Gain-of-function research of concern (GOFROC) virus research has returned to the news.[1] With it come fears of dark risks; we will either die from influenza without this research or die because of it. Each time the exchanges seem a little harsher and a little more personal. But what is it about? Briefly.
Two prestigious scientific groups are about to restart highly biosecure work on avian influenza (Flu) A virus, H5N1.[2,3] This and other viruses like Flu H7N9 and the coronaviruses SARS and MERS are described as potential pandemic pathogens (PPPs).
These two groups aim to manipulate or force the mutation of
Some of this work is expected to give the virus new properties, or gain functions, that it didn’t possess in the wild. For example, making H5N1 more transmissible. To be clear – this will all be done in the most biosecure of laboratories using expert scientists who have been thoroughly checked out.[4] Some of this work has already been done.[8] Also to be clear, a lot of GOF work poses little risk to humans. This H5N1 work is a bit different.
What benefits could this GOFROC work bring?
The most “real-world” or translatable outcomes, apart from new knowledge, were suggested to be the creation of new antivirals, vaccines, improved surveillance and help for public health experts to better understand how viruses might spread. Also, to plan for pandemics.[7]
Results in new antivirals?
Antivirals, based on newly identified changes to the proteins may be a possible benefit, should the mutant virus ever evolve naturally. These won’t be mass produced beforehand though. Commercial interests won’t go through the process to make a drug they can only sell if an H5N1 virus mutates in this specific way.
Creates better vaccines?
Simply put, vaccines don’t need this information. We are already limping toward having universal Flu vaccines. A universal vaccine won’t rely on knowledge from these H5N1 GOFROC studies to work. But we should be pushing scientists to focus on more quickly bringing universal Flu vaccine candidates to the arsenal.
Helps public health with pandemic plans?
Surveillance that identifies the emergence of
Provides public health with better PPP surveillance?
Let’s step along the surveillance pathway a little more slowly.
Viruses that cause visible illness in humans are the target for public health laboratory efforts and planning. The key word there is
Normal Flu surveillance already using methods that can detect all FluA viruses (of which H5N1 is one) including likely PPP Flu strains.
Only ill patients are tested. So if there is already an unusual and sustained (read: noticed) increase in Flu-like illness cases, it will have been picked up.
Once in the lab, gene and whole genome sequencing are performed on the Flu samples. Perhaps the new knowledge from H5N1 studies could be leveraged to allow recognition of a mutation that increased transmissibility in the PPP virus already seen causing illness. Cool. Academically anyway.
The PPP Flu virus would already be in play and spreading. It would be international before we could stop it. Almost certainly well before modelling discussions start reporting on how many new cases will be infected by every current case. this modelling may, or may not, have been contributed to by these H5N1 studies.
What risks and consequences come along with this work?
A tweet I recently saw kinda sums up the situation nicely.
My unsatisfying take is that these experiments are neither very dangerous nor particularly useful for public health, though scientifically interesting. https://t.co/N8f2Kj20e8— Stephen Goldstein (@stgoldst) February 28, 2019
The experiments themselves aren’t dangerous in the right expert hands. But they are subject to accident. Accidents happen. Probably more than we care to consider.[10] An accidental release of, for example, a mutated Flu virus that can transmit more effectively between humans, is an extremely dangerous consequence to the world. If released, people will die. There is also intent. What if someone were to steal a mutated virus from one of these labs? Realistically though, there’s probably enough expertise and imagination in the world for others to make (or have made) their own versions without needing to resort to theft.
Science divided
There are some very deep and strong feelings about GOF work and so two camps have formed. Each has taken an energetic position for (Scientists for Science) the work to be done or against (The Cambridge working group) the risk due to accidental release.
What is needed?
Oversimplifying this as much as possible: if those running the work could provide better justification of the real-world benefits arising from this work, those on the other side and the public could better judge whether the benefits outweigh the rare but hugely consequential risks to the world.[9]
One particular comment from 2014 lays this out quite succinctly..
There is no evidence that these provide any benefit in predicting the natural evolution of the flu, help to design vaccines, or aid surveillance in any way. Fouchier and colleagues have made arguments that amount to little more than hand waving, such as “this will aid our understanding of the flu.” Bluntly speaking, that is nonsense.
Steven L. Salzberg, Ph.D [5]
Gain-of-Function Deliberative Process Written Public Comments
In research applications seeking funds, scientists are expected to detail the likely outcomes from their work; they should describe the real-world benefits to the grant reviewers. This helps them get funded. Reviewers who are expert and experienced in reviewing can usually see how much thought goes into these sections. As it looks right now, too little thought has been put into these sections.
References
- Controversial experiments that could make bird flu
more risky poised to resume
https://www.sciencemag.org/news/2019/02/exclusive-controversial-experiments-make-bird-flu-more-risky-poised-resume - TRANSMISSIBILITY OF AVIAN INFLUENZA VIRUSES IN MAMMALS
https://projectreporter.nih.gov/project_info_description.cfm?aid=8728727 - https://www.sciencemag.org/sites/default/files/Mt%20Sinai%20paused%20studies.pdf
- Studies of Deadly Flu Virus, Once Banned, Are Set to Resume
https://www.nytimes.com/2019/03/01/health/bird-flu-pandemic.html - Gain-of-Function Deliberative Process Written Public Comments, 2014-2016
https://osp.od.nih.gov/wp-content/uploads/2013/06/Gain_of_Function_Deliberative_Process_Written_Public_Comments.pdf - Comment on “Gain-of-Function Research and the Relevance to Clinical Practice”
https://academic.oup.com/jid/article/214/8/1284/2218764 - Learning What H5N1 Needs to Spread
https://www.nih.gov/news-events/nih-research-matters/learning-what-h5n1-needs-spread - The Next Plague Is Coming. Is America Ready?
https://www.theatlantic.com/magazine/archive/2018/07/when-the-next-plague-hits/561734/ - The U.S. is funding dangerous experiments it doesn’t want you to know about
https://www.washingtonpost.com/opinions/the-us-is-funding-dangerous-experiments-it-doesnt-want-you-to-know-about/2019/02/27/5f60e934-38ae-11e9-a2cd-307b06d0257b_story.html?utm_term=.65b94c740f41 - Comments on Fouchier’s Calculation of Risk and Elapsed Time for Escape of a Laboratory-Acquired Infection from His Laboratory
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453553/
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Some have said that science is not democratic (that seems to be contradictory to the scientific making of discoveries and progresses: this is true until it is proved false…). So, perhaps, other Big Names are tempted to build an Ivory Tower from when they will disperse their new knowledge to the ignorant masses. Scientists – we should remind them – aren’t so innocent with respect to the current state of global affairs, namely the destructive path of economic development in all its forms. We – the ignorants – have the right to know what it is being done in that Ivory Tower and if the risks are overwhelming against any possible benefit, some experiments should be rethinked or revised or stopped. We have just done much to the ill-advised spirit of the progress: being on the brink of the 6th mass extinction might be enough?
Science isn’t democratic.