Tag: science

New forms of community

2 related articles caught my eye recently. the first one argues that the nuclear family was a mistake, and better configurations are possible:

for vast stretches of human history people lived in extended families consisting of not just people they were related to but people they chose to cooperate with. An international research team recently did a genetic analysis of people who were buried together—and therefore presumably lived together—34 ka ago in what is now Russia. They found that the people who were buried together were not closely related to one another.

When we discuss the problems confronting the country, we don’t talk about family enough. It feels too judgmental. Maybe even too religious. But the blunt fact is that the nuclear family has been crumbling in slow motion for decades, and many of our other problems—with education, mental health, addiction, the quality of the labor force—stem from that crumbling. We’ve left behind the nuclear-family paradigm of 1955. For most people it’s not coming back. Americans are hungering to live in extended and forged families, in ways that are new and ancient at the same time. This is a significant opportunity, a chance to thicken and broaden family relationships, a chance to allow more adults and children to live and grow under the loving gaze of 12 pairs of eyes, and be caught, when they fall, by 12 pairs of arms.

The second article argues that friendships, not marriage, ought to be at the center of life:

Intimate friendships have not always generated confusion and judgment. The period spanning the 18th to early 20th centuries was the heyday of passionate, devoted same-sex friendships, called “romantic friendships.” Without self-consciousness, American and European women addressed effusive letters to “my love” or “my queen.” Women circulated friendship albums and filled their pages with affectionate verse. In Amy Matilda Cassey’s friendship album, the abolitionist Margaretta Forten inscribed an excerpt of a poem that concludes with the lines “Fair friendship binds the whole celestial frame / For love in Heaven and Friendship are the same.” Authors devised literary plot lines around the adventures and trials of romantic friends. In the 1897 novel Diana Victrix, the character Enid rejects a man’s proposal because her female friend already occupies the space in her life that her suitor covets. In words prefiguring Kami West’s, Enid tells the man that if they married, “you would have to come first. And you could not, for she is first.”

Dose variation

The reason we do a second vaccination is that these later doses help to solidify immune memory, in part by giving extra training to the cells that produce antibodies, a process called affinity maturation. But this process begins with the single dose, and the evidence collected between the time of the 1st and 2nd doses in 10Ks of people in the Phase 3 trials suggests that the level of affinity maturation may provide enough protection to meet the standards we have set for vaccine approval during this pandemic even without the 2nd dose. we should begin immediate single-dose trials, recruiting volunteers from low-risk populations who are 1st in line for the vaccinations.

Magical extra doses and supply chain optimization:

some of the vaccine distribution sites had access to low dead-volume syringes, syringes that leave less vaccine trapped between the plunger and needle — the “dead volume” — after a shot is given. Thus, less vaccine was wasted in the syringe and more available for putting into arms using the low dead-volume syringes.

This is quite remarkable. Increasing vaccine supply by 20% by building more factories could cost billions. We should do that, it would be worth it. But in this case, we managed to increase supply by at least 20% use a relatively inexpensive redesign of the syringe. What this indicates is the importance of thinking along the entire supply chain for opportunities for optimization.

Single-Shot and first doses first

The FDA panel voted unanimously to authorize the J&J vaccine. Good. Note, however, that the single-shot J&J vaccine is quite comparable to the first dose of the Pfizer and Moderna vaccines. Yet, few people are demanding that J&J be required to offer a second shot at all, let alone in 3-4 weeks (What about vaccine escape! How long does immunity with a single-shot last! What about the children!). It really is scandalous how these objections to a single-shot have disappeared. This is evidence of what I call magical thinking–an undue focus on the clinical trial design as having incantatory power.

Why did J&J focus on a single-shot? Was this because of “the science”, i.e. something unique about their vaccine? No. J&J focused on a single-shot vaccine for the same pragmatic reasons that I favor First Doses First.

J&J chose to begin with the single shot because the World Health Organization and other experts agreed it would be a faster, more effective tool in an emergency. (emphasis added).

Since that time, Dr Dolittle has insisted we stick to the 2 shots regime. Criminal negligence.

Fractional doses work

in an article on new vaccine boosters there is this revealing statement:

Any revised Moderna vaccine would include a lower dose than the original. The company went with a high dose in its initial vaccine to guarantee effectiveness, but the company is confident the dose can come down, reducing side effects without compromising protection.

Arrgh! Why wait for a new vaccine??? Fractional dosing now! The article also notes:

One of Moderna’s co-founders is known for his research on microneedles, tiny Band-Aid-like patches that can deliver medications without the pain of a shot. Moderna has said nothing about delivery plans, but it’s conceivable the company might try to combine the 2 technologies to provide a booster that doesn’t require an injection.

The skin is highly immunologically active so you can give lower doses with a microneedle patch. The microneedles are sometimes made from sugar and don’t hurt.

