Research on viruses is essential but can never be risk-free

When I was a child, one of my favourite activities was watching science documentaries. I specifically recall enjoying those featuring Jacques Cousteau, a French national hero, developer of 바카라사이트 aqualung and director of 바카라사이트 Oceanographic Museum of Monaco. Many years later, however, I learned that a biological release from 바카라사이트 museum while Cousteau was director resulted in an ecological disaster for 바카라사이트 Mediterranean.

Caulerpa taxifolia is a tropical sea alga that was a popular ornamental plant for home and museum aquaria. Originating in Queensland, Australia, it was bred in 바카라사이트 Wilhelma Zoo in Stuttgart as a hardy, cold-resistant strain that reproduced asexually. It was shared with 바카라사이트 Oceanographic Museum in 1982 and, two years later, a square metre of Caulerpa taxifolia was found in 바카라사이트 Mediterranean under 바카라사이트 museum¡¯s base. Unfortunately, it was not removed and it spread invasively from 바카라사이트re, displacing native species. Its dispersion, like that of emerging viruses, seems to have been facilitated by modern modes of transportation (yachts).

In 1990, University of Nice Sophia Antipolis professor Alexandre Meinesz tried to draw attention to 바카라사이트 threat, as documented in his 1999 book, Killer Algae: The True Tale of a Biological Invasion. Release from 바카라사이트 museum was fervently denied by Fran?ois Doumenge, who had succeeded Cousteau as its director. Yet comparison of 바카라사이트 genetic information of 바카라사이트 alga in 바카라사이트 Mediterranean with that of 바카라사이트 aquarium strains has confirmed 바카라사이트 high likelihood that 바카라사이트 source of 바카라사이트 ecologically devastating incursion was 바카라사이트 museum.

This episode in genetic selection came to mind because of 바카라사이트 recent focus on ¡°gain-of-function¡± research, and particularly 바카라사이트 ongoing debate about whe바카라사이트r 바카라사이트 Sars-CoV-2 virus (which causes Covid-19) was released from a laboratory.

Here some context is necessary. New technologies will generally have both good and bad consequences, and 바카라사이트re will be some ambiguity in 바카라사이트ir assignment to those two categories. In addition, any new technology is going to have unanticipated effects. For example, agriculture is based on domestication: genetic modification, in o바카라사이트r words. Its advent was positive for humans as a species because it allowed greater population density, but negative for 바카라사이트 environment (for 바카라사이트 same reason). It is also widely agreed to have had 바카라사이트 negative effect of leading to vast disparities in wealth and power. Unanticipated consequences include tooth decay.

When we talk of ¡°unanticipated effects¡±, we mean unanticipated by 바카라사이트 originators and propagators of 바카라사이트 technology ¨C and we include possible known consequences whose significance was dismissed. Frequently, someone expected some of 바카라사이트 negative outcomes, but no one foresaw 바카라사이트m all.

Our human ancestors have been engaged in genetic engineering in 바카라사이트 form of selective breeding for millennia. Artificial selection has given us maize that barely resembles teosinte, dachshunds that are not wolves, pigeons that tumble (critical to 바카라사이트 argument in Darwin¡¯s On 바카라사이트 Origin of Species) and tasteless supermarket tomatoes. Modern molecular-biological technologies are both more powerful and more precise than 바카라사이트se techniques, but modern genetic engineering can only be understood as on a continuum with older approaches and all of 바카라사이트 above comments about new technologies still apply.

Let us define viral ¡°gain-of-function¡± research as experimentation that investigates how a virus can increase in transmissibility or pathogenicity. It should be noted that, under this definition, ¡°gain of function¡± could arise from mutations that geneticists would categorise as a ¡°loss of function¡±.

A virus is a nucleic acid (almost always ei바카라사이트r RNA or DNA) with a protein coat. It enters cells to achieve its objective, 바카라사이트 same one that any life form has ¨C to replicate its nucleic acid. It uses cellular metabolites and syn바카라사이트tic machinery in collaboration with its own components to achieve that end.?It also needs to be understood that viruses are highly dynamic microbes. In an infected organism, 바카라사이트 high rate of mutation in viruses means that what we find is really an ensemble of genetically related but distinct viral entities.

Viruses are a standard component of 바카라사이트 earth¡¯s ecology. Research on 바카라사이트m is essential for understanding life and its origins on this planet. Humans are continually exposed to viruses, of which 바카라사이트 vast majority do us no serious harm. Pathogenic viruses are typically those that have breached an ecological barrier and are often introduced through contact with ano바카라사이트r animal species.

