Gain of Function in Wuhan

William of Ockham is known for his thoughts on philosophy and logic, none more famous than Ockham’s Razor, the principle that things are usually connected in the simplest or most economical way. That when attempting to explain the relationship between two or more things, we should give precedence to the simplest explanation.

When the World Health Organization (WHO) released its report on the origins of COVID-19, or more specifically, the SARS-CoV-2, the virus that causes COVID-19, the world was left with more questions than answers.

A sentiment echoed by WHO director-general Dr. Tedros Adhanom Ghebreyesus who said that, “all hypotheses remain on the table” regarding the origin of SARS-CoV-2, during the unveiling of a WHO report on the origin of the pandemic.

The report itself is largely informative, and delves into great detail about the epidemiology and biochemistry of the virus, most of which is substantiated by clinical studies or robust modeling backed by peer-reviewed data.

The curious part of the report comes at the end, when it lists the possible origins of the virus, in the last section prior to the Concluding Remarks called, Possible Pathways of Emergence. Ostensibly, when reading the report, it would appear that the claims of the virus’s origins are derived from the meticulous research done in previous sections leading up to claims about the origins of the virus.

But the report fails to explain the basis for these claims, instead listing different degrees of likelihood for the origins, without discussing how the likelihoods were derived, nor correlating the likelihoods with specific data or facts presented in the previous sections.

In its place, the report lists four scenarios in which investigators list possible origins of the virus and provide an “assessment of likelihood” for those possible origins based upon an inherently subjective evaluation of select data and broad findings that were presented earlier in the report.

Possible to likely: Direct zoonotic spillover

Likely to very likely: Introduction through an intermediate host followed by zoonotic transmission

Possible: Introduction through cold/ food chain [goods]

Extremely unlikely: Introduction through a laboratory incident

These assessments were then followed abruptly by a three sentence conclusion which simply called for additional investigations with the final line stating:

“In conclusion, the team called for a continued scientific and collaborative approach to be taken towards tracing the origins of COVID-19.”

Perhaps that was the intention of the report, to collect data and to presume possible causes without drawing any definitive conclusions. But the perception of the report was far different – and far more political.

Secretary of State Antony Blinken said on CNN that the Biden administration has, “real concerns about the methodology and the process that went into that report.”

In Australia the media was more direct. Sharri Markson, the television host of Sky News, a prominent media outlet in the country, called the report, “a piece of propaganda”, for the Chinese Communist Party.

Across the world, the general perception of the report came off as largely exculpatory towards the Chinese, which the world has already convicted in the court of public opinion for triggering the events that led to the pandemic. Perhaps these sentiments are well placed, as the Chinese have behaved oddly since the pandemic began.

But to conflate the ambiguity of the report as somehow being exculpatory towards the Chinese misses the mark entirely.

The Chinese undoubtedly have experimented with all sorts of viruses, including different versions of the virus that caused the pandemic. And the Wuhan Institute of Virology, the laboratory in question, has a well established record of publishing research in the field of virology known as ‘gain-of-function’, which is defined as, per a joint statement from the National Research Council & Institute of Medicine in 2015:

“Research that aim to produce a gain of a desired function, such as higher yields for vaccine strains, but often also lead to loss of function, such as loss of the ability for a virus to replicate well, as a consequence.”

In other words, any selection process involving an alteration of genotypes and their resulting phenotypes is considered a type of gain-of-function (GoF) research, which also includes increasing the infectivity and pathogenicity of the virus.

Research that the National Institutes of Health (NIH) is well aware of and actively funds, both domestically and internationally, while also acknowledging the potential risk inherent in these studies. The NIH has released its own statement warning about the risks inherent in GoF studies:

“Certain gain-of-function studies with the potential to enhance the pathogenicity or transmissibility of potential pandemic pathogens (PPPs) have raised biosafety and biosecurity concerns, including the potential dual use risks associated with the misuse of the information or products resulting from such research.”

So it should come as no surprise that this type of research is vehemently contested among leaders within the field of Virology, with some advocating for it while others in fierce opposition. And the tension within the scientists is mirrored by the conflicting policies over GoF research, usually drawn along political lines.

In 2014, under the Obama administration, the US government declared a moratorium on such research – putting GoF experiments on hold so the world could discuss the risks. But in 2017, the Trump administration green-lighted GoF research, ending the moratorium. And updates from the NIH in 2019 suggests that these studies were quite active just months before the pandemic even began – in the United States, in China, and across the world.