Dose stretching works extremely well

A new paper on dose-stretching makes 3 big points. First, “Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.” Future vaccines may not have to go through lengthy clinical trials but can instead rely on these correlates of immunity.

A 50% or 25% dose of the Moderna or Pfizer vaccine looks to be more effective than the standard dose of some of the other vaccines like the AstraZeneca, J&J or Sinopharm vaccines. The point is not that these other vaccines aren’t good–they are great! The point is that by using fractional dosing we could rapidly and safely expand the number of effective doses of the Moderna and Pfizer vaccines.

Second, even if efficacy rates for fractional doses are considerably lower, dose-stretching policies are still likely to reduce infections and deaths. A 50% dose strategy reduces infections and deaths under a variety of different epidemic scenarios as long as the efficacy rate is 70% or greater.

Third, it is better to start vaccination with a less efficacious vaccine than to wait for a more efficacious vaccine. Thus, Great Britain and Canada’s policies of starting First Doses first with the AstraZeneca vaccine and then moving to second doses, perhaps with the Moderna or Pfizer vaccines is a good strategy.

Social media research

Increased data access would enable researchers to perform studies on a broader scale, allow for improved characterization of misinformation in real-world contexts, and facilitate the testing of interventions to prevent the spread of misinformation. The current paper highlights 15 opinions from researchers detailing these possibilities and describes research that could hypothetically be conducted if social media data were more readily available. As scientists, our findings are only as good as the dataset at our disposal, and with the current misinformation crisis, it is urgent that we have access to real-world data where misinformation is wreaking the most havoc.

Busy Beaver

The goal of the “busy beaver” game is to find the longest-running computer program. Its pursuit has surprising connections to some of the most profound questions and concepts in mathematics. The rub is that BB(27) is such an incomprehensibly huge number that even writing it down, much less running the Goldbach-falsifying machine for that many steps, isn’t remotely possible in our physical universe. Nevertheless, that incomprehensibly huge number is still an exact figure whose magnitude represents “a statement about our current knowledge” of number theory.

Warp Speed is Normal

one big reason we got vaccines so quickly was that work had already gone into coronaviruses:

That was a really good—well, not “guess,” I suppose, but a good hypothesis, right? That a coronavirus was going to be a problem?

We were hedging our bets. No one knew what the next outbreak would be. It could have been a variant of influenza; it could have been one of a number of pathogens. But yeah, the short answer is, if you look at a list of outbreaks over the last 20 years, if 2 of the viruses on the list are in the coronavirus family, then you shouldn’t be shocked that it comes up again. SARS was 2002. MERS was 2012. In pandemic history, that’s a pretty short timeframe.

So we did some work with Moderna on designing MERS vaccines—all early, preclinical—so we were able to test how our mRNA worked, and we could test some designs on what the RNA should teach the body to make an immune response against. We had a lot of groundwork already laid when we found out the new virus was a coronavirus.

to prepare for the next pandemic:

It took nearly 20 years to understand coronaviruses well enough to work on. But what if the next one’s not a coronavirus?

There’s a reasonable possibility that a virus could emerge from a different virus family, and we would not be as prepared. We know that there are ~20 major virus families in the world that infect humans, and almost every outbreak we’ve seen in the past 50 years or more has come from one of those 20 virus families. What if we made a concerted effort to study every family in detail, to make vaccines to every family, and do what we did for coronavirus? Make some prototypes. So that if a cousin in that family emerges, a virus we’ve never seen before, we at least have laid some groundwork for vaccine design. One could, for $20m per virus family, make a prototype vaccine and test in the clinic. You’re talking a few billion $ over 5 years for that kind of project. That used to seem like it wouldn’t be tenable. But now it’s like, well, if I could be prepared for the next pandemic, that’s probably a really good investment.

Ancient steam engines

The invention of the steam engine is usually ascribed to British engineers of the 17th and 18th centuries. James Watt is best known for inventing an especially efficient type of the engine in 1786, which was applied first to trains and then in the early 19th century to ships. It is much less known that the engine was invented in the 1st century AD by Greek engineers of Alexandria, more than 1.5 ka before Watt. The British Library holds a remarkable collection of Greek manuscripts that describe and illustrate these early steam engines in great detail.

Generic Solutions

Fighting a disease through targeting its pathophysiologies is, in a sense, an attempt to outflank it rather than attack it head-on. Instead of looking for the magic bullet that will kill the virus, or the tumor, it’s about making the body an unfriendly place for the disease to be in.

The main advantage to this approach is that there already exists a formidable arsenal to assist in this fight: 9500 drugs approved worldwide.

“We believe that in the bank of drugs we have now, the 9500 drugs there are in the world, we have the answers for virtually all diseases. Around 500 of them are still patented. So there’s opportunity to work through the other 9000 off-patent drugs — the generic drugs — and look at the impact that 1 can have for $1 a day.”
Cureosity is a repository of manually curated knowledge about novel treatments for serious, chronic, and intractable diseases.