Rejoice, our eight-month long nightmare is over. For now.

One of the most level-headed descriptions of the “current situation” comes from the former French prime minister Dominique de Villepin in an interview with Appolline de Malherbe. His answer to the question of whose fault it was:

But Ms. Malherbe, I am trained as a diplomat. The question of fault will be addressed by historians and philosophers.

Unsurprisingly, he never held elected office. That kind of nuanced thinking will never get you enough votes.

If you thought the state of American media was bad — and justifiably so — I can assure you that most of the world has it much worse. Every so often I get sent a link to a Serbian news site writing about cancer research, and it is always a disaster. Here is the most recent one, short enough to be quotted fully here (translation courtesy of Google):

A German company presented an anti-cancer drug: The tumor stopped growing in all patients

The German company Biontek (BioNTech) is currently raising hopes with its cancer vaccine CARVac.

The first research results show that tumors can be stopped from growing, and sometimes even reduced. The first successes occurred after two out of four vaccination doses.

Most study participants (59 percent) had their tumors shrink by at least 30 percent. In addition, the tumor stopped growing in almost all patients (95 percent) after vaccination. Like the covid 19 vaccine, the vaccine is based on mRNA technology.

This means that a certain protein is taken into the cell, allowing the body to repair it itself.

The new vaccine was developed by a team led by Biontek founder Ugur Sahin (58) and founder Ozlem Turecci (56).

So far, 44 patients have received it in four doses. Success was particularly high after two doses, after four doses the tumors were reduced by at least 30 percent in just under half (45 percent), and the cancer was stabilized in 74 percent of all patients.

Let me list the ways in which this is a terrible new story:

No source

Where did the data come from? Was it a paper, an abstract, a press release, or a leak? A 2-second journey to DuckDuckGo shows that they were, in fact, presented at the 2023 ESMO Congress, which is the annual gathering of the European Society of Medical Oncology. The Serbian website does mention a Bosnian article as a “source” for there copy/paste job, but that article also doesn’t list where the data came from.

Wrong data

“The first research results…”, the article begins. Being the first is big news. But this aren’t the first results. Some were presented last year at the same congress, and even that was a follow-up of data presented earlier.

Incomplete data

Vaccines make the news, so that’s what they highlight, but the trial is actually of a cell therapy with and without the vaccine. The 44 patients they mention are the ones who got the cell therapy with and without the vaccine, and there is no breakdown of how many of them got the actual vaccine. With cancer vaccine’s abysmal past record ⊕ No, they are not now being “tried in cancer” after the success in Covid-19. They were, in fact, developed for cancer treatment, experienced failure after failure, and pivoted back to infectious diseases because of Covid-19; and what a good thing for all of us that they did! I highly doubt that the effect we saw was wholly due to the cells, not the vaccine (then again, I work at a cell therapy company). The paper which came out concomitantly with the abstract shows that about the same number of participants who got the vaccine progressed and responded (see Figure 2 for that).

No context

“The tumor stopped growing in all patients”, the headline says. Well, loog at Figure 2 again, it’s what we call a waterfall plot, which is an aspirational name: if the bar goes up from baseline it means that the tumor grew, if it goes down it means that it shrank, so you want it to look like a waterfall. But in 8 of the 21 participants presented in the paper it grew! And in 5 more it barely came down — those count as “stable disease” because measuring tumors is not a precise science and a pixel here or there on the digital ruler can make all the difference. In only 8 of the participants did the tumor shrink, and in only one of those did it go away completely.

This is, I’m sad to say, about what you would expect for a Phase 1 trial of a cancer drug. Most patients who make it to such a trial have slow-growing tumors, and having a “stable disease” in that context — where you are allowed to have the tumor grow by 20% before calling it “progression” — is perfectly meaningless. Note that you will find terms like “disease control rate” or “clinical benefit rate” which combine participants whose tumors shrunk with those who had this “stable disease”. Those two metrics are also meaningless without a control group.

This became longer than I intended so I’ll stop here, but yes, it’s a sad state. It reminds me of dostarlimab, only much worse since in that case there was at least clear evidence that the drug was good, the only thing missing was context. Caveat lector!

So if not daily world news, what then? Well, Axios Local is a good option for DC, and has daily newsletter for more than two dozen other cities. StreetSense is a DC-only enterprise, and more relevant for me than whatever this is from The Washington Post. If the Council does start handing out vouchers to support local news, I know where mine will be going.

