But the 1918 Spanish flu has, as far as I know, legitimately died out. Lots of people like saying that in a sense it’s still with us. This NEJM paper (with a celebrity author!) points out that it’s the ancestor of all existing flu strains. But most of these flu strains are less infectious than it was. This didn’t make sense to me the first, second, or third time I asked about it: why would a flu evolve into an inferior flu? Sure, it might evolve into a less deadly flu because it’s perfectly happy being more infectious but less deadly. But I think the Spanish flu was also especially infectious; so why would it evolve away from that?
One possible answer is “because by 1919, everyone had immunity to the 1918 flu, so it evolved away from it – and now nobody has immunity, but it lost the original blueprint.” The 1918 flu was a really optimal point in fluspace, but during all of history up until 1918, the flu’s evolutionary hill-climbing algorithm didn’t manage to find that point, and since flu has no memory it’s not going to be any easier for it to find it the second time, after it evolved away from it. So plausibly, existing flus are strictly worse at their job than Spanish flu was, and digging up an intact copy of the latter would be really bad.
And then there’s smallpox. No mystery why smallpox died out – we killed it. But then we stopped vaccinating people against it, and now if it comes back it would be really bad.
AT A PRESS conference at the White House on June 22nd Anthony Fauci, the director of America’s National Institute of Allergy and Infectious Diseases, issued a warning. The delta variant of the SARS-CoV-2 virus, first identified in India in February, was spreading in America—and quickly. “The delta variant is currently the greatest threat in the US to our attempt to eliminate covid-19,” declared Dr Fauci. Boris Johnson, Britain’s prime minister, issued a similar warning a week earlier. To contain the rapid spread of the variant, European countries and Hong Kong have tightened controls on travellers from Britain.
According to GISAID, a data-sharing initiative for corona- and influenza-virus sequences, the delta variant has been identified in 78 countries (see chart). The mutation is thought to be perhaps two or three times more transmissible than the original virus first spotted in Wuhan in China in 2019. It is rapidly gaining dominance over others. According to GISAID’s latest four-week average, it represents more than 85% of sequenced viruses in Bangladesh, Britain, India, Indonesia and Russia. It may soon be the most prevalent strain in America, France, Germany, Italy, Mexico, South Africa, Spain and Sweden. (GISAID does not, in its summary data, distinguish between delta, B.1.617.2, and the “delta plus” mutation, AY.1, AY.2.)
Chan started emailing authors and journals to get the raw data she needed to more fully analyze what they had done. Making such data available is usually a condition of publication, but it can still be hard to obtain. After what she calls months of stonewalling, Chan finally lost her cool and blasted an accusation out from her browser. “I need the scientists + editors who are directly or indirectly covering up severe research integrity issues surrounding some of the key SARS-2-like viruses to stop and think for a bit,” she posted to Twitter. “If your actions obscure SARS2 origins, you’re playing a hand in the death of millions of people.”
Eddie Holmes, a prominent Australian virologist and coauthor of one of those papers (as well as “Proximal Origins”), called the tweet “one of most despicable things I read on the origins issue.” He felt accused, but he wondered what he was being accused of, since his paper had correctly accounted for its pangolin data sources. Holmes then circulated an intricate time line prepared by Chan of the publication dates and past connections between the authors. The chart’s dense web of arrows and connections bore an unmistakable resemblance to an obsessive’s cork board covered with red string and thumbtacks.
In gain-of-function research, a microbiologist can increase the lethality of a coronavirus enormously by splicing a special sequence into its genome at a prime location. Doing this leaves no trace of manipulation. But it alters the virus spike protein, rendering it easier for the virus to inject genetic material into the victim cell. Since 1992 there have been at least 11 separate experiments adding a special sequence to the same location. The end result has always been supercharged viruses.
A genome is a blueprint for the factory of a cell to make proteins. The language is made up of three-letter “words,” 64 in total, that represent the 20 different amino acids. For example, there are six different words for the amino acid arginine, the one that is often used in supercharging viruses. Every cell has a different preference for which word it likes to use most.
In the case of the gain-of-function supercharge, other sequences could have been spliced into this same site. Instead of a CGG-CGG (known as “double CGG”) that tells the protein factory to make two arginine amino acids in a row, you’ll obtain equal lethality by splicing any one of 35 of the other two-word combinations for double arginine. If the insertion takes place naturally, say through recombination, then one of those 35 other sequences is far more likely to appear; CGG is rarely used in the class of coronaviruses that can recombine with CoV-2.
In fact, in the entire class of coronaviruses that includes CoV-2, the CGG-CGG combination has never been found naturally. That means the common method of viruses picking up new skills, called recombination, cannot operate here. A virus simply cannot pick up a sequence from another virus if that sequence isn’t present in any other virus.
A tale of two theories. After the pandemic first broke out in December 2019, Chinese authorities reported that many cases had occurred in the wet market — a place selling wild animals for meat — in Wuhan. This reminded experts of the SARS1 epidemic of 2002, in which a bat virus had spread first to civets, an animal sold in wet markets, and from civets to people. A similar bat virus caused a second epidemic, known as MERS, in 2012. This time the intermediary host animal was camels.
Contrary to the letter writers’ assertion, the idea that the virus might have escaped from a lab invoked accident, not conspiracy. It surely needed to be explored, not rejected out of hand. A defining mark of good scientists is that they go to great pains to distinguish between what they know and what they don’t know. By this criterion, the signatories of the Lancet letter were behaving as poor scientists: They were assuring the public of facts they could not know for sure were true.
