What is gain-of-function research in genetics?

It’s the rumor that won’t go away – that SARS-CoV-2 was accidentally leaked from a high biosafety lab in Wuhan, China. The claim is that the lab was researching gain-of-function (GOF), and it produced a potent version of the coronavirus that led to the pandemic.

This has led to some skepticism and mistrust research area and whether it is necessary to conduct experiments using GOF techniques.

What is the gain from functional research?

Essentially, GOF research is used to learn how viruses acquire new functions through mutation and evolution.

A function is simply a property of an organism, such as plants who are more tolerant of Drought or disease, or enzymes that have evolved to make our bodies work.

The language on GOF has become responsible for negative connotation who associate this work with dangerous or risky research. But like the rhetoric about genetic modification, these connections do not represent the diversity of the field or the safety precautions that govern research. Basically, however, the research does exactly what the name suggests.

GOF research observes these mutations and sees how certain stimuli could affect the evolutionary changes and properties of a virus or organism.

However, in our current climate, it is often spoken of in a much narrower context, as if it were specifically about how a virus changes to move more easily between humans, or how viruses become more deadly. It just doesn’t represent the full picture of GOF research.

What is the interest of GOF research?

Viruses evolve quickly – that’s why there are so many new variants of SARS-CoV-2. GOF seeks to understand why and how these changes occur, and what environmental factors might influence the process.

In a sense, it is a know-the-enemy approach.

Beyond the benefits for basic biology research on the nature of viruses and their evolution, GOF contributes to three clear areas: pandemic preparedness, vaccine development and the identification of new or potential pathogens.

GOF research can help us understand how quickly mutations occur and how many generations it may take for a virus to change in a way that will require extra care in the community, which is information that fuels modeling. epidemiological.

This GOF information helps predict things like the likelihood of a virus becoming an unpleasant variant in a certain population size or density, during a certain season, or during a particular period or time. It indicates how we respond to a pandemic. Beyond that, it also informs how quickly a virus can mutate to defeat vaccines and provides genetic information that can be useful in vaccine development. Specifically, GOF research can accumulate potential candidate vaccines in an accessible database in the event of an outbreak due to a natural course.

In turn, this means that the development of a vaccine can be accelerated exponentially because the candidates are already available.

For example, a report of a 2015 GOF risk assessment workshop for expert organizations revealed genomic information from GOF research. This showed that the SARS-like coronaviruses transmitted by bats had many strains and mutations that had “pandemic potential against which countermeasures must be developed.”

This information has led to current pandemic responses and vaccine development – the pandemic has been already predicted due to a deep understanding of the evolution of coronaviruses.

In another example, GOF experiences on influenza showed that the virus had the potential to be transmitted between different mammals with only a few changes in the genetic code, and contributed to seasonal flu shots.

What is the science behind the research on gain of function?

GOF research is based on the evolution and changes observed in DNA or RNA.

The genome is the sum of all the genetic information of an organism. Part of this DNA or RNA is made up of genes, which often contain information on how to make a protein. These proteins perform functions in our body to make everything work.

These genes can naturally change quite a bit with each generation. This happens because, in order to reproduce, the parent’s DNA must be replicated. The mechanisms that do this are not perfect, so small mistakes can be made when DNA is copied.

Most of the time, the changes are tiny – only one unit of DNA (called a nucleotide) can be changed and this may have no effect on the proteins produced. At other times, the small change of a single nucleotide can cause a gene to acquire a whole new function, which could be beneficial to an organism.

The natural mutations that occur during reproduction are an example of evolution in action.

These changes happen with every generation, so organisms that can reproduce quickly, like flies, can evolve quickly as a species as well.

This process works essentially the same with viruses, except that viruses have RNA instead of DNA and reproduce asexually. They still make proteins and still accumulate mutations, but the main difference is that they can reproduce. very, very fast – they can start to reproduce in a few hours of “birth” – and are evolving at an unusually rapid rate.

