Discovery and Innovation Need a Healthy Dose of Inefficiency
Or, science should be a core cultural activity
👋 Hey there! My name is Abhishek. Welcome to a new edition of The Sunday Wisdom! This is the best way to learn new things with the least amount of effort.
It’s a collection of weekly explorations and inquiries into many curiosities, such as business, human nature, society, and life’s big questions. My primary goal is to give you some new perspective to think about things.
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Q: Should our curiosities always have a purpose?
In 2013, a group of doctors and scientists gave a bunch of smart physicians and medical students (from the likes of Harvard and BU) a type of problem that appears constantly in medicine: If a test to detect a disease whose prevalence is 1/1000 has a false positive rate of 5%, what is the chance that a person found to have a positive result actually has the disease, assuming you know nothing about the person’s symptoms or signs?
At this point I should insist you on taking a couple of minutes to calculate and come up with a solution to the problem, but there’s a strong chance you would just ignore it. I don’t blame you, I’d ignore myself as well. So… let’s move on!
The most common answers were 95 percent and 0.95 percent. If by some miracle of god you actually did the above calculation and came up with any of these answers, congrats, you fall into the category of Harvard and BU students. But unfortunately, you are still wrong. The correct answer that the patient actually has the disease is about 2 percent (1.96 to be exact).
It’s in fact a very simple problem for professionals who rely on diagnostic tests for a living: in a sample of say 10,000 people, 10 would have the disease and get a true positive result; 5 percent, or 500, will get a false positive; out of 510 people who test (both false and true) positive, only 10, or 1.96 percent, are actually sick. Piece of cake, especially once you know how the calculation is done.
Now the problem may not be intuitive, but nor is it very difficult. Every medical student and physician has the numerical and cognitive ability to solve it, but doctors and scientists are seldom trained in basic logic, even though it is very much needed. Sad!
Enter Arturo Casadevall.
Arturo Casadevall is a Professor and Chair of the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. He is also an MD-PhD and a star in his own domains: microbiology and immunology. He has studied AIDS and anthrax, and has illuminated important aspects of how fungal diseases work.
In response to the COVID-19 pandemic, Casadevall investigated the use of antibody-containing blood serum from patients who have recovered from the virus as a measure to help until a COVID-19 vaccine becomes available. His h-index, a measure of a scientist’s productivity and how often they are cited, surpasses that of Einstein’s.
Whoa! This guy means business.
So his new peers naturally took it seriously when, immediately after arriving at Johns Hopkins in 2015, Casadevall declared that scientific research is in crisis. His major concern was that the rate of retractions in scientific literature had accelerated, proportionally outpacing the publication of new studies. And if this continues unabated, he said with a tinge of science humour, there’s a good chance the entire literature will be retracted in a few decades.
Part of the problem, he argued, is that young scientists are rushed to specialise before they learn how to think. Thus they end up unable to produce good work themselves and are perpetually unequipped to spot bad (or fraudulent) work by their colleagues.
This is precisely one of the reasons Casadevall left his comfy post at New York City’s Albert Einstein College of Medicine and joined Johns Hopkins. This new gig gave him a chance to create a prototype of what he thinks graduate science education and, by extension, all education should be.
Casadevall’s family fled Cuba and arrived in Queens when he was eleven. At sixteen, he got his first job at McDonald’s and worked there until he was twenty. It’s still on his résumé, and he made sure to discuss it in his Johns Hopkins interview. After McDonald’s, Casadevall worked as a bank teller. But his father wanted him to have something practical to fall back on, so a community college degree in pest control operations hangs on his office wall, near a certificate of his election into the prestigious National Academy of Medicine.
Casadevall has a strong belief in despecialisation. Together with Gundula Bosch, a professor of both biology and education, Casadevall has set up the R3 Center for Innovation in Science Eduction. R3 stands for Rigour, Responsibility, Reproducibility, and has interdisciplinary classes that include philosophy, history, logic, ethics, statistics, communication, and leadership.
