What are DIY gene-editing kits?
In the few short years since its discovery, CRISPR-Cas9 has transformed bioscience like no other invention in the last half century. Already the most common technique of gene editing, CRISPR works like a satnav system joined to a pair of molecular scissors. It is essentially a couple of enzymes that can be designed to find and remove a specific strand of DNA inside a cell, and then replace it with a new piece of genetic material. CRISPR can be used to rewrite single letters of genetic code and even whole genes, and improvements such as “base editing” and “prime editing” are increasing its accuracy and reliability. It could make a significant impact on the global challenges of food security, climate change, energy; as well as in the domain of animal and human health, and the fight against antibiotic resistance (discussed in a previous On the Pulse article ‘CRISPR gene editing technology and its many applications’).
Editing genomes is immensely difficult, but as prices drop and gene-editing expertise becomes more accessible, DIY CRISPR kits have become freely available online for as little as 159 USD. They enable citizen scientists, including so-called “biohackers”, to solve problems that have foxed the professionals, make genetic discoveries, much as amateur astronomers add to the tally of known exoplanets, and devise novel applications. One such kit, on sale by The Odin, a company founded by biohacker and ex-NASA scientist Josiah Zayner, is said to contain everything needed to make precision genome edits in bacteria, all in the comfort and privacy of one’s own home (or garage).
What risks do these DIY kits pose?
DIY kits such as these have limited applications. They can make bacteria and yeast change colour, produce a fragrance or live in inhospitable places, but their lives are short. It’s claimed that they only work in prokaryotic (i.e. bacteria and archaea) cells and in yeast. But yeast, like us, is a eukaryote, so the possibility of altering human genes or producing glowing cats is at least theoretical. So could the private use of these or future DIY kits pose a risk to the environment or to human health? Could biohackers become skilled enough to introduce genes into the biosphere for nefarious purposes, creating dangerous pathogens, for example? The risk from amateur editing certainly appears low, but it is not zero, and it is magnified according to the number of kits in use. Is the law up to the challenge of such a powerful and disruptive technology?
The UK’s Nuffield Council on Bioethics investigated biohacking as part of its wider report on the implications of advances in gene editing in 2016 (here). It found that European DIY biology is “considered to be better or more consistently regulated than its US counterpart”, but concluded that new gene-editing techniques could be “game-changing” in the way they enable “non-institutional actors” to participate in cutting edge bioscience. This was prescient. The following year, two American biohackers attempted DIY gene therapy on themselves. The first injected himself with an untested gene therapy for HIV; the second aimed to knock out the myostatin gene using CRISPR, a genetic change associated with increased muscle mass. Both men livestreamed the procedures on the internet. Both procedures failed. The US Food and Drug Administration (FDA) then took a stand against such CRISPR kits for DIY (supposed) gene therapy, but biohackers argue that the biomolecular components of DIY gene therapy, such as CRISPR plasmids and guide RNAs, are not inherently dangerous by themselves and can be acquired perfectly legally. In any event, the very nature of self-administration is difficult to regulate and enforce against, and livestreaming is not compulsory. Even if the DIY kit and any domestic “therapeutic” product it might create were caught in the regulatory sieve, who would know?
Could these DIY kits be used for human germline genome editing (hGGE)?
We may get an inkling from the reaction to the astonishing and unwelcome boast of the Chinese biophysicist He Jiankui, that he had created the world’s first genetically edited babies. Calls for strict regulation swiftly moved up the international agenda, with some calling for an international moratorium on hGGE. The focus was on the development of international standards for hGGE, and on the conduct of hGGE researchers operating within scientific institutions. Setting standards is undoubtedly an urgent and important enterprise, but a scientist who goes on a frolic of his own, as He Jiankui did, would probably go undetected. If He Jiankui had implanted edited human embryos in the UK, he would have acted in contravention of the Human Fertilisation and Embryology Act 1990. But who would know? It’s extremely unlikely that any currently available editing kit is likely to facilitate hGGE, but things could change, and attempts could easily evade the eye of the law.
