Case Report of Very-Low-Dose Fentanyl Causing Fentanyl-Induced Chest Wall Rigidity Ronza Zoorob, Logan Uptegrove, Benjamin L Park Cureus. 2023 Aug 20;15(8):e43788. doi: 10.7759/cureus.43788 https://pmc.ncbi.nlm.nih.gov/articles/PMC10508708/
Opioid-induced rigidity after intravenous fentanyl C M Viscomi 1, P L Bailey Affiliations Expand PMID: 9166335 DOI: 10.1016/s0029-7844(97)81423-8 Obstet Gynecol . 1997 May;89(5 Pt 2):822-4. doi: 10.1016/s0029-7844(97)81423-8. 本文有料
Welcome back to the Deep Dive. Today we’re taking you inside one of the most legendary research labs of the 20th century.
That’s right. We’re talking about the Numakin, Dr. Shosaku Numa’s lab at Kyoto University back in Japan’s Showa era.
Numa was a giant in molecular neurobiology, active really up until his passing in 1992.
Absolutely. His work was fundamental. He and his team were the ones who first nailed down the primary structures of crucial things like neurotransmitter receptors and ion channels.
So basically giving us the molecular blueprint for how parts of the brain actually function.
Exactly. It was groundbreaking stuff. And his lab, well, it became famous, maybe infamous, for churning out Nature papers throughout the 80s and early 90s.
It’s interesting. He really burst onto that world stage relatively late, around 1979 when he was already 50.
Yeah, but the impact afterwards was just immense. Now, we need to be clear about how we’re approaching this.
Right. We’re looking at anecdotal accounts, stories from people who actually worked there. And the sources themselves point out um that by today’s standards, Reiwa era standards, a lot of this would likely be seen as academic harassment.
Definitely. We’re not here to judge it by modern ethics necessarily, but to understand it, to report on the atmosphere as it was described.
Our mission, then, is to really get inside that intense environment. What drove this incredible productivity, this culture defined by Numa’s own words, “Effort is infinite.”
Let’s start there, with infinite effort. Because it wasn’t just a slogan, it was the lived reality.
A 24/7 expectation. Numa himself set the pace, didn’t he? Staying until 2:00 AM, sometimes even 5:00 AM.
Oh yeah. He lived it. And that meant everyone was expected to be available. Always. There’s this one story. A researcher gets a call. 6:00 AM Sunday morning.
Okay, must be an emergency, right? Yeah. Lab fire, contamination.
Nope. It’s Numa just casually asking for Pst I.
Pst I, that’s a restriction enzyme, right? Standard tool. He’s calling at 6:00 AM on a Sunday for that.
Exactly. It shows how blurred the lines were between work and, well, everything else. Even made-up holidays weren’t off-limits.
You mean like New Year’s?
Precisely. A staff member worked late on New Year’s Eve, took the first off, naturally. Then, on the afternoon of January 2nd, planning to head home, the phone rings.
Let me guess. Numa.
You got it. Asking, it’s already the 2nd, when are you coming back to the lab?
Wow. The implication is just brutal. Anytime off is slacking off.
It was seen as a lack of passion, a lack of dedication. And Numa even connected this dedication, this tension, as he called it, to physical health.
How so?
He claimed he personally never got colds because he maintained constant tension, which he believed made his body secrete ACTH, the stress hormone.
So stress keeps you healthy, that’s counterintuitive today.
Well, it fit his worldview. There’s an incident where someone was late because they had to go to the hospital for a cold. Numa’s reaction.
Let me brace myself.
He told them off saying, “You should not confuse public and private matters.” Illness was a private matter, interrupting the public duty of research.
So being physically present, demonstrating that effort, was paramount. It wasn’t just about the experiments.
Absolutely. He confronted one person who was just waiting by the phone for a collaborator’s call. Numa told him straight up, “I don’t feel any passion from you. I noticed you sometimes didn’t come to the lab on Saturdays and Sundays.”
It all comes back to that visible, relentless presence. Which logically leads to the next point, the demand for absolute rigor during that time.
Zero tolerance. For mistakes, for excuses, for anything less than perfection, really. And he established this from the moment you walked in.
Like that story about the new graduate student.
Yeah, incredible. The student was working with an enzyme that wasn’t very stable at room temperature, you know, only active for a few seconds.
Okay, a real technical challenge. Right.
And when the student mentioned this instability as a reason for maybe slower progress, Numa’s response wasn’t advice, it was, “Why don’t you quit graduate school?”
Just like that.
Quit. Just like that.
The message was clear: Find a way, or you don’t belong. Excuses weren’t part of the equation. If there’s a problem, infinite effort overcomes it.
