The Frontier in 2025 (data), by Gavin Leech, Lauren Gilbert, and Ulkar Aghayeva, rated 202 of the biggest breakthroughs of last year. Some favorites, mainly public health- and society-related:

1. Diagnostics on a phone with no doctor needed (source)
2. Murder rates worldwide have fallen 25% since 2000 (source) ("On average! Potentially some confounding from improved trauma emergency care converting murders into attempted murders")
3. 5 factors explain most of the genetic variance in common mental illnesses (source)
4. Large effect for 5-MeO-DMT for treatment-resistant depression (source) ("Recall that major depression is maybe 2% of the total global burden of disease")
5. For the first time in recent history, China’s emissions might be falling (source)
6. The first evidence of a solar take-off in Africa (source)
7. A tiny number of people are functionally cured of HIV. The antibodies responsible may have been identified (source)
8. An E. coli vaccine is currently undergoing Phase III human testing (source): "E. coli is the second-most lethal bacterium in the world, with about a million deaths a year. There are currently no effective vaccines for it"
9. Extreme poverty drops from 27% of India to 5% in one decade (source)
10. Observational follow-up on the Covid vaccines shows a large decrease in all-cause mortality (source)
11. First-in-human 'prime editing' gene therapy. Cured an inherited immune disease (source)
12. Last year's biannual HIV shot available in low-income countries, $40/year (source)
13. AI designs antibodies that can turn on or off membrane signaling proteins implicated in many diseases (source)
14. AI for antibiotic design (source): "7 of 24 AI-designed and custom-synthesized compounds show selective antibacterial activity, including against N. gonorrhoeae and S. aureus"
15. AI generator for antibodies against specific protein targets (source)
16. Two promising drugs to prevent secondary and post-surgical stroke (source)
17. Challenge trial on a salmonella vaccine showed roughly 70% effectiveness (source)
18. Tiny demo of a 90% effective malaria vaccine which only takes one dose (source) ("However, the Leiden study was n=15. The followup PfSPZ-LARC2 study won't be finished until 2027 and is also n=22(!). Last year's R21 vaccine was 75% effective but takes 4 doses")
19. A candidate "gene drive" for eliminating malaria reduced parasite hosting from 80% to 30% (source)
20. A new class of treatment for malaria: 97% cured and it shouldn't suffer existing drug resistances (source): "the first new class of malaria drug approved in more than 25 years"
21. Three new countries certified malaria-free (source): Georgia, Suriname, and Timor-Leste
22. Four countries eliminated trachoma, a disease that causes blindness (source): Senegal, Egypt, Mauritania and Fiji
23. The cost to treat drug-resistant TB drops below $300 (source): "bedaquiline now available at $63 per treatment course, bringing the price of the complete BPaLM treatment to $284"
24. First successful transplant of a non-human lung into a human (source)
25. The oldest baby in history: an embryo frozen in 1994 was brought to term and resulted in a healthy baby boy (source): "The biological mother of the baby was 62 years old at the time of his birth. While incremental, this points towards eventually allowing for delayed IVF, which would be socially transformative"
26. First human infant cured of a lethal genetic disease with a personalized gene therapy (source)
27. Trevogrumab could potentially prevent muscle loss in the sedentary (source)
28. Approval of a strong non-opioid painkiller targeting a pathway specific to pain neurons (source): "It's strong, as strong as hydrocodone or low-dose morphine. It is claimed to be nonaddictive, which is the somewhat unlikely part. It does hit the brain much less, which might work"
29. Tooth regrowing procedure enters human trials (source)
30. Rising Internet access reduces prevalence of female genital mutilation (source)

Why they did this:

A couple of years ago, Gavin became frustrated with science journalism. No one was pulling together results across fields; the articles usually didn’t link to the original source; they didn't use probabilities (or even report the sample size); they were usually credulous about preliminary findings (“...which species was it tested on?”); and they essentially never gave any sense of the magnitude or the baselines (“how much better is this treatment than the previous best?”). Speculative results were covered with the same credence as solid proofs. And highly technical fields like mathematics were rarely covered at all, regardless of their practical or intellectual importance. So he had a go at doing it himself.

This year, in partnership with Renaissance Philanthropy, we took a more systematic approach. So, how did the world change this year? What happened in each science? Which results are speculative and which are solid? Which are the biggest, if true?

