Category: Science

What should I ask Noubar Afeyan?

I will be doing a Conversation with him, here is a partial bio:

Noubar was born in Beirut to Armenian parents in 1962, did his undergraduate work at McGill University in Montreal, and completed his Ph.D. in biochemical engineering at MIT in 1987.

He founded Flagship Pioneering:

Flagship has fostered the development of more than 100 scientific ventures resulting in $30 billion in aggregate value, thousands of patents and patent applications, and more than 50 drugs in clinical development.

During his career as inventor, entrepreneur, and CEO, Noubar has cofounded and helped build over 50 life science and technology startups.

Here is that link, and he is by the way co-founder and chairman of Moderna.  And on the board of the Boston Symphony Orchestra.

So what should I ask him?

One marginal Covid-19 and Fast Grants update

A number of scientists (including, but not only, those funded by Fast Grants) have reported some interesting findings related to fluvoxamine, SSRIs and sigma-1 receptor (S1R) agonists more broadly.

  • A small RCT at Washington University (n=152) published in JAMA found that patients receiving fluvoxamine had a 0% hospitalization rate (vs. 8.3% for placebo). https://jamanetwork.com/journals/jama/fullarticle/2773108
  • Another group reported (data not yet published but reported here with permission) a 0% hospitalization rate in a fluvoxamine-treated cohort compared to 11% in the non-treated group. (n=146)
  • A large observational analysis (n=7345) of hospitalized French patients found that those on SSRIs (of which fluvoxamine is one) had a very substantially reduced risk of death. (n=257, HR = 0.56.). SSRIs with the highest Sigma1 activation showed the greatest protection. https://www.medrxiv.org/content/10.1101/2020.07.09.20143339v2
  • Fluvoxamine is a potent sigma-1 receptor agonist. Following their initial report on the role of S1R in SARS-CoV2 – host interaction, Nevan Krogan’s group found that patients receiving another sigma-1 agonist (indomethacin) had a materially reduced likelihood of requiring hospitalization compared to those receiving celecoxib, which doesn’t activate sigma-1. This work was supported by Fast Grants. https://science.sciencemag.org/content/370/6521/eabe9403.full
  • Lastly, a genetic screen by a Fast Grants-funded lab (not yet published but reported here with permission) has found that genes upregulated by fluvoxamine significantly inhibit SARS-CoV2 mediated cell death.

On the off chance there is something here, fluvoxamine is relatively safe, cheap, and widely available.  We are very open to both positive and negative data in this area, and have funded a further effort.  Do let us know if you hear anything on this topic!

That’s it for this week!?

There is a new Toyota battery for electric vehicles:

A trip of 500 km on one charge. A recharge from zero to full in 10 minutes. All with minimal safety concerns. The solid-state battery being introduced by Toyota promises to be a game changer not just for electric vehicles but for an entire industry.

The technology is a potential cure-all for the drawbacks facing electric vehicles that run on conventional lithium-ion batteries, including the relatively short distance traveled on a single charge as well as charging times. Toyota plans to be the first company to sell an electric vehicle equipped with a solid-state battery in the early 2020s. The world’s largest automaker will unveil a prototype next year.

Here is the full story, via Molson Hart.  There is still Friday.

Youyang Gu will estimate vaccination numbers and herd immunity

  • We believe COVID-19 herd immunity (>60% of population immune) will be reached in the US by late summer/early fall 2021 (Sep-Nov 2021).
  • At the time herd immunity is reached, roughly half of the immunity will be achieved via natural infection, and the other half will be achieved via vaccination.
  • New COVID-19 infections may become negligible before herd immunity is reached. Our current best estimate of when daily community transmissions will drop below 1,000 per day is summer 2021 (Jul-Sep 2021).
  • Summarizing the above findings, our best estimate of a complete “return to normal” in the US is late summer 2021 (Aug-Oct 2021).
  • We estimate around 30% of the US population (~100 million) will have been infected by the SARS-CoV-2 virus by the end of 2021. This translates to a final US COVID-19 death toll of roughly 500,000 (+/-100k) reported deaths.

You can track the data here, his earlier forecasts of cases, hospitalizations, and the like were among the best.  He is here on Twitter.  For the pointer I thank CatintheHat.

How good is the Pfizer vaccine for older people?

From mathematician Gary Cornell:

For people 65 to 74, while the average number (92.9%)  looks great, the confidence interval is not. It says that what we can say is that there is a 19/20 chance that the efficacy is between 53.2 to 99.8. This kind of confidence interval says that didn’t have enough cases in this group to really say much at all and so the confidence range is too large to be really useful.

And when we get to people over 75, what they describe isn’t a confidence interval, it’s a joke. A confidence interval of -12.1 to 100 is a lot like saying they threw a bunch of darts at a dart board at random and did everything from hit bystanders (i.e. the vaccine made things worse) to perfect protection. They simply didn’t have enough cases to say anything meaningful and so what they say is just totally useless.

