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mRNA Miracle?

18 November 2020

All the usual caveats apply: don’t go out and celebrate, don’t let your guard down, it’s still going to be a long haul. This winter will be “hard”, warned Uğur Şahin, co-founder and
CEO of BioNTech, the German company that announced the first effective Covid-19 vaccine only a week ago. It can’t be rolled out fast enough to reduce infections much in the current wave, he said.

The publication on 16 November of positive results for a second vaccine, this time by the US company Moderna, strengthened the optimism. Clearly, this coronavirus can be beaten, and there are nine more potential Covid vaccines already in third-stage (final) human trials.

But again, the riders: there will be at least half a million more Covid deaths this winter – or over a million if people don’t observe the lock-downs and other restrictions meant to contain the spread of the virus. “What is absolutely essential,” said Şahin, “is that we get a high vaccination rate before autumn/winter next year.” That’s when it could really be over.

And yet there is cause to celebrate, because of the eleven vaccine candidates that were already in third-stage trials, both the front-runners are ‘messenger ribonucleic acid’ (mRNA) vaccines, an entirely new approach that allows a much faster response to novel viral infections.

Traditionally, new vaccines took around ten years to be developed, tested and approved for general use. For the new mRNA vaccines, it has been ten months.

After Chinese scientists posted the full genetic sequence of the Covid-19 virus online on 10 January, said Drew Weissman of the University of Pennsylvania, “we were making RNA within a week or so”. Weissman then supplied that RNA to both BioNTech/Pfizer (Pfizer is a large American company that gives the German innovators US distribution and regulatory clout) and Moderna.

RNA carries the genetic instructions from the nucleus of the cell to build whatever protein is needed, and for the past decade researchers have been trying to fabricate ‘messenger’ RNA that could be inserted into human cells. The mRNA would then use the cell’s own genetic machinery to make vaccines and other medically useful proteins.

By 2018 several companies had cracked the problem of getting the mRNA past the body’s immune defences. With the full RNA sequence of the new coronavirus in their possession, all they had to do was choose which bit of the coronavirus RNA to use in the vaccine.

Obviously not the whole thing, or it would rebuild the entire virus in the cell. Just a harmless segment of the virus’s RNA, copied millions of times by the vaccinated person’s cells, would alert the body’s immune system and train it to destroy any invading virus with that sequence. (They chose the ‘spike’ that the virus uses to attach itself to the human cell.)

Several companies had mRNA vaccines ready for testing within two or three months, and the results have been spectacular. BioNTech/Pfizer has just reported 95% efficacy for its vaccine, and last weekend Moderna reported 94.5%.

Even better, both BioNTech/Pfizer and Moderna included all major ethnic groups and
a significant number of elderly people in their third-phase trials. All categories responded well to the vaccines (which is not always the case with other vaccines).

Yet another mRNA vaccine in third-phase trials could be even better, because it will be far cheaper than the BioNTech/Pfizer vaccine ($39 for two shots) or the Moderna jab ($74 for 2 shots) if it pans out. At Imperial College in London, Robin Shattock’s team is working on a ‘self-amplifying RNA’ vaccine that may require as little as one-hundredth of the amount of vaccine.

The mRNA technique may mean that future pandemics can be dealt with far more quickly. The vehicle is already available and waiting to carry the next vaccine. Just ‘plug and play’ for any future coronavirus, as one researcher put it. (We have had three new coronaviruses in the past two decades.)

Pfizer boss Albert Boura went even further: “It’s the greatest medical advance in the past 100 years.” Well, maybe, though a vote taken today would probably plump for antibiotics instead. But we are only beginning to see the potential of mRNA.

There are already trials underway for a wide variety of other illnesses: not just safer, more effective influenza, polio and HIV vaccines, but immunotherapies for cancer, heart conditions, cystic fibrosis and other systemic and congenital diseases.

