Category: Uncategorized
Shoring Up the Vaccine Supply Chain
Supply chains were hit hard early in the pandemic. Disinfectant couldn’t be produced because of a lack of bottles, tests couldn’t be processed because nasal swabs or PPE wasn’t available, the decline of passenger air traffic hit commercial delivery and so forth. I worry about forthcoming stresses on the vaccine supply chain. Billions of doses of vaccine will be demanded in the next year and a lot will depend on complicated supply lines including cold storage, air traffic, styrofoam, vials, bags, needles and many other inputs. Companies and the awesome team at CEPI (give them all a Nobel prize) are planning for vials and needles and other inputs but there are many non-obvious inputs higher up in the supply chain that also need shoring up.
Writing in Bloomberg, Scott Duke Kominers and I look at some of the odder inputs to vaccines like horseshoe crab blood, shark livers and the vaccinia capping enyzme, VCE. We are actually not too worried about horseshoe crab blood and shark livers as these are used in other industries. Shark livers, for example, are used to produce a lot of cosmetics so we should be able to divert supply as needed. VCE, however, is rarer.
DNA and mRNA vaccine technologies have shown promising results, and two of the leading vaccine contenders, from Pfizer Inc. and Moderna Inc., use mRNA technology. But mRNA has never been used to produce a commercial vaccine for humans, let alone at scale. And scaling these technologies may not be easy. In particular, mRNA degrades rapidly. To prevent this, it must be “capped” by a very rare substance called vaccinia capping enzyme.
Just over 10 pounds of this VCE is enough to produce a hundred million doses of an mRNA vaccine — but the current manufacturing processes for VCE require so much bioreactor capacity that making 10 pounds would cost about $1.4 billion. More important, global bioreactor capacity cannot support production at that level while also producing other vaccines and cancer-fighting drugs.
If we work hard now, we may be able to find more efficient means of producing VCE. Expanding bioreactor production and repurposing bioreactors from existing large-scale industrial applications will also help to lessen the pressure on the supply chains for multiple types of vaccines.
In addition to supply chains per se we also face the problem that companies are not raising prices enough. Ironically, this means that we need more public investment.
Of course, we might think that private companies would have incentives to coordinate supply chains themselves — and to some extent, they are doing so. But many have pledged to keep their vaccine prices close to costs, both out of altruism and because they may fear public backlash (or legal action) if they’re perceived as “price gouging” in the middle of a pandemic. And if companies don’t stand to profit much from Covid-19 vaccines, then they don’t have much incentive to invest in increasing capacity. In short: If prices can’t rise, then the only way to encourage companies to invest more in production is to reduce their costs — and that means we need public investment.
More generally, it’s not too late to be building more vaccine capacity and to repurpose bioreactor capacity from non-GMP sources, perhaps including veterinary and food sources. There are lots of vaccines in development. The science is promising. We need to take action now so that we can deliver on that promise.
Read the whole thing.
The Covid cost of professional sports events
We compare COVID-19 case loads and mortality across geographic areas that hosted more vs fewer NHL hockey games, NBA basketball games, and NCAA basketball games during the early months of 2020, before any large outbreaks. We find that hosting one additional NHL/NBA game leads to an additional 783 COVID-19 cases during March-mid May and an additional 52 deaths. Similarly, we find that hosting an additional NCAA Division 1 men’s basketball games results in an additional 31 cases and an additional 2.4 deaths. Back of the envelope calculations suggest that the per-game fatality costs exceed consumption benefits by a wide margin.
That is from Coady Wing, Daniel H. Simon, and Patrick Carlin. I think we have not a good enough model of the heterogeneities of prevalence across regions for those to be reliable estimates. Still, I am happy to see more work on the question of what in particular causes Covid cases, and also whether sporting events play a significant role.
The polity that is Australia
The federal government is blocking three out of four applications for Australians to leave the country while the borders are closed, amid concerns they could spread coronavirus when they return home.
MPs from across Sydney, including Liberal Dave Sharma in Wentworth in the eastern suburbs, independent Zali Steggall in Warringah, and Opposition Leader Anthony Albanese and fellow Labor frontbencher Tanya Plibersek in the inner west, have been fielding numerous requests for assistance from residents stuck here because of the travel ban.
Mr Sharma said federal government MPs were starting to raise concerns internally about the travel ban, which he described as a “pretty extraordinary restriction on people’s liberty”.