But I don’t want to end on a depressing note!  My friends who think about these questions feel pretty strongly that while the vaccine will likely be less effective in people over 65 than it is in younger people, the dropoff won’t be great enough to make a big difference. For example, if it is 20-25% less effective in these age groups (which they think is the worst case scenario), you still get a vaccine that is roughly between 70% and 75% effective – which is still pretty darn good.

Still I wish they had enrolled enough people >65 to have a better signal!

There is much more useful information at the link.

Applying insights from magic to improve deception in research

Highlights

• Researchers generally receive little training in experimental deception.

• Drawing on the field of magic, we present a novel model of effective deception.

• First, deception should have many “layers” rather than a single cover story.

• Second, these layers should be subtle rather than explicitly stated.

• We provide strategies for improving deception and thus the reliability of research.

And this:

Magicians have theorised that if tricks are too smooth and perfect, they end up seeming less impressive than ones with minor flaws (Kuhn, 2019).

Here is the article, by Jay A. Olson and Amir Raz, via the excellent Kevin Lewis.

The Stargate Project

The Stargate Project was a long-running program, funded under various names, by the CIA, Army, and Defense Intelligence Agency to investigate and use psychic powers to defeat enemies of the United States, foreign and domestic. The program can be dated back to the end of World War II but it picked up in the 1970s with rumors that the Russians had a lead in ESP and with the popularity of the “psychic” Uri Geller.

Geller in fact consulted for the program and his powers were investigated under a DIA grant by the Stanford Research Institute. SRI concluded that Geller had “demonstrated his paranormal perceptual ability in a convincing and unambiguous manner.”  The CIA agreed concluding in 1975 that:

“A large body of reliable experimental evidence points to the inescapable conclusion that extrasensory perception does exist as a real phenomenon….the work at SRI, using gifted individuals, has achieved some convincing and striking demonstrations of the existence of paranormal perception, and has demonstrated perhaps less convincingly the possible existence of psychokinetic influences upon sophisticated physical instrumentation.

In fact, as late as 2017 the physicist running the SRI program thinks Geller was “clearly gifted when it came to doing certain psychic tasks.”

Need I tell you that Johnny Carson did a much better job than the DIA of showing Geller was a fraud or that a later investigation suggested that “Geller was allowed to peek through a hole in the laboratory wall separating him from the drawings he was being invited to reproduce.”

Nevertheless, the Stargate Project continued for decades and not just investigations. So-called “remote viewers” were recruited and paid to try to locate hostages, missiles and other locations of military and domestic intelligence secrets:

As he later told the Washington Post, McMoneagle was involved in some 450 missions between 1978 to 1984, including helping the Army locate hostages in Iran and pointing CIA agents to the shortwave radio concealed in the pocket calculator of a suspected KGB agent captured in South Africa.

Another remote viewer, Angela Dellafiora Ford, was asked in 1989 to help track down a former customs agent who had gone on the run, she recounted recently on the CBS News program 48 Hours. She was able to pinpoint the man’s location as “Lowell, Wyoming,” even as U.S. Customs was apprehending him 100 miles west of a Wyoming town called Lovell.

Publicly, the Pentagon continued to deny it was spending money on any kind of psychic research, even as reports leaked out in the 1980s of the details of the government’s experiments. Finally, in 1995, the CIA released a report conducted by the independent American Institutes for Research, which acknowledged the U.S. government’s long-rumored work with remote viewing for military and intelligence purposes.

In other words, don’t believe in star gates.

Why are women so prominent in vaccine development?

Here is my Bloomberg column arguing that they are prominent in vaccine development, excerpt:

Then there is the vaccine from Novovax, which is based in Gaithersburg, Maryland. The Novovax results are not yet published, but early word is that they are very promising. This vaccine also is based on new ideas, using an unusual moth cell system to crank out proteins in a highly innovative manner.

Novovax’s team is led by Nita Patel, an immigrant from Gujarat, India. Her vaccine team is identified as “all-female.” Patel is from a very poor family; her father almost died of tuberculosis when she was 4 years old, and she often had to beg for bus fare.

Immigrants too, and there is much more evidence at the link.  In fact women have been prominent in vaccine research for a long time.  But why vaccines?  What is the best hypothesis here?

New CRISPR-based COVID-19 test uses smartphone cameras to spot virus RNA

This one brings us closer to the Star Trek medical universe:

Scientists at UC Berkeley and Gladstone Institutes have developed a new CRISPR-based COVID-19 diagnostic test that, with the help of a smartphone camera, can provide a positive or negative result in 15 to 30 minutes. Unlike many other tests that are available, this test also gives an estimate of viral load, or the number of virus particles in a sample, which can help doctors monitor the progression of a COVID-19 infection and estimate how contagious a patient might be.

