Learning Potential / Utility: ★★★★★★★ (7/7)
Readability: ★★★★★★★ (7/7)
Challenge Level: 2/5 (Easy) | ~290 pages ex-notes (368 pages official)
Blurb/Description: This Pulitzer-prize winning book is one of the best pieces of science history I’ve ever read, integrating the scientific development of the vaccine and its human undercurrents into the cultural and economic context of the time.
Summary: This is hands-down the best science history book I’ve ever read, and I can’t recommend it highly enough. There are a ton of compact and thought-provoking lessons and mental modelshere, as well as a lot of cultural context that’s very interesting and surprising (such as the democratization of philanthropy and the interplay between germ theory and mass advertising creating a much cleaner environment, and thereby unintentionally creating the conditions for polio to become more of a threat).
Highlights: While Polio: An American Story doesn’t delve as deep into the science technicals as Meredith Wadman’s The Vaccine Race does at times, it still covers a lot of very interesting scientific concepts, particularly the tradeoffs between live and killed virus, and the various ways in which research was slowed or held up by bad science.
The book also does a fantastic job, as Oshinsky quotes the head of the National Foundation saying at one point, of looking outside the laboratory window. The story of polio is inseparable from the cultural context of post-WWII America, as well as the human factors that turned Salk into a national hero despite the best efforts of Albert Sabin to stand in the way of saving kids’ lives. Even if you don’t have my level of personal fascination with vaccines, I think you’ll really love this book.
Lowlights: None. The book doesn’t waste a lot of pages; Oshinsky is extremely informative yet engaging. Although I haven’t studied the primary work, he also seems to be pretty objective and not slanted.
Mental Model / ART Thinking Points: storytelling, n-order impacts, salience / vividness, tradeoffs,margin of safety, multicausality, bottlenecks, status quo bias, stress, culture, incentives, nonlinearity,correlation vs. causation, envy / ego, one to many, marginal utility / 80/20, local vs. global optimization,
You should buy a copy of Polio: An American Story if: you want an extremely enjoyable and practical (and historically important) opportunity to learn a lot about a lot.
Reading Tips: I think you’ll get more out of Polio: An American Story if you read it alongside Meredith Wadman’s The Vaccine Race, which delves deeper into some of the science (as well as the SV40 issue touched on briefly in Polio). That said, The Vaccine Race is lengthier, more detailed, and the “non-science” portion focuses more on bioethics history that I didn’t find particularly fascinating, so if you only have time to read one, don’t wait to read Polio until you also have time to read The Vaccine Race – but do pick up that book as well and plan to read it.
“Deadly Choices” by Dr. Paul Offit (VAX review + notes) – this is the best pairing with this book because of the salience x n-order impacts x feedback compare/contrast – as I discuss in the salience model.
“The Making of the Atomic Bomb” by Richard Rhodes (TMAB review + notes): the definitive book on the history of nuclear physics and the Manhattan Project; while long, it provides the background on a scientific achievement even more massive (in both impact and scope of work) than the conquest of polio.
“Other Minds” by Peter Godfrey-Smith (OthM review + notes) and “ The Violinist’s Thumb” by Sam Kean (TvT review + notes): more on cellular signaling and other topics. Other Minds is also my second-favorite science book currently (behind Polio).
Reread Value: 4/5 (High)
More Detailed Notes + Analysis (SPOILERS BELOW):
IMPORTANT: the below commentary DOES NOT SUBSTITUTE for READING THE BOOK. Full stop. This commentary is NOT a comprehensive summary of the lessons of the book, or intended to be comprehensive. It was primarily created for my own personal reference.
Much of the below will be utterly incomprehensible if you have not read the book, or if you do not have the book on hand to reference. Even if it was comprehensive, you would be depriving yourself of the vast majority of the learning opportunity by only reading the “Cliff Notes.” Do so at your own peril.
I provide these notes and analysis for five use cases. First, they may help you decide which books you should put on your shelf, based on a quick review of some of the ideas discussed.
Second, as I discuss in the memory mental model, time-delayed re-encoding strengthens memory, and notes can also serve as a “cue” to enhance recall. However, taking notes is a time consuming process that many busy students and professionals opt out of, so hopefully these notes can serve as a starting point to which you can append your own thoughts, marginalia, insights, etc.
Third, perhaps most importantly of all, I contextualize authors’ points with points from other books that either serve to strengthen, or weaken, the arguments made. I also point out how specific examples tie in to specific mental models, which you are encouraged to read, thereby enriching your understanding and accelerating your learning. Combining two and three, I recommend that you read these notes while the book’s still fresh in your mind – after a few days, perhaps.
Fourth, they will hopefully serve as a “discovery mechanism” for further related reading.
Fifth and finally, they will hopefully serve as an index for you to return to at a future point in time, to identify sections of the book worth rereading to help you better address current challenges and opportunities in your life – or to reinterpret and reimagine elements of the book in a light you didn’t see previously because you weren’t familiar with all the other models or books discussed in the third use case.
Pages 2 – 4: I might be positively biased toward the rest of the book because, being Texan, I was immediately intrigued by the book starting in post-WWII San Angelo.
In any event, Oshinsky does a great job of storytelling and presaging the rest of the book: amidst an outbreak of polio, residents responded with the newly popular mentality of “make filth the enemy and cleanliness the goal,” which had worked to combat many other diseases, but in this case, actually made polio worse. ( n-order impacts.)
