Are we ready for the new era in genome editing?

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Biotechnology is advancing faster than ever and it is proving difficult for antiquated funding, patent, regulatory and communication systems to keep up.

Emerging drug therapies, improved medical devices, novel links to cancer and exciting laboratory techniques from industry and academia are published regularly across a broadening range of academic journals. Just last week Chinese scientists published research on their attempts to edit the genome of a non-viable embryo.

Genome editing involves the editing of the wealth of genetic material in our cells. One technique which is generating a lot of excitement among scientists is the application of CRISPR-Cas9 to genome editing in both somatic cells, the cells that make up our body, and germ cells, or egg and sperm cells. Unlike somatic cell engineering, which could be used, for example, to cure genetic diseases in an individual, germ line engineering could see genetic diseases such as Alzheimer’s or cancers eradicated across generations. Proponents of germ line engineering argue this potential, while critics warn of a slippery-slope including “designer babies”, children of the affluent selected on the basis of aesthetics or intelligence or physical ability, representing the darker and increasingly possible side of germ line engineering.

The highly effective and simple to use clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system was first discovered in a bacterium, Streptococcus pyogenes, as part of the cellular adaptive immune system. In short, CRISPR RNA is used by the cell to prevent infection by identifying foreign DNA that is later removed by the Cas9 nuclease, a native form of genome engineering if you will.

New studies

In March, two separate commentaries on germ line engineering appeared in Nature and Science. Both sought to bring the discussion on the use of genome editing in humans to light, particularly with regards to germ line engineering, while calling for different approaches on continuing research in this area.

Edward Lanphier and his colleagues, writing in Nature, argue for a temporary moratorium on research into germ line engineering. They cite the tenuous benefits of the technique, the restrictions by many European countries on inheritable genetic modification and possible public confusion as reasons against continuing research.

David Baltimore and his colleagues, writing in Science, more astutely recommend a conference on the scale of the Asilomar recombinant DNA conference held in 1975, the conventions of which are still impacting modern biology, including those on enhanced safety factors and recommendations on types of experiments. This proposed conference should pull together an international range of legal experts, ethicists, scientists (from graduate students to industry), policy makers and the lay public to discuss the challenges of germ line engineering. They also strongly discourage attempts at clinical applications of human germ line genome engineering and advocate for the creation of fora for scientists and bioethicists to come together and discuss the ethical, scientific and legal challenges of genome editing.

Although Edward Lanphier and his colleagues bring up valid concerns about the uncertainties and unknown dangers of germ line engineering, I would argue that this is reason for more research, not less, with more open dialogue as advances are made.

How close are we to editing genome in the germ line? It turns out, as simple and efficient as CRISPR/Cas9 is reported to be, that we still have some major technological hurdles to overcome. Last week’s paper by Chinese scientists, published in Protein and Cell, discusses their work on editing the genome of a non-viable human embryo. The research team, led by Junjiu Huang of Sun Yat-sen University, reported they were able to successfully edit a gene in a small fraction of their pool of embryos, but they came up against great technical and biological challenges, including significant off-target effects. They cautioned that further research into off-target effects and the cell’s own DNA repair mechanisms is sorely needed before we can move this technology to the clinic. The authors further emphasised the necessity for more analysis of the molecular mechanisms of CRISPR/Cas9 gene editing in humans. It is only a matter of time before their call is answered by other research groups around the world.

From the lab to the clinic

We have entered an era where it is possible, in a lab, to edit the human germ line, but there remain great challenges before this technology can be applied to the clinic. Germ line engineering holds great potential, but also great ethical and biological risk. The fact is, we simply do not know enough about biology, human or otherwise, to make predictions on the outcomes of multiple-gene editing in distant generations. By eradicating one disease, could we be selecting for another? Is germ line engineering taking evolution into our own hands with little regard for the consequences?

The global financial crisis that started in 2007 permanently altered the landscape of scientific funding and reengaged the public in discussions on funding priorities. Care is clearly needed for this research to move forward, but it would be hugely detrimental if leading research nations cut funding to genome editing techniques because of fear or ignorance. We must work to keep science open and transparent, but we must also continue with cutting edge research into fundamental processes that will give us a better understanding of inheritance, the genetic basis for disease and the implications of genome editing on organisms and communities. A new era in biology is here. The question is whether we are ready to embrace it.

*Paul Bergen [2013] is doing a PhD in Pathology. Picture credit: http://www.freedigitalphotos.net and ponsulak.

 

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