Category: Science
*Kindred: Neanderthal Life, Love, Death and Art*
By Rebecca Wragg Sykes, an excellent book, a very responsible treatment of what we do and do not know about Neanderthals, with a bit on Denisovans as well. It is a book full of sentences such as: “Micro-morphology has also provided proof that, far from being slovenly, Neanderthals were regularly disposing of their rubbish.” It seems they enjoyed mussels and also grubs, among many other foodstuffs. The hearth was the center of the home and they had fairly advanced systems for butchery. They used leather and deployed pigments.
I enjoyed this segment:
Parisians, Londoners or Berliners today with ostensibly European heritage have very little connection even to Mesolithic people just 10,000 years ago. The vast majority of their DNA comes from a massive influx of Western Asian peoples during the Neolithic. This means that many of the first H. sapiens populations are more extinct than the neanderthals; not a great sign of evolutionary dominance.
Recommended, you can order here.
Micro-hemorrhages and the importance of vaccination
Neurological manifestations are a significant complication of coronavirus infection disease-19 (COVID-19). Understanding how COVID-19 contributes to neurological disease is needed for appropriate treatment of infected patients, as well as in initiating relevant follow-up care after recovery. Investigation of autopsied brain tissue has been key to advancing our understanding of the neuropathogenesis of a large number of infectious and non-infectious diseases affecting the central nervous system (CNS). Due to the highly infectious nature of the etiologic agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a paucity of tissues available for comprehensive investigation. Here, we show for the first time, microhemorrhages and neuropathology that is consistent with hypoxic injury in SARS-CoV-2 infected non-human primates (NHPs). Importantly, this was seen among infected animals that did not develop severe respiratory disease. This finding underscores the importance of vaccinating against SARS-CoV-2, even among populations that have a reduced risk for developing of severe disease, to prevent long-term or permanent neurological sequelae. Sparse virus was detected in brain endothelial cells but did not associate with the severity of CNS injury. We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.
That is from new Fast Grants supported research by Tracy Fischer, et.al. And here are some related earlier results from Kabbani and Olds. Here are some more general recent results about brain damage.
How bad are these micro-hemorrhages anyway? I don’t know! You may notice I have hardly lunged at the “permanent damage” papers that have been coming out on Covid (in fact many of them already have collapsed or not replicated). But there are genuine reasons for caution, these results do not seem to be collapsing, and Covid-19 is not just a bunch of people trying to make a mountain out of a molehill. And “exposing the young” decisions should not be taken lightly either. The people who are very cautious about reopening may be too risk-averse given realistic alternatives, but they are not all just statists, Trump haters, lazy teachers’ unions, and so on. There are very genuine concerns here.
New books needed on the NIH and NSF
A reader writes —
“Despite being the preeminent model for global science funding, and far more powerful than any single university, the workings of the NIH or NSF are surprisingly opaque to most people. These bodies shape who becomes a scientist, what science they pursue, and how they pursue it. I would therefore like to fund a book about how the institutions of US science actually operate, how they’ve changed, what the relevant surrounding incentives are, and how it is that they should likely evolve from here. It’s possible, perhaps even very likely, that a good version of this book would be picked up by a good publisher. Even if it isn’t, it should exist in the public domain. I will invest generously in anyone who seeks to write one.”
This reader is highly credible. If you’re interested and have relevant expertise, please email me. (Suggestions for good possible authors — people who genuinely understand the system but who could be sufficiently objective and where relevant critical — are welcome although not as useful.)
How to conduct clinical trials while releasing a vaccine
There are many ways to conduct clinical trials while releasing a vaccine—indeed, we can make the clinical trials better by randomizing a phased release. Suppose we decide health care and transit workers should be vaccinated first. No problem–offer the workers the vaccine, put the SSNs of those who wants the vaccine into a hat like draft numbers, vaccine a randomly chosen sub-sample, monitor everyone.This is the well known lottery technique for measuring causal effects often used in the school choice literature. If we use this technique we can greatly increase sample sizes and as we study each wave we will gather more confidence in the data. We won’t have enough vaccine in November to vaccinate everyone or probably even all health care and transit workers so a lottery is an ethically fair as well as statistically useful way to distributed the vaccine. We can also randomize across cities and regions.
That is from a recent post by Alex Tabarrok, on the blog Marginal Revolution, and there is more at the link. Of course I don’t have to tell you what Alex’s brother thinks of all this.
Addendum: Anup Malani notes:
BTW, those worried about ethics here should note that most product markets, even many dangerous ones (including non-FDA regulated medical care) use the population testing approach. Drugs are the exception. Elsewhere handle risk via exclusively via ex post tort liability.
