There is need for more guidance of use of CRISPR technique, say experts.
Although there is serious doubt about a Chinese scientist’s claimed role in genetically safeguarding two newborns from the AIDS virus, and widespread condemnation of his alleged approach, he may have opened the door to more such research around the world, an American bioethicist says.
He Jiankui, who runs a lab at the Southern University of Science and Technology in Shenzhen, China, said Monday that he used the powerful gene-editing tool known as CRISPR-Cas9 to eliminate a gene called CCR5 in hopes of rendering offspring resistant to HIV. The gene editing took place during an in vitro fertilization procedure, but before the resulting embryo was implanted in the mother’s womb. The pregnancy culminated in the birth of twin girls in November.
But John F. Brehany, Director of Institutional Relations of the National Catholic Bioethics Center in Philadelphia, identified a number of ethical problems with He’s work, as reported in the media, including jumping directly to implementation of new technology, skipping normal steps of responsible clinical research.
Brehany explained in an interview that in the past five to seven years, scientists have taken tools that bacteria developed to defend against viruses (by identifying and snipping out specific strands of DNA) and “hacked” them to identify and remove, replace, or insert new strands of DNA. “CRISPR-Cas9 appears to be the most accurate, efficient tool to introduce changes into DNA yet devised,” he said. “Theoretically, it is accurate down to a single base-pair of DNA (and there are about 3 billion base pairs of DNA in human cells).”
“The general ethical quality of He’s action is so poor that I doubt many people will imitate him,” Brehany commented. “However, this stunt may give rise to a sense that ‘the cow is out of the barn’ and that now scientists should proceed to offer some limited forms of gene editing of human embryos (i.e., with better ethical standards). Which may give rise to more such editing in the foreseeable future.” There is a good chance that more people will be interested in making use of this technology in the future, Brehany said.
“Many parents desire to give their children ‘a leg up’ or some other kind of advantage,” he acknowledged. “With IVF well accepted and the tools that are available (pre-implantation genetic diagnosis) to catch and dispose of ‘mistakes,’ it may be feasible in the foreseeable future to deliver to some people the healthy, advantaged children they want. This will result in many assaults on human dignity and many deaths.”
Deaths, because many embryos created in IVF procedures are never implanted in a mother’s womb.
“On a normal day, IVF already separates procreation from conjugal love,” Brehany explained. “It also introduces the option, and the temptation, of eugenics—checking out embryos by sight or sophisticated analysis to learn which exhibit optimal health or traits. Those that don’t measure up are routinely discarded. Since the embryos are small, can’t ‘suffer,’ and can’t be heard, the enormity of what is done gets lost. But it is arguably worse than the Roman tradition of exposure. He [the Chinese scientist] has added a new element, a questionable form of inadequately vetted bioengineering into this whole process.”
Many observers, including scientists and ethicists, raised that concern after He’s announcement.
“We’re not even sure that it’s safe,” Fr. Nicanor Austriaco, O.P., professor of biology and theology at Providence College in Rhode Island, said in an interview. “This scientist was allowed to do experiments with children, using technology that had not yet been deemed safe. Because when you’re just editing things, when you edit particular genes, one of the big concerns right now is that we do not know how precise that gene editing is. There’s all this concern that it will edit something else, somewhere else, and it would damage the genome in some way. I know of a lot of people who are trying to figure out how to make the technology very precise, and I’m concerned that this man did experiments on children using technologies that were not deemed safe for human use. We don’t know whether or not he will have accelerated, for example, some other disease in these children, or expose them to cancer in some way. There are so many things that could have gone wrong that we have no way of knowing.”
An international summit on human genome-editing meeting this week in Hong Kong issued a statement after He’s announcement, saying that many research groups have debated the criteria under which heritable genome-editing clinical trials could be deemed permissible:
Numerous studies have provided guidance for the conduct of heritable genome-editing clinical trials. One such study, a 2017 report by the U.S. National Academies of Sciences, Engineering, and Medicine, concluded that clinical trials might be permitted after peer-reviewed preclinical research further clarifies the potential risks and benefits, only for compelling medical reasons in the absence of reasonable alternatives, and with maximum transparency and strict oversight. The report noted that such research should be approached with caution and with broad public input. It specified a regulatory framework that included ten recommended criteria and structures. A second major report, released in 2018, which was the result of an independent inquiry by the Nuffield Council on Bioethics in the U.K., also specifies “circumstances in which heritable genome editing interventions should be permitted.” Whether the clinical protocols that resulted in the births in China conformed with the guidance in these studies remains to be determined.