And this applied even when technology seemed to offer a shortcut. Like with DNA sequencing.
Oh, absolutely. This was the era when sequence analysis software was coming in. But Numa insisted his team manually check every single nucleotide sequence the computer spat out.
Manually. Why?
His reason, “Computers make mistakes.” Yeah. He actually claimed that this painstaking manual double-checking was why his lab’s previous papers had zero errors.
So he’s directly linking this intense, almost paranoid methodology to their publication success. No trust, verify everything by hand.
It was about achieving absolute data integrity, which, you know, in cloning complex receptors, it’s critical. Mistakes could cost months or years.
That makes sense in a high-stakes environment. What about equipment failures? Things break down in labs?
Not an excuse. There’s the famous fraction collector incident. Machine stops overnight, the crucial active fractions are lost.
Okay, frustrating, but it happens. What did Numa say?
He demanded, “Why weren’t you watching it?” When the researcher said the machine failed, Numa shot back, “It’s natural for a fraction collector to fail. I always check it all night.”
He expected someone to literally watch a machine run all night long.
That was the implication. Perpetual vigilance. And he enforced this rhythm. Almost every night around 10:00 PM, he’d come down to the lab.
For what?
Daily progress reports. He wanted to know exactly what you did that day, and then he’d set specific, tough goals for the next day. No room to just coast.
It sounds incredibly hierarchical, almost military.
He even used that analogy. Apparently, when a colleague tried to push back even slightly, Numa’s response was chilling. He referenced the battlefield.
What did he say?
Something like, “I saw those who defied their superior’s orders on the battlefield. The next moment, their head was gone.”
Wow, that’s intense. But it raises a question, doesn’t it? Science is supposed to be about questioning, challenging assumptions. How did genuine breakthroughs happen under that kind of rigid authority?
That’s the paradox, maybe. The absolute compliance wasn’t necessarily about the ideas, perhaps, but about the execution. The elimination of error in the process. The data had to be perfect.
And that perfectionism, that rigor, carried right through to getting the work published.
Absolutely. Which brings us to what the researchers themselves called, the publication death match.
The death match. Sounds ominous.
And by all accounts it was. This was the final stage, writing the paper. It meant a two-to-three-week, one-on-one, intense session between Numa and the lead author.
One-on-one for weeks?
Yes. Often involving pulling multiple all-nighters in a row. And the feedback was brutal.
How brutal?
Authors were told their English was below middle school level, sometimes even preschool level. Manuscripts apparently got torn up in front of them.
After years of work on the research itself, that must have been crushing.
You’d think so. But Numa’s view was that the paper was the final product, the only thing the world sees. And the writing itself had this very peculiar method.
What was that?
He called it “English borrowing.” Basically, you were forbidden from writing original sentences, unless the finding was completely novel and required new phrasing.
So, how did you write?
You had to find established phrases, sentences used in top journals like Nature or Cell, written by native English speakers. And for every phrase you wanted to use, you had to provide Numa with multiple published examples.
So he was constantly asking, “Where’s the example? Show me where this was used before.”
Exactly. It was about minimizing any risk of awkward phrasing or grammatical error. Using language that was already validated, already accepted by the gatekeepers. Scientific precision applied to prose.
It’s like building with pre-approved blocks only.
Kind of, yeah. And the pressure wasn’t just on the writing, but the submission. He had this incredibly tight schedule.
For mailing a paper?
Yes. Specifically for Nature. To ensure the manuscript arrived in London by Thursday or Friday, making it into that week’s review batch, it had to be dropped off at the Osaka Central Post Office by 1:00 PM sharp on Tuesday.
Missing that deadline by an hour meant potentially losing a week’s lead on competitors.
That’s how he saw it. It was about controlling every variable, maximizing speed and competitive edge. Utter logistical control.
And this obsession with perfection extends to figures, illustrations, too.
Oh, absolutely. The story of the alignment figure is legendary. Numa would check figure dimensions with a ruler.
With a ruler? Seriously?
Seriously. They had this huge complex figure, B4 size, showing sequence alignments. After all the work, they found one single line was drawn solid when it should have been dashed.
Okay, a small error. Can’t they just fix it? White out, maybe?
Normally, yes, but Numa apparently hated correction fluid, forbade it. So the entire massive figure had to be redrawn from scratch.
Oh my god, for one dashed line.
And the story goes, the young secretary who made the mistake was so upset, her tears actually smudged the ink, making the redo absolutely necessary anyway.
The unbelievable pressure. Numa’s take on it captured his whole philosophy. “A paper is like a painting to a painter. You rewrite until you are satisfied. You must not lose power until the last stroke.”