In 1949, there were 40K cases of polio in the U.S. In San Angelo, 1/124 inhabitants were affected; of those affected, 5% died, 25% paralyzed.
Page 5: Oshinsky presents his topic in a pretty balanced way; polio is a great example of the vividness heuristic. This’ll come up again later, but this quote was interesting: due to its very visible/ vivid/memorable features and helped along by the National Foundation for Infantile Paralysis, which revolutionized philanthropy in America, polio rocketed to top of mind.
“No disease drew as much attention, or struck the same terror, as polio. […] polio hit without warning […] it killed some of its victims and marked others for life, leaving behind vivid reminders for all to see: wheelchairs, crutches, leg braces, breathing devices, deformed limbs.
In truth, polio was never the raging epidemic portrayed in the media, not even at its height in the 1940s and 1950s. Ten times as many children would be killed in accidents in these years, and three times as many would die from cancer.”
Google Trends obviously didn’t exist during the time of polio, but I think a nice/useful recent context that many of us have lived through was the brief panic over the Ebola and Zika viruses that dominated news headlines and the popular consciousness.
Ebola and Zika killed basically nobody in the U.S., and yet were highly salient, at least in part due to some of the uniquely “terrifying” aspects of the diseases – bleeding from every orifice (in the case of Ebola), or babies being born with microcephaly (Zika).
And yet statistically, even in affected areas, their impact paled in comparison to the flu, which kills between 3,000 to 50,000 Americans per year (per the CDC) and 300K – 650K annual deaths globally (per the WHO).
Outside of “epidemic” flu seasons like 2017-2018, though, many of us who might forget to get our annual flu shot or put it off in favor of more pressing concerns all of a sudden were hyper-sensitive to every time someone sneezed or coughed in our vicinity, washing our hands or lathering them with hand sanitizer every time we touch a doorknob.
This, of course, extends to other potential causes of mortality that are uniquely “terrifying” – my heart definitely jumps more during turbulence on an airplane than it does driving down the highway, even though the latter is statistically far more dangerous. More analysis of this in the salience and base rates mental models.
As I mention in my notes on “The Vaccine Race” ( TVR review + notes), even I’m not immune from this: I have an irrational phobia of Naegleria fowleri and won’t go swimming in freshwater even though the risk of my brain being colonized by amoebas is infinitesimal.
Pages 8 – 10: “Polio” refers to both a virus and the disease caused by that virus. How polio works: it’s spread via fecal matter and enters the body through the mouth. It reproduces in the small intestine and usually causes only mild or no symptoms, but in roughly 1% of cases, it enters the bloodstream, attacks the brain stem and central nervous system, and destroys nerve cells.
The nerve cells that survive often enlarge themselves, although (as discussed later in the book) this also means they wear out faster and cause more long-term disability than may be initially apparent. Tradeoffs x margin of safety.
There are three types of poliovirus and immunity to one does not confer immunity to others (multicausality). Although recorded since antiquity, polio never really showed up in epidemic proportions until the 1900s; the working theory is that it had something to do with people developing immunity prior to the advent of better sanitation.
Page 12: One of the challenges in studying polio was that people didn’t yet know what viruses were as of the early 1900s; later, they didn’t know how to grow and study them. See also the discussion of bacteriology / virus culture technique development on pages 19 – 25 of The Vaccine Race; great example of bottlenecks/ limiting reagents over there.
Page 14b: The discussion of medical schools in the late 1800s is particularly interesting. See also Jerome Groopman’s mention of “gentlemen’s Cs” (thankfully no longer a thing) in “ How Doctors Think” ( HDT review + notes) as well as Oshinsky’s discussion of medical education over the years in “ Bellevue” ( BV review + notes).
Pages 17 – 19: Monkeys, which often cost more than the daily pay of a scientist, were critical in the fight against polio (both as test subjects, and for their kidneys, from which cells were taken to produce the vaccine until, later, human cells were used, as discussed in The Vaccine Race.)
Also, similar to pages 23 – 25 and 57 – 59 of The Vaccine Race, some bad science and overly eager interpretations of data led to research being slowed down by flawed conclusions. Simon Flexner of the Rockefeller Institute did make some major progress (like being able to pass polio from one monkey to another), but he mistakenly found that monkeys only got sick when swabbed in the nose with polio, rather than consuming it.
Two of the problems here: first, Flexner only used a kind of monkey that couldn’t contract polio orally (animals don’t naturally get polio anyway). Second, Flexner repeatedly passed the vaccine through brains and spinal columns, which (reason not explained by Oshinsky, but likely passive selection or active optimization combined with trait adaptivity) led to a strain of the vaccine that only multiplied in nerve tissue.
Pages 20T – 21T, Pages 22 – 23: 1870s New York City saw a 20% mortality rate by age 1 (!). Ironically, in the absence of a vaccine, initial sanitation-focused efforts to combat polio (which were reasonably thoughtful given the knowledge of germ theory) backfired. Oshinsky notes that:
“Other epidemic diseases like cholera and typhoid fever had been tamed by better sanitation, attacking the filth that spread their deadly germs.”
For some reason (not fully understood but related to milder infections at a younger age and the protective effects of maternal antibodies), polio actually got worse because of these efforts reducing exposure at a young age; it was noted that cleaner neighborhoods actually had a higher incidence of polio. The theory was that unsanitary conditions might actually lead to immunization against poliovirus at an early age (somewhat similar, directionally, to why some studies suggest farm kids get sick less often than city kids.)
