By Peter Young

 

The CRISPR/Cas9 gene-editing tool, hailed by scientists as the next step towards eradicating cancer, other genetic diseases, and solving world hunger, has come under intense scrutiny over ethical issues related to the fears of designer babies, permanent germline mutations, and the potential use of viable human embryos within research.

 

CRISPR/Cas9 technology modifies a naturally occurring mechanism found in the immune systems of some bacteria, used to ward off viruses. The mnemonic CRISPR stands for “clustered regularly interspaced short palindromic repeats” and describes what scientists originally observed in bacterial DNA. These short sections of information are stored in the bacterial DNA and function as a defensive library. Each short DNA message corresponds to the DNA of a virus that once tried to invade the cell. If that virus invades again, the bacterium can recognize this, refer to its library, create a protein which recognizes the intruder DNA, and cut it in key places to render the virus harmless. Put simply, the bacterium took notes on who tried to invade in the past, stored the notes in a file, and if a similar virus ever tries to break in, they have the information needed to take out the threat.

 

What if the threat was not a virus, but instead, a genetic disorder? Or a gene that makes a staple crop vulnerable to an insect species? In the same way that the bacterium can edit to disrupt viral DNA, scientists can remodel this molecular tool to target and disrupt disease-causing genes found in plants, animals, and humans. This is not completely new to science, which has been in the business of gene mutation for many decades. What makes CRISPR revolutionary for some and scary for others, is the speed and relatively low cost of the technique, making it broadly accessible and feasible for researchers. Also important is the precision and accuracy with which scientists could impose these genetic changes, some of which could become permanent in later generations.

 

Jennifer Doudna, a co-inventor of the technology along with George Church and Feng Zhang, expressed to the New York Times that she “want[s] to see this technology help people,” but understands the profound risk it poses to human evolution.

 

Many feared this path towards profound risk after learning that scientists in Guangzhou, China set out to learn more about CRISPR earlier this year. A group, led by Huang Junjiu, conducted an experiment in which they used CRISPR to edit non-viable, triploid human embryos and published their results in April. Even if they had success with gene-editing, it would not be possible for those embryos to result in a pregnancy. Their paper, rejected by Nature and Science magazines, investigated a blood disorder, beta-thalassemia, by cutting the disease-causing gene in key places to disrupt it. They failed to produce the correct sequence in 85 attempts, citing that the effects of CRISPR initiated many off-target cuts, damaging the embryonic DNA in severe ways. The Chinese scientists argued their research followed Chinese regulations, which allow scientists to pursue research on 14-day or younger embryos.

 

The need for thoughtful and appropriate national and international policies has brought together different groups over the past year to discuss implications of this powerful and potentially frightening tool. The Hinxton Group, an international consortium of scientists, ethicists, policy-makers, and others interested in the ethical and policy challenges behind stem cell research, met this September in Manchester and reached consensus to produce their Statement on Genome Editing Technologies and Human Germline Genetic Modification. In a related part of the conversation, Debra Mathews, of the Berman Institute, along with members of the Hinxton Group steering committee sum up the key issues in the human genome editing debate in a recently published Nature Commentary, CRISPR: A Path through the Thicket.

 

The gene-editing debate has also prompted the National Academy of Sciences, Engineering, and Medicine to host an International Summit on Human Gene-Editing in Washington to address some of these widely held concerns – part of a broader human gene-editing initiative that will include a longer term consensus study conducted by a multidisciplinary group of experts including Berman Institute Deputy Director for Policy and Administration, Jeffrey Kahn. The summit, co-hosted by the Chinese Academy of Sciences and the U.K.’s Royal Society, brought together diverse experts from around the globe. At the end of the summit, organizers unveiled their four-point consensus recommendations stating that (1) basic and preclinical research should continue with the correct ethical oversight; (2) clinical research on somatic cells–cells not passed on to the next generation–may proceed after proposed trials pass rigorous evaluation of their risks and benefits; (3) clinical research on germline cells–cells passed on to the next generation–would be irresponsible before safety and efficacy issues have been resolved; and finally (4) the statement calls on the summit organizers to support the creation of an ongoing forum where the international community could strive to establish norms for gene-editing and harmonize regulations while discouraging unacceptable activities. The National Academies quickly agreed to support this endeavor.

 

While the future of CRISPR and gene-editing remains uncertain, the profusion of a vibrant ethical discussion early on points towards the possibility of finding agreeable answers, satisfying all parties at the table, and elicits hope that we, as a species, are finally learning from our research mistakes of the last century.

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One Response to “CRISPR & Gene-Editing: The Basics”

  1. […] What if the threat was not a virus, but instead, a genetic disorder? Or a gene that makes a staple crop vulnerable to an insect species? In the same way that the bacterium can edit to disrupt viral DNA, scientists can remodel this molecular tool to target and disrupt disease-causing genes found in plants, animals, and humans. [30] […]

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