It is well within the realm of possibility that the SARS-CoV-2 virus was altered in a GoF experiment in China, and inadvertently infected a lab worker – which then found the perfect nidus for spread in a meat market known for the rapid spread of zoonotic viral infections due to the close proximity of exotic animals and highly dense human populations.

Such leaks have happened before, with alarming regularity, throughout the world.

In 1978, a laboratory photographer contracted small pox in Birmingham, England where researchers were actively trying to eradicate the viral disease. Somehow, the virus escaped the lab, though it was quickly contained. In 2014, as the Food and Drug Administration (FDA) found six vials of smallpox abandoned in an old facility in Washington DC. No one even knew the vials were there.

These are not isolated incidences confined to smallpox .The Centers for Disease Control & Prevention (CDC) has reported over 1,000 incidences of stolen or lost toxins between 2005 and 2012 – which can include anything from anthrax to a number of viral species. And these were only the reported incidences.

But to be clear, most viral outbreaks in recent years have emerged from naturally occurring viruses.

In 2003, the SARS outbreak spread to more than two dozen countries in North America, South America, Europe, and Asia before the global outbreak was contained. The virus that caused that outbreak is SARS-CoV-1, a corona virus that is closely related to SARS-CoV-2, and was first found in southern China in late 2002.

All of this is to say, as with everything related to this pandemic, there is more we do not know that what we do know. And what may appear very likely now, may prove less likely the more learn about SARS-CoV-2.

Yet there will inevitably be things we will never know with absolute certainty, and the best we can do is construct the simplest, most probable explanation – the pandemic’s Ockham’s Razor. Unfortunately, the origin of the pandemic is one of these things.

The genesis of every modern viral pandemic begins with a genetic mutation – some change in the viral genomic sequence brought about by a change that either allowed the virus to jump from an animal to a human or increase the spread of the virus from human to human.

But mutations are probabilistic. They occur spontaneously at varying rates across the genomic sequence of a virus. Some parts mutate more often than others. Some mutations are corrected, some lead to no meaningful change. Some increase function, some decrease function.

The problem is that we are attempting to decipher the probability of a specific type of mutation when all we have to go off of is circumstantial evidence and outright conjectures. There is no established framework through which we can calculate the cumulative probability of specific genomic mutations, and changes in a virus’s behavior, and changes in the virus’s infectivity across different populations.

And at this time we cannot say for sure whether the mutation in SARS-CoV-2 that led to the pandemic occurred naturally or was induced artificially through experiments at the Wuhan Institute of Virology.

So we are left to posture around circumstantial evidence that can easily support or refute any argument for the possible origin.

The WHO report believes the lab leak hypothesis is unlikely because the labs in Wuhan, “all had high quality biosafety level (BSL3 or 4) facilities that were well-managed,” and staff monitoring showed “no reporting of COVID-19 compatible respiratory illnesses prior to December 2019.”

But that conclusion contradicts a 2018 report from U.S. intelligence obtained by the Washington Post, which found that U.S. diplomats who visited the Wuhan Institute of Virology that year warned of, “serious safety issues.”

And in today’s internet cyber-society, when we are left with vague, circumstantial evidence, we tend to identify with the most extreme, conspiratorial explanation. So it should come as no surprise that immediately after the WHO report came out, additional evidence insinuating a massive cover-up also emerged. We began posturing about international cover-ups and global espionage.

We learned that one of the American scientists and many of the Western European scientists contributing to the report used $598,000 in grants from the NIH to fund research into the corona virus, at the Wuhan Institute of Virology between 2014 and 2020, some of which included GoF studies.

None of which was helped by the WHO, which somehow – even after a year of navigating through the chaos of the pandemic – has not understood how to deliver consistent, confident messaging. As though almost on cue, after the release of the report, Dr. Tedros added credence to the theory that the Chinese were withholding evidence:

“The team reports that the first detected case had symptom onset on the 8th of December 2019. But to understand the earliest cases, scientists would benefit from full access to data including biological samples from at least September 2019.”

Others at the WHO subsequently back-pedaled, claiming the report was merely a preliminary report, part of a broader, ongoing investigation.

But the damage was already done, and the political rhetoric spun into overdrive, which would now make it nearly impossible for an objective study to take place in the future. Too many news reports have already implicated a Chinese cover-up, some coming from widely read news outlets around the world.