Pages 28 – 31 cover the cleanliness phenomenon and the unanticipated n-order impacts in more detail.
Page 25: I’ve been to Campobello Island. I’ve even gotten in the water there (although it was the hypothermia-cold saltwater of the Bay of Fundy, not freshwater.) I didn’t realize that was where FDR contracted polio. This is another one of those moments where, as I note in the notes for Vaccine Race, that I’m very happy about my smash-bros-style invincibility powerup circulating in my bloodstream thanks to childhood immunizations.
Pages 27 – 28: A good example of multicausality / the swiss cheese model of causality. It’s hard to pinpoint why FDR contracted polio, and had such a severe case of it, but it’s likely that multiple factors (including already being under stress, lowering his body temperature via swimming in the Bay of Fundy, his previous medical history, etc) played contributing roles.
Pages 28 – 31: It’s interesting to note how quickly cultural norms can change. Oshinsky discusses how circa 1900, toothbrushes were rare, as was daily bathing or handwashing after using the bathroom; it was common to sleep in the same bed as a complete stranger while traveling, water was not treated the way it was today, and food wasn’t refrigerated. Again, see Oshinsky’s “ Bellevue” ( BV review + notes).
This all changed with the rise of germ theory, combined with egging-on by manufacturers of consumer products like vacuum cleaners and soaps who used consumer advertising to great effect (see also The Great A&P by Levinson or New and Improved by Tedlow) to not only tout the practical benefits, but also to create social proof and play on people’s egos / desire to keep up with the Joneses.
Soap manufacturers even lobbied to get kids educated in public schools on how often to bathe, wash their hands, and change their underwear, undoubtedly creating a generation of eager future consumers. (Again, a nice example of multicausality and system interactions.)
But, n-order impacts: Oshinsky notes that:
“What Americans could not foresee was that their antiseptic revolution brought risks as well as rewards. As the nation cleaned up, new problems arose.
There was now a smaller chance that people would come into contact with dangerous microbes early in life, when the infection was milder and maternal antibodies offered temporary protection. In the case of polio, the result would be more frequent outbreaks and a wider range of victims.”
Pages 32 – 33: some interesting background on FDR’s public persona, which I did not know: he was actually profoundly physically disabled throughout the rest of his life, and it was a big struggle to merely stand. Oshinsky discusses on page 33 the elaborate preparations the Secret Service went through to hide FDR’s disability. This, Oshinsky implies, has led some to believe FDR started the modern “bubble” around the presidency.
Also interesting is the profoundly different attitude in the culture then vs. now regarding physical disabilities:
“To be crippled in this era was viewed by many as a moral failing, a sign of inner weakness, a character flaw requiring the afflicted person’s removal from society.”
On page 44, Oshinsky also relays a quote that was published in Time in 1932 about FDR:
“This candidate, while mentally qualified for the presidency, is utterly unfit physically.”
Obviously we are now, overall, in a much better and more rational place where physical disabilities are not viewed with scorn – to the extent that a young football player missing a hand (Shaquem Griffin) was drafted as an NFL linebacker.
Interestingly, the same modern paradigm is applied to intellectual as well as physical disabilities (see pages by the WHO, etc) even though the two have profoundly different causes (both genetically and environmentally speaking) and wholly disparate impacts on quality of life, and thus arguably should be analyzed separately (the same way that today, many both inside and outside of the “LGBT” community argue that it’s too often used as an umbrella for groups with disparate beliefs and interests).
As a caveat, before anyone jumps down my throat, I’m not advocating any particular viewpoint or position; simply pointing out some interesting cultural phenomena that we take absolutely for granted but once were viewed very differently. With that said: I’m sure some of the mid-1900s scientists discussed in Polio might argue that, in some ways, the pendulum has swung too far, as some of their vaccine trials were conducted, for somewhat necessary reasons (i.e. the lack of other potential populations that met the necessary conditions), on institutionalized, profoundly intellectually disabled people who consumed societal resources but had no hope of independence or quality of life.
As such, it’s strongly implied in The Vaccine Race that these scientists didn’t seem to have any moral qualms about whether what they were doing was ethical or not – in other words, they couldn’t even conceive of a reason why the world might object to their research subjects being involved in experiments, whereas most modern laypeople (on both sides of the political spectrum) would probably see strong reasons to object to the forced participation of those who weren’t capable of choosing to do so or not do so, independent of whether or not the experiments were likely to be safe.
For example, Plotkin expresses some of the implicit rationale on page 159 of The Vaccine Race when discussing whether or not women should be allowed to seek abortions to avoid having babies with the severe health problems and potential intellectual disabilities associated with congenital rubella syndrome (this was well before Roe v Wade).
This isn’t so surprising if you understand the scientific context. As Siddhartha Mukherjee discusses (albeit with a lot of slanted/useless social commentary) in The Gene, eugenics was actually a concept viewed with a lot of enthusiasm rather than disgust in the U.S. prior to WWII – “Better Baby” contests, forced sterilizations of those deemed to be deleterious to the gene pool, etc – until Hitler got a hold of it and twisted genetics into a pseudoscience used to justify the barbaric genocide of millions of Jews. As Mukherjee points out (both intentionally, and unintentionally given his own social-justice concerns), that has in some senses created strong cultural pressure against potentially revolutionary scientific progress in the area of genetics.