I liked GiveDirectly's recent update via GWWC's email newsletter:

Donations from Giving What We Can community members were delivered to Masauli, Chirtera, and Mtembo villages in Chiradzulu district in Malawi. Together, we funded transfers for 954 Malawians in poverty across all three villages. How did families spend their transfers? Here’s what follow-up surveys show:

Hear directly from Emily and David, who are just a few of the people in Masauli village who received transfers from you and other GWWC members:

Emily and her husband, Evance

“My husband and I relied on farming and casual labor to survive,” said Emily. “We grow maize, tomatoes, and cabbage, but without fertilizer, our harvests were always small. Our house also had no windows, and we used sacks instead of a proper door. I always felt unsafe because I worried people could steal from us.” “When I received my first cash payment, I used it to buy fertilizer. This changed everything. Our harvest increased from six bags to ten, and now we have enough food to last until the next harvest. This has brought a sense of peace since we know we have food. With the second payment, I focused on improving my home. I bought 11 bags of cement and used them to put in a proper floor, plaster the house, and add windows and doors. Now my house is safer, and I feel proud of it. I also started thinking about the future. I bought a goat as an investment and started a small business selling beans. I’m making sure I don’t just spend the money, but use it to build something for my family. My husband and I had been sleeping on a mat since we got married. Now, we sleep on a mattress. No more body pains when we wake up. We can sleep comfortably, something we only heard about from other people before. I also bought a bicycle, so I no longer have to borrow from my neighbors when I want to go to the hospital, market, or maize mill. When other women talk about how nice my house looks, it makes me feel proud. I can see the difference in my life now. I have more dignity, security, and hope for the future.”

David and his wife, Lucy, with their harvest

“Every year, we harvested between 15 to 20 bags of maize, but even with all that, we could not develop our home,” said David. “We had three children in secondary school, so all our money went to their education. As parents, we chose to sacrifice for them, but we always wanted to do more.” “We thought about starting a business, because farming is no longer reliable: the weather changes, and farm inputs like fertilizer are expensive. But we never had enough capital to start. Then GiveDirectly came. With our transfer, we opened a small shop using K200,000 (~$115). At first, we sold simple things, like eggs, drinks, and bread. These were the items that people bought most. The business started well, and we were making K40,000-50,000 (~$23-29) a day. We followed one important rule we were told by a friend: never keep money without restocking. Every day, we used the money to buy more goods: salt, biscuits, sweets, and more. The shop kept growing, and now we’re planning ahead. We want to build a proper shop structure. We’ve already bought 22 iron sheets and 3 bags of cement. We are waiting for the rains to pass so we can mold bricks. We’e also planning to build two rental houses for students from a nearby secondary school. We also want to buy livestock, goats, pigs, and cows, so that we can continue supporting our son who is still in school. For us, this money did not just start a business. It gave us a new path.”

All this for slightly over $800 per beneficiary. Hell of a benchmark, cash transfers.

My impression (not the author): 

• area is from slide 8 of SpaceX's FCC Starship Gen2 filing (says V2 in the table but the 2000kg mass is V3-scale)
• wattage is Forethought's guess (257 m² area x 1361 W/m² solar constant x 20% AM0 cell efficiency x 0.721 system derating = 50,400 W), not including 95% capacity factor and 8% annual degradation. It's 2.5x what Musk claimed FWIW
• not sure where array mass comes from 

Seems to be a formatting error and it's supposed to be in the main text, referencing the table.

I resonated with a lot of this, especially prior to 2022. Speaking only for myself, I think a lot of it was downstream of what Ozy Brennan wrote in The Life Goals of Dead People, but I was (unbeknownst to myself) much better at rationalisation than introspection, so it took a long time for me to realise this.

What do you think of Manheim's simple explanation for what makes good technologies good?

David Manheim's If AI is normal technology, history is not reassuring is a good read (emphasis mine): 

There’s a truism that technology is good - even if it creates winners and losers, it improves the world. Toby Ord argues that the conclusions about the benefits of technology is sensitive to the end of humanity - but this jumps over the transitions by starting from the assumption^[1] that “long-term progress in science, technology, and values have tended to make people’s lives longer, freer, and more prosperous.” That is, looking back historically, the net impact misses the immense immediate harms of large scale technological changes that can last for generations.

As I’ll explain, the largest technological revolutions in human history are arguably the agricultural revolution and the industrial revolution. In both cases, the vast majority of those immediately affected were harmed, not helped. Of course, the longer term impact was positive; those benefits are not in question^[2] - not that those alive during the transition should have cared.

The two obvious examples

The invention of agriculture led to increased food availability and around ten thousand years of greatly worsened health and lifespans^[3]. The wealthiest and most powerful people benefited immensely from the population explosion, and from the wars that larger populations enabled and required; the population suffered from both malnutrition, and that same increase in the scale of violence^[4].

The invention of industry was more beneficial to the consumer - but not to those directly involved. In 1840, over a third of the British population worked in a factory. This was bad, in part directly due to factory worker deaths, but also due to pollution and disease. Mortality shot up over the middle of the 1800s - the famed “urban penalty”, especially among children, albeit partially offset by reduced deaths because of sanitation later in the century^[5]. 

