The coronavirus pandemic has brought into sharp focus the possible benefits and potential pitfalls of biotechnology research. Although such research can be used to produce medical countermeasures to fight diseases and develop healthier crops and livestock, it can also be deployed to produce biological weapons. Even though the current pandemic, as argued by most scientific experts, is believed to have originated from natural sources, the origin of this particular pandemic does not rule out the possibility that other future infections could emerge from laboratories.

The Scope of Biotechnology

Before turning to the safety and security of biotechnology research and the need to balance risk mitigation with innovations in the field, it is important to understand the scope and applications of such technologies. Biotechnology, as defined by the Organization of Economic Cooperation and Development, refers to “the application of scientific and engineering principles to the processing of materials by biological agents to provide goods and services.” Some applications of biotechnology include developing food products, biochemicals, beverages, and pharmaceuticals, as well as services like using genetically altered organisms for water purification, waste management, and sustainable resource procurement.

Ronit Langer

Ronit Langer is a Scoville Fellow working with Michael Nelson in the Technology and International Affairs Program.

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Scientific developments in biotechnology can offer solutions to address global challenges such as combating the spread of infectious diseases, reducing hunger, and remediating environmental degradation.

Biotechnology has the potential to create novel diagnostics, vaccines, drugs, and other medical countermeasures needed to detect, prevent, and treat infectious diseases. For example, the coronavirus pandemic has highlighted the promising role that biotechnology can play in this way. Researchers around the globe are actively working to combat the pandemic. They have been using different technologies to develop cheap diagnostics, repurpose existing antivirals, discover new drugs, and create safe and effective vaccines. In addition, biotechnology can be used to create genetically engineered organisms that can be deliberately introduced into the environment for purposes such as mosquito control. As an example, advances in genome engineering technologies—such as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9)—have enabled the development of gene drives, a technology that allows desired genetic alterations to spread faster through a population over many generations. This technique can be used to cure vector-borne human diseases such as malaria and dengue fever by either making mosquitoes resistant to the parasites that cause these diseases or by completely wiping out disease-carrying mosquito populations.

Agricultural biotechnology can be used to create genetically modified crops for combating hunger and malnutrition. Traditional biotechnology techniques such as selective breeding, hybridization, and fermentation have been modifying living plants for improved yield or enhanced nutritional value from time immemorial. However, with improvements in knowledge about the role of individual plant genes, modern biotechnology techniques can be used to add, delete, or edit specific genes to produce a desired variety, thereby reducing the possibility of off-target effects. For example, golden rice, an engineered variety of rice, contains two extra genes to make it produce beta-carotene, a precursor to Vitamin A, that can help address nutrient deficiencies that lead to blindness, anemia, and weakened immune systems among children. Scientific advances can also help develop genetically modified crops that withstand natural calamities, pests, and diseases. Such varieties can increase crop yields, lessen the need to use pesticides and insecticides, lift farmers out of poverty, and ensure food security. Beyond that, biotechnology can help produce healthier and faster-growing animals and improve the quality and quantity of milk, eggs, and meat for human consumption.

Shruti Sharma

Shruti Sharma is a research analyst with the Technology and International Affairs Program at the Carnegie Endowment for International Peace. She works primarily on the safety, security, and ethical implications of emerging biotechnologies.

Environmental biotechnology has the potential to help mitigate pollution by using microbes and their byproducts, instead of chemical methods, to treat solid, liquid, and gaseous wastes. Plastic pollution, one of the most pressing environmental concerns, can also be addressed through biotechnology. For example, some bacterial enzymes can digest the raw material used to produce single-use bottles for beverages. Moreover, bioplastics can be produced with renewable raw materials such as plants, vegetables, and other recycled forms of waste that can be environmentally friendly alternatives to oil-based plastics.

Biotechnology Applications in the Real World

Real-world applications are integral to the successful development and use of biotechnology. In the pharmaceutical industry, for instance, streamlining the process of getting new treatments to market is called translational medicine. Standard procedures for proving that a new treatment is safe and effective include animal models and clinical trials.

For agricultural biotechnology, this process is less defined. Many countries, particularly members of the European Union, ban the growing of genetically modified organisms (GMOs) or crops. In countries where GMOs are allowed, regulations are often shifting due to public pressure from anti-GMO organizations and differing definitions of the term genetically modified. Once a GMO product enters the market, companies must navigate the complicated information landscape surrounding GMOs and provide evidence to consumers that their product is safe.