Anyway, The Vaccine Race has some interesting insights in this direction if you’re into it (I didn’t personally find the bioethics stuff particularly interesting personally, because it seems to be a more or less settled debate now and there wasn’t a ton to learn from it.)
Page 34: Basil O’Connor, a Most Likely to Succeed sort, became FDR’s partner at a new law firm they started in the 1920s.
Page 39: FDR purchased the Warm Springs in Georgia and turned it into a nonprofit haven for “polios” (people afflicted by polio). It doesn’t seem to have been a great financial decision, but it was obviously something he wanted very much, because he believed in the curative power of the waters and conceivably it gave him some sense of control ( agency / placebo effect).
Pages 43 – 44: thanks to the Great Depression, Herbert Hoover was the George W. Bush or Barack Obama of the 1930s – everyone blamed him for everything, rightly or wrongly
Pages 48 – 51: A man named Carl Byoir, a public relations standout, helped revolutionize the field of philanthropy. Prior to the early 1900s, philanthropy was seen as something only for the rich – the Carnegies, the Rockefellers, etc.
The Great Depression helped change that; as Oshinsky notes, “large gifts were hard to come by in the 1930s; the secret lay in small donations. Who wouldn’t want to contribute something to see a crippled child walk again?”
Enabled by the new media, charitable giving was democratized. To raise money for FDR’s Warm Springs, Byoir suggested having everyone celebrate FDR’s birthday.
Page 53: The National Foundation for Infantile Paralysis became a big deal; it made the fight against polio into “a top national priority, America’s greatest medical crusade.”
Pages 54 – 55: I did not realize until reading this book that the March of Dimes involved literal, well, dimes, and that explains why FDR is on the dime. (Do note that $1 in 1938 equated to $17 – $18 today, so a dime in 1938 was more like a couple bucks today – certainly not a huge amount of money, but also not a “keep the change” type rounding error, and explains why it would make sense to mail a dime to someone – postage rates for first-class mail were $.03 at that time, or roughly equivalent to the current postage rate in the $0.40s, so it made more sense to mail a few bucks.)
At the time, a feature called March of Time was shown during movie previews, so radio celebrity Eddie Cantor came up with the idea of a “March of Dimes” – send a dime to the president.
It was so popular that the head of the White House mail room noted that “the Government of the United States darned near stopped functioning because we couldn’t clear away enough dimes.”
Page 57: interesting bit on “probably safe?” “used in children?” Yeah, definitely chilling today.
Page 58: in a recurrent theme from earlier, the bad science of the 1930s, which resulted in fatal and paralytic polio cases, sort of discouraged the idea of polio vaccines for a while. Culture and status quo bias. Cat, hot stove, etc.
Pages 59 – 60: Basil O’Connor wanted to “build our case from the ground up […] draw up a list of research priorities, so that we can emphasize first things first.” Disaggregation. He hired Thomas Rivers from the Rockefeller Institute Hospital to head up the research.
Rivers eschewed the “magic bullet” approach and decided to do what O’Connor said: learn about polio so they could then make a proper treatment, vaccine, or so on. Areas of study ranged from epidemiology to pathology.
Page 62: interesting background on the iron lung, a full body machine to assist breathing that was supposed to be short-term but in some cases (such as Fred Snite) was used indefinitely
Page 69: March of Dimes boxes at the movie theaters led to solid annual contributions through the mid-1940s; meanwhile, polio cases crept up and started turning into full-blown epidemics.
Page 75 – 76: interesting anecdote about Sister Kenny, a nurse who didn’t understand how polio worked but (broken clocks can be right) actually helped a lot of kids recover via exercise. Luck vs.skill.
Page 80: FDR had a lot to do with the popularity of the March of Dimes – theaters stopped collecting for it after he passed away. Salience. Also, Basil O’Connor wasn’t having any of the idea of “federated giving” a la the United Way – that’s for socialists! He viewed polio as a unique disease that needed dedicated support.
Pages 81 – 83: Some of my favorite pages in the book. It’s worth buying for these three alone, honestly.
First of all, lemons from lemonade: losing the movie theaters catalyzed positive improvement; Oshinsky notes that a foundation official recalled that it “forced [us] to expand and diversify fund-raising efforts.”
So there’s that, and then a nice reiteration (in different words) of the vividness heuristic stuff introduced on Page 5 earlier. Oshinsky notes that statistically, polio was not something to be worried about… but it had a “profound” psychological impact due to its vividness/salience.
Again, it’s hard to imagine being alive at that time (later, Oshinsky cites the example of a kid asking someone who had polio whether or not their parents were part of some weird religious cult that didn’t allow vaccines – because the kid grew up in a world where the vaccine had always been around!) But Ebola/Zika are, I think, recent examples that provide just a taste. Polio, of course, was far more serious, but news also traveled more slowly in those days and perhaps wasn’t as alarmist as it is today.
And then! And then and then and thennnn. I use the phrase “poster child” all the time and I literally, shamefully, did not know that there were literally children on posters. I’d never stopped to think where the phrase came from. Well, it comes from the March of Dimes; six-year-old Donald Anderson was the first actual poster child. Here is that original poster:
This was honestly so cool.
