Meredith Wadman’s “The Vaccine Race”: Book Review, Notes, and Analysis

Poor Ash’s Almanack > Book Reviews > Science + Engineering + Math > biology

Overall Rating: ★★★★★ (5/7) (solid for its category)

Learning Potential / Utility: ★★★★★★ (6/7)

Readability: ★★★★★ (5/7)

Challenge Level: 2/5 (Easy) | ~370 pages ex-notes (448 official)

Blurb/Description: Rhodes Scholar and doctor Meredith Wadman provides an illuminating, eye-opening, extremely easy to read history of human cell strains and their tangible impact on modern vaccines.

Summary: Vaccines have always fascinated me; when I was in seventh grade, Jonas Salk of polio vaccine fame was my favorite example to cite for pretty much any SAT essay prompt.  I’m not knowledgeable enough about medical history to rank them amongst all the marvels of modern medicine, but I do think it’s pretty cool that we all walk around with the biological equivalent of the invincibility power-up from Super Smash Bros: a painless shot inoculating against MMR or HPV and we get to go all MC Hammer on those viruses.  (Public service announcement: if you’re in your teens/20s, or if you’re older and have kids, make sure you or your child gets at least two doses of the HPV vaccine, because it provides meaningful benefits.  It wasn’t a standard part of the immunization schedule when I was growing up, so I got my doctor to write me a prescription.)

I’ve thus long been interested in reading about the scientific history of vaccines.  I was expecting The Vaccine Race to be more about vaccines than it actually was; it turns out to be equally about vaccines and the human cell strains in which those vaccines are developed, along with an unexpected but wonderful closing look at some genetics topics like telomeres.

Highlights: Wadman does an exceptional job of making technical scientific concepts accessible to lay readers without dumbing anything down; the writing isn’t quite as lucid as Jonathan Waldman’s in Rust: The Longest War or quite as raconteurish as Sam Kean’s, but it’s still quite engaging while still being extremely informative and educational.  

A lot of unexpected mental models popped up in this book; I was reading it more for personal interest than anything else but it turned out to provide some really illustrative/useful examples.

Lowlights: The book does spend a decent amount of pages on biographical background that I generally found uninteresting (though not diving too deep).  The book also has a slight focus on bioethics, particularly the involuntary testing of vaccines on institutionalized populations, which I didn’t find terribly interesting (because it’s a settled issue with few to no modern ramifications).  

That said, I think these issues are addressed in an objective and balanced way, free of the partisan politics and distracting / irrelevant social commentary of, for example, Siddhartha Mukherjee in The Gene ( TG review + notes).

There is some contrast bias here, but in my estimation, Polio: An American Story is so thoroughly excellent and interesting from the first page through the last that I notice the length and occasional lack of interest in The Vaccine Race moreso than I might otherwise.  Overall, while this book is lengthy and could perhaps have been condensed a bit, I don’t have a lot of unkind things to say about it: it’s really solid science writing and I learned a lot from it.

Mental Model / ART Thinking Points: bottleneck, exponential growth, a/b testing, saliencetrait adaptivityinversionschema, inentives, opportunity costsfairness, ego, confirmation bias, envy,utilitytradeoffs

You should buy a copy of The Vaccine Race if: you have read (or are planning to read) Polio: An American Story and want a book that will help you fill in some of the details and subsequent events, while enriching your learning of many mental models.

Reading Tips: Consider skimming some of the biographical and bioethics pages (unless those interest you).  Also consider reading along with Polio: An American Story… and if you only have time for one book in the vaccine space, I would recommend Polio because (on the whole) I found it more interesting to a general audience, and briefer.

Pairs Well With:

Polio: An American Story by David Oshinsky (PaaS review + notes): a thoroughly enjoyable and learning-rich discussion of the fight against polio.  This book should be read before, or immediately after, The Vaccine Race.

How Doctors Think by Jerome Groopman (HDT review + notes): a great discussion of the cognitive factors that can cause trained medical professionals to make poor decisions, like continuing to block human diploid cells from being used to produce vaccines.

Deadly Choices” by Dr. Paul Offit (VAX review + notes).  If you want an example of the  salience x n-order impacts x  feedback phenomenon that led the DoD to be complacent about the lack of adenovirus vaccine, look no farther than the parallel to parents believing rigorously debunked conspiracy theories about the safety of childhood immunizations.

