Gene Editing and Human Identity: Promising Advances and Ethical Challenges

Innovations in gene editing, and particularly CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defense system that forms the basis for CRISPR-Cas9 genome editing technology ), have the potential to treat a range of genetic conditions, but also to fundamentally alter the heritable germline. As scientists and society  continue to grapple  with the legal, ethical, and cultural dimensions of this rapidly shifting technology, DoSER hosted a symposium at the 2018 AAAS Annual Meeting in February  on “Gene Editing and Human Identity: Promising Advances and Ethical Challenges.” 

Four experts expressed interest in the positive prospects and also concerns about the safety of these technologies, their potential for commodification and/or marginalization of persons, and the ways in which social inequalities could be reinforced by limited access to them. 

Rice University professor of bioengineering Gang Bao opened the discussion with an introduction to CRISPR/Cas9 technology and the cutting edge work his lab conducts in pursuit of advances in the treatment of sickle cell disease using a gene correction strategy. His work has also shown that the sickle cell gene mutation in the beta-globin locus in hematopoietic stem and progenitor cells from SCD patients can be corrected with high efficiency, resulting in a significantly decreased amount of sickle cells. 

Bao said off-target effects remain a major concern as do other safety and ethical implications of gene editing. “If we are not careful enough in treating sickle cell disease, we could induce another disease,” he said.

“We should work very hard on developing gene editing to help people who are sick and we should not touch the human germline,” said Marcy Darnovsky, executive director of the Center for Genetics and Society in Berkeley, California.

Outlining issues of concern about germline editing, she said known and unknown risks in resulting children and future generations, such as off-target effects, unintended changes at targeted sites, mosaic embryos, developmental dynamics, and gene-gene interactions should be considered. She also expressed concern about societal and policy issues, such as difficulty in limiting germline editing to medical or therapeutic uses, normalizing enhancement uses, worsening discrimination and inequality, and who makes decisions about these things. 

”Darnovsky concluded that  germline modification would offer a social rather than a medical benefit should be evaluated using a risk benefit analysis that takes into account the small number of people who would benefit against the risks society would incur. She noted that parents at risk for having children with sing-gene disorders already have alternatives to germline editing via third-party gametes and/or preimplantation genetic diagnosis.  

“Whether we’re for or against germline modification, we don’t want to encourage a kind of genetic determinism that oversimplifies what the role of genes is in who we are as humans,” she said.

(L-R) panelists Marcy Darnovsky, Gang Bao, Robert O'Malley, Christopher Scott, Nicanor Austriaco | Credit: AAAS/ Elizabeth Crocker

The Vatican’s most recent document on bioethics, Instruction Dignitas Personae, published in 2008,  states that “the dignity of a person must be recognized in every human being from conception to natural death.” This is relevant for evaluating gene editing uses, said Providence College professor of biology and bioethics Father Nicanor Austriaco. Austriaco compared faith-based and secular approaches to evaluating the ethical questions, centering his talk on a discussion of human dignity. 

While many faith-based traditions claim that persons have both intrinsic and extrinsic value, secular conceptions of human dignity are based in extrinsic value, he said. For example, Grundgesetz or “basic law” of Germany, adopted in response to the Holocaust, states that  “The dignity of man is inviolable. To respect and protect them  is a duty of all state authority.” The difference, he said, is that intrinsic value refers to the inherent worth of the person as priceless and extrinsic value refers to their worth to society. 

Having grown up in a Buddhist culture, Austriaco noted that not all religions adopt this framework. The account of reincarnation in Buddhism doesn’t because, for example, if a mosquito could be your great-great-grandmother the intrinsic worth of a person and a mosquito are much closer. 

For Christians, intrinsic dignity is based on the theological claim that human persons are made in the image of God, he said. Therefore, Christian bioethics says that all human actions need to protect, preserve, and advance both intrinsic and extrinsic human dignity. Regarding human genome editing, the question then is: will CRISPR protect and advance the dignity of the human person? “For some, human dignity means no more than respect for personal autonomy. So, personal autonomy should be the capstone for the entire ethical framework in which we are supposed to think about these kinds of issues,” said Austriaco.

He questioned why autonomy should be worthy of respect. “The capacity to think and to choose are evolutionary adaptations that are not intrinsically more valuable than other adaptations,” he said, such as having talons or wings. “The secular approach tends to focus primarily on an extrinsic dignity, which you can gain or lose, while a Christian approach, in addition to that, claims that there is something incredibly priceless that cannot be removed from you or given to you by anyone around you,” he said. 

Christopher Scott, Dalton Tomlin Chair of Medical Ethics and Health Policy, at Baylor College of Medicine served as a discussant and responded to each speaker.

First, he rhetorically asked Bao what levels of safety and risk he would be willing to tolerate in considering clinical trials if a member of his own family had sickle cell disease.

Next, he agreed with much of what Darnovsky outlined, especially regarding the potential for social inequalities to be worsened by limited access to gene editing technologies, but said he doesn’t believe in prohibition of germline editing. “I don’t think we should stop science that would tell you if that science is safe,” said Scott. Regarding the boundary between therapy and enhancement, he added, “We struggle with these sorts of boundary issues all the time as a society and we do a pretty good job collectively of understanding where that stick in the sand is.” 

“We need greater levels of public engagement so that we can take discussions beyond echo chambers of experts and scientists and into communities so that we understand where communities and cultures want to go with this and what we should do next,” said Scott, agreeing with a National Academies report recommendation.

Finally, he noted that discussions of human dignity arise in his work as a clinical bioethicist, saying, “I’ve struggled at times with separating notions of dignity and respect in literature. He landed on “aspirational dignity” or the ability to realize oneself fully as a concept that makes sense in light of this work in which patients experience a loss of such dignity. What complicates this is making decisions today that influence future generations, he said, concluding that “we need to unpack this in a systematic, rigorous way and I think the way to do that is to actually talk to the public.”