“This is an extreme measure for extreme times but it cannot be something we contemplate keeping in place for the long term,” Mr Sharma said. “There’s no other country of which I’m aware that is imposing an exit permit system, like we’ve got in Australia.”
…Prime Minister Scott Morrison warned recently that the resumption of international travel was “not foreseeable” and unlikely to occur this year.
Good or bad? In which countries would you be more or less upset by this policy decision? Here is the article, and here is further coverage.
Via the excellent Samir Varma.
Tuesday assorted links
1. Relative to age, India’s Covid-19 fatality record is not so great.
2. Markets in everything: underground gyms.
3. Pandit Jasraj has passed away, here is some music.
Monday assorted links
1. New podcast on (serious) natural philosophy.
3. “Her TikTok account as of August 2020 has over 78 million followers.” Link here, can you name her?
4. Thread on the basics of herd immunity claims. And the NYT covers herd immunity. A very good piece in fact. Semi-herd immunity says I, or “imperfect immunity” to use the terminology of the article. And you will note the extreme epistemological conservatism emanating from the mainstream experts interviewed. Appropriate in some ways, not in others.
5. Was Winky Dink the first interactive TV show?
7. WSJ review of new Bruno Macaes book on America. The predictions of the book are holding up very well so far!
Real estate markets in everything
From Fayette, Missouri, listed at $375,000:
1875 Howard County Sheriff’s House and Jail. Extremely unique opportunity!! Extensive renovation in 2005 (supposedly $1.5 million) captures modern high end finishes with traditional architecture and character. This home is 2465 sq ft with three levels of living area, 2 bedroom. 1.5 bath, high end finish throughout, appears to have been totally rewired, replumbed and new HVAC zoned system installed. AND THE BEST PART, connected to the home is a 2500 sq ft legitimate jail with 9 cells, booking room and 1/2 bath. The cell door lock throws appear to be operational. Full basement under the home with lighting throughout. Possibilities are amazing with this property.
Via Anecdotal.
What I’ve been reading
1. Christopher Tugendhat, A History of Britain Through Books, 1900-1964. Most of all a look at the “well-known in their time, and reflecting their age, but not read any more” books from the stated period, using short, capsule portraits of each work. It induced me to order some more Elizabeth Bowen, C.P. Snow, and other works. There should be more books like this.
2. Maggie O’Farrell, Hamnet. Perhaps my favorite novel of the year so far, noting this is from Northern Ireland and my #2 pick by Anne Enright is from Ireland proper. Usually I dislike stories with a “gimmick” — this one recounts part of the life of Shakespeare’s family during plague times — but this one was tasteful, subtle, and suspenseful.
3. Charles Freeman, The Awakening: A History of the Western Mind AD 500-1700. A gargantuan work at over 800 big pp., the size and the breadth and title all might seem to herald trouble. Yet it is really good. It has chapters on whether England really had a scientific revolution, what was actually published with the new printing press, and how medieval universities really worked. There were fewer tired summaries of “the usual” than I was expecting. The author is a specialist on the ancient world, and so there is coverage of Cassiodorus, and what Montaigne took from Plutarch, and numerous other “ancient world” sorts of topics. Which is a good thing.
4. Despina Strategakos, Hitler’s Northern Utopia: Building the New Order in Occupied Norway. What did the Nazis have planned for Norway after a supposedly successful conclusion of the Second World War? Lots of reformed urban townscapes, and with plenty of detail to boot. Sometimes it is books like this, rather than the recounting of atrocities, that make WWII seem like the truly bizarre event it was. I am still not sure if restructuring Norway is something fascinating to do, or still super-dull.
Thomas A. Schwartz, Henry Kissinger and American Power: A Political Biography is consistently good and readable.
I found David Broder’s First They Took Rome: How the Populist Right Conquered Italy to be a useful explainer of a complex situation.
Jacob Goldstein, Money: The True Story of a Made-up Thing is a good introduction to its chosen topic.
Heterogeneities, is the more infectious strain of Covid-19 spreading to Asia?
Malaysia has detected a strain of the new coronavirus that’s been found to be 10 times more infectious.
The mutation called D614G was found in at least three of the 45 cases in a cluster that started from a restaurant owner returning from India and breaching his 14-day home quarantine. The man has since been sentenced to five months in prison and fined. The strain was also found in another cluster involving people returning from the Philippines…
The mutation has become the predominant variant in Europe and the U.S., with the World Health Organization saying there’s no evidence the strain leads to a more severe disease.