So, let’s step back. We have this image of immense pressure, infinite effort, brutal critiques, but also incredible success. What was the core philosophy Numa tried to impart beyond just getting papers out?
Well, he really emphasized learning through doing. He’d say things like, “Knowledge from textbooks is important, but you must actually do experiments to gain living knowledge. It is more important to think while doing experiments.”
The less armchair theorizing, more getting your hands dirty.
Exactly. And he pushed people to aim high with their research topics, not just safe bets.
What did he advise there?
He told them, “Do work that is as important and meaningful as possible.” He apparently worried that younger researchers were playing it too safe, choosing projects that were easy to publish but didn’t tackle the big questions. He called it poking around in the corners of a heavy box.
He wanted them to try and lift the whole box.
Right. He believed scientists needed to take risks. He even compared it favorably to high-altitude climbing, arguing that, you know, research failure doesn’t actually cost a life.
That puts it in perspective. Did he have advice on timing those big, risky projects?
He did. He had this very specific idea. “A theme that is too early or too late compared to the flow of the world is not good. Choosing a theme that is half a step early ensures success.”
Half a step early. Not too far ahead, but just ahead of the curve.
Precisely. And you can see that in his own work, like the acetylcholine receptor cloning. It was a huge undertaking, right when the techniques became feasible and the field was ready for it. Landed him a Nature cover. Perfect timing.
His career really models that advice. High risk, perfectly timed, massive reward.
It does. And after all that intensity, all that demand, there is one quote that shows maybe a tiny sliver of understanding the human cost.
What’s that?
He apparently said, “A little alcohol is good. Sometimes you need it to bear the hardships of life.”
A rare concession to the pressure, maybe? So, looking back, we see this incredible engine of discovery. The Numa lab produced foundational work, changed neuroscience. But the anecdotes paint a picture of immense personal sacrifice demanded from everyone involved.
Exactly. And that’s the tension, isn’t it? Today, we rightly prioritize well-being, ethical treatment, work-life balance. These things are crucial. But Numa’s story, however extreme, poses a persistent question about what it takes to achieve truly transformative breakthroughs.
That relentless focus, that demand for absolute precision and unlimited effort on difficult, important problems.
It remains a benchmark, even if the methods are now unacceptable.
Tackling the very hardest questions often requires something beyond a standard nine-to-five commitment.
Numa himself said, “The most important thing I want to leave behind is the challenge to attempt something difficult.” So, thinking about that, and his idea that effort is infinite, where do you, listening now, draw the line?
How do you balance that necessary drive for excellence, for pushing boundaries in your own field, with the need to maintain a sustainable, whole life?
It’s the fundamental challenge, perhaps, for anyone aiming high. Where does that infinite effort stop? That’s something to think about.”
Constructing Research Questions: Doing Interesting Research (Mats Alvesson and Jorgen Sandberg 2024 SAGE Publications Ltd) Kindle版（電子書籍）7028円 ”a problematization methodology for identifying and challenging the assumptions underlying existing knowledge, and for generating research questions that can lead to more impactful theories.”（アマゾン書籍紹介より）
“Hi. Just checking in on your Kakenhi application. We’re a bit past the internal deadline now, and I don’t seem to have it yet. Just wanted to make sure everything’s okay.”
” I need to be direct. Your Kakenhi application is now overdue, and it’s starting to hold up the submission process for everyone else. I really need you to get it to me by the end of today.”
“Look, this is the final warning. Your application is now significantly overdue. If it is not on my desk by noon tomorrow, we are officially withdrawing it from the submission cycle. There are no exceptions.”
Joseph Goldberger’s Filth Parties A crusading doctor’s stomach-churning efforts to beat back pellagra in the American South. by Sam Kean September 8, 2020 Health & Medicinehttps://www.sciencehistory.org/stories/magazine/joseph-goldbergers-filth-parties/
Joseph Goldberger’s research on the prevention of pellagra Alfredo Morabia J R Soc Med. 2008 Nov 1;101(11):566–568. doi: 10.1258/jrsm.2008.08k010 https://pmc.ncbi.nlm.nih.gov/articles/PMC2586852/
The unwavering doctor who unraveled a medical mystery Sarah Schmitz 1,2,⁎, Eve J Lowenstein 1,2 https://pmc.ncbi.nlm.nih.gov/articles/PMC6451741/ Int J Womens Dermatol. 2018 Oct 17;5(2):137–139. doi: 10.1016/j.ijwd.2018.09.001
With the goal of making Japan the most attractive country in the world for researchers, the relevant ministries and agencies are working together to advance related policies in a coordinated manner. 日本が研究者にとって世界で最も魅力的な国となることを目指して、関係府省が一丸となって関連施策を推し進めています。https://pitmc.org/
J-RISE stands for Japan – Research and Innovation for Science Excellence. It is a national policy announced by the Japanese government on June 13, 2025, with the stated goal of making Japan “the most attractive country in the world for researchers.” The initiative promotes international brain circulation and calls for cross-ministerial reforms to strengthen Japan’s research environment.