3 more examples via ChatGPT/Manheim (which provided 5 including the 2 above; I omitted them -- again emphasis mine):

1. Writing and external symbolic storage - Administration, law, history, mathematics, scripture, bureaucracy, long-distance coordination. Early writing mostly helped palaces, temples, tax systems, accounting, property claims, labor control, and bureaucracy before it helped ordinary people read novels or do science. So the near-term “users” benefited, but many affected subjects may have faced more legible extraction and administration. Evidence from early Mesopotamia links writing with larger government buildings and multi-level bureaucracies.
2. Metallurgy, especially iron - Tools, weapons, plows, empires, deforestation, intensified agriculture, military expansion. Bronze matters too, but iron’s scale and availability make it more transformative. Better tools helped agriculture and craft production, but weapons, fortifications, conquest, inequality, and elite control plausibly dominated early experience for many. The case is less clean because metal tools also had immediate productive benefits, but the war-and-hierarchy channel is very real.
3. Electricity + computation + telecommunications - I’d bundle these reluctantly as the “information-electrical stack”: telegraph, telephone, radio, electric grids, computers, internet, AI. This led to surveillance, labor displacement, attention capture, military command/control, financial acceleration, and dependence on fragile networks^[8].

Manheim's argument for what makes good technologies good:

There have been a couple of revolutionary changes in medicine and public health over the past couple centuries. The vaccine revolution, the advent of modern sanitation, and infection control each include a strong case that they were immediately beneficial, and stayed that way indefinitely^[9]. Refrigeration, washing machines, and bicycles^[10] are arguably more examples in this class. So some technologies really are just positive - but we need to ask which ones.

I think there’s a simple explanation; directly good things are good, but many other classes of transformative change end up disruptive in ways that hurt before they can help^[11]. Technologies that have first order impacts on coordination and production, or that empower groups in other ways, tend to differentially benefit the powerful in ways that are harmful to others, either directly or indirectly^[12].

I find myself instinctively resisting Manheim's explanation, since I'm generally keen on improvements to empowerment and coordination, but have to admit it parsimoniously explains the small-n historical track record above. The issue, as always, seems to be the gap between the beautiful ideal ("more empowerment! more coordination!") and the unavoidably-messy realities of implementation, people being people, etc.

Tangentially, this reminds me a bit of Holden Karnofsky's maximally-conservative utopia, which is just "status quo minus clearly-bad things". 

This isn't really a utopia in the traditional sense. It's trying to lay out one end of a spectrum.

Start here:

In this world, everything is exactly like the status quo, with one exception: cancer does not exist.

It may not be very exciting, but it's hard to argue with the claim that this would be better than the world as it is today.

This is basically the most conservative utopia I can come up with, because the only change it proposes is a change that I think we can all get on board with, without hesitation. Most proposed changes to the world would make at least some people uncomfortable (no inequality? No sadness?), but this one shouldn't. If we got rid of cancer, we'd still have death, we'd still have suffering, we'd still have struggle, etc. - we just wouldn't have cancer.

You can almost certainly improve this utopia further by taking more baby-steps along the same lines. Make a list of things that - like cancer - you think are just unambiguously bad, and would be happy to see no more of in the world. Then define utopia as "exactly like the status quo, except that all the things on my list don't exist." Examples could include:

• Other diseases
• Hunger
• Non-consensual violence (not including e.g. martial arts, in which two people agree to a set of rules that allows specific forms of violence for a set period of time).
• Racism, sexism, etc.

"Status quo, minus everything on my list" is a highly conservative utopia. Unlike literary utopias, it should be fairly clear that this world would be a major improvement on the world as it is.

I note that in my survey on fictional utopias, it was much easier to get widespread agreement (high average scores) for properties of utopia than for full utopian visions. For example, while no utopia description scored as high as 4 on a 5-point scale, the following properties all scored 4.5 or higher: "no one goes hungry", "there is no violent conflict," "there is no discrimination by race or gender."

Megaprojects for animals (or an updated version perhaps, this list being from 2022) seems more pertinent than ever. 

Your experience reminded me of how Holden Karnofsky described his career so far:

The general theme of my career is just taking questions, especially questions about how to give effectively, where it's just like no one's really gotten started on this question. Even doing a pretty crappy analysis can be better than what already exists. So often what I have done in my career, what I consider myself to have kind of specialized in, in a sense, is I do the first cut crappy analysis of some question that has not been analyzed much and is very important. Then I build a team to do better analysis of that question. That's been my general pattern. I think that's the most generalizable skill I've had