Reread Value: 3/5 (Medium)

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.

Page 2: example of a bottleneck / limiting reagent: while the idea of making vaccines was not new, to make a vaccine against a virus, you first had to isolate the virus (nontrivial).  See also pages 23 – 25.

Also, a good explanation of how vaccination works (antibody formation) for anyone who’s been living under a rock.

Pages 4 – 5: example of exponential growth: I don’t think I’ve seen a better example than Wadman’s discussion of how Leonard Hayflick’s WI-38 cells, derived from the lungs of a single fetus, could provide a theoretically infinite supply of cells for developing vaccines.  See also pages 88 – 90.

Page 7: unintentional a/b testing of inoculation:

“[…] U.S. military recruits […] died from adenovirus infections when the Pentagon stopped giving service members the vaccine against that virus.”

As we’ll see later, this is also an example of  salience.

Page 8: good contextualization: if you want to think about what life was like in the 1960s rubella epidemic, think about the panic over Zika microcephaly… just much broader and far worse.

Page 19: Microbiology, previously named “bacteriology,” is the study of viruses and bacteria.  It started in the 1870s when practical methods of growing bacterial methods were discovered by a German microbiologist, Robert Koch.

Pages 20 – 22: These pages (and really, the book more broadly) are a great example of bottleneckslimiting reagents: before you can study something, you have to be able to isolate it.  Once scientists learned how to consistently grow bacteria in lab dishes, they were able to develop antibiotics that killed them (sometimes unintentionally, such as the discovery of penicillin mold repelling Staphylococcus bacteria), as well as vaccines – for example, against diptheria, whooping cough, and tuberculosis.

Viruses, much smaller than bacteria, were much trickier, however: they’re not really alive.  They don’t have their own cellular machinery; only DNA, and they can only reproduce in living cells, so you have to be able to keep cells alive in an artificial environment if you wish to study viruses.  As such, it wasn’t until the 1950s that the polio vaccine was created and until the 1960s that the first antiviral drugs were discovered,

Pages 23 – 25: In another great example of bottlenecks / limiting reagents, it took the development of two key technologies: first, a tube-rotation tool that allowed cells to receive both nutrition and air.  Second, antibiotics, which kill bacteria but not viruses, and thus can eliminate potential competitors to the viruses.

Meanwhile, some bad science (overinterpretation of data) set back the polio hunt: Albert Sabin and a colleague managed to successfully grow poliovirus in cultures of fetal nerve cells, but not in other cells for fetuses; nerve cells do not make for good vaccines (injecting them can cause allergic encephalomyelitis, i.e. inflammation of the brain and spinal cord).

It turns out that polio can and does grow in other types of cells – John Enders, for example, noticed that poliovirus is found in large quantities in fecal matter (suggesting it grows in the intestines, which don’t have a profusion of nerve cells like the brain and spinal cord.)  The specific strain of polio tested would only grow in nerve tissue, but it was not representative of all strains.

See also pages 17 – 19 of Polio: An American Story (PaaS review + notes) for some background on Simon Flexner, who (at least per Oshinsky) was likely one of the primary reasons that the strain of polio often studied only reproduces in nerve cells.  Oshinsky doesn’t specify there, but my intuition is that it’s a function of trait adaptivity and selection or optimization (Flexner repeatedly passed the virus through nerve tissue, so the virus ended up either via selection or optimization only being able to reproduce in that sort of tissue.)

Enders’ discovery that poliovirus could grow successfully on cultures of skin, muscle, and connective tissue:

“[threw] open the doors to virology”

by allowing scientists to

“readily study the effects of those viruses on cells in the lab, rather than in living animals.”

See also pages 121 – 127 of “ Polio: An American Story” ( PaaS review + notes) for another good discussion of tissue culture and Enders’ discovery that poliovirus could grow in non-nerve tissue.

Pages 34 – 35: I’m not taking hugely detailed notes on the polio-related issues here because they’re covered in quite some depth in Oshinsky’s Polio, but a couple interesting mental models pop out.  You should probably skip if you’re eating.

