The Covid-19 pandemic has brought the Gain of Function (GoF) research back into the limelight. But what does GoF research means? And what does it has to do with the advent of the Covid-19 virus? GoF means to gain a “function” that didn’t exist before. This means that the organism can acquire a new property or enhance an existing one. Which organisms can achieve GoF? Literally any organism – from a virus to an elephant (though it would be challenging to do a GoF research on an elephant). Imagine if a fish’s pectoral fins somehow gain the ability of that of the wings of a bird because of which it could fly, the fish’s fins would have “Gained a function” of flying. Now how can an organism acquire a new property or ability? There are two ways to do it – one is “Natural selection”, and the other is a “forced research experiment”. Though the prior one happens in nature over time, the latter is conducted in an experimental laboratory, making the results much quicker.

Now, as far as Covid-19 is concerned, the WHO has still not made its stance clear whether the virus was a result of a GoF research leak or somehow it jumped from animals to humans. But the incident has undoubtedly revived the GoF research debate.

The need for GoF research to handle future pandemics

The first step towards eliminating the enemy is to understand the enemy. Now, working with dangerous viruses in laboratories may sound scary, but GoF research aims to reveal targets to predict emerging infectious diseases better and develop vaccines and therapeutics. The more complicated the virus, the more urgent for scientists to understand it. If we are to go on a war tomorrow, wouldn’t it make sense to study the enemy and strategize a winning plan against it? The same goes for conducting the GoF research. It helps scientists understand fundamental questions about how a virus behaves- What mechanism does it use to enter a host cell? How does it replicate? Which genes are responsible for specific protein activation? How does the host immune system respond to these cruel invaders? So even though it makes sense to avoid these dangerous microscopic enemies for an average person, scientists must study them closely and securely to learn how they work.

Antimicrobial Resistance (AMR) – the India-specific problem

Antimicrobial resistance (AMR) is a phenomenon that helps bacteria, viruses, fungi, and parasites mutate over time to a stage when they no longer respond to antibiotics and other antimicrobial medicines, thereby making corresponding infections harder to treat and manage. The rate at which an average human consumes antibiotics nowadays has made antibiotics the favourite “past-time snack” of humans. As per Lancet, in 2019 alone, more than 1.2 million people died worldwide due to AMR. Some data estimates indicate that this number may rise to 10 million/ year by 2050. Further, AMR can pull down the gross domestic product (GDP) by 2-3 per cent, costing about $100 trillion to the world by the year 2050. India has been referred to as the AMR capital of the world. The emergence of newer multi-drug resistant (MDR) pathogens continues to pose a severe burden on the health infrastructure of the country, given the fact that India is still aiming to combat old nemeses such as tuberculosis, malaria, and cholera pathogens (which are themselves giving rise to drug-resistant strains).

How are GoF research and AMR issues intertwined? And can GoF research help mitigate the impact of AMR in India?

As bacteria & viruses become more resistant to antibiotics due to overuse by humans, it is necessary to study their path of evolvement beforehand. The Union government of India in the year 2011 came up with a draft of the National Policy for Containment of Antimicrobial Resistance in India. A March 2016 article in PLOS Medicine titled ‘Antibiotic Resistance in India: Drivers and Opportunities for Action.’ highlighted the gravity of the AMR problem in India. The report stated, “Antibiotic resistance is a global public health threat, but nowhere is it as stark as in India. Today, India’s crude infectious disease mortality rate is 416.75 per 100,000 persons, twice the rate in the U.S. (200) when antibiotics were introduced.” In his “Mann Ki Baat” on 31st July 2016, Hon’ble. PM Shri. NarendraModi spoke about the perils of antibiotic resistance (ABR) and the pressing need to tackle it. He underscored that people should not turn to antibiotics for quick relief without prescriptions and that self-medication should be avoided at all costs for antibiotics and/or antimicrobials. The National Centre of Disease Control and the Indian Council of Medical Research is engaged in anti-microbial resistance surveillance and have earlier placed restrictions on the sale of antibiotics by making necessary statutory changes. Nevertheless, the prevention and containment of AMR shall require a multi-sectoral& multi-stakeholder – driven approach.

Regulated GoF research can be thought of as a viable strategy to counter the deleterious impact of AMR on the Indian population in the future. Such advanced research should be under the surveillance of responsible scientists and backed by a robust policy framework. The GoF research during the original SARS coronavirus outbreak in 2003 is a case in point. One of the critical experiments designed under this research was to study mice’s viral (SARS-CoV) life cycle. This led to the development of a model for experimenting with viruses and identifying & testing potential vaccines. Similarly, GoF research experiments can be designed to test the effect of antibiotics or antimicrobials on resistant strains, and this can help predict deleterious mutations and identify containment strategies rather pro-actively.

Caution – “if unchecked, it’s the next pandemic under construction.”

Dr Anthony Stephen Fauci, the Chief Medical Advisor (CMA) to the President of the USA, once wrote in an article in 2012- “benefits of GoF experiments and the resulting knowledge outweigh the risks”. The GoF research indeed involves significant risks, and if not conducted properly, it could potentially become the cause of a pandemic. But it is also true that there is no such thing as “zero risk” in any endeavour, hence the need for regulations. So, the right question to ponder here would be: Can GOF research be adopted as a policy and be performed at an optimal level of safety and security by adopting risk-mitigation strategies in parallel? These mitigation strategies could be the mandated adoption of BSL 4-5 safety protocols at all laboratories conducting such research, the implementation of exposure control plans, strict operating manuals and training, incident response planning to name a few. In this regard, some of the critical questions for policymakers (5Ws) to consider should be: –

a. What shall be the role of the funding agency and expert-level review group while considering the merits and possible research benefits?

b. What is the potential for the experiment to create, transfer or use an enhanced potential pandemic pathogen (PPP), including antibiotic-resistant microbial strains?

c. Are there other equally efficacious but less risky alternatives as a substitute to the GOF-based experiment?

d. Can the scientific cohort and facility perform GOF experiments safely and securely and respond proactively in case of any accidents, protocol lapses, or security breaches?

e. Whether the research results can be responsibly communicated, based on applicable laws, regulations, and policies, along with terms and conditions of funding?

Options for going forward will necessitate developing a broader consensus on technical aspects, such as issues, principles, definitions, and terminology. Nevertheless, member state funding, monitoring, and support are essential regardless of what approach is taken to reap GOF research’s benefits to address the AMR problem in India.