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Apr2019

Past disregard for human rights in studies such as the Tuskegee experiment, has left some individuals (rightly so) with an inherit distrust of the clinical research process. Over time, in response to civil rights violations, increased regulatory oversight of the clinical research environment (e.g., the Common Rule, etc.) was put into effect to protect those who participate in research, particularly those who might be more vulnerable.

Yet, regardless of the level of oversight or scrutiny a clinical study has, subject protections are only adequate when an ethical investigator is at the helm. A session at the 2018 Advancing Ethical Research Conference titled “Vulnerability Explored: Concepts and Applications,” ended with a quote by Henry Beecher regarding his thoughts on subject protections: “…a more reliable safeguard is provided by the presence of an intelligent, informed, conscientious, compassionate, responsible investigator.” Guidance and regulations are necessary to define experimental standards and expectations and clearly state how legal norms might be enforced, but sometimes the regulations don’t keep up with developments in the modern research enterprise.

In the latest example of regulations not keeping up with technology, He Jiankui claims that he helped create the world’s first gene-edited babies using CRISPR-Cas9 technology. He claims the twin girls in the study, Lulu and Nana, were born with their CCR5 gene edited so that they would be resistant to HIV infection. Soon after an AP News article was released announcing the births, He published videos on YouTube, where he announced the twin girls were “as healthy as any other babies.” He also presented what he believes should be the five ethical principles for reproductive technologies (including gene editing) and used the term “gene surgery” instead of “gene editing”.

While there have been numerous examples of fraudulent studies in Asia and internationally (e.g., Hwang Woo-suk in the field of stem-cell research), the consensus is that He’s claims are likely legitimate. Technically, CRISPR is pretty easy to do—in fact, a new biotech company is currently developing an at-home CRISPR diagnostic kit. It is this very ease of access to and practice of CRISPER that is often concerning for ethicists.

And He’s study is, indeed, concerning for many scientists. A similar experiment that caused the death of a young man named Jesse Gelsinger in 1999 set the field of gene therapy back light years. And in this case, we have no idea whether or not the twins, with their mutated CCR5 gene, may now have a higher risk for infections from other viruses, such as Zika or West Nile, which could lead to significant health related problems down the road. He’s arrogant conduct could increase the arguments of those who have called for a freeze on the gene editing of human embryos, bringing even basic research studies to a halt.

The second Human Genome Editing Summit organizing committee issued a statement the last week of November 2018 criticizing He’s study and calling for a suspension of any further germline editing clinical trials. David Baltimore, a Nobel laureate in Physiology or Medicine, stated:

The scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time… Even if the modifications are verified, the procedure was irresponsible and failed to conform with international norms. Its flaws include an inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures.

Similarly, Francis Collins, director of the National Institutes of Health, called for “a binding international consensus on setting limits for this kind of research,” saying that “without such limits, the world will face the serious risk of a deluge of similarly ill-considered and unethical projects. Should such epic scientific misadventures proceed, a technology with enormous promise for prevention and treatment of disease will be overshadowed by justifiable public outrage, fear, and disgust.”

In brief, regulations and guidelines are needed sooner rather than later and the “Year in Review” session, discussing legal and regulatory changes that occurred this past year, highlighted the lack of oversight on this topic.  Unfortunately, a regulatory void, accompanied by a lack of guidance, is bound to lead to clinical tragedies followed by public anger and further distrust of the scientific community.

Gretchen Parker, PhD, RAC, CIP, serves as co-chair for Pearl IRB and provides regulatory and clinical research support services for clients. Throughout her career, she has been deeply involved in regulatory affairs, clinical research, and medical writing for the pharmaceutical and medical device industries.  She led the AAHRPP accreditation efforts at Pearl IRB and has assisted FDA inspectors on site. She is currently leading the efforts to update Pearl IRB institutional policies and procedures to comply with the revised Common Rule.

Dr. Parker began her career as a Regulatory and Compliance Analyst at a consulting firm, where she worked with clients, ranging from biotech start-ups to Fortune 500 companies, to plan and implement regulatory strategies, submissions, and research protocols.  Her duties engaged her with several US governmental agencies, including FDA, USDA and EPA.

Dr. Parker received a PhD in Molecular Endocrinology and Biochemistry from Purdue University, and completed her Post-Doctoral Fellowship in Biochemistry and Molecular Biology at the Indiana University School of Medicine Center for Diabetes Research.  She has authored and published dozens of scientific articles in major peer-reviewed journals, holds a patent for a diagnostic assay, and is a member of PRIM&R. She is Regulatory Affairs Certified (RAC) and a Certified IRB Professional (CIP).

Members of PRIM&R’s Blog Squad and other guest contributors are valued members of our community willing to share their insights. The views expressed in their posts do not necessarily reflect those of PRIM&R or its employees.


Save the date for PRIM&R's 2019 Advancing Ethical Research Conference (and Social, Behavioral, and Educational Research Conference) taking place this year in Boston, MA, November 17-20.

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