Gene Drive Research – Exploring the Undiscovered Country

Gene Drive Research – Exploring the Undiscovered Country

by Guest Blogger,
Tyler Kokjohn, Ph.D.

HamletScientists writing research proposals devote a great deal of effort to divining the future.  Outlining for peer reviewers the actions they intend to follow, the investigators also specify how they will avoid foreseeable pitfalls and the measures they will use to ensure their work will be conducted safely and ethically.  Sometimes the work actually proceeds as originally planned.

A recent report from the U. S. National Academies of Sciences, Engineering and Medicine on gene drive research notes their possible environmental impacts and risks are not understood (1).  While suggesting the potential benefits warrant continuing gene drive research and field trials, the authors noted their unique dangers and called for more work before any releases are considered.  Testing gene drives for safety and efficacy will be an involved process and although the National Academy endorsed the open sharing of best practices it did not delve into specific requirements for conducting field experiments.  Scientists, their institutions and funding entities will literally make up the rules as they go along.

There is an instructive model for the challenges associated with conducting research on complex biological systems – the drug development work performed by the pharmaceutical industry (2).  Experience reveals that solidly rationalized and precisely targeted research efforts sometimes fail to produce useable products.  Even more interesting is the fact that pure luck can be factor in the drug discovery process.  Researchers attempting to develop a treatment for angina pectoris, chest pain due to coronary heart disease, found the trial results disappointing.  However, trial volunteers reported an unusual side effect – a restoration of the erectile response.  Today that failed angina treatment is famous as the blockbuster treatment for erectile dysfunction, Viagra (2).

The drug development process is long and complicated, but the research is still not complete when a product reaches the market.  Once large numbers of persons begin using the drug, rare side effects, ‘adverse events’ in the scientific jargon, become detectable.  The harsh reality is that because physiology is complex and dynamic, even thoroughly tested drugs may carry some unknown and unpredictable risks which only become apparent over time (2).  The final testing phases are actually performed on the public.

Gene drives will empower humans to change highly complex and dynamic ecosystems.  Whether these perturbations will induce emergent adverse consequences is unpredictable.  However, the first laboratory experiments with them have certainly been illuminating.  Gene drives introduced into fruit flies were not passed along predictably even within the bodies of single individuals (3).  And a gene drive designed to prevent one mosquito species from transmitting the most dangerous type of malaria to humans worked extremely well in males but slowed down in females (3, 4).  The reasons for this female-specific transmission failure are under investigation.

Reasonable research hypotheses sometimes fail, the full ramifications of experiments on complex systems are not always predictable and well-intentioned investigators may make errors.  Both the National Academy and key opinion leaders are encouraging the scientific community to adopt the open sharing of gene drive research best practices (1, 5).  Because gene drive work involves indeterminate environmental risks with such potentially far-reaching consequences to all members of society, the general public must be represented in the decision-making processes involving their research and development.  This technology is about to take us into the undiscovered country.

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(1)     H. Ledford. 2016.  Fast-Spreading Genetic Mutations Pose Ecological Risk.  Nature, 8 June 2016. http://www.nature.com/news/fast-spreading-genetic-mutations-pose-ecological-risk-1.20053

(2)            E. Jay.  2010. Viagra and Other Drugs Discovered by Accident.  BBC News 20 January 2010. http://news.bbc.co.uk/2/hi/health/8466118.stm

(3)            Tina Hesman Saey.  2015.  Mosquitoes Engineered to Zap Ability to Carry Malaria. Science News, 23 November 2015.  https://www.sciencenews.org/article/mosquitoes-engineered-zap-ability-carry-malaria

(4)            Proceedings of the National Academy of Sciences of the United States of America.   Science Sessions Podcasts – Anthony James   http://www.pnas.org/site/podcasts/podcasts.xhtml#top

(5)            K. Esvelt.  2016.  Gene Editing Can Drive Science to Openness.  Nature, 8 June 2016.  http://www.nature.com/news/gene-editing-can-drive-science-to-openness-1.20043

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