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International Summit on Human Gene Editing by Rhiannon Morris and Chris Wallis

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by Rhiannon Morris and Chris Wallis

Last week scientists and science enthusiasts alike tuned in to listen to what is arguably one of the most important discussions in medical science today; human gene editing. The three day International Summit on Human Gene Editing was attended by some of the major players in academic and clinical genetics including David Baltimore who chaired the event, George Church form Harvard Medical School, Eric Lander head of the Broad Institute at MIT, Jennifer A. Doudna (co-discoverer of the CRISPR/Cas9 gene editing tool), Feng Zhang who reported the first application of CRISPR for gene editing in human cells, and many other scientists, lawyers and ethicists representing 4 major scientific societies (National Academy of Sciences, National Academy of Medicine, Chinese Academy of Sciences and The Royal Society) charged with discussing the future and implications of human gene editing.

Convening this summit has sparked huge interest and a necessary debate across the globe over the prospect of human gene editing and where these gene-editing technologies may take us in the future. The main drive for the summit came with the rise of the newest gene editing technology, CRISPR/Cas9, which is arguably one of the most significant gene editing tools we currently have available, and who’s unprecedented and rapid adoption by researchers has outpaced the ability of ethicists and policy makers to regulate its use in a laboratory and clinical setting. Other gene editing tools include TALENs and ZFNs, which have similar gene editing capacities but have been developed more slowly. The group discussed the many applications of these technologies, particularly focusing on the uses in editing both human somatic cells and the human germline, which is recognizably where ethics and standards in science come in to play in this discussion. Currently as it stands, the rules regarding gene editing tools are differing across the globe, with each nation having a different set of rules governing the use of genomic tools to edit human genes, an issue that was addressed in a recent Nature article.

Why hold the summit?

With the current rapid advances in genomic sciences (sequencing, gene editing tools etc.) it was obvious that at some stage we would need to address and discuss the questions looming on everybody’s mind as to where we go from here. When researchers in China made the first ever attempt to edit genes in human embryos, the urgency of this discussion grew even more and calling together the major scientists in the field to take place in a global summit was obviously the next logical step.

Over the course of the three-day summit there were a variety of opinions shared on this issue, coming from numerous backgrounds in science and ethics. In order to bring these opinions together in a meaningful way there were three main questions posed at the proceeding of the summit as follows:

  • When, if ever will we want to use gene editing to change human inheritance?
  • When will it be safe?
  • When will it be therapeutically justified and when will we be prepared to say that we are justified to use genome editing for enhancement purposes?

These three questions were the main focus of the summit over the three days and were kept in consideration during the proceeding discussions. Understandably one of the main topics of discussion was the
ethics and implications of editing human genes, particularly in germline cells or embryos. With this in mind, the summit aimed to achieve the following:

Acknowledge that the development and upsurge in the use of CRISPR/Cas9 technology has brought realistic ethical concerns about gene editing out of the realm of theory or science fiction. This gene editing technology makes these concerns real, and leads us to a discussion on how we ought to be regulating the use of these tools globally.

Address the current state of the art of genome editing technology. Discuss potential uses, both current and future, the kinds of things possible with this technology and possible alternatives if there are any.

Assess the current risks of gene editing technology in terms of off target effects. What need to be improved and what level of risk is acceptable before we consider proceeding with permanent human germ line modification? It is worth mentioning here that during the summit it was announced that researchers at the Broad have overcome a huge gene editing hurdle with CRISPR and have reduced the editing errors.

Create an ongoing international forum to discuss potential clinical uses of gene editing; help inform decisions by national policymakers and others; formulate recommendations and guidelines; and promote coordination among nations.

Conclusions of the summit

At the end of the three day summit, the organizing committee met to formally address the topics covered and put out a formal statement summarizing the outcomes of the global discussion. Given that, although influential, the scientific societies and organizations represented at the summit have zero legislative power or authority, a number of solid conclusions were agreed upon:

Firstly, the importance of continued basic and pre-clinical research was underlined and emphasized. The committee gave three reasons for this, firstly the technology its self needs to be studied further and advanced, especially in human cells. Second, the potential benefits and risks will only be properly elucidated with more research. Lastly, our basic knowledge of human embryology is limited and needs to be elucidated further before we can use gene editing on human embryos and predict the outcomes. With this in mind, researchers that do use editing to modify early human embryos or germline cells should not allow these to be used to establish a pregnancy.

Secondly, the clinical use of these technologies in somatic cells was discussed. “Examples that have been proposed include editing genes for sickle-cell anemia in blood cells or for improving the ability of immune cells to target cancer.” As changes to the somatic cell genome are not passed on from one generation to the next, the clinical affects can be assessed in clinical trials as per other conventional therapies. One risk that needs to be assessed in this instance is the possibility of off-target effects and inaccurate editing.

Third on the agenda was the clinical uses of gene editing in germline cells, which is one of the biggest ongoing debates surrounding these technologies. Editing human germline or embryonic cells would allow us to edit those cells that are ultimately passed on to subsequent generations. This capability would allow us to do things such as prevent genetic diseases or potentially enhance human capabilities. Obviously human germline editing poses a plethora of important issues, which include: Risks of off-target editing and the possibility of mosaicism. Difficulty of predicting harmful effects due to environmental interactions with genes and other genetic variants. Obligation to consider future generations, which will ultimately carry these genetic alterations. And the idea that once in the human population, it will be very difficult to remove these changes made- this could lead to exacerbation of social inequities. Lastly, the moral and ethical considerations in altering human evolution.

At present we cannot begin altering human germline or embyonic cells as we need to lay down the foundations in our policy before we move further in our science. For now the safety issues have not been explored enough and therefore most countries have a ban on germline modification. Overall, the group said it would be “irresponsible to proceed” until the risks could be better assessed and until there was “broad societal consensus about the appropriateness” of any proposed change. The group also held open the possibility for such work to proceed in the future by saying that as knowledge advances, the issue of making permanent changes to the human genome “should be revisited on a regular basis.”

Lastly, there was discussion as to the obvious need for an ongoing forum. Although each nation has the authority to regulate these activities under their own jurisdiction, we need to recognize that the human genome is something that is shared across all nations and life on this planet. Therefore the international community should try to establish a consensus and attempt to harmonies regulations in order to discourage unacceptable activities. Said forum should be inclusive across all nations and furthermore should include a broad range of perspectives.

Overall the conclusion reached by everybody was the same. Yes, gene editing will likely be used in the future and it will be a HUGE advance in medical science for us. But before we begin to use these technologies we need to put in place policies and study the technologies in more depth to understand the consequences of use in human gene editing. Hopefully in the future we will see the use of these technologies for the betterment of humankind.

The full agenda of the summit with a list of all the attendees can be found here, and an interview with Prof. Charpentier and Prof. Doudna about CRISPR/Cas9 can be found on PLOS DNA Science Blog here. You can follow the authors on twitter @RheeStrikesBack, @wallischris10 our on their blog.

 

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