Page 94: While the Peter Thiel approved “reason from first premises” approach instituted by Basil O’Connor in 1940 sounded pretty good, the scientists didn’t end up exerting concerted effort in any particularly productive direction. By 1947, it wasn’t clear that a lot of progress had been made. O’Connor had spent much of WWII as the head of the Red Cross and, upon returning, appointed Harry Weaver in the new position of director of research. The scientists, unsurprisingly, didn’t like having an administrator looking over their shoulders… especially because Weaver discovered “only an appallingly few [are] really trying to solve the problem of poliomyelitis in man.”
Pages 97 – 99: Jonas Salk joined the City College of New York – which was the meritocratic peak for working-class students. Salk started there at sixteen and, after a semester in pre-law, decided to become a doctor, entering medical school at NYU at nineteen (NYU didn’t have the anti-Semitic policies of many major universities at the time). He wasn’t very involved on campus as an undergraduate. Salk ended up interning at Mt. Sinai.
Pages 102 – 104: Thomas Francis helped Salk escape being drafted in WWII. He was a pioneer in virology, becoming the first to isolate the human influenza virus and pass it to mice. The book briefly touches on the live-vs-killed virus debate; Francis favored killed viruses, which had an impact on Jonas Salk, who had come to work for him.
Page 108:a nice picture of Pittsburgh, called by one 1880s guidebook the “Great Furnace of America.” Pittsburgh was the city of steel (y’know, the Steelers and all.) Nice background to the chapter in “Rust: The Longest War” ( Rust review + notes) where Jonathan Waldman tours the abandoned, rusty Bethlehem Steel Works with photographer Alyssha Eve Csuk..
Pages 110 – 111: Salk left Francis in Ann Arbor and officed up in a few spare basement rooms in the Pittsburgh Municipal Hospital in what was supposed to become a high-powered research facility but was still mostly a “story stock.” He planned to work on influenza vaccines and polio research… but not explicitly a polio vaccine. Oshinsky notes that as of 1947, it was not yet clear that a polio vaccine could be developed.
Pages 112 – 114: Harry Weaver is portrayed as a mini-Oppy (though without the technical prowess). He managed to corral the scientists and keep everyone on track toward the goal. He also figured out how to account for indirect costs.
In an interesting contrast to Meredith Wagman’s excellent recounting in The Vaccine Race of the partisan bickering over non-human-diploid HPV-77 vs. WI-38 based RA/27 in the rubella vaccine development process, Weaver didn’t let the Sabin-vs-Salk live-vs-killed ideological difference get in the way: Oshinsky notes:
“the simmering feud between live-virus and killed-virus advocates didn’t much matter […] the foundation was willing to bankroll both sides at once.”
Pages 115 – 116: as discussed analogously in the microbiology section of The Vaccine Race (Pages 19 – 25, for example), before you could create a vaccine against a virus, you needed to be able to study that virus. In the case of polio, Oshinsky notes that there were three primary challenges: identifying all the types of poliovirus, developing a supply of each for use in vaccines, and figuring out just how polio created infections (to target the vaccine).
Reminiscent of the tediousness of sequencing involved in the Human Genome Project (as discussed, for example, on pages 302 – 303 of The Gene), typing polio was an extremely laborious and monotonous process that luminaries like Albert Sabin obviously wouldn’t deign to spend their time on. It was not glamorous; Oshinsky notes dryly that it “was not the fast track to a Nobel Prize.” Incentives.
Also, extrinsic motivation. This opened the door for Salk – at the time, a nobody – to pick up a grant to do some of that monotonous typing work.
Pages 118 – 120: Salk’s lab did most of the polio typing from 1949 – 1951, at a cost of $1.2MM (twelve million in today’s dollars). Oshinsky notes that “a large chunk” of that expenditure was for monkeys, which were so expensive and sometimes difficult to procure that the National Foundation started its own veterinary facility for monkeys. More than 17,000 monkeys were killed for typing research – intentionally infected so that their brains and spinal cords could be studied to determine.
Also, Albert Sabin sounds like a major jerk, doing nothing but putting down Salk repeatedly (here and elsewhere).
There were “conveniently,” as Oshinsky puts it, only three “types” of poliovirus despite all the strains. Why does that matter? Because if there were tons and tons of types, it would be near-impossible to develop a virus – which is why we’ve been able to tame many deadly diseases, but have made “little progress over 50 years” in developing a vaccine against rhinovirus, which causes the common cold.
If you want to nerd out on the science, here’s how it all works: that paper I linked to notes that “antigenic heterogeneity amongst the >150 HRVs (human rhinoviruses) has been regarded as a major barrier to effective vaccine development” and the highlights note that “Limited antigenic cross-reactivity amongst rhinoviruses is a barrier to vaccine design” – what that basically means is that immunity to one kind of rhinovirus doesn’t provide immunity to all the other kinds of rhinoviruses. Multicausality.
I’m probably gonna botch the science here, and I would welcome a rewrite suggestion from anyone who actually knows what they’re talking about. But specifically, our immune systems don’t necessarily recognize the entire virus or bacterium; they usually recognize some specific surface protein (the antigen) [seems in some cases lipids/sugars can also be antigens?]. The antibodies produced bind to those antigen. The various kinds of rhinovirus don’t have the same antigens as each other, and that’s why we can get a cold every year – previous colds don’t generate antibodies that are useful against new colds.