Here is the Bloomberg story, please consider this subject to further revision!
Sunday assorted links
1. Assorted links on progress studies.
2. James Altucher is bearish on NYC. Not my view, but worth a hearing. Of course I would never live there, but that has always been the case.
3. Arbitrage with stolen books?
4. Manufacturing vaccines, excellent piece (Bloomberg).
6. Professional sports already increase influenza mortality (shh!).
The new quicker, cheaper, supply chain robust saliva test
The FDA has just approved a new and important Covid-19 test:
“Wide-spread testing is critical for our control efforts. We simplified the test so that it only costs a couple of dollars for reagents, and we expect that labs will only charge about $10 per sample. If cheap alternatives like SalivaDirect can be implemented across the country, we may finally get a handle on this pandemic, even before a vaccine,” said Grubaugh.
One of the team’s goals was to eliminate the expensive saliva collection tubes that other companies use to preserve the virus for detection. In a separate study led by Wyllie and the team at the Yale School of Public Health, and recently published on medRxiv, they found that SARS-CoV-2 is stable in saliva for prolonged periods at warm temperatures, and that preservatives or specialized tubes are not necessary for collection of saliva.
Of course this part warmed my heart (doubly):
The related research was funded by the NBA, National Basketball Players Association, and a Fast Grant from the Emergent Ventures at the Mercatus Center, George Mason University.
The NBA had the wisdom to use its unique “bubble” to run multiple tests on players at once, to see how reliable the less-known tests would be. This WSJ article — “Experts say it could be key to increasing the nation’s testing capacity” — has the entire NBA back story. At an estimated $10 a pop, this could especially be a game-changer for poorer nations. Furthermore, it has the potential to make pooled testing much easier as well.
Here is an excerpt from the research pre-print:
The critical component of our approach is to use saliva instead of respiratory swabs, which enables non-invasive frequent sampling and reduces the need for trained healthcare professionals during collection. Furthermore, we simplified our diagnostic test by (1) not requiring nucleic acid preservatives at sample collection, (2) replacing nucleic acid extraction with a simple proteinase K and heat treatment step, and (3) testing specimens with a dualplex quantitative reverse transcription PCR (RT-qPCR) assay. We validated SalivaDirect with reagents and instruments from multiple vendors to minimize the risk for supply chain issues. Regardless of our tested combination of reagents and instruments from different vendors, we found that SalivaDirect is highly sensitive with a limit of detection of 6-12 SARS-CoV-2 copies/μL.
No need to worry and fuss about RNA extraction now. Here is the best simple explanation of the whole thing.
The researchers are not seeking to commercialize their advance, rather they are making it available for the general benefit of mankind. Here is Nathan Grubaugh on Twitter. Here is Anne Wyllie, also a Kiwi and a Kevin Garnett fan. A further implication of course is that the NBA bubble is not “just sports,” but also has boosted innovation by enabling data collection.
All good news of course, and Fast at that. And this:
“This could be one the first major game changers in fighting the pandemic,” tweeted Andy Slavitt, a former acting administrator of the Centers for Medicare and Medicaid Services in the Obama administration, who expects testing capacity to be expanded significantly. “Rarely am I this enthusiastic… They are turning testing from a bespoke suit to a low-cost commodity.”
And here is coverage from Zach Lowe. I am very pleased with the course of Fast Grants more generally, and you will be hearing more about it in the future.
The T-Cell immune response that didn’t bark
T-Cell immune response (not to be confused with invulnerability) is hardly a new idea in public health. Yet what is striking is how long it took you to hear about it — from the mainstream at least — in the context of coronavirus.
If you go back to February, March, even April or dare I say May, you will not find too many mainstream public health commentators suggesting “there is some possibility of T-cell immunity playing a major role here. That could significantly ease the future casualties and economic burden of Covid-19.” David Wallace-Wells dates the beginning of the discussion to late May, and the “dark matter” hypothesis of Friston, though I believe earlier precursors will be found.
You didn’t even hear much of: “We really are not sure T-cell immunity is a factor. But it could be a factor with probability [fill in the blank], and it is worth keeping that in mind.”
The major New York Times piece on T-Cell immunity doesn’t run until August 6. And the Wallace-Wells piece is dated August 9.
Think about the underlying equilibrium that could lead to such a strange result.
if you do public health, your status incentives are to deliver warnings, not potential good news.
Your status incentives are always to hedge your bets, and to be reluctant to introduce new hypotheses.