There was no independent confirmation of He’s claim, and it has not been published in a scientific journal, where it would be vetted by other experts, said the Associated Press, which first reported the development:
Several scientists reviewed materials that He provided to the AP and said tests so far are insufficient to say the editing worked or to rule out harm.
They also noted evidence that the editing was incomplete and that at least one twin appears to be a patchwork of cells with various changes.
The Catholic Church, long a leading voice in bioethics, has established guidelines covering various aspects of reproductive technologies and research. In an interview with Catholic News Agency last year, National Catholic Bioethics Center ethicist John DiCamillo said that editing sperm, eggs, or early embryos presents serious concerns. “Manipulating sperm and ova requires removing them from a person’s body; if conception is achieved with these cells, it is nearly always through in vitro methods. This practice of in vitro fertilization is held by the Church to be ethically unacceptable because it dissociates procreation from the integrally personal context of the conjugal act.”
In addition, for research on embryos to be ethical, therapies should be ordered to treating and benefiting “that particular embryo, not just for garnering scientific knowledge or seeing what’s going to happen,” DiCamillo said. He condemned policies that see destruction of embryonic persons as a back-up if research does not go as planned, as well as current U.S. policies that require destruction of human embryos as standard procedure.
The Church has not issued further guidance since the development of CRISPR-Cas9, however, and there is need for “much clearer guidance,” Fr. Austriaco opined. In regards to secular bioethics, he said he is not hopeful that there will be a global consensus on the ethics of genetic engineering.
“I don’t think the world has the moral fiber to try to deal with this situation,” Fr. Austriaco said. “It’s going to happen in someone’s backyard, and then it’s going to be damage control. … I’ve spent so much time traveling around the world that I can see there’s no common consensus on what the common good calls for.”
The Church needs to explain that “it is all about preserving and protecting the inherent dignity of every human being,” he said.
Said John Brehany: “I think it would also be good if an international code or statement of principles could be promulgated to set a standard that all scientists should follow and that could be used to discourage people from violating a minimal set of ethical standards.”
Also weighing in was Catherine Glenn Foster, President & CEO of Americans United for Life, who condemned He’s approach as human experimentation.
“We didn’t condone human experimentation in the last century when totalitarian regimes engaged it, and the international community does not condone it today,” Foster said in a statement. “At a time when we’re increasingly uneasy about medical experimentation on animal subjects, it’s unconscionable that we would abandon our ethical principles in a regressive embrace of experimentation on human subjects. While CRISPR itself is still largely unregulated as a specific technique, the basic tenets of medicine and research as they relate to the rights of human subjects clearly indicate that what He Jiankui and others are attempting with this sort of research is unethical and simply dangerous. This is true not only for the subjects of such human experimentation but also for every human person who will subsequently be at risk of acquiring heritable genetic modifications whose implications are totally unpredictable.”
Another problem with CRISPR-Cas9 is that it creates a permanent change in the genetic line. Rebecca Taylor, writing at the website LifeNews in 2015, said, “I am a parent. I have the legal and moral authority to authorize invasive medical procedures for my children. Yet germ-line genetic engineering would not just be for my child, but for my grandchildren, great-grandchildren, great-great grandchildren and so on. Do I have the legal and moral authority to intentionally modify the genes of my great-great-great grandchild?”
“We hope that the dialogue at our summit further advances the world’s understanding of the issues surrounding human genome editing,” said the statement from the Hong Kong summit on human genome editing. “Our goal is to help ensure that human genome editing research be pursued responsibly, for the benefit of all society.”
He Jiankui addressed the summit today, defending his work and saying his research has been submitted to a scientific journal for review, according to CNN. He did not name the publication but apologized for the result leaking “unexpectedly.” He also said there is another “potential” pregnancy of a CRISPR-treated baby.