Editing human germlines may be less exciting to geeks than hacking animal and plant genomes, an activity which has abruptly become heavily regulated: too heavily, some would say. Again, the mote in the eye of the regulations is the assumption that altering genomes is the exclusive preserve of institutions and well-behaved scientists. Could the irrationality of these laws tempt those on the fringes to breach them behind closed doors?
Impact of the GMO Directive
Prior to the discovery of CRISPR in 2012, the EU implemented regulations for the deliberate release of “genetically modified organisms”. That’s a legal term: the GMO Directive (Directive 2001/18/EC) defines a “GMO” as “an organism…in which the genetic material has been altered in a way that does not occur naturally by mating and/or natural recombination”. In July 2018, the Court of Justice of the European Union (CJEU) ruled that products of “directed mutagenesis” (i.e. of an endonuclease editor such as CRISPR-Cas9) are “GMOs”, and regulated to the fullest extent as such. The decision has been widely criticised for failing to place edited organisms under the Directive’s clear exemption for products of mutagenesis, leading to the ironic result that organisms derived by random mutagenesis are exempt from the strictures of the Directive, while those created by precision mutagenesis are not. The UK implements the GMO Directive in its Genetically Modified Organisms (Contained Use) Regulations 2014 (GMO Regulations), which state that a “person responsible for the contained use must ensure that a suitable and sufficient assessment of the risks to human health and the environment created by the use is carried out”. This is a considerable burden, and the competent authority has the power to require any user to suspend, terminate or not to commence a particular contained use which has been notified to them under the GMO Regulations. It carries the same maximum penalty as under the Health and Safety at Work etc. Act 1974: six months imprisonment, an unlimited fine, or both. In response, crop scientists and others claim that the GMO Directive is being construed in a way that neglects scientific evidence, is wholly disproportionate to any likely harm, and fails to reflect the danger of impeding the development of organisms having positive human and environmental effects, notably CRISPR-Cas9. New legislation has been urged, but until it appears, if ever, the present regulation is challenging. Except, perhaps, to biohackers. The regulatory powers ultimately depend on notification by the user to the relevant authorities. Would biohackers feel obliged to comply? Who, really, is going to find out that those delicious tomatoes were engineered in a potting shed?
The GMO Directive is in large part a child of the millennial Cartagena Protocol on Biosafety to the Convention on Biological Diversity (Cartagena Protocol), Article 16(3) of which requires signatories to take “appropriate measures to prevent unintentional transboundary movements of living modified organisms”. Following the CJEU’s decision last year that gene-edited organisms are GMOs for purposes of the GMO Directive, the same has become true for Cartagena purposes. Do Cartagena signatories in Europe now have a precautionary duty to regulate domestic kits in order to prevent transboundary movements? The US is not a Cartagena signatory, but some US scientists have argued for rules to reduce the likelihood of a bioengineered “super-microbe” escaping from the lab or being deliberately unleashed. Should these extend to the world of the biohacker, and if so, how? Would this even be feasible?
What’s next in the regulatory landscape for these DIY kits?
It remains to be seen what else regulators and law-enforcement agencies will do to try to contain the ambitions of DIY biologists operating outside conventional scientific environments, especially those who stray into procedures that could affect the environment, are used as medical treatments or developed as weapons.
For now, the only real thing stopping determined people from modifying organisms (human and non-human) is the fiendish complexity of the process. Indeed, the European Centre for Disease Prevention and Control (ECDC) has placed assessing the risks posed by DIY gene editing kits on the backburner, particularly in light of more pressing gene-editing issues. It has, however, advised that the risk assessment should be revised, should further information indicate that the distribution of such DIY kits extends more widely across the EU. Clearly, this is a developing area, with wide-ranging consequences, and may lead to more regulation when the use of such kits becomes more widespread.
 He Jiankui has now been convicted and imprisoned in China (discussed in Bristows article ‘Beware of cheap imitations: justice and He Jiankui).
 Case C-528/16 Confédération Paysanne EU:C:2018:583