Gain-of-function research
Gain of function research (GoFR) is a field of medical research focused on the serial passaging of bacteria or viruses in vitro, accelerating mutation processes to adapt their transmissibility, virulence and antigenicity, to better predict emerging infectious diseases and develop vaccines.
Types of research
Virology
Gain-of-function research is employed to better understand current and future pandemics.[1]
Vaccine development
Gain-of-function research is conducted in order to gain a head start on a virus and to develop a vaccine or therapeutic before it emerges.[1]
History
The 1925 Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or other Gases, and of Bacteriological Methods of Warfare (aka the Geneva Protocol) was imprecise on virii. In addition, it was unclear when the Biological Weapons Convention was ratified in 1975 that virii were regulated by it, because viruses lie "at the edge of life", ie, they possess some but not all of the characteristics of life. Synthetic biology was a figment of imagination at the time. This backdoor allowed curious scientists with pliable ethics committees to study gain-of-function.[2]
In February of 2000, a group at the Utrecht University led by Peter Rottier published a paper on their gain-of-function studies titled "Retargeting of Coronavirus by Substitution of the Spike Glycoprotein Ectodomain: Crossing the Host Cell Species Barrier" detailing how they constructed a mutant of the coronavirus mouse hepatitis virus, replacing the ectodomain of the spike glycoprotein (S) with the highly divergent ectodomain of the S protein of feline infectious peritonitis virus. According to the paper, "the resulting chimeric virus, designated fMHV, acquired the ability to infect feline cells and simultaneously lost the ability to infect murine cells in tissue culture".[3]
In May 2012, a Japanese group of scientists operating out of the University of Wisconsin with funding from the Bill & Melinda Gates Foundation, ERATO, National Institute of Allergy and Infectious Diseases and support gifts from the National Institutes of Health and the Vietnamese National Institute of Hygiene and Epidemiology published a paper in the journal Nature about airborne transmission of the H5N1 bird flu introduced via respiratory droplet transmission from one ferret to another. The group "had altered the virus’s amino acid profile, allowing it to reproduce in mammal lungs, which are a bit colder than bird lungs. That small change allowed the virus to be transmitted via coughing and sneezing, and it solved the riddle of how H5N1 could become airborne in humans... (Some) members of Congress, among other critics around the world, responded to the publication of the research with alarm and condemnation." A New York Times editorial described the event as "An Engineered Doomsday."[4][5]
In May 2013, Hualan Chen, who was then director of the China's National Avian Influenza Reference Laboratory, and colleagues successfully created a new strain of influenza virus through a gain-of-function experiment at the BSL3 approved Harbin Veterinary Research Institute.[6] The Chinese scientists "deliberately mixed the H5N1 bird-flu virus, which is highly lethal [to birds] but not easily transmitted between [humans], with a 2009 strain of H1N1 flu virus, which is very infectious to humans."[7] This event caused consternation in European biotech circles, as Professor Simon Wain-Hobson of the Pasteur Institute the Chinese scientists "haven’t been thinking clearly about what they are doing. It’s very worrying... The virological basis of this work is not strong. It is of no use for vaccine development and the benefit in terms of surveillance for new flu viruses is oversold," while Lord May of Oxford said: "The record of containment in labs like this is not reassuring. They are taking it upon themselves to create human-to-human transmission of very dangerous viruses. It’s appallingly irresponsible."[7]
In 2014, The White House under the Obama administration instituted a moratorium on gain-of-function research into influenza, MERS, and SARS, and paused funding for all projects for three years.[8][9]
In 2016, synthetic virology scientists and bioethics experts again raised concerns with the dual-use of gain-of-function research.[1][9]
By March 2016, funding for gain of function research was provided by government agencies, pharmaceutical research companies, venture capital funds, colleges and universities, nonprofit research institutions, foundations, and charities.[10]
Criticism
In about 2015, a writer on GoFR observed that "there is little international enforcement of limitations on bioweapons. For chemical materials like sarin gas, the Chemical Weapons Convention provides a treaty-based legal framework for stopping proliferation, and a watchdog group, the Organization for the Prohibition of Chemical Weapons, [investigates] potential violations." While the Biological Weapons Convention exists, "No similar watchdog exists around biological weapons."[5]
Society and culture
During the 2020 COVID-19 pandemic a number of conspiracy theories spread about the origin of the SARS-CoV-2 virus, sometimes deployed as a form of political propaganda. One popular version of the story invoked previous gain-of-function work on coronaviruses to promulgate the idea that the virus was of laboratory origin. Virologist Angela Rasmussen writes that this is ironic, since in reality such research had enabled scientists to gain a better understanding of the novel virus.[11]
See also
References
- ^ a b c Selgelid, Michael J. (2016-07-06). "Gain-of-Function Research: Ethical Analysis". Science and Engineering Ethics. 22 (4): 923–964. doi:10.1007/s11948-016-9810-1. PMC 4996883. PMID 27502512.