This means that even if the pandemic began as a genuine accident, China will be implicated as though it was criminally liable.

But as Alison Young recently reported at USA Today, “these and similar safety lapses are happening with disturbing regularity at elite U.S. labs operated by government agencies, the military, universities and private firms. There is no reason to believe they aren’t happening at labs in other countries as well.”

A notion corroborated by former CDC director, Dr. Robert Redfield while being interviewed on CNN:

“If I was to guess, this virus started transmitting somewhere in September, October in Wuhan. It’s not unusual for respiratory pathogens that are being worked on in a laboratory to infect the laboratory worker.”

Yet, with the blame game in full spin, we are unlikely to obtain any further information beyond what we have, from any country or government agency, which means we have to make due with what we already have – in order to identify the most likely explanation – the pandemic’s Ockham’s Razor.

This means we are left to glean the most likely origin of the pandemic based upon the most probable type of viral mutation.

In a recent press conference, Dr. Anthony Fauci was asked to comment on Dr. Redfield’s belief that the virus originated in a lab. Dr. Fauci provided the following response:

“It [Dr. Redfield’s theory] is based on the idea that when the virus was first identified in late December of 2019, it seemed well adapted to transmission among the human population, suggesting it was adapted in the lab.”

Dr. Fauci went on to explain that most health professionals believe the virus had been circulating in China for weeks if not months, giving it plenty of time to adapt to rapid human to human transmission after adapting from animal to human.

Yet, Dr. Fauci’s explanation requires the virus to have mutated twice in a relatively short period of time, which from a probability standpoint is less likely than mutating only once.

But it is something we have seen SARS-CoV-2 do before, as there are numerous variants already circulating across the world, some still ravaging countries like Brazil. In India, some variants have already expressed a double mutation, which means the virus has benefited from two naturally occurring GoF changes.

In an interview with British Broadcasting Corporation (BBC) Virologist, Shahid Jameel, explained that a “double mutation in key areas of the virus’s spike protein may increase risks [of spread] and allow the virus to escape the immune system”, making it more infectious.

This means there is a precedent to multiple GoF mutations taking place over a rapid period of time.

But one mutation, no matter where in the genomic sequence it takes place, will always be more likely than two mutations, even in highly volatile areas of the genome. Which means the lab leak theory appears more likely, simply because it appears more probable – because one GoF mutation is more likely than two GoF mutations.

But until we fully sequence SARS-CoV-2 and study the patterns of mutation at different parts of the viral genome, we will never know for sure which mutations are most likely to occur. And even after we sequence the virus, we will only know the most probable origin – which may not be the actual origin, only the simplest explanation – the pandemic’s Ockham’s Razor.

Unfortunately, the simplest explanation has the greatest geopolitical implications.

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Vaccine Passports: what we need to know

The COVID-19 pandemic has killed more than half a million people in the US and has seriously impacted our daily lives. The granting of Emergency Use Authorizations for COVID-19 vaccines has been a game changer in helping to reverse the pandemic onslaught. Demand for the vaccines currently far exceeds supply nationwide. They have become the golden ticket that can transport us back to a time when routine activities, such as attending school or taking vacations, didn’t seem fraught with danger. What’s the best way to go about re-establishing these activities? One idea that’s getting discussed seriously is giving those who have been immunized a vaccination passport (VP).

What is a vaccination passport?

Let’s start by clarifying some terminology. VPs are documents that show that someone has been given a vaccine(s) and is therefore presumed to be immune from getting and sharing that disease. These are distinct from diagnostic tests to determine if a person is or is not infected with a particular virus (PCR and viral antigen tests) or has been exposed to a virus (antibody tests). VPs are the modern day equivalents of the “letters of transit” that played a key role in the film Casablanca. They’ll enable you to travel freely.

Why give vaccine passports?

Vaccinated people are unlikely to transmit the virus that causes COVID-19 with others, though this has yet to be definitely proven. So, what’s the primary rationale for giving vaccination passports? It seems the goal is to incentivize people to get vaccinated. Folks might be more likely to seek out the vaccine if it bestows upon them certain privileges, such as being able to travel freely. While the idea might sound appealing at one level, the road to vaccine passports is pockmarked with political potholes and littered with logistical land mines.