In evaluating the effectiveness of live/attenuated (Sabin) vs. killed (Salk) polio vaccines, researchers were considering not only immediate efficacy (i.e. in the inoculated person), but also the n-order impacts on herd immunity, which turned out to have some tradeoffs.  As Wadman puts it ever so clinically, a live, oral vaccine of the type Sabin favored:

“would be shed in recipients’ feces and, in environments with poor sanitation and unclean water, passed on to other, unvaccinated people, provoking a protective immune response in some of them too – so-called passive immunization.”  

Great, right?  Yeah, except:

“The corresponding danger was that a live vaccine virus, shed in the feces, could mutate over time, reverting to an infective form and spreading the disease, rather than protecting people.”

In general, live vaccines required precision:

A scientist needed to weaken the virus enough to stop it from causing disease, but not so much that it failed to cause a mild infection that provoked a protective immune response.”

See also  dose-dependency.

Page 39: Hilary Koprowski turned The Wistar Institute into a state-of-the-art mecca of unconstrained, imagination-fired biological research.”

Pages 41 – 42: These scientists weren’t always working with the same sort of equipment that college students (or even some high schoolers) have access to today.

There’s a reference here to the famous HeLa cell line and the now-famous story behind them in The Immortal Life of Henrietta Lacks, which I plan to read soon.

Terminology: “cell lines” divide infinitely in the lab (because they’re cancerous.) Later, on page 70, Wadman establishes that Hayflick used “cell strain” for normal (non-cancerous) cells that would eventually die.

Page 45: Viruses can cause cancer.  Back to my PSA about HPV.

Pages 48 – 50: an example of reasoning by inversion: when looking around for cells in which to grow viruses:

Hayflick had reservations about using leftover surgical samples, or even skin samples from volunteers […] cells from any human being who has been on the planet for any length of time are potentially contaminated with disease-causing viruses

[…] if the ostensibly normal cells became cancerous, he wouldn’t know if this was due to a virus from the fluide or to some hidden virus already residing in the cells.  

However, there was one obvious source of tissue that […] was far more likely to be clean.”  

That is, fetal tissue.

Also, some interesting history on abortion that I didn’t know.

Pages 54 – 55: Hayflick’s rationale for using cells from an aborted fetus: “It was definitely going to end up in an incinerator.  If it was used for research purposes, some good could possibly come out of it for people.”

The process for growing the cells involved using trypsin, a digestive enzyme, to loosen the cells from the side of the bottle in which they were being grown; they would then be nourished with growth medium and half moved into a new bottle (using a mouth-driven pipette).

Pages 57 – 59: an example of Feynman’s commentary about bad ideas being the disease of culture (pun, in this case): in the early 1900s, conventional wisdom was that cells should live forever in lab dishes, if properly handled and cared for.

It turns out that only cancerous cells live forever.   Culture / status quo bias.

Pages 61 – 63: A great example of scientific thinkinginversion, and process; the opposite of satisficing: upon observing an unexpected result (that one of his cell cultures was starting to show signs of struggling), Hayflick methodically ruled out potential causes such as dirty glassware, bacterial or viral contamination, etc.  Noticing that many others started to have problems, he mentioned it to a colleague – immunologist Lionel Manson – who suggested aging.

Also as an example of normal distributions and  luck / randomness:

“cells, like people, vary in their vigorousness.  Some cells divide more sluggishly, while some are eager, rapid replicators.  So over a given period of time, some cells will replicate fewer times than others […] which means that the only conclusion that can be drawn when the floors of the two bottles are eventually covered with cells is that the initial population in the mother bottle has doubled in size [SP: as opposed to meaning that every cell has divided once.]”

Pages 64 – 67: Another example of good scientific process: to determine whether it was something intrinsic to the cells or environmental that caused cell death, Hayflick mixed some young female fetal cells, and some elderly male fetal cells that had been dividing for a while, in the same bottle.  After a few months and many divisions into new bottles, chromosome expert Paul Moorhead used a microscope to determine there were few to no Y-chromosomes left.

Also, incentives on page 67: a technician for the scientist who proposed the idea of infinitely-living cells had actually noticed and pointed out that there might be problems with the experimental methodology, but it was the Great Depression and she was told “to forget what she was seeing or risk losing her job.”  And so a scientific myth persisted for decades.