This is why we have identified so many new variants of SARS-CoV-2 since the start of 2020. Each time the virus enters a new host, it reproduces quickly and mutations occur. Over time, these mutations change the properties of the virus itself.

For example, new mutations can end up making the virus more virulent or making symptoms worse because the proteins have changed their properties.

In these cases, we would say that the mutant strain has acquired function, and this is what GOF research aims to understand.

What happens in a virology lab?

Viruses in a lab don’t have a human host in which to grow, so researchers instead grow them in petri dishes or animals.

There are two ways to use GOF in a lab: you can watch the virus mutate on its own (without intervention), or you can control small changes through genetic modification.

The first type of use is to put the virus in different situations to see how it will evolve without intervention or help.

This video is an example of GOF research with bacteria (not a virus, but the method is similar). The researchers placed bacteria on a giant Petri dish with different concentrations of antibiotics. They leave the bacteria behind and watch its natural evolution to overcome the antibiotic.

The new strains of bacteria could be genetically sequenced to see what genetic changes caused them to become resistant to antibiotics. This experiment can show how quickly bacteria evolve, which can indicate when or how often antibiotics are given, and whether there is a high enough concentration of antibiotics to stop the rate at which the antibiotic is overcome by the disease. resistance.

Similar experiments can be done with viruses to see how they might change to overcome human antibodies and other immune system protections.


Read more: What happens in a virology lab?


The second type of use consists of small changes using genetic modification. This type of experiment occurs after a lot of other genetic information has already been gathered to identify which nucleotides in the RNA of the virus could particularly contribute to a new function.

Once these are identified, a single or small nucleotide change will be made to the virus to confirm predictions from genomic research. The modified virus will then be placed on a Petri dish or inserted into an animal, such as a rabbit or a mouse, to see how the change affects the properties of the virus.

This type of research is performed in specialized laboratories that are tightly controlled and heavily regulated under biosafety laws that involve containment and decontamination processes.


Read more: HHow are dangerous viruses contained in Australia?


Concerns about gaining function search.

As the benefits of GOF virus research focus on preparing for a pandemic, concerns have been raised about whether the research is ethical or safe.

In 2005, the researchers used this technique for viruses when they reconstructed influenza (H1N1) from samples taken in 1918. The goal was to learn more about the properties of influenza and future pandemics, because the flu is still circulating, but the controversial study has sparked heated debate over whether it should be acceptable.

The two main concerns are whether it poses a threat to public health if a virus escapes from the lab, or whether the techniques could be used for nefarious purposes.

In the past year, 16 years after the H1N1 study, there has been debate as to whether SARS-CoV-2 spontaneously had zoonotic origins, or if it was’created‘in a GOF laboratory, then escaped.

So now, 16 years after the first controversial H1N1 study, this speculation has pushed GOF research back into the public eye and has led to many Criticisms research and regulation of laboratories using this technique.

In 2017, the US government bans lifted on GOF pathogen research after the National Institute of Health concluded that the risks of influenza and MERS research outweighed the benefits, and that few posed significant threats to public health.

However, following concerns about the origins of SARS-CoV-2, the rules surrounding GOF research, risk assessments and disclosure of experiences are now in the study again, to clarify the policy.


Read more: The COVID Laboratory Leak Hypothesis: What Scientists Do and Don’t Know


Beyond that, speculation sparked other ask for information on the origin of SARS-CoV-2, although the World Health Organization concluded that a viral escape from a laboratory was very unlikely.

It doesn’t matter, it’s never a bad thing review the biosecurity, biosecurity and transparency policy as new evidence becomes available, and it has been frequently revised throughout history.

As for the fear that a government or private entity might misuse scientific techniques for malicious purposes, scientists can, and do, support research bans they deem ethically irresponsible, such as the controversy. “CRISPR babies’.

Ultimately, the parameters around how scientific techniques like GOF are used and by whom are not a scientific question, but a question ethicists must answer.

About Alma Ackerman

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