Think about it as if antibodies are security guards who only recognize people wearing specific uniforms; say, blue ones. If a virus dresses up in a different uniform, say, a green one, the antibody you have against it won’t work. So antibodies against one type of virus will only protect against viruses that have the specific kind of antigen the antibody is targeting; the antibody is useless against other viruses. However, if multiple strains of viruses wear the same uniforms, the antibody will recognize and attack all strains wearing the same uniform. Thus, all the disparate strains of polio end up in three “types” – i.e. “uniforms” – so inoculation is only needed against one strain from each of those three types.
If you want to nerd out even more on the science, check out pages 167 – 170 in Sam Kean’s The Violinist’s Thumb for more of a discussion of immune targeting (specifically the major histocompatibility complex), or the early part of Peter Godfrey-Smith’s awesome Other Minds for a deeper look at cellular recognition and signaling.
Pages 121 – 127: some of the core science is presented here. First off, tissue culture is discussed – similar to the discussion on pages 20 – 25 of The Vaccine Race, to study viruses, you need to be able to keep cells alive in the lab, and need to keep bacteria out (antibiotics).
John Enders discovered that polio could grow in non-nerve tissue (important because nerve tissue doesn’t make good vaccines – allergic reaction), while Albert Sabin discovered the route of polio infection: orally rather than olfactorily (through the nose), and via the blood before hitting the nervous system. So if you could put antibodies in the blood before polio got to the nervous system… polio would be prevented. Structural problem solving.
Bottom of page 126: researchers hadn’t found polio in the blood because it didn’t manage to survive there after antibodies were generated. That didn’t mean it had never been there to begin with… disaggregation and probabilistic thinking.
Makes me think a little bit of Tetlock’s “ Superforecasting” – SF review + notes – specifically, the part where Tetlock discusses the question about whether or not a lab would be able to detect polonium. Even if they didn’t, that didn’t mean it wasn’t there in the first place.
Page 132: I always find women in science (in an era where they were rare) to be interesting/notable. Dr. Isabel Morgan might have discovered the vaccine before Salk, if she hadn’t stopped to become a homemaker and mother, and if she hadn’t been scared of human testing (for reasons that are understandable, given the 1930s disaster discussed earlier.)
Pages 133 – 136: Hilary Koprowski of Lederle is discussed here; also discussed is the liberal use of the term “volunteer” in medical research in the era. See also Page 71 of The Vaccine Race (on “volunteer,”) and the rest of The Vaccine Race on more detailed examples of not-so-”volunteer” testing of vaccines on orphans and the institutionalized.
Page 140: researchers died handling monkeys after being bitten and contracting polio.
Page 145: no mental models here – just a nice summary of how America in 1950 differed from today. Cigarette ads in medical journals is perhaps the craziest.
Page 147: circa McCarthyism, Salk was put through the ringer by the FBI, similar to Robert Oppenheimer (Oppy!) being followed around during The Manhattan Project, as discussed in Richard Rhodes’ The Making of the Atomic Bomb. I’m looking forward to reading Oshinsky’s A Conspiracy So Immense: The World of Joe McCarthy as well as Bird and Sherwin’s Oppenheimer: American Prometheus.
Pages 151 – 152: more human testing under circumstances we would not now allow; also, Albert Sabin is still a jerk (as far as I can tell, that never changes. I’m on Team Jonas here.) Salk, given his lowly origins, is described as an outsider doing “dog’s work,”; Sabin’s in the in-club.
Page 152 – 153!: Salk meets Basil O’Connor; they both “looked upon the conquest of polio as a goal to be achieved quickly – not as a distant, elusive dream.” Goals. Sabin didn’t have any sense of urgency. O’Connor’s adult daughter actually contracted polio – not terribly severely, but she did have some abdominals permanently destroyed.
What did O’Connor think made Salk special? “He sees beyond the microscope.” Oshinsky describes Salk as “a scientist who connected his laboratory work to the lives of ordinary people.”
Pages 154! – 156!: Lots here. First of all, monkey kidneys (which come up a lot in The Vaccine Race). It apparently took 199 tries to come up with the right growth medium.
Also the tradeoff, discussed in Vaccine Race as well, of keeping the vaccine strong enough to provide protection without risking infection. You had to kill it with formaldehyde, but not kill it too much. The concentration was important. ( dose-dependency)
Pages 159 – 160: an interesting scientific experiment, on actual volunteers. Salk injected vaccine with polio matching the type kids with polio already had, to see if it would stimulate further antibody production (but it wouldn’t make them sicker, because they already had polio). And then a scientific experiment on institutionalized kids.
Page 163: chilling
Pages 167 – 168: Weaver quasi-leaks the progress on the vaccine to the press (indirectly). Salk starts stepping into the spotlight. Albert Sabin is still a jerk holding up scientific progress because of his own incentives and ideology.
Pages 170 – 173: O’Connor invites journalists, health officials, and medical researchers to hear Salk talk; his fame goes parabolic. This was obviously helpful for fundraising. He then formed an advisory committee including experts from outside the field of virology to break the logjam. Back to O’Connor talking about pointing out to the researcher what’s going on outside the lab in the real world. (In this case, people are dying.)
Pages 175 – 176: for all of Salk’s successes, he was also sort of a jerk; Oshinsky, quoting his top assistant, states that Salk more or less plagiarized a paper written by his own team, refusing to give them credit. His non-Carnegie-ness crops up again soon.
Pages 177 – 178: so across The Vaccine Race and this book, this is the most interesting (to me) and thought-provoking discussion of bioethics. The question: “Was it proper, in short, to deny someone access to a potentially lifesaving vaccine in the name of statistical accuracy?”
