The implicit promise of good luck

Last summer, five year old Rebecca Meyers was diagnosed with brain cancer.   It was one of those bizarre situations where, aside from the malignant mass growing in her brain, she seemed to be really lucky.  Her family was vacationing far from home but near one of the best hospital she could hope to go to, and multiple family members and family friends were vacationing close enough to support her parents during the first few weeks.  The tumor extraction was a miracle of modern medicine.

Seven months later her brain is lighting up with new tumors.  She may not live long enough to have her Make-a-Wish Foundation wish granted.

I’ve been reading her father’s updates since she was diagnosed.  I have no connection to the family, but he’s a good writer and it’s a naturally dramatic story.  I didn’t realize till I read that she was definitely going to die that I had taken the initial luck as some sort of promise.  Subconsciously I believed that someone/thing must have arranged things so that she could receive such good care, and they wouldn’t bother unless they knew they could manage to pull her out on the other side.  I feel betrayed, and it’s definitely because of the initial good fortune, not the intervening positive results.

Maybe being by Children’s Hospital of Philidelphia was random chance.  Maybe there really was something magic taking care of her, but it ran out of juice or was given a higher priority or just screwed up.  And now a little girl is going to die and it just feels so unfair.

Flu Week/Book Review: Flu, by Gina Kolata

Flu‘s full title is Flu: The Story of the Great Influenza Pandemic of 1918.  It does not deliver what it promises, but what it does deliver is pretty neat.

From the title, I expected it to be about the biology and/or social effects of the 1918 flu pandemic.  I would have been perfectly fascinated by either of these.  The 1918 pandemic is one of very few plagues that was more deadly to healthy young adults than children and the elderly.  The only other disease I can think of that does that is HIV, and in that case it’s caused by the mechanism of transmission.  Both children and the elderly breathe, so that’s not the issue with the flu.  On a sociological level, the 1918 flu killed 3-5% of the world’s population, wiped entire villages off the map, and complicated the logistics of WW1.  How did people react to that?  How did it change society?  Flu talks a lot about how little the pandemic was talked about in the early aftermath, but nothing about how it affected society.

On the biological level, Flu raises several interesting mysteries. One, how did infections go from 0 to everyone so fast?  Even accounting for rapid transit, the disease seemed to spontaneously generate in multiple cities simultaneously.  Two, why did most of the victims suffer from an additional bacterial infection.  Was in opportunistic?  A co-infection that led to especially devastating outcomes?  She even hints that the answers may be related, but never returns to either.  My inner epidemiologist was heartbroken.

What Flu does talk about is how scientists have investigated these questions.  The anti-body work to demonstrate it was probably pig flu.  The ingenious methods of finding samples from a disease that died out 30-80 years ago.  Some of the politics of handling potential modern epidemics.  These are all fascinating, and important, and really hard to do well.  Demonstrating how science progresses is in many ways more valuable than any given scientific fact, which has a 50% chance of being proven wrong   I do wish Kolata hadn’t gotten my hopes up so high with the medical mysteries, but I would have happily read a book that promised exactly what this one delivered.

 

Flu week: herd immunity

Vaccinations are one of the wonders of the modern world.  Most people think primarily of the first order benefits- I got a vaccination, therefor I don’t get sick.  Hurray!  Then there are the second order benefits- I got a vaccination, therefor I don’t get sick, therefor I can’t infect anyone else.  Hurray!    If enough people are vaccinated, this culminates in  a third order effect, herd immunity.

Most diseases are only infectious for a short period of time.  If they don’t infect at least one other person while you’re contagious, that line dies out.*  If a disease’s average transmission rate falls below one because there are so few infectable individuals, it will be impossible for the disease to sustain itself.  This is called herd immunity, and it means even vulnerable people (such as those with compromised immune systems) are safe.  If the population is “the entire world”, you can eradicate a disease entirely  This is what we did with smallpox.

This is why refusing to vaccinate your child didn’t have many consequences for the early adopters.  As long as vaccination levels in your local population (e.g. school) were high enough to provide herd immunity, and you didn’t travel to an area where the disease was endemic, you were safe.  But when enough people in the same population forego vaccines, the disease is able to get a foothold, with disastrous consequences.

The idea that vaccines cause autism is conclusively disproven, but I don’t find it unimaginable that some vaccines have some subtle negative side effects, or rarely trigger massive negative reactions  in unpredictable individuals.  But the cost of the vaccine only exceeds the cost of not getting the vaccine when everyone else is getting vaccinated.  If you’re in a population without herd immunity, the MMR vaccine is waaaay better for you than measles or mumps.**

This concept can extend beyond vaccinations to anything that lowers transmission rate, including hand washing, face masks, condoms, and HIV pre-exposure prophylaxis.  This why “what makes sense for an individual?” and “what is best for the population?” often have very different answers.

 

*You might be asking “But won’t they run out of people eventually?  How does any disease persist?”.  That is the subject of my undergraduate thesis, and also decades of work by hundreds if not thousands of brilliant people.  We have only a fraction of the answer.

**Rubella is actually not very dangerous at all, except for being absolutely devastating to the fetus if the mother catches it in a certain stage of pregnancy.  We vaccinate for it to protect those fetuses, not the vaccine recipients.

Flu week: why the flu is special.