A course titled “How do we know? Theory & Practice of Science” examines types of evidence through history and across disciplines. In “Anatomy of Scientific Error,” students hunt for signs of misconduct or poor methods in real research, while also learning how errors and serendipity have led to momentous discoveries.
I dunno about you, but I would love to take these course any day. These already sound so much better than the drudgery I had to endure in collge.
Casadevall has a point though.
Even though biomedical research funding has risen exponentially over a recent forty-year period, scientific discovery has almost come to a halt.
Life expectancy in countries at the biomedical cutting edge, like the United Kingdom and the United States, has declined after decades of improvement. The flu annually kills hundreds of thousands of people worldwide while humanity fights it with cumbersomely produced vaccines and medicines from the 1940s. And it’s very likely that someone in their nineties are taking medicines that were discovered in the 60s or 70s, if not 50s.
The culprit is hyperspecialisation. It’s preventing researchers from exploring multiple frontiers. Casadevall knows that even if you write an interdisciplinary grant proposal, it goes to people who are really, really specialised in either A or B, and you’ll have to be extremely lucky for them to have the capacity to see the connections at the interface of A and B.
Everyone acknowledges that great progress is made at the interface, but there’s nobody who has enough knowhow to defend the interface.
In his excellent book Range, author David Epstein mentions that a single conversation with Casadevall is liable to include Anna Karenina, The Federalist Papers, the fact that Isaac Newton and Gottfried Leibniz were philosophers as well as scientists, why the Roman Empire wasn’t more innovative, and a point about mentoring in the form of a description of the character Mentor from The Odyssey.
Casadevall always advises his people to read outside their field. He strongly believes that those who complain that they don’t have the time to read outside their field simply don’t understand that it’s far far more important. Your world becomes a bigger world when you read multiple domains, and the odds of making connections increases drastically.
To an outsider, Casadevall is hyperspecialised in his field. And it’s important to note that someone of his stature has no trouble getting research grants. In fact, he is frequently one of the scientists who helps determine who else gets grants. Despite this, he considers his attempt to shatter the hyperspecialisation status quo the most important work of his life. His biggest fear is that basic science is slowly moving away from meandering exploration towards hardcore efficiency. If this continues, we’ll have lesser and lesser chance at solving humanity’s greatest challenges.
Chances are you had never heard of Casadevall until now, but there’s a good chance you would have heard of Laszlo Polgar, who in so many ways is the polar opposite of Casadevall.
Polgar is a Hungarian chess teacher and educational psychologist who is best known for his experiment in raising his three daughters, Susan, Sofia, and Judit, to become world-class chess players.
Polgar believed that genius is made, not born, and that it was possible to cultivate genius in children through hard work and dedication. He began his experiment in the 1970s, training his oldest daughter, Susan, in chess when she was just four years old. He homeschooled his daughters, devoting several hours each day to chess training and practice, and exposed them to a wide range of chess literature and competitions.
The experiment was a resounding success. Susan became the Women’s World Chess Champion in 1996, and her younger sisters Sofia and Judit both became Grandmasters and ranked among the top players in the world.
Laszlo Polgar was a staunch proponent of hyperspecialisation. In the midst of his chess experiment, he proclaimed that the problems of cancer and AIDS would more likely be solved if his system of narrow specialisation and efficient education were used beyond chess, to educate a thousand kids.
It doesn’t take a genius to concur that this endeavour won’t bear any fruit. While mastery needs hard work and discipline, discovery on the other hand needs a lot more than just hard work and discipline — it needs experimentation, exploration, creativity, chance, luck, and more. There are no best practices. There are no beaten down paths. The road is unknown. One isn’t even sure if there is any road at all.
Before the 1980s it was thought that retroviruses do not cause human diseases. (Retroviruses are basically a type of RNA virus that use reverse transcription to convert their RNA genome into DNA, which can then integrate into the host cell’s genome. In simpler words, they are like spies that sneak into your body’s cells and use their own instructions to make copies of themselves.)