It’s a good question. My answer is no. You say screw the control group and go for saving lives. (I suppose reasonable people, particularly scientists, might differ.)
Joseph A. Bell, director of the trials, sent over from the NIH, came to the a different answer, on the other hand. “kind of” – give half the kids a flu shot.
Page 180: And Salk, reasonably, is like wait what why NO. No you will NOT give kids a placebo. Or, in his actual words: “I would feel that every child who [gets] a placebo and becomes paralyzed will do so at my hands.”
Pages 182 – 183: Sabin is still a jerk and nobody likes him anymore; one of his colleagues, David Bodian – who Oshinsky calls “perhaps the most respected of all polio researchers” and a person who avoided the feuds and petty squabbling that had occurred – pens a letter to Sabin telling him that attacking Salk would be viewed as obstructionism.
Thomas Francis (remember him? Influenza researcher in Michigan who got Salk on the killed-virus path) also sends Sabin a sharp note, pointing out his personal interests, twisting of what other people said, and so on.
Pages 184 – 185: Francis, btdubs, was also the guy who was going to evaluate the results of this trial.
Pages 185 – 187: The trial ends up being partially double-blind – bigger states wanted that.
The sample size needed to be large to prove that the vaccine worked, and needed to be broad to represent lots of different types of populations. Who would they vaccinate? They couldn’t get all kids, so (in some cases) they decided to use second graders, with first and third graders as controls.
It ended up being 1.5 million kids in 211 counties – 127 with observed controls, 84 with injected controls – it was the “largest public health experiment in American history.”
Pages 188 – 191: How big of a deal were the Salk trials? More people knew about them than knew the full name of the President; two-thirds of people had donated to the March of Dimes, and seven million people had volunteered.
Interestingly, in another cultural contrast, the National Foundation didn’t want federal funding – Basil O’Connor had called such funding “Communistic” and “un-American.” Polio research was almost entirely privately funded by donations.
This was a huge logistical challenge; keep in mind this was way before e-mail and cell phones; it involved 50K teachers, 40k nurses, and 200k+ volunteers.
Nice example of framing on the top of page 191 – the permission form to parents was worded “I hereby request” rather than “I give my permission,” to make it a privilege.
Pages 191 – 193: vaccine manufacturing was initially given to one company (Parke-Davis), which experienced troubles with live poliovirus in the batches (another company, Cutter, later had way worse trouble with this). O’Connor brought in other pharma companies like Eli Lilly and Wyeth, which built production facilities and were required to sell the vaccine at no profit for the trials… but obviously the benefit was that if the vaccines worked, they’d make a lot of money going forward.
Eli Lilly and Parke-Davis ended up being used for the 1954 trials, while four other companies entered the market the next year.
Pages 198 – 199: the book discusses some of the problems that occurred, including some suspicion in the vein of post hoc fallacy / correlation vs. causation – some kids who got the shots died of polio, but it had to be determined whether they had already contracted polio prior to receiving the vaccine, which in most cases it seems like they did.
The modern equivalent is the discredited, fraudulent paper that purported to link MMR vaccination and autism; autism often shows up around the time that the MMR vaccine is recommended – see here and here from the CDC, as well as, of course, Dr. Paul Offit’s wonderful “ Deadly Choices” – VAX review + notes – which in and of itself is a great exploration of salience x n-order impacts x feedback. Great compare/contrast with Polio.
Page 201: Over Salk’s objections, a preservative (Merthiolate) was added to the vaccine; it prevented the growth of bacteria and molds if the vaccine was stored for a long time, but reduced its effectiveness against Type I poliovirus.
Meanwhile, in the catalog of “wait it was really done that way???” – Thomas Francis basically spent a year, solo, reviewing the results from the trials, and then spent another month to write his final report. Seems inefficient to me…
Page 203: The press conference announcing that the vaccine worked was a big deal. The news got out before Francis’s presentation, which one reporter compared to “the sleep deprivation techniques of a torture squad.”
Pages 205 – 206: Salk still doesn’t recognize the contributions of his own team in his victory speech, and they are not happy. They felt “betrayed” and one of them “wept most of the way” on the train ride home to Pittsburgh. Dale Carnegie might have something to say about that; a great example of the importance of empathy.
Pages 208 – 209: fantastic example of envy in action – the broader virology community, which had never respected Salk much anyway, certainly did not like him becoming famous. As Oshinsky puts it: “What had [Salk] done to deserve so much attention? Who was [Salk] to reap all these rewards?”
Pages 211 – 212: The Salk “patent the sun” quote gets a lot of airtime, but I think the backstory is more interesting. It wasn’t so much that Salk was totally anti-commercialism (see later discussion of the Salk Institute and Salk’s other activities in the book, esp. page 277 mention of “Immune Response Corporation”), but that Salk didn’t feel like he’d done anything novel – an example of one to many (the future is here, it just isn’t evenly distributed yet).
As Oshinsky puts it:
“he had never claimed to be charting a completely new course; his objective was to show that an inactivated vaccine, a well-established but heretofore limited commodity, could be made to induce long-term immunity against a viral disease.
And in doing so, he had used the work of others to demonstrate a principle that most virologists, especially those involved in polio research, were loath to admit: that durable immunity did not depend exclusively upon a natural infection.”