Pages 67 – 69: Hayflick got something named after him: the “Hayflick limit” refers to the number of divisions a normal (non-cancerous) cell can undergo before it ceases to divide.  In Hayflick’s case, this was 50 divisions, plus-minus ten.

Hayflick’s WI cells made good candidates for vaccine development because they didn’t face the risks, such as the harboring of other viruses, that other types of cells (such as SV40 virus in green monkey kidney cells) caused.

Page 71: the definition of “volunteer” (in terms of research) used to be very different than it is today; for example, journal articles would refer to dying patients who doctors enlisted as “volunteers” (even if they hadn’t actually volunteered.)

Page 74: not quite a Central Dogma, but here’s a nice clean presentation of Hayflick’s eventual conclusions about the relationships between chromosome number, cancerousness, and cell lifespan.

Pages 76 – 77: even eminent figures in authority can be wrong, Theodore Puck edition.  Nice anecdote.

Page 79: In addition to the safety benefits of using human diploid cells rather than monkey kidney cells, there was the economic benefit of not having to buy monkeys.  (Discussed more extensively in Polio: An American Story.)

Page 79f: vaccines eradicated smallpox

Pages 80 – 81: the interesting thing about Hayflick’s discovery is that it was more creativity than technical engineering.  Swedish virologist Sven Gard was a fan of the idea of using human fetal cells, but his team, by their own admission, “never thought of” replicating fetal cells in lab dishes to grow enough to make vaccines.

Page 82: back to the idea of making lemonade from lemons: in Wadman’s words, Sven Gard’s chief lab technician, Eva Herrstrom, viewed the fetus that may well have gone on to create Hayflick’s cell lines as incredibly beautiful.”  How did she deal with it?  Schema and  opportunity costs.

 “You got used to it.  You turned the tragedy around.  You said to yourself that at least in this case, something life-giving might emerge from death.”

Pages 88! – 90!: How could the finite-lived cells from a single culture tested rigorously for safety create enough cells to manufacture decades worth of vaccines?  In one of the best practical examples of exponential growth I’ve seen anywhere outside of the context of finance/investing, Wadman relays, paraphrasing Hayflick’s 1961 paper “The Serial Cultivation of Human Diploid Cell Strains”:

“Suppose […] you began with just one small glass bottle […] measuring a mere 5.5 inches but not quite 3 inches.  Such a bottle held roughly ten million cells when those cells had grown to confluence […] on its side.

[…] if at this point you split these newly planted cells into two bottles, and split the bottles again when the floors of those two bottles were covered, yielding four bottles; and if you then kept splitting the bottles […] until the original cell population had doubled fifty times […] the cells in that one original bottle would therefore produce twenty-two million tons of cells […] a potential ten sextillion cells.”  

Even if you doubled the cell population only twenty times rather than fifty, Wadman notes you would:

 “produce 87,000 times more vaccine than is made by a typical vaccine-making company, setting out today to make one year’s worth of a typical childhood vaccine that it will ship to more than forty countries.”

Page 91: the U.K. was one of the first countries to use human diploid cells.  The theoretical maximum discussed above was limited, amongst other things, by a preference to use younger (less-divided) cells that hadn’t developed abnormalities.

Page 92: Again in the “science didn’t used to be advanced” column: sterilization techniques in the 1960s left a lot to be desired; the scientific equivalent of a sophomore’s dishwashing technique.

Page 96: a brief reference to the Cutter incident, covered in way more detail in Polio: An American Story.

Pages 97 – 100: discusses the discovery of the potential for SV40 virus to lurk in the green (rhesus) monkey kidney cells used to create the live polio viruses; this was a problem because the live vaccine, unlike the killed vaccine, wasn’t treated with formaldehyde that would’ve killed the SV40.  (Later, on page 104, Wadman discusses the potential for SV40 to actually not be killed by formaldehyde as quickly as poliovirus, so it might’ve been in Salk’s vaccine too.)

Page 102: on tradeoffs: a reasonable argument in favor of vaccines potentially contaminated with SV40 at the time was that they might be harmful but certainly paled in comparison to the dangers of, for example, smallpox.