Administrative issues

There are a lot of important questions that need to be answered before VPs can become widespread; it’s unlikely there will be a “one size fits all” solution. What might VPs look like? Pieces of paper (that could easily be lost or counterfeited), or a digital key or document you store on your smartphone (that many older folks still don’t have)? If you lost one, how would you get it replaced? Would your vaccination records be tied to your other medical records, and if so, what kind of privacy and security protections would be needed to safeguard your data? How would the passport administrator verify that you got vaccinated in the first place? Who is responsible for correcting any errors that crop up? Given how much we’ve struggled as a nation to simply solve the scheduling of vaccinations, VPs might be significantly more difficult to manage.

Who’s going to run the program?

A coalition of health tech leaders (including Epic, the Mayo Clinic, Microsoft and Salesforce) has started the Vaccination Credential Initiative to create an internationally accepted digital health card. Its vision – as stated on its website – is “to empower individuals to obtain an encrypted digital copy of their immunization credentials to store in a digital wallet of their choice. Those without smartphones could receive paper printed with QR codes containing World Wide Web Consortium (W3C) verifiable credentials.” Some European countries (e.g. Denmark) are working on developing their own immunization passports, and the President of the European Union Commission has voiced support for them.

We already have a hodgepodge system designed to keep folks with COVID-19 from traveling. Many airlines are requiring proof of non-infectivity to board a plane – these are distinct from VPs. The methods adopted vary from airline to airline: United uses Travel Ready Center, American uses VeriFly while others use Common Pass. Saga cruises are the first in the UK to demand proof of vaccination, but not everyone is on board with the concept. The World Travel and Tourism Council stated its opposition to allowing travel only by those who have been vaccinated, on the grounds that it is discriminatory.

Discrimination concerns

The concept of gaining advantage from one’s immunological status is not a new one. In New Orleans in the mid 19th century, great economic value was attached to those who survived the onslaught of epidemic waves of yellow fever. A mix of structural racism and a system valuing “immunocapital” ranked men and women highly if they were yellow fever survivors. Those that had not had the disease yet found it difficult to obtain work or obtain credit and women could not marry. Slaves were similarly revalued, with larger assessments attached to survivors. This legacy of viral discrimination casts a long shadow over current discussions surrounding vaccination passports.

Also problematic is the fact that not everyone will be eligible for VPs. Some people can’t be vaccinated for medical reasons but would still like to participate in whatever activities the passports enable (such as travel opportunities). These individuals will likely file complaints if they are denied VPs, arguing that they’re discriminatory in nature. Vaccine opponents will no doubt also file lawsuits seeking to block the use of VPs, claiming they represent an attack on their freedoms and personal choice.

Others may be shut out of VP programs because they don’t have the computer skills to register online, a problem that’s turned out to be widespread with the vaccinations. Don’t have any ID? In some places this prevents the most vulnerable from getting the COVID-19 vaccine, and therefore VPs as well. Many Black and marginalized communities are already deeply suspicious of the medical establishment, and wary of receiving a COVID-19 vaccine. Restrictions that prevent these groups from participating in various societal activities because they don’t have VPs will echo the Jim Crow days of poll taxes and literacy tests that were required to vote.

Enforcement issues

VPs bring up a similar issue as mask mandates: who is going to enforce them? It is one thing for a cruise line to do so, since reservations are required and extensive paperwork needs to be filled out in advance. Who is going to keep non-vaccinated people out of restaurants or concerts that require proof of vaccination? We’ve already seen anti-maskers storm department stores, ignore requirements to wear masks on planes and even kill a security guard who confronted them.

Black market for vaccine passports

Many airlines are now requiring proof of a negative COVID-19 test before they will let their customers fly. This has led to a black market for fake negative COVID-19 test results for those who are looking to game the system. Similarly, bogus cards claiming that the cardholder was exempt– for medical reasons – from having to wear a mask, have been manufactured and distributed. It’s not hard to imagine that a similar market will emerge for VPs.

Overcoming vaccine hesitancy

Given the multitude of issues and concerns listed above, moving forward with issuing vaccination passports seems highly problematic. If the primary purpose of having VPs is to drive up immunization rates, that can be better accomplished by running public service announcements and ads illustrating how liberating it is to start doing normal activities once vaccinated. A nationwide campaign to do just that is already in the works. I personally can think of a better use for the time and money that will be spent on establishing VPs: use them to focus efforts on overcoming vaccine hesitancy in concert with combatting the high tide of online vaccine misinformation and disinformation.

Source: Technology Networks

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