There is a long, dark winter still ahead of us, no doubt, but miracles may await us over the horizon. And we can now be sure that the light at the end of this particular tunnel is not an oncoming train.
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To shorten to 725 words, omit paragraphs 6 and 11. (“After…Moderna”; and “Even…vaccines”)

Four-Day Work Week

As countries in Europe and North America emerge from lock-down and start trying to rebuild their devastated economies, the great concern is jobs.

Unemployment in the US and Canada is over 13%, a post-Second World War high. If it weren’t for subsidies that keep up to a fifth of the working population in paid ‘furloughs’ from their jobs, jobless rates in Europe would be as high or higher. That can’t go on forever, so there is a frantic search for job-saving strategies – and the ‘four-day work week’ keeps coming up.

Like that other proposed magic bullet, the guaranteed basic income, the notion of a four-day working week has been kicking around for a long time. The current emergency has given both ideas a second wind, and neither is nearly as radical or extreme as it sounds.

Less than a century ago the whole industrialised world transitioned from the traditional six-day working week (Saturdays included) to a five-day work-week, for the same pay, with no political upheaval and no significant loss of production. So why don’t we do that again, spread the work around, and save lots of jobs?

Because it doesn’t work like that. The four-day week is not about spreading the load. It is about finding ways for people who already have jobs to squeeze the same work into four 10-hour working days instead of five 8-hour days, or to work ‘smarter’ so that they can get the same work done (or more) in only four 8-hour days.

The 40-hour week done in four days is the only available option for most process workers on assembly lines or other repetitive physical tasks. Ten-hour workdays are even harder than they sound, but the prize is a three-day weekend and some people are willing to pay the price.

If everybody buys into that, then management can shut the plant down one extra day and save on power. If only some do, then management has the headache of scheduling some 10-hour shifts and other 8-hour shifts, plus the cost of the mistakes that may accumulate when exhausted people are approaching the end of a 10-hour shift. And no saving on electricity costs.

Nevertheless, it does make for a happier workforce, by all accounts, and maybe therefore a more efficient and productive one. There are already a few examples of this kind of four-day working in every industrial country, and now the prime ministers of Finland and New Zealand are both talking it up. Neither woman, however, is proposing to impose it nationally, and nobody is suggesting that it will create more jobs.

The four-day week is an easier and more attractive package for people in administrative and sales jobs, because everybody knows that there is a lot of wasted time in office work: social media, pointless emails, long boring meetings, etc. You could get the job done a lot quicker if everybody was motivated to concentrate on the bits that are actually useful and skip the rest.

So motivate them. Tell them that they can drop to four 8-hour days a week for the same pay as the old five days if they can still get the same work done – and leave it to them to figure out how. If they can’t, then it’s back to the same old five-day grind.

Miraculously, they almost always do manage to find the time. In many cases, indeed, productivity actually rises: happy workers do better work. The four-day week is an excellent idea whose time may finally have come, but it is not a magic bullet. Companies don’t ever hire more people just to spread the work around.

So what might spread the available work around? The US Congress had a brilliant idea in 1938, when it passed the Fair Labor Standards Act, which required employers to pay overtime at 150% of the normal hourly wage for anything over 40 hours of work a week.

The idea was to make employers hire more people. If they had 40 employees working 50 hours a week, they would have to pay each of them overtime for the last 10 hours. So why not just hire another 10 people and save all that overtime pay? It worked quite well at the time, but it would not work now. Don’t hire more people; just put in more automation.

The coronavirus is just an accelerator. The real problem with employment ever since the 1990s has been automation, which has been eating up good jobs and excreting low-paid, insecure ones instead – or none at all. Six million good manufacturing jobs were automated out of existence in the US in 2000-2010, which led fairly directly to the election of Donald Trump in 2016.

The current pandemic is speeding the process by driving more jobs online, especially in sales (a different kind of automation), and fiddling with working hours or minimum wages is not going to stop it. So what’s left? Maybe a guaranteed basic income would help, but that’s a discussion for another day.
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To shorten to 725 words, omit paragraphs 12 and 13. (“So what…work now”)

Trump and the Yellow Peril

It was completely predictable that Donald Trump would try to blame China for the fact that at least 30 million Americans are unemployed and that 70,000 Americans have already died of Covid-19. His polling numbers are down and the election is only seven months away. What else was he going to do? Blame himself?