Pages 102 – 106: again on incentives and ego: Hilary Koprowski flipped from minimizing the risks of SV40 to raising the alarm when his rival, Albert Sabin, got ahead in the vaccine race.

Meanwhile, one challenge for Hayflick to test the efficacy of his WI38 attenuated live-polio vaccine was that antibodies were widespread already thanks to previous vaccination programs.  The solution was to test babies born at a women’s prison (the women were allowed to wander into the community, it seems.)

Pages 107 – 108: nice discussion of the thorough (Hayflick described it as “exhaustive”) safety testing done prior to injecting the vaccine.

Pages 115 – 116: more on vaccinating and testing babies

Centerfold: the pictures are great

Page 126: I laughed at “as many people in power who are faced with thorny decisions continue to do today, Murray outsourced the problem.”  (Roderick Murray was one of the chief vaccine regulators at the time.)

Pages 126 – 128: here is an example of a cascade of cognitive errors that probably includes, among other things, incentive biasconfirmation biasegoframing, and schema: a group of NIH experts (some of whom had worked with monkey kidney cells) published a paper in 1963 that made the spurious argument, per Wadman, that “there can be no absolute guarantee that a given strain of continuously cultured cells will never yield a previously unknown virus… that is infective and [disease-causing] for some cells… under some conditions.”  

Wadman goes on to point out, rightly, that “Hayflick’s cells were going to be held to that standard, regardless of the real, demonstrated, and costly deficiencies of freshly harvested monkey kidney cells.”

Internationally, things were different (and more rational).  The WHO’s experts believed that human diploid cells represent at the present time the nearest approach to an acceptable system” for vaccine production.

Pages 134 – 137: Not that actual science would convince any of your less-rational friends who are idiotic enough to keep their kids from getting the MMR vaccine, but this section (and other parts of the book) are pretty chilling.  Rubella is a relatively mild disease in most cases, but when pregnant women contract rubella, it can cause serious birth defects and intellectual disability in the baby.

The Zika panic was only a relatively mild taste of what the world would be like without the MMR vaccine.  See also page 157 and Page 161 and Dr. Paul Offit’s “ Deadly Choices ( VAX review + notes).

Pages 147 – 149: some really interesting science on how rubella causes birth defects: basically, in the first half of pregnancy, the embryo has minimal maternal antibody protection, and rubella can get into the placenta.  Rubella doesn’t kill all cells, but it inhibits mitosis in the patches of cells that it does infect, leading to the fetal damage.

Page 151T: the quote at the top of the page is a great example of the vividness or salienceheuristic: Wadman quotes William S. Webster of the University of Sydney Medical School as stating in 1998 that:

“rubella does not seem to invoke the fascination of thalidomide despite the fact that in a single epidemic in the United States it caused more birth defects in one year than thalidomide did during its entire time on the world market.”

There’s some similar discussion in Oshinsky’s Polio: An American Story about how polio, thanks in no small part to the March of Dimes / National Foundation for Infantile Paralysis, as well as its highly visible/terrifying effects, at times occupied a disproportionate spot in the American consciousness relative to its risk.

Another useful example is on pages 4 – 5 of Henry Petroski’s To Engineer is Human where he contrasts automobile accidents with those from building or bridge collapses; elsewhere, he discusses people’s fear of flying (which is statistically irrational).

Hell, I’m not immune (… I’m sorry, I swear that wasn’t intentionally a pun) despite all my focus onmental models and rationality: as most of my friends know, I don’t swim in freshwater because of Naegleria fowleri, notwithstanding that the chances of me getting a brain-eating amoeba up my nose are somewhere between “zero” and “infinitesimal.”

Pages 155 – 156: Stanley Plotkin studied rubella in WI-38 cells and noted the mitotic inhibition discovered earlier.  However, that didn’t stop vaccines from being made – there were still plenty of rubella particles.

Page 157, Page 161: more on the horrors of rubella.