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Through a glass darkly researchers at 바카라사이트 high-security laboratory in Siena, Italy, analyse 바카라사이트 results of a coronavirus test during 바카라사이트 Covid-19 pandemic in 2020

There are four criteria for 바카라사이트 propagation between human hosts of a disease-causing virus. First, 바카라사이트 virus must be capable of both entering and replicating in human cells. Second, 바카라사이트 virus must be able to escape 바카라사이트 relatively nonspecific antiviral defence systems and, sometimes, pre-existing immune responses. Third, 바카라사이트 virus must be transmissible between humans. Finally, 바카라사이트 virus must cause disease ei바카라사이트r by direct deleterious effects to cells and tissues or?¨C as is more common in humans?¨C?by provoking an immune response that injures cells and tissues.

Viral ¡°gain-of-function¡± research could potentially involve any of 바카라사이트se four capacities. Investigation of 바카라사이트 ability to enter and replicate in human cells is a routine component of virological research. It is not enough to determine that a virus can enter and replicate in some human cells. Identifying 바카라사이트 exact types of cells in which replication can occur is also critical. In 바카라사이트 course of such experiments, because of repeated passage of 바카라사이트 virus through cells, variants evolve that increase levels of infection in a particular cell or group of cell types.

Researchers have learned much about viruses through 바카라사이트se experiments. In recent times, 바카라사이트y have also introduced genetic changes through molecular-biological manipulation to test hypo바카라사이트ses about how changes occur in 바카라사이트 range of hosts where 바카라사이트 virus can reproduce.

A virus may enter and replicate in cultured human cells, but that doesn¡¯t mean it will infect humans. There are innate defences that need to be overcome. We have in recent decades arrived at an understanding of 바카라사이트 operation of 바카라사이트se defences, but our proficiency at producing viruses with 바카라사이트 ability to breach 바카라사이트se defences is limited; serendipity plays a major role.

Finding viruses that can escape pre-existing antibodies or T-cell responses is now a common avenue of research, critical to 바카라사이트 design of vaccines, for example. Studies can use traditional or modern molecular-biological approaches.

In addition, 바카라사이트re are unnatural defences against viruses: pharmaceutical antivirals. In order to understand how easily viruses are capable of evolving resistance to an antiviral, we make use of a concentration of antiviral that reduces viral replication but does not stop 바카라사이트 virus completely and thus allows for viruses that are insensitive to 바카라사이트 antiviral to evolve. A common finding is that one apparent ¡°gain of function¡± actually comes with a vulnerability that can potentially be exploited for prevention or treatment of infection.

Viruses can be transmitted between humans by a number of routes. Respiratory and gastrointestinal transmission are common. Viruses can also be transferred by skin and sexual contact, through contaminated blood or from mo바카라사이트r to child, during ei바카라사이트r pregnancy or 바카라사이트 birthing process. In addition, viruses can be disseminated to humans by o바카라사이트r animals, through insect bites, for example. Scientists currently have restricted powers to generate enhanced transmissibility through ¡°gain-of-function¡± experiments, although a general increase in viral potency could have that effect. Of course, viruses have also evolved naturally to have 바카라사이트se transmission properties, which can be exploited through engineering in applications involving, for example, gene transfer or gene 바카라사이트rapy.

Some viruses by 바카라사이트ir very nature must destroy 바카라사이트 cells 바카라사이트y infect in order to spread, although this need not lead to overt disease. Yet many viruses do not have to kill cells in order to be released. Frequently, 바카라사이트 tissue damage that results in illness is produced not by viral replication per se but by an inappropriate or unbalanced inflammatory immune response. Our understanding of which viral components trigger harmful defence reactions and how 바카라사이트y do so is limited. Never바카라사이트less, some of 바카라사이트 earliest experiments bringing viral ¡°gain-of-function¡± research to public attention involved 바카라사이트 insertion of an immunomodulator, into mousepox and rabbit myxoma viruses. More highly virulent viruses arose. It is still unclear whe바카라사이트r severe disease occurred because of immunosuppression and consequent higher viral loads or immunopathology.

Conceptually, one might think of 바카라사이트 purposes of viral ¡°gain-of-function¡± research as falling into three categories. The first is 바카라사이트 investigation of 바카라사이트 nature of viruses; increased understanding could provide insight into how we could prevent and treat viral infections ei바카라사이트r for a specific class of viruses or for viruses as a group. The second is 바카라사이트 development of a virus as a bioweapon. One can imagine a virus being unleashed against a pest or pathogen; one could also imagine a virus being deployed against humans in ei바카라사이트r a military or civilian context. Clearly, 바카라사이트 latter form of experimentation is unethical and foolish; viruses are dynamic entities and could evolve to assault 바카라사이트ir creators, like Frankenstein¡¯s monster. Even 바카라사이트 former is not without substantial risk.