Retroviruses were found only in some animal tumours, and they were nothing more than a scientific curiosity. But in 1981, a new disease emerges that nobody knows anything about. In 1984, it’s found to be a retrovirus, HIV. In 1987, you have the first therapy. In 1996, you have such effective therapy that people don’t have to die of it anymore.
How did that happen? Was it because companies all of a sudden rushed to make drugs? No! If you really look at the history you’d realise that before HIV had arrived, society had spent some of its very hard-earned money to study a “curiosity” called retroviruses. So when HIV actually arrived, society already had a huge amount of knowledge from investments made in a curiosity that originally had no practical purpose.
Unlike Polgar, Casadevall strongly believes that you can very well take all the research funding in the world and put it in Alzheimer’s disease and still never get to a solution.
The answer to Alzheimer’s disease may lie in a misfolding protein in a cucumber, or a carrot, or some kind of weed that grows only in the city of Arequipa in Peru. On what basis are you going to write a grant on a cucumber, or a carrot, or a weed? And who are you going to cajole into “specialising” on cumbers, or carrots, or Arequipan weeds?
But… if scientists, at least a few of them, have varied interests, one of them may get interested in cucumbers purely by chance. They may especially get interested in a particular folding protein in a cucumber on their own. Then all you have to do is leave them alone. Let them pursue their curiosity. Give them some grant and let them torture the cucumber with that.
It’s also important to note that hyperspecialisation had played a critical role in the 2008 global financial crisis. While insurance regulators regulated insurance, bank regulators regulated banks, securities regulators regulated securities, and consumer regulators regulated consumers, there was nobody to look across those markets, even though the provision of credit goes across all those markets.
At its core, even though hyperspecialisation is a well-meaning drive for efficiency, discovery and innovation need some cultivation of inefficiency too.
The wisdom of a Polgar-like method of laser-focused specialisation is only applicable in a narrowly constructed, kind learning environment such as developing a sports skill, assembling a product, or learning to play an instrument.
Yoshinori Ohsumi is a Japanese cell biologist who was awarded the Nobel Prize in Physiology or Medicine in 2016 for his work on autophagy, a fundamental process in cells that involves the degradation and recycling of cellular components.
Ohsumi’s work on autophagy has led to a deeper understanding of a wide range of human diseases, including cancer, neurodegenerative disorders, and infections. His research has also highlighted the importance of basic science in driving scientific discovery and innovation.
His Nobel acceptance speech highlights the core problem of our obsession with hyperspecialisation and drives the central idea of this essay home:
“My autophagy research has always been driven by nothing more than intellectual curiosity and a thirst to get a better understanding of life through protein dynamics of the cell. When I started my work, I never thought it would become relevant in diseases as diverse as neuro-degeneration, infectious disease, cancer, and others… Truly original discoveries in science are often triggered by unpredictable and unforeseen small findings. Nowadays, the distance between basic discoveries and practical applications is getting closer. While this is exciting, scientists are increasingly required to provide evidence of immediate and tangible applications of their work. It is my sincere hope that society is able to nurture not only purpose-oriented science, but also science as a core cultural activity.”
Today I Learned
There was a time when people used to think that the peripheral glands of the body — your pancreas, your adrenal, your ovaries, your testes, and so on — had “minds of their own.” That they could “decide” when to secrete their chemical messengers (such as hormones), without directions from any other organ.
This erroneous idea gave rise to a rather silly fad during the early part of the twentieth century. Scientists noted that men’s sexual drive declined with age, and assumed that this occurs because the testicles of ageing men secrete less male sex hormone, testosterone.
Well… no one actually knew about testosterone at the time. They just referred to mysterious “male factors” in the testes. Truth is, testosterone levels do not plummet with age. Whatever the decline, it is usually moderate and highly variable from one male to the next. And even a decline to perhaps 10 percent of normal levels does not have much of an effect on sexual behaviour.