Page 159: Plotkin amidst the rubella epidemic with an interesting response to a pathologist who opposed the notion of rubella-infected mothers being able to seek abortions to avoid having babies with a high statistical likelhood of severe, often terminal birth defects.  Plotkin specifically objected to the critic’s:

 “sense of ethics […] so fine that it enjoins others to suffer.  What justification is there for increasing the burden of a family by a child with heart disease or deafness?  … We have no right, because of personal moral or religious imperatives, to demand acceptance of an unnecessarily high risk of congenital abnormality.”

Trying as hard as I can to stay away from (obviously very personal and hot-button) issues around bioethics, there’s an interesting thread between the critic that Plotkin responds to and, for example, Siddhartha Mukherjee’s politically rather than rationally-based qualms about genetic engineering and therapy in The Gene.  The core argument (by Mukherjee and the critic) is essentially bright lines / slippery slopes: once you start, where do you drawn the line?  

The counterpoint by Plotkin and others is along the lines of, I suppose, statistics and probabilistic thinking: there are no bright lines or certainties, but there are situations in which the probability of failure is sufficiently high that the risks seem to outweigh the rewards.

I didn’t find much of the bioethics discussion in the book interesting, because it’s more or less a settled question now… but this topic I did find interesting, although perhaps that’s only because I’ve removed myself enough from politics and ideology altogether that I don’t have any deeply personal ex ante views on the topic.

See also my note on pages 32 – 33 of Polio: An American Story ( PaaS review + notes).

Pages 164 – 165: on the pathology of rabies.  It, like polio, attacks nerve cells.

Pages 166 – 167: interesting

Page 169: I found particularly fascination the discussion of both passive and active immunization against rabies, which occurs to this day.  Basically, if you get bitten by a rabid animal, you’re injected with both a rabies vaccine designed to stimulate your own immune system, as well as actual antirabies antibodies.  Why?  They serve as a stopgap/supplement while your body is developing its own immunity.   Multicausality.

This immediately called to mind the parallel uranium-enrichment approach described in Richard Rhodes’ The Making of the Atomic Bomb on pages 550 – 553, which is a great example of a schema bottleneck and applying multicausality via inversion.  ( TMAB review + notes).  Previously, the scientists/engineers at the Manhattan Project had been focused on a silver-bullet approach to enriching uranium all the way via one metho

Later, they realized that a thermal-diffusion process could provide a lot of slightly enriched uranium to plug into another process, thereby speeding things up massively.  Robert Oppenheimer called the failure to notice this earlier a “terrible scientific blunder” and Leslie Groves described it as “one of the things I regret the most.”

Page 171 – 172: the duck-embryo vaccine available in the mid-1960s wasn’t doing a very good job.

Pages 179 – 181: Plotkin’s first attempt at a WI-38-based rubella vaccine did create antibodies, but also caused rubella infection – an unacceptable side effect, because while it wasn’t dangerous to the toddlers, it had the potential to spread to pregnant women (or women who might become pregnant.)

Page 189: back to the challenge of making the virus weak enough to avoid infection, but strong enough to generate an immune response

Pages 190 – 191: here, among other interesting things, Wadman describes the previously-referenced thalidomide episode.

Page 192: Plotkin basically created a lot of variations of the vaccine to be tested experimentally – different temperatures, different passage levels.  (Incubating polio at lower temperatures weakened it; he thought the same might apply for rubella.)

Page 194: an interesting description of one of the facilities where Plotkin ran his tests.  Many of the townspeople were employed in caring for the profoundly disabled residents; it was sometimes a dangerous job.  See also Pages 32 – 33 of Polio: An American Story and my note thereon to better understand the surprisingly large delta between the protective modern view of the disabled and prevailing social notions in the early-to-mid-1900s.

Page 195: one of the more interesting bioethics issues in the book is the ethics of not providing a potentially lifesaving treatment in the interests of having a control group.  Wadman discusses some doctors withholding penicillin from airmen with strep throat and chloramphenicol from charity typhoid patients. Cross-reference Polio: An American Story.

Page 197: the combination of higher passage levels and lower incubation temperatures combined to create a vaccine that created antibodies but not sickness.

Page 198: nice example of framing and interpreting the same data two different ways

Pages 199 – 203: chilling discussion of Marburg virus, the lesser known cousin to Ebola.  Somehow, this monkey-caused outbreak still didn’t change the prevailing tone on human diploid cells.