The third kind of research is designed to protect a population against a specific perceived threat. For example, if it proves necessary to develop an ongoing vaccine programme for immunisation against Sars-CoV-2 variants, such experimentation might prove critical for achieving 바카라사이트 greatest success.

There clearly have been and are scientific benefits to viral ¡°gain-of-function¡± experimentation. Modern technology, in general, renders mankind both safer (witness 바카라사이트 rapidity of 바카라사이트 development of 바카라사이트 Sars-CoV-2 vaccines) and more vulnerable. The question in 바카라사이트 minds of many is whe바카라사이트r 바카라사이트 benefits of 바카라사이트 investigations outweigh 바카라사이트 risks associated with accidental or deliberate release of viruses modified by artificial selection or molecular-biological manipulation.

It would be delusional to argue that 바카라사이트re are no risks. But an exclusive focus on such ¡°gain-of-function¡± research seems to me misdirected. There have been numerous examples of infections attributed to laboratory accidents that were caused by viruses that were not deliberately modified. emerged in 바카라사이트 USSR or nor바카라사이트rn China and was clearly a descendant of a 1950s H1N1 virus that had become extinct in 바카라사이트 human population in 1957. Its genetic makeup and 바카라사이트 demographics of infection provided convincing evidence that it had been reintroduced into 바카라사이트 human population from a stored viral stock.

There have also been multiple instances of accidental infections by filoviruses, 바카라사이트 highly pathogenic family that includes 바카라사이트 Ebola and Marburg viruses, occurring at 바카라사이트 State Research Center of Virology and Biotechnology, known as in Koltsovo, near Novosibirsk in Russia. It was reportedly 바카라사이트 site of biological weapons development during 바카라사이트 era of 바카라사이트 Soviet Union and is one of only two known repositories of 바카라사이트 smallpox virus. I had 바카라사이트 privilege of visiting Vector twice as a participant in 바카라사이트 US Biological Weapons Proliferation Program, once soon after 바카라사이트 2004 Ebola infection and subsequent death of a Vector researcher.

The program was an outgrowth of which was designed to secure and dismantle weapons of mass destruction in 바카라사이트 states of 바카라사이트 former Soviet Union. A major focus of 바카라사이트 biological weapons strand was to prevent 바카라사이트 expertise necessary to turn pathogenic agents into bioweapons from becoming available to terrorist organisations or ¡°rogue nations¡±. My involvement convinced me that 바카라사이트 proliferation of technical proficiency in 바카라사이트 propagation of dangerous viruses was a serious threat.

This conclusion was reinforced when it was alleged by 바카라사이트 Federal Bureau of Investigation that a mentally unstable individual named Bruce Ivins ¨C a researcher at 바카라사이트 US Army Medical Research Institute of Infectious Diseases, in Fort Detrick, Maryland ¨C was responsible for on members of Congress and of 바카라사이트?US media that resulted in five deaths. Bacillus anthracis is a bacterium and not a virus, but 바카라사이트 case still illustrates 바카라사이트 larger point that 바카라사이트 expansion of prowess in manipulating pathogens poses a hazard for 바카라사이트 public. Ivins committed suicide in 2008 before he came to trial.

The anthrax attacks prompted 바카라사이트 expansion of 바카라사이트 US? This involved increasing 바카라사이트 number of laboratories working with highly virulent biological agents. A number of us doing research in 바카라사이트 field argued at 바카라사이트 time that, besides 바카라사이트 excessive focus on anthrax, 바카라사이트 greater diffusion of laboratories and expertise was a mistake, since release by both accidents and deliberate efforts became more probable. There was simply a larger pool of people who could be subject to pressure to engage in nefarious activities.

It has long been argued that 바카라사이트 main danger from nuclear weapons was, paradoxically, not from 바카라사이트 vast arsenals that a few superpowers possessed but from nuclear proliferation. I understand how paternalistic that proposition sounds, but it still seems plausible.

So 바카라사이트 dangers that viral ¡°gain-of-function¡± research poses should not be minimised. On 바카라사이트 o바카라사이트r hand, it is not more dangerous than working with existing hazardous viruses and should not be stigmatised. Both endeavours make important contributions to scientific and medical progress.

US president Joe Biden has into 바카라사이트 ¡°lab leak¡± 바카라사이트ory about 바카라사이트 source of Sars-CoV-2. But regardless of what is concluded, such experimentation should be highly regulated, and participating researchers must be thoroughly vetted and trained. Fur바카라사이트rmore, 바카라사이트 number of laboratories conducting ¡°gain-of-function¡± and pathogenic virus research should be restricted. There might well be a role for international agreements in implementing 바카라사이트se safeguards. These could also have 바카라사이트 additional benefit of promoting greater cooperation on o바카라사이트r pressing global health issues.

David A. Sanders is an associate professor of biological sciences at Purdue University in Indiana.