That’s why we’re now getting the good old ‘Yellow Peril’ defence, fresh from the late 19th century. As a memo sent out by the National Republican Senatorial Committee to Republican candidates put it: “Don’t defend Trump, other than the China Travel Ban – attack China.”

The coronavirus now spreading death across the world certainly originated in China. The Chinese government itself said so, before it started prevaricating after Donald Trump began using China as a scapegoat.

There was at least a week’s delay in late December when officials in Wuhan didn’t report the outbreak to Beijing, fearing they would be blamed for alarmism, or simply for letting it happen. That’s when Dr. Li Wenliang wrote in a private WeChat group: “7 confirmed cases of SARS were reported [to hospital] from Huanan Seafood Market.”

It wasn’t really Severe Acute Respiratory Syndrome. It was a new coronavirus closely related to SARS, which had caused a much smaller but lethal epidemic in 2002. But Wuhan officials didn’t want to believe it, and on 3 January Li got a warning from the local police to stop “making false comments on the Internet”.

Six days later the first person in Wuhan died of what we now call Covid-19. On the same day, 9 January, the World Health Organisation (which Trump now vilifies as ‘China’s public relations agency”) announced that China had reported the emergence of a new coronavirus like those that caused the SARS and MERS epidemics.

So there was at least a week when Chinese officials at the local or national level had the information and hesitated to publish it, partly because they weren’t sure yet themselves. But only two days later Chinese scientists published the full genetic sequence of Covid-19 so that researchers everywhere could start working on potential treatments and vaccines.

Other East Asian countries that had experience of SARS understood the seriousness of the WHO warning and promptly began diligent testing, tracing and isolation of infected persons. As a result, they never had to go into lockdown (South Korea has had 250 deaths; Taiwan had 6). China did a partial lockdown, but is now up and running again.

But then the real delay happened, and it had nothing to do with when China reported the disease. The point is that Western countries did nothing serious about the pandemic for an astonishing TWO MONTHS after that.

Trump boasts that he banned travel from China to the United States early, but in fact the United States was the 41st country to declare such a ban, on 2 February. And it was a very leaky ban, affecting only non-US citizens. Another 40,000 US citizens and permanent residents flew in from China during the next two months, many not being checked for coronavirus at all.

Italy started locking down some municipalities in the country’s badly hit north in late February, but no European country went into national lockdown until 9 March. The United Kingdom waited a further two weeks after that, until 24 March. The United States never did a national lockdown, but most states had social distancing policies in place by early April.

Those even longer delays explain why the UK and the US are on track to be the two countries with the highest Covid-19 death rates, but why did they all wait so long. Why weren’t they at least setting up comprehensive testing, tracing and contacting systems and making more ventilators and protective clothing back in January? Did they think they were exempt?

That’s probably what they did think, and their people are now being punished for their governments’ arrogance. But Donald Trump’s attempt to shift the blame for a huge US death toll and a looming economic disaster onto China is utterly cynical and false. The problem wasn’t a week’s delay in China; it was a couple of months’ delay in America.

If it should turn out that the first human infections with Covid-19 were due to a leak from the Biosafety level 4 Wuhan Institute of Virology, not at the Huanan Seafood Market in the same city, it changes nothing. BSL4 labs (there are around twenty in the world) routinely work with dangerous viruses, because otherwise we’d never develop defences against them.

An accidental leak from a BSL4 lab would be a rare and very serious mistake, but that’s probably not what happened in Wuhan, and in any case it’s clear that no hostile intent was involved. The US national intelligence director’s office has determined that Covid-19 “was not manmade or genetically modified.”

That will not stop Donald Trump from scapegoating China, even at the risk of causing a new Cold War. Never mind the fate of the world. It’s the fate of Trump’s presidency that’s at stake here.
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To shorten to 725 words, omit paragraphs 8 and 10. (“Other…again”; and “Trump…at all”)

Time for Fauci to Quit?