Page 211, Page 212: the kidney-based HPV-77 vaccine (unrelated to Gardasil – HPV here stands for “high passage virus” not “human papilloma virus”) didn’t really work well… but Roderick Murray was still opposing human Wi-38 based vaccines

Page 214: somehow I get the feeling the TSA would no longer allow you to carry onto an airplane a “liquid nitrogen refrigerator that looked like nothing so much as a one-hundred-pound bomb, minus the fins.”

Page 215: although WI-38 cells hadn’t gained traction stateside, overseas, they were being used quite broadly.  In fact, the top vaccine regulator in the U.K. developed a cell strain called MRC-5 (Medical Research Council) that could be used similarly to WI-38

Page 225T: another great chapter heading quote, this one from a French bacteriologist, about the messiness of the ongoing process of science vs. the beauty of hindsight bias.

Pages 231 – 237: Lots of intriguing stuff here.  At a conference wherein data on the four competing anti-rubella vaccines was presented, Plotkin’s WI-38-based RA 27/3 vaccine proved to be highly effective at creating antibodies, without some of the undesirable side effects, like arthritis in adult women.

Albert Sabin makes the technically true but practically myopic argument, dismissable via reductio ad absurdum, that there is no full characterization for any cell line,” – i.e., as Wadman puts it, that you could keep looking for a virus until doomsday and never be sure.”  

Plotkin absolutely massacres Sabin, just outright destroys him: after reviewing the fairly comprehensive safety testing that had, to date, been done on WI-38, Plotkin highlights the wanton intellectual inconsistency on the part of WI-38 skeptics:

“It has always been curious to me that the same people who worry about WI-38 do not worry about the unknowns in other tissues.”  After pointing out how many of the same questions could apply to HPV-77 / monkey kidney cell viruses: “One cannot disprove the existence of ghosts.  But that is not, to my mind, a basis for making intellectual decisions.”

He gets a thundering ovation for that.

Pages 245 – 248: incentives: Roderick Murray finally approves a human cell-based vaccine when whistle-blower J. Anthony Morris, a veteran scientist at the DBS, provided what Wadman calls a “long and extremely damaging catalog of the DBS’s alleged incompetence” ranging from partisanship to squashing of science

Page 251: lobbying led to the (now viewed as inferior by the CDC) green monkey polio vaccine being the only live polio vaccine available on the market from 1977 – 2000.  Reminds me of Jerome Groopman’s discussion of the impact of lobbying on what medicines doctors prescribe, from pages 206 – 238 of “ How Doctors Think (HDT review + notes

Pages 254 – 258: Dr. Dorothy Horstmann, a pediatrician, did some great, objective research on the efficacy of the rubella vaccines and discovered that the HPV77 duck vaccine generated different kinds of antibodies from those made during a natural infection; this difference – in addition to pure antibody levels – proved important, and it turns out that Plotkin’s RA 27/3 vaccine was superior in this regard.

Pages 260 – 261: Success at last: RA 27/3 is licensed by the FDA in 1978 and is now (as of the book’s publication) the only one on the market.

Pages 267 – 268: when faced with false allegations, Hayflick went full-on Dale Carnegie… didn’t work though.

Page 271: Hayflick steals… or safeguards… the WI-38 cells.

Pages 271 – 278: This is an interesting story that I won’t recount in full detail, but basically the short version is that Hayflick, for a variety of reasons – including probably ego or “ fairness”  moreso than pure materialism – started monetizing the WI-38 cells, which didn’t technically belong to him (not all of them, anyway).  At the time, as Wadman notes, “biology was not thought of as a commercial venture, and most biologists looked askance on any colleague who moved in that direction.”  The biotech industry didn’t really get started until a few decades ago… I’ve read about this elsewhere.

There’s also a reference to recombinant DNA here; see also “ The Violinist’s Thumb (TVT review + notes) (recommended) and “The Gene” (TG review + notes) (recommended, with severe caveats.)

Pages 281 – 283: there was certainly a bit of confirmation bias on the part of the NIH investigator…

Page 288T/291: Going back to what I said in the notes on Pages 271 – 278, while I obviously haven’t done enough reading to have a strong belief on the topic, I do think some additional points later in the book provide credence to my ideas.  For example, the (again wonderful) chapter intro quote on page 288 is from Nicholas Wade in Science in 1976:

“Because of the government’s decade long cold-shouldering of WI-38s, it is hard not to feel sympathy with Hayflick’s sense of irony and outrage that the same government now claims the cells to be its own precious property.”  