For environmental biotechnology, the processes of getting products to market has not been established yet. The applications of environmental biotechnology often fall outside of existing regulatory frameworks. Applications often span many national borders, such as gene drives being considered to help eradicate malaria-causing mosquitoes in sub-Saharan Africa. In some cases, these applications fall outside of national borders altogether, such as in the case of bacteria designed to break down oil from oil spills.

Safety and Security Threats Emerging From Biotechnology

Biotechnology has the potential to revolutionize the societies that humans live in and the organisms that they live alongside. Recent advances include cheaper and more accessible DNA sequencing, faster DNA synthesis, the discovery of efficient and accurate gene-editing tools such as CRISPR/Cas9, and developments in synthetic biology. Meanwhile, there is a growing do-it-yourself (DIY) community of independent biotechnology practitioners and enthusiasts who are unaffiliated with any single lab. Despite their promise, developments in the field do raise certain safety and security concerns that policymakers and scientists must bear in mind.

Safety Threats

To understand the safety threats emerging from biotechnology, let’s consider two hypothetical scenarios.

In the first scenario, researchers in a top-level biosafety lab rearrange DNA fragments to synthetically create a live Ebola virus. This pathogen was originally transmitted to people from wild animals, but it has the potential for human-to-human transmission, causing severe (and often fatal) symptoms in humans. These scientists are working on a weakened strain of the Ebola virus to understand its epidemiological characteristics, like the virus’s virulence and transmission factors. While the aim of the research is to develop vaccines or other treatment options that can help save human lives, the manipulation experiment accidently produces a strain of the virus with unexpected characteristics.

In the second scenario, scientists are working on a new symbiotic plant bacterium to improve the microbiome of the soil. An organic farm fifty miles away notices a slight increase in their crop yields, so they test the soil. The farmers find evidence of the synthetic bacteria, which they trace back to the lab, and they accuse the lab of trying to force GMOs on their consumers. The scientist conducting the research denies the allegations and hypothesizes that some live bacteria accidentally got out of the lab, either on people’s clothing or through the lab’s water system.

These two fictional scenarios illustrate the safety threats that can emerge from developments in biotechnology, both inside and outside the laboratory. While the first case represents accidents that can occur in a lab, the second case highlights the unintended consequences in cases when a genetically engineered organism accidently escapes a lab.

These fictional scenarios have become reality in numerous cases. For instance, in 2001, Australian scientists hoping to genetically engineer the mousepox virus to render lab mice infertile accidentally created a lethal mousepox virus. In another instance, researchers at the State University of New York developed a synthetic strain of the polio virus in 2002 from chemicals and publicly available genetic information. And the virus that caused the 1918 influenza pandemic—a pathogen that killed an estimated 50 million people globally in 1918 and 1919—was resurrected by a group of U.S. scientists in 2005. In another case, a team at the University of Alberta recreated an infectious horsepox virus, a close relative of the smallpox virus, by ordering DNA fragments online for about $100,000.

Although none of these experiments have led to an infection or an outbreak, there have been instances when the accidental release of pathogens either has led to infections among laboratory personnel or has resulted in disease outbreaks. For example, although smallpox was eradicated from the UK in the early 1970s, the virus escaped from a smallpox research lab in Birmingham and infected a researcher, who subsequently succumbed to the disease in 1978. In another incident, an experienced Russian scientist died of Ebola after accidentally injecting herself with the deadly virus while working on the Ebola vaccine. More recently, almost 3,000 people were infected in China with a bacterial infection called Brucellosis after a leak occurred at a biopharmaceutical company in 2019.

Since these accidents happened in regulated research labs, it was easier to minimize the societal impacts of such mishaps. However, the DIY community involves individuals, enthusiasts, and small organizations dabbling in genetics that are not linked to any formal institutions and hence are not regulated. Such unaffiliated communities have been in the news even during the coronavirus pandemic, when some of them joined the quest for an effective and safe vaccine. Since these groups sometimes have limited formal training on the safety and ethics of using such biotechnology, it might be difficult to contain and mitigate the impact of any accidents that might emerge from their experiments. Even though no unfortunate incident has happened so far, the absence of regulations to monitor this community has emerged as another safety threat.

Safety concerns extend beyond pathogens that may escape from research laboratories. Genetically engineered organisms that are introduced into a natural environment for beneficial purposes can also sometimes have unintended consequences. For example, although CRISPR/Cas9-enabled gene drives have the potential to eradicate vector-borne diseases, tackle invasive species, and control pests that target crops, the self-propagating nature of gene drives and the possibility that they could either spread indefinitely or accidently manipulate nontargeted species have raised concerns among regulators.

