Happy Friday and welcome back to our 63rd Weekly Dose of Optimism.

Fall is upon us in NYC. It’s Q4 (for those who celebrate.) The Phillies won their Wild Card Series and are moving onto the NLDS. The Eagles are 4-0. It’s Nobel Prize week.

Life is good.

Let’s get to it.

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(1) WHO recommends malaria vaccine that will be rolled out next year

Gabrielle Tétrault-Farber and Leroy Leo for Reuters

The World Health Organization (WHO) recommended on Monday the use of a second malaria vaccine to curb the life-threatening disease spread to humans by some mosquitoes.

We’re getting a second malaria vaccine, and this time we’re getting it at scale.

Malaria kills 600,000 people per year, mostly children in Africa. It’s spread by mosquitoes, and once it gets into the body, it shape-shifts to hide from our immune systems. That makes it hard for our bodies to develop immunity, and has presented a huge challenge to the scientists who have been trying to develop a vaccine for over a century.

Two years ago, the WHO recommended broad use of the world's first malaria vaccine called RTS,S. The first ever approved malaria vaccine was a huge deal, and if the Weekly Dose had been around, it would have been our headline story.

This newly recommended vaccine, R21/Matrix-M, shows similar efficacy as RTS,S but is also able to produced at scale. The world's largest vaccine manufacturer - the Serum Institute of India - is already lined up to make more than 100 million doses a year and plans to scale up to 200 million doses a year, and with scale comes lower costs. The vaccine will cost about half as much as RTS,S, and SII projects that supply will match demand for the new vaccine in 2024.

Suck it, mosquitoes.

(2) 2023 Nobel Prize Winners Announced

Nobel Week baby! If there’s one week that reminds us that there are some very smart, dedicated optimists out there pushing humanity forward, it’s Nobel Week. Here’s a quick roundup of the winners.

All of the winners are wicked smart and impressive, but the story of the week is Katalin Karikó, the UPenn researcher who’s been working on mRNA for nearly 35 years.

Karikó joined the University of Pennsylvania in 1989 on a tenure track to work on mRNA, but struggled to get funding. By 1995, UPenn demoted her. She bounced from lab to lab, before finally ending up in Drew Weissman’s lab. The two figured out a way to get the immune system to ignore mRNA in order to make it effective as a vaccine.

They still couldn’t get funding or publications — the lifeblood of academic research — but Penn still filed patents on their work. When Karikó and Weissman spun out a company, RNARx, they couldn’t come to a licensing agreement with Penn. Instead, Penn sold the patents to a small company for $300,000. When Moderna’s backers called Karikó to license the patents, she didn’t have them. They licensed from the company that bought them, Cellscript, instead. Moderna and BioNTech would end up paying out hundreds of millions of dollars to Cellscript for Karikó and Weissman’s work; meanwhile, RNARx shut down in 2013.

Karikó told a Nobel interviewer, “I was kicked out from Penn, was forced to retire.”

It’s thanks to her dogged determination in the face of a chilly reception from the academic community that we had mRNA vaccines when we needed them during COVID. Her story begs the question: how many similarly brilliant ideas have been lost because others just gave up?

How do we make sure the next Karikó doesn’t get lost in the shuffle? Last October, Elliot Hershberg and Dr. Jocelynn Pearl wrote a Not Boring piece, Gassing the Miracle Machine, on exactly that topic. It’s worth reading in light of Karikó’s Nobel.

Here’s the full list of this year’s winners (economics is being announced Monday):

1. Physiology or Medicine:

   • Winners: Katalin Karikó and Drew Weissman

   • Achievement: Pioneering work on messenger RNA (mRNA), which directly paved the way for the creation of mRNA vaccines for Covid-19. According to some reports, these vaccines saved 3 million lives, 18 million hospitalizations, and $1 Trillion in the US alone.

2. Physics:

   • Winners: Pierre Agostini, Ferenc Krausz, and Anne L’Huillier

   • Achievement: Groundbreaking work on attosecond physics, allowing scientists to capture the ultrafast motion of electrons. L’Huillier initiated the understanding by studying light interactions at the electron level, while Agostini and Krausz developed methods to produce incredibly short light pulses, providing unprecedented insights into the dynamics of atomic and molecular processes.

3. Chemistry:

   • Winners: Moungi G. Bawendi, Louis E. Brus, and Alexei I. Ekimov

   • Achievement: Recognized for the discovery and development of quantum dots. Quantum dots are semiconductor nanoparticles that have applications in various areas, from medicine (like medical imaging) to technology (like quantum dot displays in TVs).

4. Literature:

   • Winner: Jon Fosse from Norway

   • Achievement: Fosse's work is known for its minimalist style and deep exploration of human psychology, emotions, and existential themes, which often touch on topics that are hard to articulate.

5. Peace

   1. Winner: Narges Mohammadi

   2. Achievement: Mohammadi is an Irianian human rights activist and freedom fighter. She’s been arrested 13 times, convicted five, and sentenced to 31 years in prison and 154 lashes for fighting against the Iranian regime’s oppression of women. She’s currently in prison.

