Looking for a curator of the human species

Illustration by Frank Neufeld

IT’S PRONOUNCED CRISPER. Clustered regularly interspaced short palindromic repeats (abbreviated as CRISPR; pronounced a ‘crisper’) is a new genome-editing tool that allows scientists to edit genomes with unprecedented precision, efficiency and flexibility. To the minds of many researchers, the technology has the potential to eliminate genetic disease by making changes to DNA that will pass down the generations.

The Curator

Wikipedia defines a curator as a manager or overseer, a keeper who normally works in a cultural institution to preserve a certain heritage. Her tasks include the organization of a collection and the interpretation of the collected materials. A curator deals with a past that, for some reason, society considers important to preserve for future generations. Ideally, this preserved past might be reactivated in the future to reintegrate itself in the circuit of human activities. Whereas most curation takes place in the realm of culture, recently, curation of digital data objects and biocuration (eg., biobanking, barcoding) have expanded the list of curatorial professions. This is about to grow with the inclusion of a curator of Homo sapiens, a profession to be created with the goal of preserving the natural history of the human genome. The reason is we are entering a new phase of technological editing of the human germline genome. This means, very soon, it will possible to create a different branch of humans.

HILL

HILL

Curation and Culture

The need for curations derives from the fact humans have always archived information deemed important for the survival of subsequent generations using collections of artifacts, objects, rituals, language, books, music and paintings. Many of these objects would enter the circuit of education and social practices to end up affecting the behaviour of groups and individuals. Culture depends on a process of externalization that frees up memory in the brain and helps to extend the space of attentionality and the potential size of human groups. The Internet and social networks, like Facebook, with more than 1.3 billion users around the world, are good examples of how human cultural curation works to preserve and spread culture. In contrast, curation of Homo sapiens has been intrinsic and achieved via genome inheritance.

LUIS SUAREZ

LUIS SUAREZ

Enter CRISPR

The rapid progress and viral popularization of the CRISPR technique of gene editing, over the last few months, has changed forever how we curate Homo sapiens. CRISPR allows the passing of information that affects the behavior of individuals and groups to the next generation by artificial means, that is, by introducing targeted modifications in the genome of the human embryo. CRISPR also permits development of therapeutic means to cure genetic diseases and start speciation beyond Homo sapiens: create new hominids. This new generation of gene-editing technologies is about to dissolve one of the traditional conundrums around human beings. The division between nature and culture will not make sense anymore as, allegedly, we will be able to store behavior-changing information within the genome. Culture will happen in nature.

CRISPR technology

But, what is CRISPR and why the buzz around it this past year?

CRISPR/Cas9 refers to a new genetic engineering technology proclaimed ‘breakthrough of the year’ by Science and ranked second in the Top 25 Science stories of 2015 by ScienceNews.

The CRISPR/Cas9 system is an adaptive immune system found in prokaryotes (e.g., bacteria) that protects from foreign DNA invasion by targeting and cleaving foreign DNA and storing a record of invading information for future targeted destruction of similar invaders. CRISPR loci store collections of short sequences of foreign DNA the host organism has been exposed to. These are transcribed to RNA message guides for Cas9-mediated destruction of complementary foreign DNA.

Cas9 is particularly important in gene editing because it has been engineered to improve specificity for robust on-target activity and to reduce off-target cleavage. That is, it is very accurate. In gene editing, the CRISPR/Cas9 system has been adapted to use a single guide RNA (sgRNA) to target and modify by inserting the guide sequence into the host genome. The appeal of the CRISPR/Cas9 system is the precision achieved, the ease of use and the ability to edit multiple genome regions simultaneously.

Controlling CRISPR

On Dec. 13, 2015, around 500 experts and social advocates from more than 20 countries met in Washington, D.C., to discuss the main issues concerning gene editing in human beings, and to produce the guidelines that should regulate its research practice and medical applications. The International Summit on Human Gene Editing was organized by the U.S. National Academy of Sciences along with National Academy of Medicine, the Chinese Academy of Sciences and the Royal Society of the UK in response to the controversy emerging from the publication of a study by Chinese researchers who applied gene-editing technology CRISPR/Cas9 to modify a gene in nonviable human embryos.

On Feb. 1, the Human Fertilization and Embryology Authority regulator in the United Kingdom approved a license for a researcher at the Francis Crick Institute in London to perform gene editing on human embryos, although those embryos cannot be implanted into women. The goal of the research is to figure out the genes that take part in the early phases of human fertilization. In terms of policy and practice, it means the official acceptance in the Western world of gene editing of human embryos as an important scientific and ethically acceptable technique.

In the meantime, there is a patent war between Berkeley and MIT about the rights to commercialize the CRISPR/Cas9 and, subsequently, who can use it for what. On Feb. 11, #HumanGeneEditing was trending while the Consensus Study Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations held a public session and live webinar to hear input from select stakeholder groups. Notably absent from the agenda were some key stakeholder groups, including social scientists and ethicists. However, there were representatives of stakeholders affected by hereditary conditions who see CRISPR as the tool to stop some terrible diseases. In theory, the technology could also be used to choose other human features. The dialogue motivated by this committee will continue until a full report is produced in late 2016.

Do’s and Don’ts?

CRISPR/Cas9 gene editing technology has opened up an exciting field that is highly attractive to private industry focused on technology development and therapeutics. In fact, the technology has already fuelled industry development. There is a positive commercial landscape for CRISPR technology with its efficient therapeutics aimed at disease cure rather than symptom management. It is one technology of many others already in a clinical testing stage as a gene therapy. Ophthalmologic, autoimmune, immune-oncology and hematopoietic stem cell therapies are also under investigation. Private industry and research are focused on continued improvements in making the correct cut, making the delivery of the machinery and evaluating target accuracy and efficient repair. Fueling the momentum of CRISPR popularity is the swift translation from bench top to bedside of this science for therapeutic gene editing.

Nonreproductive somatic cell-based therapies are the intentional focus of industries with clear statements against reproductive CRISPR/Cas9 applications. This reaction stems from the strongly voiced concerns regarding ethical and safety implications and even fears of delays for therapeutic gene editing in somatic cells.

Dilemmas

CRISPR/Cas9 is a technology that has progressed at a speed exceeding the dialogue of the ethical implications and the development of policy and law. Calls have been made for a moratorium on experimentation with human embryos, but scientists and social groups in favor of continuing the research processes and therapeutic trials are prevailing so far.

The loudest dialogue about CRISPR/Cas9 has been through year-end announcements of cutting-edge science and commentaries and editorials. Louder still are the TED Talks, YouTube videos, Twitter feeds, science journal feeds and researcher blogs offering multiple views on the issue.

At this point, there are three clear conclusions:

  1. Research is going to continue at light speed, and to a great extent it will be self-regulated by the global science community;
  2. Dialogue and policy-making are necessary in all constituencies, including Ontario and Canada, to keep the public informed, involve all stakeholders, study the ethical consequences, and regulate how to apply this technology; and
  3. We need to start thinking about what we want to do with the genome of the Homo sapiens. For that, we need curators.

Biology professor Kathleen Hill has expertise in Molecular Biology, Genetics, Cell Biology. Modern Languages and Literatures professor Juan Luis Suárez is Director of The CulturePlex Lab.