So please don’t offer some kind of passive, under-argued Twitter comment on how unacceptably unethical it is — do some analysis and empirics on the trade-offs! And read up on surgical procedures while you are at it.
The tubarial salivary glands
In case you think any of us understand the world very well:
Oncologists have stumbled on a “previously unnoticed” pair of salivary glands while studying the effect of radiotherapy on salivation and swallowing. The elusive glands are in an inaccessible spot and can be spotted only with very sensitive imaging, such as positron emission tomography and computed tomography. Researchers say the glands could help to explain why cancer treatment can cause dry mouth and swallowing problems, especially because doctors haven’t known to spare the organs from damage.
Here is the link, here is an associated NYT piece. Here is the original research.
Keynes on what is required to make a great economist
The study of economics does not seem to require any specialized gifts of an unusually high order. Is it not, intellectually regarded, a very easy subject compared with the higher branches of philosophy and pure science? Yet good, or even competent, economists are the rarest of birds. An easy subject, at which very few excel! The paradox finds its explanation, perhaps, in that the master-economist must possess a rare combination of gifts. He must reach a high standard in several different directions and must combine talents not often found together. He must be mathematician, historian, statesman, philosopher – in some degree. He must understand symbols and speak in words. He must contemplate the particular in terms of the general, and touch abstract and concrete in the same flight of thought. He must study the present in the light of the past for the purposes of the future. No part of man’s nature of his institutions must lie entirely outside his regard. He must be purposeful and disinterested in a simultaneous mood; as aloof and incorruptible as an artist, yet sometimes as near the earth as a politician.
That is from Keynes’s 1924 essay on Marshall, reprinted in Essays in Biography. Most of all, it is Keynes describing himself!
Could we detect it if we are living in a simulation?
“If quantum computing actually materializes, in the sense that it’s a large scale, reliable computing option for us, then we’re going to enter a completely different era of simulation,” Davoudi says. “I am starting to think about how to perform my simulations of strong interaction physics and atomic nuclei if I had a quantum computer that was viable.”
All of these factors have led Davoudi to speculate about the simulation hypothesis. If our reality is a simulation, then the simulator is likely also discretizing spacetime to save on computing resources (assuming, of course, that it is using the same mechanisms as our physicists for that simulation). Signatures of such discrete spacetime could potentially be seen in the directions high-energy cosmic rays arrive from: they would have a preferred direction in the sky because of the breaking of so-called rotational symmetry.
Telescopes “haven’t observed any deviation from that rotational invariance yet,” Davoudi says. And even if such an effect were to be seen, it would not constitute unequivocal evidence that we live in a simulation. Base reality itself could have similar properties.
Here is further discussion from Anil Anathaswamy. Via Robert Nelsen. As you may already know, my view is that there is no proper external perspective, and the concept of “living in a simulation” is not obviously distinct from living in a universe that follows some kind of laws, whether natural or even theological. The universe is simultaneously the simulation and the simulator itself! Anything “outside the universe doing the simulating” is then itself “the (mega-)universe that is simultaneously the simulation and the simulator itself.” etc.
Why I reject the Great Barrington Declaration
Here is my 2x normal length Bloomberg column on that topic, as had been requested by Daniel Klein. The argument has numerous twists and turns, do read the whole thing but here is one bit (I will indent only their words):
“Here are the key words of the Great Barrington Declaration on herd immunity:
The most compassionate approach that balances the risks and benefits of reaching herd immunity, is to allow those who are at minimal risk of death to live their lives normally to build up immunity to the virus through natural infection, while better protecting those who are at highest risk. We call this Focused Protection.
What exactly does the word “allow” mean in this context? Again the passivity is evident, as if humans should just line up in the proper order of virus exposure and submit to nature’s will. How about instead we channel our inner Ayn Rand and stress the role of human agency? Something like: “Herd immunity will come from a combination of exposure to the virus through natural infection and the widespread use of vaccines. Here are some ways to maximize the role of vaccines in that process.”
And the close:
“In most parts of the Western world, normal openings for restaurants, sporting events and workplaces are likely to lead to spiraling caseloads and overloaded hospitals, as is already a risk in some of the harder-hit parts of Europe. Reopenings, to the extent they work, rely on a government that so scares people that attendance remains low even with reopening.
In that sense, as things stand, there is no “normal” to be found. An attempt to pursue it would most likely lead to panic over the numbers of cases and hospitalizations, and would almost certainly make a second lockdown more likely. There is no ideal of liberty at the end of the tunnel here.