Similar experimental techniques, like sterilizing insects en masse, have been conducted in the past. One technique involves the mass sterilization of a targeted pest, such as fruit flies, using irradiation. Scientists advocating for gene drives argue that irradiation can cause random mutations, which might also have unintentional effects on the environment. Such off-target mutations can be avoided using gene drive technology that relies on genomic information obtained through reliable DNA sequencing tools. Although the technology has immense beneficial applications, it is important to update existing regulations and initiate public discourse on the benefits and the risks of this emerging technology.

Security Threats

Recent advances in synthetic biology, a technology that can be used to artificially create organisms in labs, carry the foreboding potential to develop biological weapons. Moreover, the emergence of the DIY community and the open-source nature of this movement have sparked concerns that terrorists could easily acquire the information needed to weaponize biotechnology, although none of these DIY groups have exhibited any nefarious intentions. Nefarious actors who previously acquired pathogens from a lab or from nature with the intention of developing a bioweapon can now either order DNA fragments online and assemble them to create dangerous pathogens or synthesize lethal pathogens from scratch using genomic information available online. Moreover, such actors can leverage vulnerabilities in the cyber defenses of labs and private companies to gain access to sensitive information that is not publicly available online.

To better understand the security threats emerging from recent developments in biotechnology, it is worthwhile to return to the aforementioned hypothetical Ebola scenario. Imagine for a moment that the researchers involved, in collaboration with an editor at an esteemed journal, decided that they would publish a redacted version of the methods and the results section of their research due to security concerns. A month after the paper was published, the lab noticed unusual activity on their servers. The lab immediately reported the incident to the university’s information technology department. The department contacted local law enforcement officials, and together they traced the hack to a suspected terrorist organization. The group was trying to gain access to the methodology that led to the accidental creation of a more virulent Ebola strain so as to launch a deliberate biological attack. Law enforcement put DNA synthesis companies on high alert for any orders that closely aligned with research on the Ebola virus or other high-risk pathogens. Thankfully, a company was able to flag an order and law enforcement was able to cooperate with local officials to shut down the unauthorized lab before it began creating and releasing harmful products.

In reality, individuals have at times tried to acquire deadly pathogens and other sensitive biological information. For example, two Canadians were arrested in the city of Buffalo, New York in 1984 after they were suspected of illegally acquiring and smuggling strains of botulism and tetanus to Canada. The Japanese cult Aum Shinrikyo made unsuccessful attempts in 1995 to acquire strains of Ebola from Central Africa to develop the group’s biological weapons program. More recently, two Chinese hackers were indicted in the United States for seeking to obtain intellectual property related to coronavirus treatments and vaccines. Similar incidents were reported in Spain; allegedly Chinese hackers were trying to steal data from Spanish labs conducting vaccine research.

In addition to strategically embedding members into research organizations to acquire these deadly pathogens, some terrorist organizations also have sought to rely on lab insiders to either develop biological weapons or grant access to organisms or sensitive information. For example, a Malaysian scientist tried to develop anthrax weapons for Osama bin Laden, the founder of al-Qaeda.

While most countries have national guidelines for handling safety and security threats, the examples described above highlight the global implications of such threats. It is therefore important to evaluate global best practices, treaties, and conventions that deal with such risks and devise strategies to update these safeguards to govern dual-use applications of emerging biotechnologies.

International Treaties and Other Risk-Mitigation Measures

There are numerous international treaties and regimes in place to help mitigate the risks at play with biotechnology. Three of the most significant ones are the Convention on Biological Diversity, the Biological Weapons Convention (BWC), and the Australian Group. Each of these agreements or regimes tackles a different aspect of the risk profile—biosafety, bioweapons, and banned substances—but each of them comes with limitations, such as limited scope, sparse funding, and inadequate verification and monitoring mechanisms. None of the agreements create a binding framework to holistically address biosafety and biosecurity risks, making for an overall lack of accountability and rendering the development of international standards piecemeal and incomplete. In this regulatory environment, it is difficult to keep up with rapidly emerging advances in biotechnology or address pressing issues such as releasing biotechnology products, like gene drives, into nature.

The Convention on Biological Diversity

The Convention on Biological Diversity is an international legal instrument for ensuring that countries work together to promote a sustainable and equitable future that protects biological diversity. It has been ratified by 196 countries. The convention has two protocols, the Cartagena Protocol on Biosafety and the Nagoya Protocol, that promote the safe and equitable use of biotechnology with respect to biodiversity.

The Cartagena Protocol on Biosafety governs the use and transport of GMOs to protect biological diversity and human health. The Nagoya Protocol is a benefit-sharing agreement that mandates that—when researchers enter another country and use genetic sequences from indigenous plants, animals, or microorganisms and/or employ indigenous procedural knowledge—indigenous people are either compensated up-front or receive a fair share of the profits from commercialization.

