Public Access Evolution: Global Action Needed to Maintain the Stability of The Human Genome

Photo Credit: NHGRI

By Bennett Batten
Contributing Writer

In November 2018 the scientific community was stunned when the guest speaker to the second International Summit on Human Genome Editing, He Jiankui, decided to share a fun surprise. He had successfully edited the embryonic DNA of twin girls! He deactivated a gene called CCR5 with the goal of  decreasing the risk of acquiring HIV. In reaction to this event an international body of scientists called for a temporary global moratorium on heritable genome editing, and the World Health Organization (WHO) formed an advisory committee on “Developing Global Standards for Governance and Oversight of Human Genome Editing”. While both of those developments are positive, they do not fix the problem that was highlighted.  

Advancements in genetic engineering have far surpassed our global institutions’ ability to regulate them. With the development of genetic engineering tools such as CRISPR and gene drives, paired with the growing popularity of DIY labs, access to bioweapon creation or human enhancement has become open to the public.

Back in 2014 a scientist at Vanderbilt University stated that experiments that previously required 18 months and $20,000 now only take 3 weeks and $3,000. It’s been 6 years since that statement, so it’s safe to assume that prices have fallen farther. Entrepreneurs have met these falling prices with DIY biohacker labs. The first of their kind opened in 2010. By 2017 there were more than 50 in the USA alone. Lack of regulation and security at these private biolabs have concerned the FDA and FBI, but no cohesive protocol has been put in place by the federal government to address safety and ethical concerns. 

A vulnerability from open access genetic engineering is an inability to contain negative side effects. Most genes affect and are affected by others. When Jiankui “deleted” the gene CCR5 in the twin girls, he knowingly increased their likelihood of health complications from viral infections and improved their cognitive abilities. The study of how genes interact with one another is complex and incomplete. How these side effects will manifest in the twins is unknown. If a germline genetic alteration is made unbeknownst to governments or academia, a containment crisis to the alteration could occur.  

Unlike the threat of nuclearization, creating a bioweapon doesn’t have its own version of a radiation footprint. Even with detectable signs of nuclearization, misguided wars of suspicion have destabilized parts of the globe. “Gene editing could allow scientists to develop biological weapons capable of discriminating among target populations based on ethnic, racial, or other genetically defined characteristics.” Having the capacity to carry out genocide by use of bioweapns is a threat of equal concern to having nuclear capabilities. Since the creation process of bioweapons has no obvious tells built in, paranoia on the weapons capacity of enemy groups could rise.

So, what tools do we have to prevent illegal bioengineering? The Bioweapons Convention (BWC) of 1975 resulted in the multilateral disarmament of treaty member states. Members agreed to ban the development, production, and stockpiling of these weapons. Currently the BWC holds a review conference every five years, and one annual week-long meeting of government experts. The annual meeting is intended to track progress and raise issues. Attendee, Malcolm Dando, and Professor of international security at the University  of Bradford, UK raised concerns that the goal of these meetings are not being accomplished. “In 2013, for example the experts’ meeting scheduled a mere six hours of discussions on science and technology — less than a day. That is not enough time for complex science to be presented, digested and discussed, and not enough to consider its implications and suggest revisions to the BWC.”  

The World Health Organization committee on Developing Global Standards for Governance and Oversight of Human Genome Editing has been actively responding to the problem. In March, 2019 they called for a temporary ban on clinical application of human germline genome editing (heritable changes to genes), while developing a mandatory registry for all planned and ongoing research relevant to gene editing. 

The main objectives of any new policy need to ensure global security by preventing unregistered experiments from contaminating the public gene pool, or privately used for human enhancement. Another objective is the protection of human rights. No unborn person should be subjected to genetic experimentation without the endorsement of the scientific community, its guardians, and society. This will ensure the safety of the child, and that social morality associated with editing human DNA is not violated.  

A focal concern about He Jiankui’s experiment on the twins is how easy it was for him to keep it under wraps. An international registry for all genome editing studies will serve as a deterrent to ambitious scientists, if unregistered studies are prohibited from accessing funding, and barred from publication. This does not deter private moneyed interests that have no desire in publication. Jiaunkui kept his experiment under wraps by lying to, and concealing information from staff, as well as exploiting “… loosely worded and irregularly enforced regulations…” in China. This is exemplary of how one person under current protocol has the ability to shirk regulations and laws by mislabeling actions, and misinforming staff. 

To prevent unsanctioned bioengineering, awareness of humanity’s growing ability to control the future of our species’ evolution needs to be raised. From as early as elementary school, we should instill in the coming generations a humble and almost sacred approach to gene editing. Requiring all DIY labs to host a security guard and in-house lab technician to monitor what is being conducted is low hanging fruit, but still impactful. 

All the necessary materials to perform genetic experiments is basic lab equipment, and since the Cas9 enzyme (the key tool used in CRISPR) is a protein, controlling distribution is not logical. Currently there is no way to detect at home laboratories.  Modifying a centrifuges energy footprint, or frequency discharge into a pattern that identifies itself could provide a way to locate unregistered experiments. 

