Last week I went to Bethesda for the NIH hematology/oncology fellowship’s “career panel”. They didn’t have those back in my day so I can’t attest to their value for the heme/onc fellows, but I learned a lot! One interesting tidbit noted by a panelist: academia emphasizes owning the idea, industry emphasizes owning the execution.

Some wise words from Thomas Basbøll:

It is not whether what you are saying is true, but how you respond when someone tells you that you are wrong, that determines whether you’re an academic (or at least what kind of academic you are.)

He blogs at Inframethodology, which is a wonderful resource for academic writers.

By the way, these were just the lectures that interested me. The entire NIH calendar of lectures and courses is freely available to everyone, and the ones that are videocast and/or provide CME are marked as such, so feel free to make your own autodidact list.

The first one is tomorrow, and it’s a good one!

• The Ethics of Using Large Language Models by Nick Asendorf, PhD. Wednesday, October 4, 2023 at 12pm EDT.
• Clinical Center Grand Rounds: Pericles and the Plague of Athens by Philip A. Mackowiak, MD, MBA. Wednesday, October 11, 2023 at 12pm EDT.
• Understanding and Addressing Housing Instability for Cancer Survivors by Angela E. Usher, PhD, LCSW, OSW-C and Brenda Adjei, MPA, EdD (and no, I don’t know what most of those acronyms mean). Tuesday, October 17, 2023 at 2pm EDT.
• WALS lecture: The Lives of Bacteria Inside Insects by Nancy A. Mora, PhD. Wednesday, October 25, 2023 at 2pm EDT.
• Reading Remedy Books: Manuscripts and the Making of a National Medical Tradition by Melissa B. Reynolds, PhD. Thursday, November 2, 2023 at 2pm EDT. And yes, I know it’s in November, but I likely would have missed it for the next post since it is so early in the month.

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.

If there was any doubt whether I’m middle-aged, ⊕ I am, in fact, past middle age, as I will turn 40 in December. The average life expectancy for a 39-year-old male in the United States is 37.85 years per the Social Security Administration actuary tables. the kids started school last month and it has been one back-in-my-day moment after another ever since.

This is the most recent one: the eldest has started 6th grade, which in the US is considered Middle School, and is apparently a big deal because that is when they start getting actual grades. Now, back in my day and — this is probably the more relevant fact — in Serbia, you started getting properly graded scored The unfortunate characteristic of the American school system is that it uses the term “grade” for too many distinct but adjacent concepts, so I will stick to “grade” for the yearly cohort of kids, and use “score” for the number they get on assignments and at the end of each year. in 1st grade: there was none of this descriptive assessment shenanigans. It was also probably the reason why the teachers were so interested in what your parents did for a living. But this is not a tirade against descriptive scoring; I had that moment 5 years ago at our first encounter with the 1st grade. The 6th grade b-i-m-d moment was that the scoring is performed nearly real-time, is viewable by both parents and children via an online portal, and — this is what got me — includes whether you:

1. wrote your full name instead of only the first name on a line that says just “Name”;
2. checked all of the boxes on an end-of-class exit form, regardless of whether you performed the tasks outlined next to those boxes;
3. turned in your field trip forms on time.

This is all incorporated into your Science class score. Science. Class. Score.

Now, if the main goal in your life as a scientist is to apply to as many NIH grants as possible and perhaps even win some of them, then yes, science is mostly about box-checking and meeting deadlines. But if you want to call these endeavors “science”, I encourage you to scroll through Adam Mastroianni’s newsletter Experimental History and check your beliefs against some persuasive evidence that science is, in fact, the complete opposite of checking boxes and worrying about the next deadline, and that part of the reason it is stagnating (well, some sciences more than others) and that younger generations are more interested in becoming influencers, content creators, crypto millionaires or whatnot is that they have this misshapen idea about what science actually is from the backwards way it is being presented to them.

With good intent, I should add! There absolutely should be a way to encourage tweens, teens, and adolescents to be more responsible and contentious and middle school is as good of an age to start as any. Heck, there is even a ready-made textbook for it. But call it “life skills”, call it “civics”, call it “behavior” if you will, as we did back in my day. Just please don’t call it Science.

Update: if you thought my quip about box-checking skills being important for NIH grants was facetious, here is the winner of the 2021 Nobel Prize for Medicine describing a recent desk rejection from the NIH for failing to properly format his references on a grant application. Quo vadis, scientia?

We are three weeks into our clinical trials course for the UMBC graduate program. This remark will surprise absolutely no one, but: it was refreshing to see a classroom full of attentive, engaged students, interrupting, asking questions, having a dialogue, others jumping in, etc. Alas, I cannot take any credit for the interactions, as we have guest lecturers on for most weeks.