Making another giant leap, they concluded that ageing happens due to diminishing sexual drive and lower levels of male factors. So… if we can treat that, we can beat ageing once and for all. Astounding!
One may wonder though why females, without testes, manage to grow old. But back then nobody bothered to care much about females, so even if this question was their in people’s minds, it was never brought up or debated.
Now, the burning question is, how then do we reverse ageing? Simple! Give the ageing males some testicular extracts.
Soon, aged, monied gentlemen were checking into impeccable Swiss sanitariums and getting injected daily in their rears with testicular extracts from dogs, from roosters, from monkeys.
You could even pick out a goat of your liking from the stockyards of the sanitarium. More than one gentleman arrived for his appointment with his own prized animal in tow.
Then somebody came up with a brilliant idea. Why just give them testicular extracts; why not give them a part of the testes itself! This soon led to an offshoot of such “rejuvenation therapy,” namely, “organotherapy” — the grafting of little bits of testes themselves. Yet another giant leap!
Thus was born the “monkey gland” craze. Journalists were forbidden to print the racy word “testes” so they replaced it with “monkey”. No clue whose idea this was and what was he even thinking!
Soon captains of industry, heads of state, at least one pope (not sure why he needed male factors anyway) — all signed up. And in the aftermath of the carnage of World War I, there was such a shortage of young men and such an uptick in marriages of younger women to older men, that the market was ripe for a therapy of this sort.
But the problem was that it didn’t work. First, there wasn’t really any testosterone in the testicular extracts anyway. Patients were injected with a water-based extract, but testosterone does dissolve in water. So, no testosterone for you. Second, the pieces of organs that were transplanted would die almost immediately. Duh! But the scar tissue remained, which gave the impression of a healthy graft.
Even if these grafted organs didn’t die, they still wouldn’t work anyway. If an ageing pair of balls is secreting less testosterone, it is not because the testes are failing, but because another organ (their boss basically) is no longer instructing them to secrete testosterone. Even if you replace with a brand-new set of balls they would fail too, for lack of a stimulatory signal.
But… this was not a problem. Nearly everyone reported wondrous results. I mean, if you’re paying a fortune for painful daily injections of extracts of some beast’s testicles, there’s a certain incentive to decide you feel like a young bull. One big placebo effect.
Thankfully, with time, scientists figured out that the testes and other peripheral hormone-secreting glands were not autonomous. They were under the control of something else: the real master glad, the boss of all, aka the brain.
Timeless Insight
If you want to test your knowledge about the concept of something, say energy, then try to rephrase what you know about it in your own language, but without using the word “energy”.
For example, without using the word “energy,” try to explain in simple words what makes a toy, a bicycle, and an automobile go.
If you cannot, you may have learnt nothing about science. Truth is, most of us have not. Most of us simply know the jargon, not the concept.
What I’m Reading
Males will often cite pseudo-scientific fields of study such as ‘biology’, ‘medicine’ or ‘endocrinology’ to prove that men are the physically stronger sex, although you’d be hard pushed to find a respectable feminist who takes any of this seriously.
— Titania McGrath, Woke: A Guide to Social Justice
Mind you, this book is a complete satire. I was cracking up the whole time I was reading it. But… don’t read it if you are easily offended, or too woke (I’m still not sure if I understand what it actually means), or into cancel culture (whatever that is). Although there’s a strong chance you wouldn’t be reading my newsletter if you were any of that. Therefore, I bet you would really enjoy this book, especially if you love satire. It’s entertaining as hell.
Tiny Thought
If you accept substandard work from yourself, you’ll only get average work from others.
Before You Go…
Thanks so much for reading! Send me ideas, questions, reading recs. You can write to abhishek@coffeeandjunk.com, reply to this email, or use the comments.
Until next Sunday,
Abhishek 👋