The Cartagena Protocol, which entered into force in 2003, promotes a precautionary approach enshrined in the fifteenth principle of the Rio Declaration on Environment and Development, which states, “Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.” In essence, if the scientific community is uncertain about how a new organism will impact the environment, this principle states that scientists should proceed with extreme caution. In general, the Cartagena Protocol attempts to balance between the propensity of advances in biotechnology to help countries protect their biodiversity and develop economically alongside the threats that biotechnology poses to biodiversity and human health if something were to go wrong.

The Cartagena Protocol mainly covers the handling, transport, and use of GMOs across borders. The protocol established the Biosafety Clearing-House to facilitate the implementation of its guiding principles. The clearinghouse is designed to “facilitate the exchange of scientific, technical, environmental and legal information on, and experience with, living modified organisms [or GMOs].” All members of the protocol must inform the clearinghouse when countries make a new transfer agreement on GMOs, of any unintentional releases of GMOs that may cross borders, and any national laws that pertain to the effects GMOs may have on sustainability. While the protocol ensures safe use and transport of GMOs, it does not include any penalties for violations or have any accountability mechanisms for accidental releases of pathogens from labs or any other laboratory-acquired infections.

One key limitation is that the Cartagena Protocol only covers the transfer of physical material, whereas much of the information that tends to be transferred involves digital DNA sequences. The Nagoya Protocol, which was adopted in 2010, specifically focuses on benefit sharing from the genetic information of regional biological diversity or regional know-how. The Nagoya Protocol sets the standards for transfer agreements between a potential commercial actor and a local population to ensure that the local population is properly compensated for the use of its regional biodiversity. Similar to the Cartagena Protocol’s Biosafety Clearing-House, the Nagoya Protocol has an Access and Benefit-Sharing Clearing-House to help coordinate implementation and exchanges of information on benefit sharing. Although the protocol monitors fair utilization of genetic resources until indigenous communities are compensated, it does not monitor the safety and security of experiments that occur once fair compensation has taken place.

Both the Cartagena Protocol and the Nagoya Protocol are therefore limited in scope and do not protect against a wide range of biosafety threats. For example, neither protocol covers safety concerns from the transfer of DNA sequences and, therefore, would not prevent a nefarious actor from ordering sequences that might be used for the development of dangerous pathogens. In addition, the Cartagena Protocol only covers GMOs, not DNA sequences or other precursors to GMOs, while the Nagoya Protocol only covers indigenous benefit sharing, not transborder data on pathogens.

Fundamentally, the Cartagena Protocol and the Nagoya Protocol are trade mechanisms designed to protect local biodiversity from being overtaken by GMOs or exploited by biotech companies. They do not provide international guidelines for establishing biosafety protocols. Nor do they protect against the dangers of cheaper and faster DNA sequencing, easy DNA synthesis, online access to genomic information, and developments in synthetic biology, among other issues. Given these limitations, there is a need for the scientific community to expand on global biosafety standards to minimize risks from laboratories undertaking biotechnology-related research.

The Biological Weapons Convention

The BWC is a multilateral disarmament treaty banning the development, production, and stockpiling of biological weapons. The BWC, which entered into force in 1975, was the first treaty of its kind to ban an entire category of weapons. In consideration of the inherent dual use problems in biotechnology, the BWC does not outright ban any biological material. Rather, it bans the creation and stockpiling of biotoxins and other biological agents above the amount required for peaceful purposes, and it bans the use of any biological material as a weapon.

Any member of the BWC can initiate a bilateral or multilateral consultation to deal with any problems that come up during the implementation of the treaty. In the event of a suspected biological weapons attack, members of the BWC can report the perpetrating member to the UN Security Council for further action. However, the BWC currently has ­­­no mechanism for monitoring to ensure compliance or any means of verification. There is no set threshold for the amount of biological agents “required for peaceful purposes” and without monitoring and verification, there is no way to know if the biological agents a country has are being used peacefully.

Over the years, various review conferences have tried to implement self-reporting requirements and other confidence-building measures for members, such as declaring high containment research centers and vaccine production facilities, but these efforts have largely failed due to a lack of consensus among members. The difference in approach to biological weapons was most evident in 2001, when attempts to establish an international organization to monitor and verify compliance failed following a decade of efforts after the United States withdrew from the negotiations. The United States argued that the verification process would put the proprietary information of biotech and pharmaceutical companies at risk while not solving the problem because, it was argued, biological activities are inherently impossible to verify, a position the U.S. government has maintained to the present. On the other hand, the United States and India have recently supported a proposal that would strengthen export controls on biological material, but they received pushback from developing countries who want to keep biotechnology accessible and increase knowledge transfer. Russia, after backing off of verification in the last few years, has placed a special emphasis on bioweapons response protocols in the wake of a biological attack. In that vein, the Russian government has supported the development of mobile medical units for treating victims of bioweapons and natural epidemics and has recently gained support for this idea from the UK, but not from the United States.