Regardless, the course has reminded me about how absolutely wrong I was back in December 2019, when during a post-conference The link is for the 2019 ASH Annual Meeting abstract book, ASH being the American Society of Hematology, and I am only now realizing that — in what could be described as our profession’s version of burning man, which is actually quite fitting for an organization called ASH — they tear down the conference website each year to make a new one. So, the 2019 version is no more, but here is one for the 65th annual meeting in December 2023 although if you go to the website after December 2023 I am sure it will point you to the 66th and beyond. I could have linked to the Internet Archive version of the website from 2019 instead — in fact, here you go — but why relinquish myself of the opportunity for that burning man’s ash pun? dinner I stood on my soapbox and wondered in amazing why we were still wasting our time meeting in person once per year like barbarians, when we could in fact be having continuous virtual conversations on Zoom. Timely spread of scientific information and all that.

Well, I have apologized — in person! — to everyone who had to suffer through my Orlando diatribe, because the last 3 years have shown that while video conferencing may rightfully replace most business calls and other transactional meetings, it is absolutely abysmal for education for all parties involved. And it’s not just that any kind of non-verbal communication is lost, it is that even spoken language is stilted, muted, suppressed. With the slide-up-front, speaker-in-the-corner layout that is so common for lectures, you may as well be pre-recording it. It makes absolutely no difference.

And, attending a few online lectures every month myself, it is hard to decide what is worse: having it be completely online and trading off the quality of the lecture for more opportunity for interaction, or watching a live/hybrid lecture and being completely shut out from the discussion (because the in-person attendees take priority when it comes time to ask questions, and rightfully so).

Even at the most basic practical level: technology failure with an online lecture means no lecture; technology failure in-person means, at worst, using the whiteboard and interacting more, which actually makes me wish for more technology to fail. And if you absolutely need to have the slides to make your points, just print them out for your own reference, and share them beforehand for the students to view on their own screens, of which they will have many.

Craig Mod had similar thoughts this week about work in general:

After the last couple of weeks of in-person work, I have to say: Some things simply can’t be done as efficiently — or at all — unless done in person. The bandwidth of, and fidelity of, being in the same room — even, maybe especially, during breaks and downtime, but during work periods, too, of course — of being able to pass objects back and forth, to have zero latency in conversation between multiple people. To not fuss with connections or broken software (Zoom, a scourge of computing, abjectly terrible software (I prefer … Google Meet (!) by a mile)) or cameras that don’t allow for true eye contact — where everyone’s gaze is broken and off and distracted. To dispatch with all of those jittery half-measures of remote collaboration and swim in the warm waters of in-person mind-melding is a privilege for sure, and a gift.

Education is one of those types of work that can not easily be replicated online. ⊕ AR/VR being a big and obvious caveat here, but that will take a while. For evidence, look no further than the persistence of the physical university campus despite the plethora of free and paid online options. Were it not for the in-person factor, the higher education equivalent of The New York Times would have gobbled up the market by now. I’ll know the tide has turned once Harvard and Yale — which would be my first proxies for the NYT and WaPo of higher ed — start investing more in their online offerings to the detriment of in-person experience.

Kudos to the two physicists who plotted all objects in the Universe onto a single 2D plot, most of all for the breadth of their ambition, but also for planting their tongue firmly in cheek with a tiny, sub-Planckian-sized quip:

Humans are represented by a mass of 70 kg and a radius of 50 cm (we assume sphericity), while whales are represented by a mass of 10^5 kg and a radius of 7m.

Someone please update Wikipedia! (ᔥJason Kottke)

Target-based drug discovery is a waste of time, says a systematic review of 32,000 articles and patents from the last 150 years:

…only 9.4% of small-molecule drugs have been discovered through “target-based” assays. Moreover, the therapeutic effects of even this minimal share cannot be solely attributed and reduced to their purported targets, as they depend on numerous off-target mechanisms unconsciously incorporated by phenotypic observations. The data suggest that reductionist target-based drug discovery may be a cause of the productivity crisis in drug discovery.

So it would seem. And even those drugs initially developed to target a single protein or mutation end up having many more unanticipated effects. Back to the jungle and the ocean depths, then?

(ᔥDerek Lowe)

As a prolific child fabulist, I very much appreciated @ayjay’s reminiscence. Most people are, in fact, reflexive embellishers, but not everyone can recognize it in themselves or turn it into a healthy skepticism. At least that’s what I tell myself!