Humans rock. Especially Katalin Karikó.

(3) Focused Ultrasound

From The Focused Ultrasound Foundation

This tweet from Steve Jurveston brought Focused Ultrasound (FUS) to our attention. Focused ultrasound utilizes ultrasonic energy to target tissue deep in the body without the need for surgical incisions. Here’s how Jurveston summed it up, “You have probably seen ultrasound images of babies, but if you arrange an array of ultrasound transducers to focus to a point, they can manipulate cells and membranes like a magnifying glass focusing sunlight to a burning hot point.” It's a form of non-invasive therapy, and while it’s still mostly in trial phases, its applications could range from tumor treatment to drug delivery.

At the same time, the technology does have some potential setbacks: imprecise targeting and overheating cells unintentionally. To be clear, we’re still early here and tons of more research is currently underway, but the idea of using ultrasound to zap tumors is cool enough to include early.

There were no major announcements related to FUS this week (Jurveston tweeted about it after apparently attending a conference on it) but it’s not hard to imagine that the folks behind this technology could one day join the ranks of the Nobel winners we highlighted above.

(4) Poverty is back to pre-COVID levels globally, but not for low-income countries.

From The World Bank

The economic setbacks of the COVID-19 pandemic resulted in the largest increase in global extreme poverty in decades. Global poverty has now receded to levels closer to those prior to the pandemic, but this means that we have lost three years in the fight against poverty.  The recovery is also uneven: while extreme poverty in middle-income countries has decreased, poverty in the poorest countries and countries affected by fragility, conflict or violence is still worse than before the pandemic. 

Good-ish news and bad news from the World Bank this week.

Good-ish news first: Global poverty levels have recovered since COVID setbacks. We’ve now reverted back to pre-pandemic levels.

Bad news: The poorest countries are still worse off than before the pandemic.

Taken together, we’ve essentially lost 3 years of improving global poverty levels and during that time the most poor became poorer. That’s a pretty bleak story, but when you zoom out even just a few more years, the progress we’ve made on poverty is astounding.

Since 2011, extreme poverty rates have plummeted. Nearly 500 million people worldwide have been lifted out of extreme poverty. Today about 9% of the world population lives on less than $2.15 per days; that % was nearly double at the start of the 2010s.

A lot of work to be done. And certainly we’ll face pandemic-like setbacks in the future. But if we extend that curve another decade, our bet/hope is that another few hundred million folks will be lifted out of extreme poverty.

(5) Towards Monosemanticity: Decomposing Language Models With Dictionary Learning

From Anthropic

Packy here. On Wednesday, I made a very funny joke about Google’s rumored investment in Anthropic at a $20-30 billion valuation:

Yesterday, Anthropic responded by dropping a paper that demonstrates a big step towards understanding language models. As they tweeted, “The fact that most individual neurons are uninterpretable presents a serious roadblock to a mechanistic understanding of language models. We demonstrate a method for decomposing groups of neurons into interpretable features with the potential to move past that roadblock.”

I’m not smart enough to understand the paper, but according to people who are, Anthropic solved the hard problem of mechanic interpretability, which might mean that we can make superintelligent AIs that won’t kill us.

Lesson learned: I won’t even make pessimistic jokes anymore.

Bigger lesson: there’s been so much hand-wringing about AI killing us all, and then humans just go out and turn mechanistic interpretability into a solvable engineering problem. That’s not to say “don’t worry, everything will be fine.” Anthropic was founded to do research and build products that “put safety at the frontier.” People have to do the work, but it keeps turning out that there are no insoluble problems as long as you’re not trying to break the laws of physics.

Bonus: Boats, Boats, Boats

They say the two best days in a boat owner's life are the day they buy a boat and the day they sell it. The same could probably be said of startup investing. Which makes this new wave of boat-tech startups particularly interesting trend.

Arc: The electric boat company raised a $70M Series B to commercialize its water-sport vehicle. Beyond its low-noise, low-gas, and high performance characteristics, the EV boat it also better for the environment. Oh And it looks cool, too.

Navier: And earlier this week, Jason Carman opened season two of his must-watch YouTube series S³ with a profile of Navier.

Navier’s “N30” hydrofoiling craft that is 10x more efficient than traditional gas powered boats, and has many of the same benefits as Arc. Watch the video — hydrofoilin’ e-boats are just fun to watch.

Regent: The electric seaglider company just announced its $60M Series A lead by 8090 and Founders Fund. The seaglider operates a few meters off the ground and couples the speed of airflight with the operational ease of boating. The plan is to use these craft to facilitate transportation between coastal cities.

And it just might be a step towards answering our favorite question: Where is My Flying Car? As Delian tweeted, “Our investment here is us continuing to double down on the thesis that flying boats are the predecessor to flying cars.”

The future of boating is bright. But I think that’s enough water action for me today. Before I get seasick, let’s call it a newsletter.

That’s all for this week. If you have some time this weekend, check out a16z Crypto Startup School.

We’ll be back in your inbox on Tuesday.

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Thanks for reading,

Dan + Packy