Don’t get me wrong: The Great Barrington strategy is a tempting one. Coming out of a libertarian think tank, it tries to procure maximum liberty for commerce and daily life. It is a seductive idea. Yet consistency of message is not an unalloyed good, even when the subject is liberty…
My worldview is both more hopeful and more tragic. There is no normal here, but we can do better — with vigorous actions to combat Covid-19, including government actions. The conception of human nature evident in the Great Barrington Declaration is so passive, it raises the question of whether it even qualifies as a defense of natural liberty.”
MR Tyler again: You will note I do not make the emotional, question-begging argument that herd immunity strategies will kill millions (though I do think more people die under that scenario). If you argue, as many herd immunity critics do, that the elderly cannot be isolated, it seems you also should not be entirely confident that the currently non-infected can be isolated. The brutal truth is simply that a Great Barrington strategy put into practice would lead to rapidly spiraling cases and a rather quick and oppressive second lockdown, worse than what the status quo or some improved version of it is likely to bring. Total deaths are likely higher, along with more social trauma, due to the more extreme whipsaw effects, but no not by millions.
Let’s accelerate those biomedicals, people!
Solve for the rational Bayesian equilibrium
I now read quite a few public health experts on matters of the day, and I have noticed that none of them have condemned the British government for proceeding with the AstraZeneca vaccine trial, even after two adverse health events experienced by participants, noting that those events presumably have been examined and considered by the oversight committee.
At the same time, the American trial for AstraZeneca has remained halted. I also have not read any public health experts criticizing that decision either.
What is the most likely equilibrium to be holding here?
1. Public health experts don’t express many opinions, especially these days.
2. Plenty of commentators think the British decision to resume is rash, Tyler just isn’t reading enough of them.
3. Most public health experts think it is fine for the British to keep on going. But they won’t criticize the American trial halt, because their incentives and natural temperamental tendencies are to express mainly the risk-averse opinions, and rarely if ever say that the regulatory process should allow for more risk to be taken.
4. The mainly American experts actually are happy to see America free-riding upon British data, so they are content with things as they stand, but don’t want to quite come out and admit they enjoy exploiting the Brits.
5. In reality the commentators think the whole trial is so risky it never should have been started in the first place.
6. What they really enjoy writing is philosophical pieces about how social process have all these twists and turns, and natural bumps in the road, and so they don’t wish to work too hard to remove those bumps.
7. The public health experts think that Americans and British have optimally different tolerances for risk, and the split regulatory outcomes reflect that difference.
Your choice?
The public is fine with Human Challenge Trials
A vaccine for COVID-19 is urgently needed. Several vaccine trial designs may significantly accelerate vaccine testing and approval, but also increase risks to human subjects. Concerns about whether the public would see such designs as ethically acceptable represent an important roadblock to their implementation, and the World Health Organization has called for consulting the public regarding them. Here we present results from a pre-registered cross-national survey (n= 5; 920) of individuals in Australia, Canada, Hong Kong, New Zealand, South Africa, Singapore, the United Kingdom, and the United States. The survey asked respondents whether they would prefer scientists to conduct traditional trials or one of two accelerated designs: a challenge trial or a trial integrating a Phase II safety and immunogenicity trial into a larger Phase III efficacy trial. We find broad majorities prefer for scientists to conduct challenge trials (75%, 95% CI: 73-76%) and integrated trials (63%, 95% CI: 61-65%) over standard trials. Even as respondents acknowledged the risks, they perceived both accelerated trials as similarly ethical to standard trial designs, and large majorities characterized them as “probably” or “definitely ethical” (72%, 95% CI:70-73% for challenge trials; 77%, 95% CI 75-78% for integrated trials). This high support is consistent across every geography and demographic subgroup we examined, including people of diverging political orientations and vulnerable populations such as the elderly, essential workers, and racial and ethnic minorities. These findings bolster the case for these accelerated designs and can help assuage concerns that they would undermine public trust in vaccines.
Here is the paper by David Broockman, et.al.
*Editing Humanity*
That is the new book by Kevin Davies, and the subtitle is The CRISPR Revolution and the New Era of Genome Editing. So far I am on p.74, but it is one of the best science books I have read in some while, maybe the best this year. Excerpt:
…Cas9 normally takes about six hours to search through every PAM sequence in the bacterial genome, pausing at each prospective site for a mere twenty milliseconds to peer into the double helix to see if it has found the correct target. But the packaging of DNA in a eukaryotic cell nucleus is far more complex than bacteria. During lectures to his students at the University of Edinburgh, Andrew Wood shows a diagram of a bacterial cell alongside a winding, looping mammalian DNA fiber. “Cas9 didn’t evolve to work in the environment in which we now put it,” he says. “It’s mind-boggling that it is possible to interrogate hundreds of millions of nucleotides in a matter of hours.”