The policy process began on May 19, 2025, when Prime Minister Shigeru Ishiba received a formal proposal from the Liberal Democratic Party’s Special Committee on Science, Technology and Innovation Strategy, chaired by Keitaro Ohno. The proposal urged the government to enhance Japan’s capacity to accept foreign researchers, referencing the outflow of scientists from the United States in response to research budget cuts under the Trump administration.
Following this proposal, on June 4, during a meeting of the Council for Science, Technology and Innovation (CSTI), Prime Minister Ishiba instructed relevant ministries to accelerate efforts to promote international researcher mobility. The Cabinet Office, working in coordination with all ministries, compiled and released the J-RISE Initiative just nine days later, on June 13.
While the initiative positions Japan as an open and globally competitive destination for scientific talent, it has drawn critical reactions on social media platforms such as X (formerly Twitter). Users have pointed out that for more than a decade, the Japanese government has failed to address longstanding challenges faced by domestic researchers—such as unstable employment due to fixed-term contracts, limited career advancement opportunities, and insufficient institutional support. In this context, some have described the sudden shift toward international recruitment as contradictory, noting that the country appears eager to welcome foreign scientists while continuing to overlook the precarious conditions of its own.
政府、「優秀な研究者」獲得に１０００億円…研究費削減で米国から流出のトップ研究者らの受け皿に 6/13(金)/2025 2:03 コメント775件 読売新聞オンライン YAHOO！ JAPAN ニュース 政府は、日本人を含む海外の優秀な研究者を獲得するため、政府が設けた１０兆円規模の「大学ファンド」の運用益の活用など、総額１０００億円規模の資金を投じる方針を固めた。米トランプ政権下の研究費削減で失職したトップ研究者が米国外に流出する中、世界で激化する人材獲得競争に日本も本格参戦する。The Japanese government has decided to invest a total of around 100 billion yen to attract top researchers from around the world, including Japanese nationals. The funding will include profits generated from the management of a 10-trillion-yen university endowment fund established by the government. Amid intensifying global competition for talent—fueled in part by the exodus of leading researchers from the United States following research budget cuts under the Trump administration—Japan is making a full-fledged entry into the race to secure top scientific minds.
“Japan aims to become the most attractive country for researchers,” says the J-RISE Initiative. Seriously? This is the same country that made research the least attractive job for its own scientists. After 10–20 years of neglect, the gov’t suddenly launches this in days? https://t.co/z5Fq1hPBIi
The gov’t wrecked Japan’s research and stripped scientists of a decent life. Now it rushes to invite foreigners in days. It’s outrageous. First, stop firing Japanese researchers with solid records—give them a chance to keep working. https://t.co/znp5c5syk9
Japan’s science policy is insane. Talented Japanese researchers publishing regularly and winning grants are discarded when their contracts expire, while foreign researchers are imported at outrageous costs. Why does no one try to stop this absurdity? https://t.co/Fmb2SyvMgR
I asked Grok 3 to help articulate my opinion on J-RISE.
A Critique of the J-RISE Initiative: A Misguided Policy that Undermines Japanese Researchers
The J-RISE Initiative, officially titled Japan Research & Innovation for Scientific Excellence, claims to aim for making Japan “the most attractive country for researchers worldwide.” Yet, this policy, as outlined by the Cabinet Office, reveals a profound disconnect from the realities faced by Japanese researchers and a troubling prioritization of foreign talent over domestic expertise. While international collaboration is valuable, the initiative’s approach—importing foreign researchers at potentially exorbitant costs while neglecting the systemic issues plaguing Japan’s own academic workforce—is not only illogical but also a betrayal of the very researchers who have sustained the nation’s scientific output. Below, I outline the core absurdities of this policy, grounded in reason but fueled by the frustration shared by many in the academic community.
