I read with great interest Sam Altman’s essay *How to Be Successful. ⊕ Five years after it came out! Better late than never. It presented many interesting nuggets of wisdom, such as:

You get truly rich by owning things that increase rapidly in value.

…

The best way to make things that increase rapidly in value is by making things people want at scale.

So, can someone please explain to me, like I am a nine-yer-old, how did Sam Altman become successful? It couldn’t possibly have been Loopt, a little-known geo-social service. Well, the very last sentence in the essay, added as a response to Hacker News comments, gave it away:

I am deeply aware of the fact that I personally would not be where I am if I weren’t born incredibly lucky.

He should have started with that! Silicon Valley people apparently like talking about “first principles”, and it seems clear to me that the first principle of being wildly successful (or “truly rich”, which Altman tellingly equates) is to be lucky; everything else is ex post narration. I want to read an essay that starts with luck: how to recognize it, how to expose yourself to it, how to benefit from it. This will inevitably become an essay about probability, so Nassim Taleb would be the perfect person to write it, and indeed he did! Only the topic is much too complex for a short essay so yes, it’s a book, and to fully appreciate it you may as well read the whole of Incerto.

And if I am contrasting Taleb with Altman — which may be an unfair comparisson to Altman as there is a bit of an age differential — here is what Sam says about hard work:

I think people who pretend you can be super successful professionally without working most of the time (for some period of your life) are doing a disservice. In fact, work stamina seems to be one of the biggest predictors of long-term success.

The parenthetical is doing a lot of work here, and the thing left unsaid is that with this ethos you can end up working really hard your whole life and end up safe from poverty, but not wildly successful… like most Americans! Here is prof. Taleb:

Solid financial success is largely the result of skills, hard work, and wisdom. But wild success (in the far tail) is more likely to be the result of reckless betting, extreme luck, & the opposite of wisdom: folly.

Indeed.

P.S. While the essay reads better than the recent Techno-optimist hocum (a low bar), did he really need 17 people to review his drafts, including… Diane von Fürstenberg? Seriously?

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!

Gorgeous weather in DC today. Even the sky was smiling.

We are at the pediatrician’s office for an annual physical. The gowned offspring is holding my phone, reading a school-assigned book. The phone is also logged into a work meeting, which I’m listening to via AirPods. That same phone is also a hotspot for my laptop, which I’m using to write this. So there is a reason Apple is a trillion-dollar company, and I do hope they sort out their issues with China, lest we lose some of the magic.

Serbia in the 1990s had a peculiar mass media landscape in that movies were rarely officially released, yet were shown on TV days after premiering through the magic of pirating, practiced by both broadcast and cable networks. The most successful of these was TV Pink, now a horror show of reality TV, and one of the many peculiar features of TV Pink was that its daytime content would rely heavily on those E! making-of fillers and patter interviews with exhausted celebrities on their movie-promoting circuit. While home-bound sick kids of America filled their days with Bob Barker and Jerry Springer, in Serbia it was all Hollywood all the time — unless you were the weirdo who liked to watch reruns of 1960s kids shows and their poorly made hyperinflation-era remakes, which was the only thing state TV was capable of producing.

But that wasn’t me! So when I got bacterial pneumonia back in 6th grade and was stuck at home for two whole weeks while receiving twice-daily intramuscular right-into-the-gluteus aminoglycoside antibiotics — the lackadaisical attitude of Serbian pediatricians towards dosing and toxicities is a different story — Pink took up more of my time than I care to admit, and making-of videos from that period got engrained in my memory more so than the movies themselves. Topping the list was the 1995 comedy Get Shorty starring John Travolta, which back then I thought must have been the biggest blockbuster ever if they were talking about it so much.

All this is a preamble to what I heard said by Travolta, or his co-star Danny DeVito, or maybe it was the director Barry Sonnenfeld, and it was this: the movie was based on a book, and the book was outstanding and written by Elmor Leonard who had a way with writing dialogue, and whenever they had an urge to improvise their lines they would hold back because Leonard must have already thought about the things that came to the actors minds first and decided that, no, this thing on the page was better.

And I have heard that line so many times — my pre-frontal cortex still developing — that I have now completely internalized it and act on it unconsciously. When evaluating someone’s work — outside of grading papers, for that is a different matter entirely — I start with the assumption that they have thought long and hard about the paper they’ve submitted for my peer review, certainly longer than the few hours I can dedicate to reviewing it, and I give them the benefit of the doubt. My first impression is probably something they thought about and dismissed, to come up with what they are submitting. Now, some papers are so egregiously wrong that they will still be red all over after I’m done; but if there is a small difference of opinion, or a nit to pick with style, or something I would maybe have done slightly differently, I just let it be, in deference to the authors' work and respect to their, the editor’s, and — why hide it? — my own, time.

After being on the receiving end of quite a few paper and grant reviews myself ⊕ Oh, and meetings. So many meetings., I am beginning to suspect that not everyone is following the Get Shorty ethos.

Now, the worst peer review I have ever received was also the shortest. It was for a paper about a clincial study in rare disese that had a one-sentence rejection from the first journal where it was submitted: “Only 11 patients, they need more”. But most other reviews are not “bad” in that sense, but rather overly verbose and nit-picky about the tiniest of details with dozens of comments per review, the purpose of which is not to improve the article, but rather to show to the editor of the prestigious journal — the higher the impact factor, the more nits to pick — that the reviewer was worthy of the invitation to provide his or her services free of charge to the academic publishing machine. Look at me, ma', I’m paying attention!

Which is fine for papers, I guess, since the reviewers will be in the ballpark of your field (those that aren’t won’t accept the review), and you may at least get a chance to respond. Grants are worse: not only are the reviewers forced into it for the prestige of being on a study section, there is little chance if any that they will have the knowledge of your field ⊕ This is why, I suspect, the best predictor of receiving an NIH grant is already having received an NIH grant. Not only have you been stamped as a success for the “educated lay-people” on the study section, but if you reapply to the study section their knowledge of your field will have been what you told them, and the Program Officer, in prior grant applications. The problem is trebled if you apply with a clinical trial, because all the people with clinical trial expertise across all of the NIH study sections could probably all fit in a Mini. But how much more difficult could designing a clinical trial be from running a lab, eh?

The examples are many and I’m not at liberty to discuss most of them, but back when I was opening trials in T-cell lymphoma a grant was not funded mostly because they didn’t think we could enroll patients for this “rarest of the rare” disease in time (we were well over half-way done with enrollment by the time we heard of this decision). In case you were wondering why all the money goes to breast, colon, and lung cancer research, well, no one ever had a problem recruiting for those!

There is a role for peer review: to weed out the impossible and the truly un-fundable. But after that it may as well be a lottery: why would rolling the dice be worse than adding up laundry lists of small, irrelevant issues that could sink an application which gets assigned to two or three particularly detail-oriented reviewers. It would also save a hell of a lot of time for everyone involved.

As the holiday season approaches, let me note that a great use for LLMs, be it ChatGPT or Bard — and I’ve switched to Google’s lately — is for gift ideas. I now someone who likes DixIt and Mysterium, and it came up with Obscurio in seconds. It also pointed me to a good game for a tween who likes cats. For a six-year-old, too. And not a sponsored link in sight! Let’s see how long the honeymoon period lasts.

Speaking of honeymoon periods and tech: Bing has become unusable, with slowdowns, plain unavailability, and the occasional gobbledygook. So — goodbye, Edge, it was nice while it lasted. Bard is faster, better-formatted, and available on Safari, to which I keep coming back.

🏀 Basketball is back! Nuggets on the West coast, Wizards on the East, popcorn at the ready.