Promise and Peril: Gene Therapy Research and Globalization

Promise and Peril: Gene Therapy Research and Globalization

by Guest Blogger,
Tyler Kokjohn, Ph.D.


Attachment-1Two proposals to begin gene therapy clinical trials recently received approvals from the Recombinant DNA Advisory Committee (RAC) of the U. S. National Institutes of Health (1, 2).  These decisions will allow investigators to continue through a complex review process to ensure the research will be conducted in a safe, ethical and scientifically sound manner.  Before work begins, the investigators must still obtain formal approvals from several oversight bodies, including in these particular cases, the U. S. Food and Drug Administration.

The U. S. National Academies of Sciences, Engineering and Medicine report on human gene editing will not be completed until the end of this year (3), but gene editing using CRISPR-Cas9 technology continues its blistering pace. The RAC approval means the first steps to determine if cells modified using this method are safe in human subjects could begin in a matter of months (1).  Although no additional projects using the CRISPR-Cas9 method have been submitted for review, it seems a safe bet that this trickle is quickly going to turn into a torrent.

Another proposal to treat ornithine transcarbamylase deficiency using a virus to introduce a good copy of the gene was approved unanimously by the RAC, but with a list of attached conditions (2).  Gene therapy trials illustrate both the promise and perils of scientific research.  Although the ornithine transcarbamylase therapy will not break new technical ground, the history of prior work in this area is particularly troubled.  An earlier effort to correct this genetic disorder using a different delivery system led to the death of Jesse Gelsinger, a healthy 18-year-old volunteer (4).  Jesse had the genetic disorder the therapy was intended to correct, but a combined low-protein diet and drug regimen had kept it under good control.  His tragic death exposed several significant problems (4, 5) and a determination to avoid repeating them prompted the RAC to add new requirements to the proposed new trial work plan (2).

Gene therapy clinical trials pose multiple risks.  Consequently, the approval process is a complicated multi-agency affair intended to safeguard patient wellbeing as well as ensure all work will be conducted in a safe and environmentally protective manner.  RAC evaluation of research employing novel methods or involve challenging ethical issues is required, but this group serves only in an advisory capacity.  A Nature editorial (2) revealed that the researchers proposing the ornithine transcarbamylase gene therapy trial disagreed with most of the conditions set forth by the RAC maintaining some would increase study costs without adding any benefits.  Expressing concerns that their work is being held to standards that are not applied to other studies and the urgency of the situation, the Chief Scientific Officer of the sponsoring company indicated they would conduct these trials overseas if necessary.

Threats to relocate clinical trial work must be taken seriously because scientific research has become globalized.  This new reality complicates the creation of guidelines to govern activities with emerging technologies such as CRISPR-Cas9 gene editing (6).  Economic considerations have encouraged corporations to shift clinical trials to less expensive locations (7).  The complex regulations and monitoring demands in countries like the United States which allegedly increase the costs and time to develop products may provide additional motivations to outsource trials.  Although companies seeking to ultimately market products in the U. S. have incentives to maintain high standards, moving studies offshore raises concerns about scientific transparency as well as the adequacy of safety and subject protections permissible at foreign sites (7).

Apparently frustrated by the pace of genetic therapy development in the U. S., one biotech company executive recently revealed she had received treatments to combat aging and muscle degeneration in a foreign country (8).  Perhaps if groups overseeing ornithine transcarbamylase gene therapy trials make approvals contingent on conditions the company has declared unacceptable, similar exasperation will induce them to move the work overseas.  And maybe other research programs will follow if they deem the U.S. regulatory demands too burdensome and costly.

After some serious setbacks, gene therapy research seems to be entering a phase of renewed optimism (9).  However, the tools and methods are far from perfected and the long-term impacts of the manipulations on human subjects are unknown.  The situation demands a patient and systematic approach toward the development and use of gene therapy.  Unfortunately, such caution may not be compatible with the desires and needs of private corporations.  In principle, shifting clinical trials to new locations might enable safe new gene therapy products to be delivered quickly and at reduced costs to consumers.  Perhaps the increasing globalization of biomedical research which enables the outsourcing of gene therapy trials overseas will deliver on that promise.


(1)   S. Reardon.  2016.  First CRISPR Clinical Trial Gets Green Light From US Panel.  Nature, 22 June 2016.

(2)   The Editorial Board.  Gene Therapy Trials Must Proceed with Caution. Nature, 28 June 2016.

(3)   U. S. National Academies of Sciences, Engineering and Medicine,  Human Gene Editing: Scientific, Medical and Ethical Considerations.

(4)   S. G. Stolberg.  1999.  The Biotech Death of Jesse Gelsinger.  The New York Times, 28 November 1999.

(5)   J. Couzin and J. Kaiser.  2005.  As Gelsinger Case Ends, Gene Therapy Suffers Another Blow. Science, 18 February 2005  307(5712):1028

(6)   D. Baltimore et al., 2015 A prudent path forward for genomic engineering and germline gene modification. Science, 18 March 2015, 348(6230):36-38  (

(7)   S. W. Glickman et al. 2009.  Ethical and Scientific Implications of the Globalization of Clinical Research.  The New England Journal of Medicine 360:816-823.

(8)   A. Regalado.  2015.  A Tale of Do-It-Yourself Gene Therapy. An American biotech CEO claims she is the first to undergo gene therapy to reverse aging. Judge for yourself.  MIT Technology Review, 14 October 2015.

(9)   L. Naldini. 2015.  Gene Therapy Returns to Center Stage.  Nature, 14 October 2015, 526:351-360.




One thought on “Promise and Peril: Gene Therapy Research and Globalization

  1. Pingback: Promise and Peril: Gene Therapy Research and Globalization — JayVay | Talmidimblogging

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s