1. Disregard for Japanese Researchers’ Plight
For decades, Japanese researchers have endured precarious employment conditions, with many facing non-renewable contracts and “employment termination” (yatoi-dome) despite consistent academic output and success in securing competitive funding like Kakenhi grants. These researchers—often at the peak of their productivity—are discarded as if their contributions are expendable. The J-RISE Initiative, rather than addressing this crisis, turns a blind eye to it. Instead of investing in stable career paths for domestic talent, the government proposes to lure foreign researchers with promises of resources and opportunities that Japanese academics can only dream of. This is not just a policy oversight; it is an insult to those who have dedicated their lives to advancing Japan’s scientific legacy under grueling conditions.
2. A Questionable Allocation of Resources
The initiative’s focus on attracting foreign researchers at “premium” costs raises serious questions about fiscal responsibility and fairness. Japan’s research ecosystem is chronically underfunded, with universities struggling to maintain basic infrastructure and researchers scraping by on meager budgets. Yet, the government seems prepared to allocate significant resources to import foreign talent, potentially at salaries and benefits far exceeding those offered to Japanese researchers. This creates a two-tier system where domestic researchers are treated as second-class citizens in their own country. Why should foreign researchers be courted with lavish incentives while Japanese academics are left to compete for scraps? The government’s failure to prioritize equitable investment in all researchers undermines the very excellence J-RISE claims to pursue.
3. A Hollow Promise of Global Competitiveness
The J-RISE Initiative’s lofty rhetoric about making Japan a global hub for research rings hollow when viewed against the backdrop of the past two decades. The government has systematically eroded the attractiveness of research careers through stagnant funding, bureaucratic red tape, and a lack of permanent positions. As posts on X have pointed out, Japanese researchers face wages so low that many struggle to afford basic living expenses or start families, driving talent abroad or out of academia entirely. For the government to now claim it will make Japan “the most attractive country for researchers” without addressing these foundational issues is not just unrealistic—it’s disingenuous. A policy crafted in mere days cannot undo decades of neglect, and expecting foreign researchers to flock to a system that has failed its own is naive at best.
4. Undermining National Talent for Short-Term Gains
The emphasis on importing foreign researchers risks perpetuating a cycle of dependency rather than building a sustainable research ecosystem. Japanese researchers have a proven track record of producing world-class results, as evidenced by numerous Nobel Prizes and groundbreaking discoveries. Yet, the J-RISE Initiative seems to assume that foreign talent is inherently superior or necessary to elevate Japan’s scientific standing. This not only demoralizes domestic researchers but also risks the outflow of proprietary knowledge, as foreign researchers may return to their home countries, taking expertise with them. A truly forward-thinking policy would invest in retaining and nurturing Japan’s own talent, ensuring long-term stability and innovation.
5. A Lack of Transparency and Engagement
The J-RISE Initiative appears to have been developed with minimal input from the very community it claims to serve. As one X user noted, the initiative’s website is little more than a portal redirecting to other sites, lacking substance or appeal to attract serious researchers. This suggests a rushed, top-down approach that fails to engage with the realities of academic life in Japan. If the government is serious about fostering excellence, it must involve researchers—both Japanese and foreign—in shaping policies that reflect their needs and aspirations. Anything less is a bureaucratic exercise in optics, not a genuine commitment to science.
A Call for Reason and Respect
To the Japanese researchers who have toiled under precarious conditions, who have published consistently despite dwindling resources, and who have kept Japan’s scientific flame burning: your frustration is valid. The J-RISE Initiative, in its current form, dismisses your sacrifices and contributions in favor of a flashy, poorly conceived plan to import solutions rather than build them from within. Excellence in research cannot be bought with foreign hires; it must be cultivated through fair treatment, stable careers, and genuine investment in the talent already here.
The government must reverse course. Prioritize funding for permanent positions for Japanese researchers. Address the systemic issues driving talent abroad. Engage with the academic community to craft policies that actually work. Anything less is not just a policy failure—it’s a betrayal of the researchers who are the backbone of Japan’s scientific future. Stop this madness before it further erodes the trust and morale of those who have given everything to this field.
日本語はこちら：
J-RISEイニシアチブの批判：日本の研究者を裏切る誤った政策
J-RISEイニシアチブ、正式名称「Japan Research & Innovation for Scientific Excellence」は、日本を「世界の研究者にとって最も魅力的な国」にするという目標を掲げています。しかし、内閣府が公表したこの政策は、日本人研究者が直面する過酷な現実を無視し、国内の才能よりも外国人研究者を優先する、深刻な矛盾に満ちたものです。国際連携は重要ですが、外国人研究者を高額で招聘する一方で、日本自身の研究者の苦境を放置するこのアプローチは、非論理的であるだけでなく、国の科学を支えてきた研究者への裏切りです。以下に、この政策の不条理さを、理路整然と、しかし研究者の怒りと共感を込めて批判します。