Here is an obvious analogy for you: the physical world — meatspace, if you will — as “meat” of an actual body, both skeletal (muscles, ligaments, tendons and such), and visceral (entrails, the liver, vital organs); the internet as nerve impulses connecting the various parts both sensorially (how are the navels of the world doing these days?) and in effect (from Facebook groups to GoFundMe pages bringing actual change).

You know how X and other social networks made everything feel connected to everything else? Well, there is an organic counterpart to this phenomenon, and it’s called a generalized tonic-clonic — or grand mal — seizure, manifesting, in the clonic phase, in widespread convulsions of the body.

The reason why our bodies are usually not convulsing is that the nerve impulse pathways are tightly controlled in space: there are separate nerves, differentiated brain areas for different roles, and let’s not forget the biggest separation of them all: two semi-independent brain hemispheres connected only by the corpus callosum which, imagine this, is sometimes cut completely for treatment of refractory seizures. There is also chemical separation: many of the pathways are inhibitory, and the most abundant neurotransmitter in the body is not dopamine, serotonin, acetylcholine or others you’ve heard of because they go haywire, but glycin, a modest amino acid which people don’t hear about because it is so good at its job of tamping down bad impulses.

The world’s ongoing convulsions started — after an initial tonic phase — right after we have all become interconnected: Hezbollah, Hamas, and your neighborhood association all hooked up to the same firehose. There is a feeling at the edge of my consciousness that the answer to solving them is in ourselves, and not in a new age self-fulfilment way but in pragmatic steps we can take to extrapolate from this most obvious analogy.

Nassim Taleb in Antifragile: ⊕ The link points to an excerpt posted on the Farnam Street blog, which I stopped following years ago — too much noise in the form of wisdom nuggets — but still has its uses. You should really read the whole of Incerto

The more frequently you look at data, the more noise you are disproportionally likely to get (rather than the valuable part called the signal); hence the higher the noise to signal ratio. And there is a confusion, that is not psychological at all, but inherent in the data itself.

…

Now let’s add the psychological to this: we are not made to understand the point, so we overreact emotionally to noise. The best solution is to only look at very large changes in data or conditions, never small ones.

Alan Jacobs today:

If you’re reading the news several times a day, you’re not being informed, you’re being stimulated. Try giving yourself a break from it. Look at this stuff at wider intervals, and in between sessions, give yourself time to think and assess.

Always good to see convergence on important topics. I now get most of my news from books.

Epsilon Theory is a Web 3.0-adjacent website which I discounted simply by the virtue of its co-founder having a laser-eyed profile on X, but their article about news coverage of recent events is spot on:

After the deadly explosion at the al-Ahli Arab Hospital, Hamas issued a statement through its Health Ministry claiming as many as 500 or more deaths as a result of an Israeli airstrike. Instead of reporting what was known – an explosion with casualties – while working to confirm details about the scale of the blast, the number of deaths and the source of the explosion, each of the major newswires simply rushed to repeat each of the claims of Hamas verbatim. The Associated Press did it. So did Reuters. So did AFP. The west’s largest English-language news organizations followed suit. The Washington Post did it. So did CNN. So did the Wall Street Journal.

None of it was a huge surprise — things haven’t changed much since the 1999 NATO bombing of Serbia, when I witnessed in real time how pure speculation from a local TV network that was literally accross the street became Sky News scrolling text within the hour — but still disheartening to see after so much ink has been spilled about fake news and sundry.

Even more disheartening: when the stakes are high and facts are uncertain, journalists error on the side of blurting out whatever will get the highest emotional reaction — for the sake of a click. When stakes are low and there is plenty of time for research — they do the same!

This is the part where I note how not all journalists are alike, and indeed they are not! James Fallows' newsletter Breaking the News ocassionally has some brilliant dissections of the prevalining narrative, though he is too often obsessed with airplanes. I already wrote about The Washington Post’s great long pieces. Even The New York Times, has moments of brilliance. And there is always the local news, which is closer to the ground, less able to test the readers' credulity, and on the chopping block.

So with useful daily news (which is to say, local) becoming extinct, and good weekly/monthly journal articles becoming ever more rare, at least the amount of cognitive noise in our lives should decrease! If only we weren’t such suckers for noise-generating machines (which is to say, most social networks).