Your status incentives are to steer talk away from the virus “simply continuing to rip,” even if you are quite opposed to that outcome. Other than hitting it with an immediate scold, you are not supposed to let that option climb on to the discussion table for too long.
Your status incentives are to discourage individuals from thinking that they might be have some pre-existing level of protection. That might lead them to behave more irresponsibly, and then you in turn would look less responsible.
Since public health commentators are so concerned with “doing good by us,” they fail to see that their altruistic (and status) motives in these matters mean they do not end up telling us the truth. Not the entire truth, and not upfront in a very prompt matter.
To be fair, I don’t recall seeing mainstream commentators making false claims about T-cell immunity, rather their filters end up being very selective ones and they bring it up only slowly. And because they smush together in their minds the actually quite distinct concepts of “doing good,” “status,” and “informing the public,” they genuinely have no idea that they are not entirely on the side of truth.
And they genuinely have no idea why so many smart people look to “the cranks” for advice and counsel.
And, to be clear, the commentary of “the cranks” in this area has plenty of problems of its own, even though in some ways they have turned out to be a more informative (as distinct from accurate) source on T-cell immunity.
Finally, to recap, we still are not sure how much overall social protection T-cell immunity will bring. Furthermore, we are pretty sure that not many places have a chance of current herd immunity from “a mix of previous Covid exposure plus pre-existing T-cell immunity.”
So I am not trying to induce you to overrate the T-cell immunity idea. I am trying to illuminate the biases of the filters at work in your everyday consumption of Covid-19 information. Those biases too, the mainstream commentators are not so keen to tell you about.
Using Social Media to Bring Down the Power Grid
Social media are a coordination device and coordinated behavior has many advantages. Social media was used to motivate, organize and coordinate movements like the Arab Spring and Black Lives Matter. Of course, coordination can also lead to conspiracy theories like QAnon, twitter mobs that police political correctness and riots that lead to death and destruction. For better or worse, coordinated behavior is likely to increase, creating more and more quickly moving mobs. The use and abuse of such mobs is only just beginning. One insidiously clever prospect is the use of seemingly benign coordination to bring down a power grid. What if everyone turns on their air conditioner and lights at the same time? In How weaponizing disinformation can bring down a city’s power grid, Raman et al. discuss how such a scenario could be generate by something seemingly as simple as sending fake coupons!
Social media has made it possible to manipulate the masses via disinformation and fake news at an unprecedented scale. This is particularly alarming from a security perspective, as humans have proven to be one of the weakest links when protecting critical infrastructure in general, and the power grid in particular. Here, we consider an attack in which an adversary attempts to manipulate the behavior of energy consumers by sending fake discount notifications encouraging them to shift their consumption into the peak-demand period. Using Greater London as a case study, we show that such disinformation can indeed lead to unwitting consumers synchronizing their energy-usage patterns, and result in blackouts on a city-scale if the grid is heavily loaded. We then conduct surveys to assess the propensity of people to follow-through on such notifications and forward them to their friends. This allows us to model how the disinformation may propagate through social networks, potentially amplifying the attack impact. These findings demonstrate that in an era when disinformation can be weaponized, system vulnerabilities arise not only from the hardware and software of critical infrastructure, but also from the behavior of the consumers.
Hat tip: Kevin Lewis.
Addendum: California is once again issuing rolling blackouts. Welcome to the future.
Saturday morning assorted links
Claims about Richard Wagner
The truth is that Wagner’s popularity was already in relative decline during the Weimar Republic and simply fell further, more quickly, under the Nazis. During the last years of the Kaiser’s Germany (and despite the cost and privation of the First World War), the Master’s works were still hugely popular, accounting for over eighteen per cent of all opera performances, a share no other composer came to matching. By the mid-1920s, though, the figure had dropped to around fourteen per cent.
After Hitler took power, Wagner’s share plunged to well below ten percent.
The truth is that many Nazis, in high and low places, were bored to tears by Wagner.
That is all from Jonathan Carr’s excellent book The Wagner Clan.
Friday assorted links
2. Deaton interviews Sen, with Tim Besley moderating, full of interesting content.
3. 80,000 hours Shruti Rajagopalan interviewed by Howie Lempel podcast, “What India did to stop Covid-19 and how well it worked,” self-recommending.
4. The British economy in pandemic (NYT).
5. Herbert Blomstedt back to conducting at age 93, an example for us all.