The BWC has been successful so far in its mission of keeping bioweapons from being developed and utilized in warfare. For it to be successful in preventing the weaponization of gene editing, it should quadruple the time it’s experts and delegates meet yearly in order to dedicate adequate time to policy development. How the BWC evolves is up to debate. Two main paths are available: – one that prioritizes state sovereignty and holds that each state is responsible for all bioterrorism threats within its borders, and another that prioritizes the global genetic stability of the species over state sovereignty. However, many states do not have the capacity to fund programs of surveillance and security to prohibit extremist groups from using their territory

Article 39 in The Charter of the United Nations gives The Security Council (UNSC)  authority to label threats to international peace, and the duty of deciding what actions to take to restore/protect peace. Any action taken requires approval of all five permanent member states (US, GB, FR, CHN, RU). To facilitate productive policy development that would address ranking the priorities of sovereignty and genetic stability, the BWC should request annual discussions with the five permanent member states of the UNSC. 

It is the duty of our global institutions to be predictive of future threats to international peace. To minimize the occurrence of genetic crisis events, effective deterrents must be developed. It is time now to raise cultural awareness of this issue and to pressure our global institutions to take action. 

BIOETHICS IN EBOLA CLINICAL TRIALS

Mobile Ebola Lab in Guinea

By Alexandra Reich
Staff Writer

There are certain drugs that may successfully treat the Ebola virus that is currently epidemic in West Africa and has captured the world’s attention. Several experimental Ebola drugs are currently in production, with optimistic experimental success rates. One of them is ZMapp, created by Mapp Biopharmaceutical. It takes months to make a small dose, so this is not viable as a long-term Ebola treatment. A few other Ebola treatments are currently being researched by other pharmaceutical companies.

Now that several Ebola drugs may soon become approved for use in treating people in West Africa, world health powers are expressing conflicting views on how these are to be implemented. The World Health Organization (WHO) has approved the use of experimental drugs in the treatment of Ebola, with the patient’s informed consent. The long-term side effects of the under-tested drugs are not closely scrutinized when the short-term result may be a cure for Ebola. However, epidemiologists estimate that the supply of these experimental drugs is insufficient for the number of people estimated to be infected. Widespread distribution of trial drugs isn’t a viable option due to the barriers of cost and availability.

There is another issue; the U.S. Food and Drug Administration (FDA) is supporting the standardized clinical trial process for the experimental Ebola drugs, where one group receives the potentially life-saving experimental drug, and the other group receives a placebo. The placebo groups acts as a control, so that the scientists can observe an experimental drug’s effect while monitoring the results under the exact same experimental conditions without the drug. This system of study is widely accepted in the scientific community under less urgent conditions. However, with the death rate of Ebola documented as high as 70 percent, one has to consider the social constructs and morality issues surrounding Ebola clinical trials in the field. A clinical trial participant who is placed in the placebo group has basically been handed a death sentence by the scientific community, for the purpose of advancing scientific knowledge. In epidemic conditions, the ethics of medicine must be considered, in addition to scientific advancement.

How can researchers, in good moral conscience, give only half of research participants a life-saving drug? The WHO expressed concerns about both the morality and safety of having randomized-placebo clinical trials. Global health scholar Trudie Lang argues that this form of clinical trial implementation is unethical, and potentially dangerous for healthcare workers who would deliver life-saving drugs to only some patients. A clinical trial participant, knowing the placebo group likely means death, could act out in order to access the lifesaving drug.

This brushes against the larger issue concerning trust of foreign healthcare products and workers in African nations. Violence against foreign healthcare workers is not unheard of. In February 2013, nine people working in Nigerian polio immunization clinics were shot and killed by armed men. The implementation of standardized clinical trials in Ebola-impacted nations could result in similar mistrust that could lead to violent actions. If pharmaceutical companies conduct randomized clinical trials that intentionally leave a placebo group to face Ebola without treatment of drugs in the name of scientific advancement, Ebola-infected nations have every right to be skeptical. Any scientific research on the Ebola epidemic needs to be done with the consideration of moral standards first, and scientific advancement second.

Bioethics is frequently debated during epidemic outbreaks, especially concerning the responsibilities of developed nations. Wealthier nations are depended upon to provide research into new, and potentially life-saving, drugs. However, this does not rationalize a paternalistic position towards the impacted countries. Scholars argue that to alleviate concerns of exploitation of Ebola-impacted communities for scientific advancement, research teams should make contributions to improving their host communities, such as working to improve the local healthcare facilities. Efforts made by clinical trial researchers toward truly improving the Ebola-impacted communities may help to lessen any distrust of the researchers.

If given access to the resources needed to save lives, pharmaceutical companies have a moral obligation to give people access to these drugs. As noted before, widespread distribution of experimental Ebola drugs is not feasible because there is not a large enough supply. Considering the smaller numbers of people in clinical trials, there is no morally sound reason to keep the placebo group. While the furthering of scientific knowledge of Ebola is important, it should not be collected by means of human experimentation.

Image by European Commission DG ECHO