Is it time for Dr Anthony Fauci to quit?

Brazil’s health minister, Luiz Mandetta, was fired last Friday for criticising the country’s mini-Trump, Jair Bolsonaro. Like Trump, President Bolsonaro needs a booming economy in order to be re-elected, and denies the threat from coronavirus because shutdowns hurt the economy.

Mandetta did what he could to control the berserker president, but eventually called Bolsonaro out on his attempts to force Brazilian state governments to end their shutdowns prematurely. He was duly fired, but it does raise the question: should Dr Fauci do the same thing?

Fauci, the director of the National Institute of Allergy and Infectious Diseases for the past quarter-century, has served six US administrations loyally through various health crises, starting with the AIDS epidemic. He’s done his best to keep Donald Trump from doing the wrong thing. Sometimes he succeeds – but sometimes the most useful thing an adviser can do is resign.

Fauci has become a familiar figure standing beside Donald Trump at media briefings, never openly contradicting him but subtly trying to steer him away from his worst ideas. It’s a humiliating position to be in, but he has probably saved at least a few tens of thousands of American lives, and many people admire him for patiently, even humbly doing the best he can in impossible circumstances.

There comes a time, however, when staying on the inside and trying to limit the damage by staying on good terms with the author of the disaster shades into complicity in letting the disaster happen. Dr Fauci undoubtedly examines his conscience on this question every single day, and fully understands how tricky his position is.

There was a revealing moment recently when Science Magazine asked him why he hadn’t challenged Trump’s claims to have saved millions of American lives by banning flights from China. “Let’s get real,” Fauci replied. “What do you want me to do?…I can’t jump in front of the microphone and push him down.”

Well, he could, obviously, but that would be the end of any positive influence he has on Trump. He’s 79, so he’s not worried about saving his job. He’s ignoring Trump’s exaggerations and lies so he can preserve his influence for some more important occasion. We now know what it is.

Trump bangs on obsessively about his ‘China ban’ decision on 31 January because it’s the only thing he did about the coronavirus for the next six weeks, even as the pandemic silently spread among the US population. Last week he even claimed that “It could have been billions of people (who died) if we had not done what we did.”

Around 2,000 Americans are now dying from Covid-19 every day, so Trump clings desperately to his China story. Fauci lets the lie pass because it’s just history and can’t be changed. He’s focussed on the decisions being made now that will determine how many Americans die in the future.

Trump is now frantically trying to end the lockdowns and get Americans back to work because he believes the economic damage is sabotaging his re-election prospects in November. He’s even urging his base to demonstrate against (Democratic) state governors who take a more cautious line, texting “LIBERATE MINNESOTA”, “LIBERATE MICHIGAN” and “LIBERATE VIRGINIA”.

Maybe this is the hill that Fauci should choose to die on, because ending the lockdowns early could needlessly kill an extra hundred thousand Americans. The United States now has one-third of all the Covid-19 cases in the world (with only 4% of the world’s population), and the number is still going up fast.

‘Liberating’ Americans from lockdown before the number of new infections is clearly in decline will just add fuel to the flames.

The rule is: never lift a lockdown until you are able to test huge numbers of people for the disease. The virus will inevitably start to spread again when you turn everybody loose, but if you test enough people, isolate the infected ones, and trace all of their recent contacts and isolate them too, then you can avoid a new spike in cases.

You will need tens of millions of test kits and hundreds of thousands of trained contact-tracers to do that. Those facilities are currently scarce or non-existent in most of the United States, and so far there is little visible effort to expand them. Ending the lockdowns without them will cause a new peak of cases and deaths by mid-summer, necessitating a new round of lockdowns.

If Fauci’s resignation could prevent this carnage, he surely would not hesitate, but Trump is not as stupid as Bolsonaro. If Fauci hangs in there and stresses the inevitability of a second wave of deaths closer to election time if the lockdowns end prematurely, he might just manage to steer Trump away from this cliff.

So his long martyrdom must continue.
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To shorten to 700 words, omit paragraphs 9 and 10. (“Trump bangs…future”)