When the “Nobel Prize for Economics” gets announced, and people cry out that well-actually it’s the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel and it’s not part of Alfred Nobel’s original endowment, it is because this joker has won it, so how valuable could it possibly be? On the other hand, the most recent award went to the genuinely brilliant Claudia Goldin — here is a good pre-award interview — and the other Nobel prizes also went to some real ding-dongs. Things are never so clear-cut.

When I last wrote about crime in D.C a man was murdered while watching a soccer game right next to my kids' elementary school. This was back in July. Since then, the murders increased even more in August and decreased to (still high!) 2022 levels in September. Then a congressman got carjacked in front of his apartment building and the news media were all over it.

I mentioned in passing how you can trace a direct line from bad decisions to even worse consequences. While there has been movement to correct some of the more egregious mistakes, I haven’t seen even a suggestion of a mea — or sua — culpa from a council member. Until now!

When the stakes are lower, such as lets say public transit fare evasion, there is more space for assigning responsibility. The press release announcing the new legislation and the history behind the reversal is as good of an example of unintended (but not unforeseen) consequences and externalities as I’ve seen. You could, of course, trace the same well-intentioned path from calls for justice to murders on the soccer field, but that would of course not be so politically palatable.

All of this has reminded me of medical reversals and the unfortunately-titled (but good!) book about ending it. ⊕ This is why it is unfortunate: medical reversal is when something that is standard medical practice despite lacking evidence of benefit goes out of fashion once data, usually from a randomized controlled trial, show it doesn’t work. Now, ending reversal could mean two things: that you keep doing the thing despite the new evidence, or that you never start doing the thing to begin with. The authors meant the latter, where my common-sense interpretation is the former. People do dumb stuff. We should promote their reversal. Now, “legislative reversal” and “legal reversal” are terms already reserved for when an appeals court overturns a lower court’s decision, so what should we call “medical reversal” for written law? There are plenty of examples: from customs enshrined in old legislation than is then abolished (like traditional medicine disappearing with evidence showing it doesn’t work) to seemingly progressive legislation which is in reality a fountain of unintended consequences becoming quickly reversed.

Whatever the name, the consequences are at least more definitive than with medical reversals, which are rarely full — people still insert intra-aortic balloon pumps and perform kypholasties, I hear — and outside of a full FDA withdrawal of approval never have as clear of a demarcation line as written law. And we shoud strive to promote it, not end it.

The 2023 Nobel Prize in Medicine went to Katalin Karikó and Drew Weissman, and deservedly so. I do not look forward to the re-writing of history that will inevitably come about the role that the NIH, University of Pennsylvania, and academia in general had in their work. As a reminder:

“Every night I was working: grant, grant, grant,” Karikó remembered, referring to her efforts to obtain funding. “And it came back always no, no, no.”

By 1995, after six years on the faculty at the University of Pennsylvania, Karikó got demoted. She had been on the path to full professorship, but with no money coming in to support her work on mRNA, her bosses saw no point in pressing on.

She was back to the lower rungs of the scientific academy.

“Usually, at that point, people just say goodbye and leave because it’s so horrible,” Karikó said.

She didn’t quit. But even when the breakthrough came, the leading journal saw it as “incremental”:

“The breakthrough, as you put it, we first sent to a Nature journal, and within 24 h, they rejected it as an incremental contribution. I started learning English only at university, so I had to look up the meaning of the word incremental! Anyway, we then sent it to Immunity, and they accepted it (3). We literally did all the work ourselves, Drew and I. Even at the age of 58, I didn’t have much help or funding to perform the experiments, so I did them with my own hands. It took us a while to publish the follow-up paper in Molecular Therapy in 2008, where we presented data on the superior translation of the pseudouridine-containing mRNA and the lack of immune activation in mice.”

The story gets more tangled from there: Karikó and Weissman co-founded a company that failed, then joined BioNTech, and in parallel Moderna started working on their own modified RNA platform, and none of it would have mattered an iota if SARS-CoV-2 hadn’t provided the unfortunate opportunity for mRNA vaccines to shine. For all of our (deserved!) ex post glorification of everyone involved, no Covid-19 — no glory.

Which reminds me very much of The Tartare Steppe’s lonely soldier Drogo who wastes away his life guarding a fortress from the barbarian hordes that don’t arrive until it is too late for him to shine in battle. How lucky for us all that humanity has enough Drogos, and how lucky for this particular pair of soldiers that their Tartars showed up on time.