once was. Indeed, within weeks of the calls for a moratorium, a Chinese team performed a modification of non-viable embryos, a proof-of-concept experiment that fell smack into the ethical grey zone and further shook confidence in the prospects for an effective moratorium.
With events moving so quickly, the summit organized by the U.S. National Academies, along with its British and Chinese counterparts, will need to face a few key ethical issues. How can technical risks, like “off target” effects that change an important gene instead of the one intended, be avoided? Are there any diseases that could justify attempts to diffuse genetic changes in a human population? And who is to make such monumental decisions on behalf of unborn generations? Recommendations from the Academies aren’t law but they can establish guiding principles for legitimate scientific practices.
Ten years ago a National Academy of Sciences committee that I co-chaired set rules for doing human embryonic stem cell research that were voluntarily adopted in many parts of the world. When it comes to the ethics of science, the scientific community needs to lead but also needs to listen to non-scientists. Especially in the case of the human germline, one principle worth defending is that between therapy and enhancement. Even if population-wide disease prevention is sometimes acceptable, attempts to otherwise “improve” the human race should be banned.
Other principles will apply mainly to agricultural research. Genetically modified plants and animals are the focus of a parallel National Academies study on the ecological risks of gene drive experiments that might someday lead to deliberate changes of non-human populations in the wild. New techniques like CRISPR will make the recently approved fast growing salmon look old fashioned.
The experiments that are both the most promising and the most risky are that those that involve rapidly propagating species like insects, like eliminating the ability of mosquitoes to carry the malaria parasite. And accidents are always possible so best biosafety practices will have to be reviewed and strengthened, including perhaps inbred biological barriers like the “suicide genes” that will cause modified organisms to die if they escape the lab.
One thing is clear: CRISPR and its descendants will have lives beyond the laboratory.
Jonathan D. Moreno is the David and Lyn Silfen University Professor at the University of Pennsylvania where he teaches bioethics and the history of science. He is the author of “The Body Politic: The Battle Over Science in America.”