- ^ Johnson, Durward; Kraska, James (14 May 2020). "Some Synthetic Biology May Not be Covered by the Biological Weapons Convention". The Lawfare Institute.
- ^ Kuo, L.; Godeke, G. J.; Raamsman, M. J.; Masters, P. S.; Rottier, P. J. (2000). "Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: Crossing the host cell species barrier". Journal of Virology. 74 (3): 1393–406. doi:10.1128/jvi.74.3.1393-1406.2000. PMC 111474. PMID 10627550.
- ^ Imai, Masaki; Watanabe, Tokiko; Hatta, Masato; Das, Subash C.; Ozawa, Makoto; Shinya, Kyoko; Zhong, Gongxun; Hanson, Anthony; Katsura, Hiroaki; Watanabe, Shinji; Li, Chengjun; Kawakami, Eiryo; Yamada, Shinya; Kiso, Maki; Suzuki, Yasuo; Maher, Eileen A.; Neumann, Gabriele; Kawaoka, Yoshihiro (2012). "Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets". Nature. 486 (7403): 420–428. Bibcode:2012Natur.486..420I. doi:10.1038/nature10831. PMC 3388103. PMID 22722205.
- ^ a b Tucker, Patrick (n.d.). "To Protect Ourselves From Bioweapons, We May Have to Reinvent Science Itself". Defense One.
- ^ Zhang, Y.; Zhang, Q.; Kong, H.; Jiang, Y.; Gao, Y.; Deng, G.; Shi, J.; Tian, G.; Liu, L.; Liu, J.; Guan, Y.; Bu, Z.; Chen, H. (2013). "H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet". Science. 340 (6139): 1459–1463. Bibcode:2013Sci...340.1459Z. doi:10.1126/science.1229455. PMID 23641061. S2CID 206544849.
- ^ a b Connor, Steve (2 May 2013). "'Appalling irresponsibility': Senior scientists attack Chinese researchers for creating new strains of influenza virus in veterinary laboratory". The Independent.
- ^ Kaiser, Jocelyn; Malakoff, David (17 October 2014). "U.S. halts funding for new risky virus studies, calls for voluntary moratorium". Science. Retrieved 28 July 2016.
- ^ a b Imperiale, Michael J.; Casadevall, Arturo (2016). "Zika Virus Focuses the Gain-of-Function Debate". mSphere. 1 (2). doi:10.1128/mSphere.00069-16. PMC 4894681. PMID 27303723.
- ^ Board On Life, Sciences; Division on Earth Life Studies; Board on Health Sciences Policy; Health Medicine, Division; Committee On Science, Technology; Policy Global, Affairs; National Academies Of Sciences, Engineering (March 2016). Millett, Piers; Husbands, Jo; Sharples, Frances; Thevenon, Audrey (eds.). Gain-of-Function Research: Summary of the Second Symposium" (PDF). doi:10.17226/23484. ISBN 9780309440776. PMID 27403489. Retrieved January 29, 2021.
{{cite book}}:|author3=has generic name (help) - ^ Rasmussen A (2021). "On the origins of SARS-CoV-2". Nature Medicine. 27 (9): 9. doi:10.1038/s41591-020-01205-5. PMID 33442004. S2CID 231606580.