“Monitoring the course of a patient’s infection could help health care professionals estimate the stage of infection and predict, in real time, how long is likely needed for recovery and how long the individual should quarantine,” said Daniel Fletcher, a professor of bioengineering at Berkeley and one of the leaders of the study…

The new diagnostic test takes advantage of the CRISPR Cas13 protein, which directly binds and cleaves RNA segments. This eliminates the DNA conversion and amplification steps and greatly reduces the time needed to complete the analysis.

“One reason we’re excited about CRISPR-based diagnostics is the potential for quick, accurate results at the point of need,” [Jennifer] Doudna said. “This is especially helpful in places with limited access to testing or when frequent, rapid testing is needed. It could eliminate a lot of the bottlenecks we’ve seen with COVID-19.”

In the test, CRISPR Cas13 proteins are “programmed” to recognize segments of SARS-CoV-2 viral RNA and then combined with a probe that becomes fluorescent when cleaved. When the Cas13 proteins are activated by the viral RNA, they start to cleave the fluorescent probe. With the help of a handheld device, the resulting fluorescence can be measured by the smartphone camera. The rate at which the fluorescence becomes brighter is related to the number of virus particles in the sample.

And:

Now that the CRISPR-based assay has been developed for SARS-CoV-2, it could be modified to detect RNA segments of other viral diseases, like the common cold, influenza or even human immunodeficiency virus. The team is currently working to package the test into a device that could be made available at clinics and other point-of-care settings and that one day could even be used in the home.

“The eventual goal is to have a personal device, like a mobile phone, that is able to detect a range of different viral infections and quickly determine whether you have a common cold or SARS-Cov-2 or influenza,” Fletcher said. “That possibility now exists, and further collaboration between engineers, biologists and clinicians is needed to make that a reality.”

I recall once asking Silvana Konermann: “What am I going to buy at the CRISPR store?”  Well, this is what you are going to buy at the CRISPR store.

Here is the article.  And funded by Fast Grants, I am happy to say.  Quite the week for science, yes?

Computational sentences to ponder

From a very smart correspondent:

“incidentally forgot to say that this is
basically the death of the
“extended Church-Turing hypothesis”
which roughly states that all reasonable computational models can be simulated on a Turing machine with only polynomial cost.  but it now sure looks like quantum computers are physically realisable and are non-polynomially faster

– in other words we now almost certainly know that computational complexity does depend on laws of physics”

The indentation was his, and with reference to this earlier reported quantum computational result from China.

So what does Friday bring us?

Researchers in China have claimed to have achieved quantum supremacy, building a quantum computer capable of carrying out calculations trillions of times faster than today’s most powerful supercomputers…the computer, developed by a team of scientists at the University of Science and Technology of China in central Hefei, completed a calculation almost 100tn times quicker than existing supercomputers. The breakthrough comes a year after Google proclaimed itself the first to reach the milestone with its Sycamore machine. According to Lu Chaoyang, a professor in charge of the experiment at USTC, the Chinese computer achieved the breakthrough by manipulating particles of light.

Ho hum! Here is the FT article, more here, via John-March Russell here is extensive Scott Aaronson commentary, with many useful links.  Here was my Thursday post.  What is it — Sunday that is the day of rest?

“What will they do on Thursday?”

So wondered Eli Dourado.  Well, from the front page of Nature:

Sight restored by turning back the epigenetic clock [in mice, to be clear]

Neurons progressively deteriorate with age and lose resilience to injury. It emerges that treatment with three transcription factors can re-endow neurons in the mature eye with youthful characteristics and the capacity to regenerate.

OK people, are you ready for Friday?  C’mon, Eli, give ’em another dare!

Via Tom Jens.

This has been quite a week for science

Vaccine approval in the UK, protein folding advances, isn’t there a SpaceX launch today?, and now this:

Cultured meat, produced in bioreactors without the slaughter of an animal, has been approved for sale by a regulatory authority for the first time. The development has been hailed as a landmark moment across the meat industry.

The “chicken bites”, produced by the US company Eat Just, have passed a safety review by the Singapore Food Agency and the approval could open the door to a future when all meat is produced without the killing of livestock, the company said.

…The product would be significantly more expensive than conventional chicken until production was scaled up, but Eat Just said it would ultimately be cheaper.

…The growth medium for the Singapore production line includes foetal bovine serum, which is extracted from foetal blood, but this is largely removed before consumption. A plant-based serum would be used in the next production line, the company said, but was not available when the Singapore approval process began two years ago.

As Eli said on Twitter, what are they planning for Thursday?  Here is the full story, via Michelle Dawson.  Just yesterday I was rereading my CWT with her, it is very good.