One of the very few establishment scientists to have questioned the virologists’ absolute rejection of lab escape is Richard Ebright, who has long warned against the dangers of gain-of-function research. Another is David A. Relman of Stanford University. “Even though strong opinions abound, none of these scenarios can be confidently ruled in or ruled out with currently available facts,” he wrote. Kudos too to Robert Redfield, former director of the Centers for Disease Control and Prevention, who told CNN on March 26, 2021 that the “most likely” cause of the epidemic was “from a laboratory,” because he doubted that a bat virus could become an extreme human pathogen overnight, without taking time to evolve, as seemed to be the case with SARS2.
Author(s): Nicholas Wade
Publication Date: 5 May 2021
Publication Site: Bulletin of the Atomic Scientists
About 32% of the U.S. population is now fully vaccinated, but the vast majority are people older than 65 — a group that was prioritized in the initial phase of the vaccine rollout.
Although new infections are gradually declining nationwide, some regions have contended with a resurgence of the coronavirus in recent months — what some have called a “fourth wave” — propelled by the B.1.1.7 variant, first identified in the United Kingdom, which is estimated to be somewhere between 40% and 70% more contagious.
As many states ditch pandemic precautions, this more virulent strain still has ample room to spread among the younger population, which remains broadly susceptible to the disease.
Vaccine makers like Pfizer, Moderna and Johnson & Johnson coped with intense global demand for their original shots by manufacturing millions of doses while the vaccines were still in clinical trials. But that is not an option now, because the companies are still racing to fulfill orders for their existing Covid-19 vaccines — and some, including Johnson & Johnson and AstraZeneca, are struggling with major production setbacks. Pumping out second-generation shots would require factories to switch over manufacturing lines now used for the first wave of vaccines, and in some cases fire up new production processes.
The potential manufacturing gap is the latest challenge to President Joe Biden’s promise to bring the pandemic to a close. South Africa has already rejected AstraZeneca’s vaccine because an early trial showed it wasn’t effective against the B.1.351 strain that dominates there and has now reached the United States. Another variant spreading in America — P.1, first found in Brazil — has raised similar concerns about its ability to evade some of the vaccines now in use globally. Biden administration officials are working overtime to understand how the variants’ spread could alter vaccination strategies. But the lack of manufacturing capacity is limiting America’s options.
A Harvard immunologist said current vaccines appear to be effective enough to end the pandemic, despite growing concerns that more infectious COVID-19 variants would severely blunt the effectiveness of the preventative treatments and set the nation back in its fight against the disease.
As Americans anxiously watch variants first identified in the United Kingdom and South Africa spread in the United States, scientists are finding a number of new variants that originated here. More concerning, many of these variants seem to be evolving in the same direction — potentially becoming contagious threats of their own.
In a study posted on Sunday, a team of researchers reported seven growing lineages of the novel coronavirus, spotted in states across the country. All of them have evolved a mutation in the same genetic letter.
“There’s clearly something going on with this mutation,” said Jeremy Kamil, a virologist at Louisiana State University Health Sciences Center Shreveportand a co-author of the new study.
British government scientists are increasingly finding the coronavirus variant first detected in Britain to be linked to a higher risk of death than other versions of the virus, a devastating trend that highlights the serious risks and considerable uncertainties of this new phase of the pandemic.
The scientists said last month that there was a “realistic possibility” that the variant was not only more contagious than others, but also more lethal. Now, they say in a new document that it is “likely” that the variant is linked to an increased risk of hospitalization and death.
Alongside antibodies, the immune system produces a battalion of T cells that can target viruses. Some of these, known as killer T cells (or CD8+ T cells), seek out and destroy cells that are infected with the virus. Others, called helper T cells (or CD4+ T cells) are important for various immune functions, including stimulating the production of antibodies and killer T cells.
T cells do not prevent infection, because they kick into action only after a virus has infiltrated the body. But they are important for clearing an infection that has already started. In the case of COVID-19, killer T cells could mean the difference between a mild infection and a severe one that requires hospital treatment, says Annika Karlsson, an immunologist at the Karolinska Institute in Stockholm. “If they are able to kill the virus-infected cells before they spread from the upper respiratory tract, it will influence how sick you feel,” she says. They could also reduce transmission by restricting the amount of virus circulating in an infected person, meaning that the person sheds fewer virus particles into the community.
T cells could also be more resistant than antibodies to threats posed by emerging variants. Studies by Sette and his colleagues have shown that people who have been infected with SARS-CoV-2 typically generate T cells that target at least 15–20 different fragments of coronavirus proteins1. But which protein snippets are used as targets can vary widely from person to person, meaning that a population will generate a large variety of T cells that could snare a virus. “That makes it very hard for the virus to mutate to escape cell recognition,” says Sette, “unlike the situation for antibodies.”
Two variants of the SARS-CoV-2 coronavirus that causes covid-19 have combined their genomes to form a heavily mutated hybrid version of the virus. The “recombination” event was discovered in a virus sample in California, provoking warnings that we may be poised to enter a new phase of the pandemic.
The hybrid virus is the result of recombination of the highly transmissible B.1.1.7 variant discovered in the UK and the B.1.429 variant that originated in California and which may be responsible for a recent wave of cases in Los Angeles because it carries a mutation making it resistant to some antibodies.