Due to these ongoing tensions, instead of creating an international monitoring organization— similar to the Organization for the Prohibition of Chemical Weapons, which implements the Chemical Weapons Convention—the BWC instituted an implementation support unit (ISU) that is housed in the UN Department of Disarmament Affairs in Geneva. The Organization for the Prohibition of Chemical Weapons is an international organization in its own right and is managed by a large technical secretariat, which is composed of both political appointees from member states and permanent staff. The technical secretariat focuses on verification of compliance with and implementation of the Chemical Weapons Convention. By contrast, the ISU has a permanent staff of just three people. The ISU’s mandate is not verification and monitoring but rather to offer administrative support and help facilitate confidence-building measures among members.

In addition to a lack of verification, the BWC is often perceived by scholars as not readily addressing the impact of emerging technologies, such as synthetic biology and artificial intelligence, despite regular meetings of the member states (and expert meetings) to keep members up to date on pertinent issues. Another issue for the BWC is a lack of funding, as many member states have outstanding dues—in 2019, ninety-five members owed a collective total of over $140,000. The funding shortage for the BWC’s current activities, and the lack of consensus about how to expand its mandate, make it highly unlikely that the convention will be able to expand its role or the role of the ISU.

The Australia Group

The Australia Group is a multilateral export control regime designed by an informal group of countries. The group’s goal is to help countries decide which substances need to be governed by export controls to minimize the risk that exporters may unwittingly assist in the creation of a biological or chemical weapon. The group, first convened in 1985 with fifteen countries and the European Commission, is not a legally binding agreement, but rather a coalition with a shared commitment to the nonproliferation of chemical and biological weapons. The group currently has forty-two members plus the European Commission. The Australia Group claims within its remit eighty-seven controlled compounds, some human and plant pathogens and toxins, and “dual-use biological equipment and related technology and software.”

While the Australia Group does fill in some gaps left by the Cartagena Protocol on Biosafety and the BWC, namely an expansive list of precursors to biological weapons that should be subject to tight export controls, it is not a legally binding agreement. Furthermore, many countries are not included in the group, limiting its reach. Overall, there is a need for more international cooperation to help mitigate the threats of emerging breakthroughs in biotechnology without curtailing technological progress.

Conclusion

Continuing advances in biotechnology provide a plethora of opportunities to address global challenges such as the spread of infectious diseases, food insecurity, and environmental degradation. However, the same technologies can be deployed by nefarious actors or hostile states to create deadly pathogens that can deliberately cause human infections, negatively target agricultural supply chains, or disrupt existing ecological balances. The world has already seen some troubling historical precedents of the deliberate misuse of biotechnology to develop bioweapons, instances of accidental releases of living organisms from labs, and cases of laboratory-acquired infections.

To tackle such challenges, most countries have adopted informal guidelines or laws to ensure the safety of biotechnology-related research, instituted mechanisms to prevent unauthorized access to biological material, and created export control regimes to govern the transfer of sensitive biological material.

At a global level, treaties, conventions, and guidelines have been drafted to ensure the fair and transparent promotion of biotechnology, but these mechanisms fall short of providing the oversight needed to promote the responsible conduct of biotechnology-related research. This is because these global mechanisms either have not been updated regularly and therefore fail to keep pace with recent technological developments or because they lack the expertise and financial resources needed to monitor global biotechnology developments.

Moreover, there are no mandatory global standards on biosafety and biosecurity that all research laboratories must abide by, and there is no mechanism that introduces accountability and proper procedures for judging claims of liability when experiments go awry. For example, when state actors deliberately misuse biotechnology, the signatory states of the BWC, in the absence of a verification and monitoring protocol, can only consult with each other or lodge a complaint with the UN Security Council.

The above examples highlight that these global mechanisms are ill-equipped to handle threats emerging from breakthroughs in biotechnology. To ensure that biotechnology-related research is conducted responsibly, the international community needs to collaborate to develop standards that govern the safety and security of experiments, formulate the long-debated verification and monitoring mechanism under the BWC, and incorporate clauses that institute liability and accountability mechanisms in cases of violations. These steps would go a long way toward increasing the odds that the world can make good on advances in biotechnology while mitigating the risks and downsides.

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