Back to fairness.  This is discussed in more depth in page 291; the NIH had, in fact, for quite a long time, just not really pursued the cells even though they were aware that Hayflick had been selling them (see also Page 298).

Page 294: Hilleman at Merck: He should have been celebrated as a scientific hero instead of being persecuted.”

Pages 302 – 303: back to rabies!

Pages 304 – 305: WI-38-based rabies vaccines demonstrated 10x the antibody production of the duck vaccine

Pages 307 – 309: vaccines such as hep A, the new rabies vaccine, the shingles vaccine, and so on began to be based on the British MRC strain rather than Hayflick’s WI-38 strain, due to concerns about availability and other things.

Pages 314! – 315!: can you patent a living thing?  In responding to an application for a genetically modified, oil-eating bacterium that could clean up spills, the US Patent and Trademark Office (PTO) said no in 1977… but the Supreme Court overturned that decision 5 to 4 in 1980.  That led to the development of the biotech industry. Genentech comes up here.

Page 318: Hayflick is granted title to some of the WI-38 cells, finally.

Pages 320 – 323: Aging!  Earlier in the book, some scientist (… Hayflick?  Someone, I forget) described aging as a catch-all bucket to describe phenomena not otherwise understood.  Nobody really thought of studying cellular aging until it was determined that normal (non-cancerous) cells did not divide forever, and did so in a relatively predictable (though not precisely so) way.  Interestingly, the cell division potential was not purely correlated to age… adult lung cells double less than fetal cells, but it’s not a linear correlation.

Pages 324 – 325: a useful, if brief, discussion of telomeres.  Replicating the end of DNA is hard; telomeres serve as finite buffers (noncoding DNA that gets lost over time) and when they’re gone, that’s your Hayflick limit.  Cancer cells work around this.

Pages 326 – 331: on telomerase and the length of telomeres.  Telomeres are not the only pathway that leads to eventual cell death and aging; other mechanisms include inflammation and oxidativestress.  Nonetheless, long telomeres seem to be correlated with health. Telomerase is active in cancer; cells’ ability to shut down their own division “may have evolved as an essential defense against cancer.”

Pages 336 – 337: back to the A/B test on adenovirus, including a  salience effect.  this quote reminds me a lot of a much longer quote from high school debate about a natural A/B test on the public health effects of public smoking bans (which are wildly effective):

“In 1995 Wyeth […] ceased production.  The supply [of adenovirus vaccine] ran out in 1999.  Still nothing was done. Senior military leaders had become complacent.  Within a short time the rate of adenovirus infections in boot-camp barracks returned to what it had been in the 1950s, prior to mass vaccination, when physicians estimated that 10 percent of all new enlistees were infected.”

See also  salience where I discuss the interaction between salience and  n-order impacts and feedback; also see the aforementioned “ Deadly Choices” by Dr. Paul Offit ( VAX review + notes).

Pages 339 – 340: the Catholic Church did not see fit to suggest against parents vaccinating their kids with fetal cell vaccines.  

Page 342: no commentary needed; I just liked it: “Biology builds on itself, discovery after discovery, and apportioning credit in just the right measure to individual revelations is not terribly useful and often impossible.  What’s more, findings that may at the time seem to be of only limited interesting […] can launch whole fields of endeavor and lead to major discoveries and ever-deepening understandings.”  on  utility.

Pages 343 – 344: More cool vaccine stats.  Another useful stat: “In the first decade after 1995, when American infants began receiving a single chicken pox injection […] U.S. hospitalizations and deaths declined by about 90 percent.  In 2006 the CDC recommended that children receive a second chicken pox shot […] the incidence of varicella-caused disease then fell another 81% through 2013.”

Page 346: vaccines have eliminated endemic rubella in the Western Hemisphere

Pages 348 – 349: we’re all connected to WI-38.  Wadman thinks it’s kinda cool. I do too.  I actually got a little emotional while reading this book.

 

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