Recommended. Emmanuelle Charpentier and Jennifer Doudna, the two Nobel winners from last week, are so far the central characters of the story.
Are Nobel Prizes worth less these days?
It would seem so, now there are lots of them, here is one part of my Bloomberg column:
The Nobel Peace Prize this year went to the World Food Programme, part of the United Nations. Yet the Center for Global Development, a leading and highly respected think tank, ranked the winner dead last out of 40 groups as measured for effectiveness. Another study, by economists William Easterly and Tobias Pfutze in 2008, was also less than enthusiastic about the World Food Programme.
The most striking feature of the award is not that the Nobel committee might have gotten it wrong. Rather, it is that nobody seems to care. The issue has popped up on Twitter, but it is hardly a major controversy.
I also noted that the Nobel Laureates I follow on Twitter, in the aggregate, seem more temperamental than the 20-year-olds (and younger) that I follow. Hail Martin Gurri!
And this:
The internet diminishes the impact of the prize in yet another way. Take Paul Romer, a highly deserving laureate in economics in 2018. To his credit, many of Romer’s ideas, such as charter cities, had been debated actively on the internet, in blogs and on Twitter and Medium, for at least a decade. Just about everyone who follows such things expected that Romer would win a Nobel Prize, and when he did it felt anticlimactic. In similar fashion, the choice of labor economist David Card (possibly with co-authors) also will feel anticlimactic when it comes, as it likely will.
Card with co-authors, by the way, is my prediction for tomorrow.
Does economic value reside in the brain?
I do not feel qualified to have an opinion here, but this piece, by Benjamin Y. Hayden and Yael Niv, seems of some interest:
Much of traditional neuroeconomics proceeds from the hypothesis that value is reified in the brain, that is, that there are neurons or brain regions whose responses serve the discrete purpose of encoding value. This hypothesis is supported by the finding that the activity of many neurons and brain regions covaries with subjective value as estimated in specific tasks. Here we consider an alternative: that value is not represented in the brain. This idea is motivated by close consideration of the economic concept of value, which places important epistemic constraints on our ability to identify its neural basis. It is also motivated by the behavioral economics literature, especially work on heuristics. Finally, it is buoyed by recent neural and behavioral findings regarding how animals and humans learn to choose between options. In light of our hypothesis, we critically reevaluate putative neural evidence for the representation of value, and explore an alternative: that brains directly learn action policies. We delineate how this alternative can provide a robust account of behavior that concords with existing empirical data.
Via Benjamin Lyons.
What should I ask Jimmy Wales?
I will be doing a Conversation with him. So what should I ask?
Here is his um…Wikipedia page, presumably it is fairly accurate!
A Cost/Benefit Analysis of Clinical Trial Designs for COVID-19 Vaccine Candidates
I am very happy to see this new and urgently needed study. They have heeded the stricture to show their work. The authors are Donald A. Berry, Scott Berry, Peter Hale, Leah Isakov, Andrew W. Lo, Kien Wei Siah, and Chi Heem Wong, and here is the abstract:
We compare and contrast the expected duration and number of infections and deaths averted among several designs for clinical trials of COVID-19 vaccine candidates, including traditional randomized clinical trials and adaptive and human challenge trials. Using epidemiological models calibrated to the current pandemic, we simulate the time course of each clinical trial design for 504 unique combinations of parameters, allowing us to determine which trial design is most effective for a given scenario. A human challenge trial provides maximal net benefits—averting an additional 1.1M infections and 8,000 deaths in the U.S. compared to the next best clinical trial design—if its set-up time is short or the pandemic spreads slowly. In most of the other cases, an adaptive trial provides greater net benefits.
And what is an adapted trial you may be wondering?:
An adaptive version of the traditional vaccine efficacy RCT design (ARCT) is based on group sequential methods. Instead of a fixed study duration with a single final analysis at the end, we allow for early stopping for efficacy via periodic interim analyses of accumulating trial data…While this reduces the expected duration of the trial, we note that adaptive trials typically require more complex study protocols which can be operationally challenging to implement for test sites unfamiliar with this framework. In our simulations, we assume a maximum of six interim analyses spaced 30 days apart, with the first analysis performed when the first 10,000 subjects have been monitored for at least 30 days.
That means of course you might cut the trial short. Kudos to the authors for producing one of the most important papers of this year.