This is one of my favorite parts of the book; it holds special resonance if you read not only Polio, but also Meredith Wadman’s The Vaccine Race, which spends a lot of time on the underlying WI-38 cells that Leonard Hayflick later developed. While the popular conception of science is “zero to one” Peter Thiel leaps, the reality is that a lot of it simply involves utilizing existing techniques more broadly, or in novel applications.
Pages 217 – 220: The Secretary of Health, Education, and Welfare (Oveta Culp Hobby, wife of TX Governor William P. Hobby) was good at a lot of things… but not health administration, apparently. Dwight “Ike” Eisenhower didn’t pay much attention to her department.
In an astonishing lack of foresight, the government had “made no plans for the distribution of polio vaccine” and Mrs. Hobby stated to the Senate that “I think no one could have foreseen the public demand.”
This was somewhat driven by ideology: at the time, furor against “socialized medicine” was perhaps even stronger (the way Oshinsky presents it) than you’d find on Fox News today. The government simply expected the private sector to handle things; the private sector didn’t necessarily want anything different… but meanwhile, kids were awaiting vaccines.
Contrarily, in Canada, “polio was viewed as a national crisis requiring an appropriate national response.”
Pages 225 – 227, Pages 230 – 231: here, the Cutter fiasco is discussed… they didn’t properly kill the virus and some kids got polio. Cutter totally botched it; when they found injected monkeys getting polio, they just “released the vaccine anyway.”
Page 229: setting aside Sabin (who frankly at this point is just annoying), there’s an interesting case of tradeoffs here. Salk’s killed vaccine for Type 1 used the extremely virulent “Mahoney” strain, which caused better antibody production but also meant that, if not properly killed, the virus would be quite challenging. The attenuated live-virus vaccines later developed used less virulent strains – but, obviously, ran a greater risk in the first place of causing polio if the strain wasn’t attenuated enough.
Page 233: it was clear that Salk’s vaccine could be improved upon, but the rational attitude was taken by Tom Rivers and Joe Smadel, who argued something was better than nothing and that perfectionism slows progress (marginal utility/ 80/20): Smadel asks:
“Shall we use what we have now, or shall we wait an indefinite period […] until we have something which we think is perfect at that time, and then use it?”
The panel votes 8 to 3 in favor of continuing.
Pages 234 – 235: Basil O’Connor goes apeshit on Albert Sabin, which I greatly enjoyed. O’Connor noted that the difference between Jonas Salk and his rivals was that “Salk hoped to save children while his opponents hoped to further their careers.” Oshinsky, via O’Connor, notes that envy, jealousy, and incentives-driven local optimization were getting in the way of the greater good.
Page 238: thanks to fallout from Cutter, some parents were (understandably) hesitant to vaccinate their kids… and as a result, 28K+ cases were resulted that might have otherwise been avoided.
Pages 239 – 240: Earlier I noted the parallels between polio and Ebola/Zika. There is a nice table on this page where Oshinsky compares the money raised for polio, which was more or less equivalent to seven other major health charities that, cumulatively, had way more cases. One newspaper noted that you were statistically three times more likely to be murdered than to die of polio, although I imagine that the likelihood was much higher in favor of polio for kids.
Page 242 – 243: Maybe it’s just Oshinsky’s portrayal, but Albert Sabin just seems like a bad human being. Oshinsky cites someone who noted Sabin actively wanted to “prevent Salk from running away with the prize.” It wasn’t necessarily a race (Sabin, as noted earlier, had no sense of urgency) – but Sabin did everything he could to get in the way of Salk’s success, even if that meant thousands of kids dying. Envy / ego are powerful forces.
Pages 248 – 249: Back to the tradeoff mentioned earlier on page 229 – Hilary Koprowski’s live-virus vaccine saw some challenges; the attenuated virus reverted to virulence in the human intestine.
Page 252: so the Russians got one thing right: no control groups and no placebos. The sole objective in administering Sabin’s vaccine was “to wipe out polio.”
Pages 272 – 273, Page 279: back to the tradeoffs on live vs. killed vaccines: Oshinsky notes that setting aside the (controllable) Cutter manufacturing problems, “not a single case of polio in the United States had been attributed to the Salk vaccine. No one could question its safety, if properly prepared.” However, the Sabin vaccine – even if prepared properly – caused about one case of polio per million doses.
The Sabin vaccine was, overall, more effective But there was a clear problem with it. And after wild poliovirus was eliminated, from the 1980s on, polio was almost exclusively caused by the Sabin vaccine. In 1996, the CDC switched to a mix of Salk and Sabin vaccines; from 2000 onward, the Salk vaccine became the standard (and this is still the case as of 2018, 10 years after the book’s publication, per the CDC), although the Sabin vaccine was still used in cases of travel to areas where polio outbreaks were in progress. Trait adaptivity.
Page 275: Sabin was the academic hero and Salk was the public hero, although he never won the Nobel Prize – that went to John Enders, Fred Robbins, and Thomas Weller for discovering poliovirus could be grown in non-nervous tissue.
I may not admire Jonas Salk as much as I did when I was 12, but I still think he’s a hero and I honestly got a little teary-eyed finishing this book.
Pages 279 – 281: there’s also a discussion here about SV40. See The Vaccine Race for way, way more on this.
First Read: early 2018
Last Read: early 2018
Number of Times Read: 1 (+ 1 time-delayed re-encoding via notes)
Review Date: early 2018
Notes Date: early 2018