Your immune system is faster to respond to pathogens similar to those that have infected you previously than it is to respond to completely novel pathogens, because it holds a memory of past infections.  I have read many descriptions of this process and they always read like magic to me.  I don’t know if I’m dense for not getting it, or if I correctly recognize the explanations as oversimplified.  Immunizations are designed to give your immune system that memory without the negative effects of an actual infection.  The common ways to do this are to kill the pathogen before it’s injected, or to use a weakened form of the pathogen that can reproduce but has fewer side effects.

The magic that allows the immune system to recognize pathogens is generally based on recognizing surface proteins.  If a pathogen’s surface proteins change too much, the past immunity is useless.  This is why it is so hard to fight HIV: it mutates so rapidly that the immune system can’t keep up.  It is also why flu immunity (natural or induced) rarely carries over from year to year: the virus’s surface proteins vary too much.

Variability can come from many sources.  One is a spontaneous mutation within a viral particle.  Another is when two similar viruses co-infect the same cell and exchange genetic material.    All viruses follow the same very basic pattern: they infect a cell with their own genetic material (either DNA or RNA), hijack the cellular machinery to copy that genetic material and to produce the proteins those genes encode for, and package up the DNA or RNA in those proteins into a new viral particle and escape the cell.  While the DNA/RNA is floating around, it may cross over.  In order to exchange alleles, two strands have to line up at equivalent points to cross over (e.g. the same position on the same gene).  If the DNA/RNA is circular, they must cross over twice, at equivalent positions, or the DNA/RNA strand is nonviable.  This is statistically very rare, but a single host cell can produce millions of new viral particles, so it still happens enough to be a concern.

The flu is special.  Most viruses have one long strand of DNA or RNA, which may be linear or circular.  Influenza has 8 strands, each of which carry one gene.  They are not actually chromosomes, but for our purposes they’re pretty equivalent.  When a flu particle is manufactured, the assembly machinery grabs 8 strands and packages them up.  If memory serves, the grab is random, but that gives only a (1/8)^8 chance of given viral package being viable, so I suspect I am wrong.

Either way, when a cell is co-infected by two different strains of flu, the viral assemblers will naturally mix and match from all available strains.  This makes it much easier to exchange genes between  different flu strains.

Tomorrow: it gets worse.

medical measurements

A lot of our medical metrics are really terrible.  For example, cancer interventions are generally evaluated by n-year survival rate.  The problem is that the count starts at diagnosis, so you can raise your “survival rate” just by catching it earlier, by, say, widespread testing of people with no symptoms.  And in doing so you’ll catch a bunch of cases that get the same name (such as breast cancer) but would never have been caught by a symptom-driven search because they were never going to cause problems.  And this metric heplfully ignores any of the costs of testing, which can include cancer.  This is one reason the US has a higher cancer survival than Europe- we test much more aggressively.

Or take infant mortality, which is defined as [deaths shortly after a live birth]/[total number of live births]. This measure actually has two problems, if you’re trying to decide where you should have your baby.  One is that while Europe’s infant mortality rate is much lower than the US, the survival rate for a birth during any given week of pregnancy is higher in the US.  Europe’s advantage is that it has fewer premature births.  We don’t know why.  It’s certainly possible that this is another example of the USA’s sympathy-based aid distribution, which drives us to spend ungodly amounts of money on rare but high profile cases and neglect basic care that everyone would benefit from (like pre-natal care).  Or non-medical but still government-spending-driven interventions, like financial aid.  Or government-controlled-but-non-spending-policies, like pesticide usage or maternity leave.  Or non-government factors, like cultural norms and likelihood of close social bonds.  
 
Additionally, the definition of live birth is surprisingly malleable.  The US is much more into heroic intervention/batshit crazy belief that a 20 week old fetus is a person/tax deductions for babies that live for 12 hours, and events that would have been scored as miscarriages or stillbirths in Europe are counted as live births followed by rapid death here.   Theoretically there are statistical models that could give you comparable numbers for cancer survival, and backing out the effect of more premature births in the US is trivial, but there are no numbers that can tell us the magnitude of this discrepancy.
 
So if you’re an individual deciding where to live based on infant mortality, where do you go?  If G-d gives you a signed piece of paper saying you will go into labor at week N, you go to the US, no matter what N is.  Without that certainty?  My best guess is that sufficient money will buy you the advantages of Europe while living in the US, but the reverse is not true.  So this is another case where the rich are better off in the US and the poor in Europe.
 
So much comes down to what the number is used for. The fact that the infant mortality metric is driven by so many things beyond the medical system in front of you during birth makes it almost useless for individuals choosing where to give birth*.  But all those external factors actually make it more useful for large organizations trying to evaluate the health of a country as whole.  
 
The same thing is true of BMI.  As a quick and dirty metric to evaluate the change in a country’s average fat % over time, it’s not terrible.  It diminishes the risk of scoring an increase in average height- almost always a sign of improved health- as negative.  If your current population is of the same genetic stock as the previous, individual variation in ideal body composition will come out in the wash.  BF% is of course a much better metric, but it’s a billion times harder to measure, and given a fixed amount of money for a study, it’s entirely possible the wider sampling allowed by the cheaper metric leads to more informative results.  But BMI is completely and utterly <i>useless</i> as an assessment of an individuals health.  Genetic and epigenetic variation is simply too high.  When you are an individual (or their doctor), the time to measure BF%, or actual metrics of health like activity level and blood pressure, will always be worth it.
 
Further reading:

Being happy without being Neo

I trained very seriously in martial arts for almost two years.  I quit a year and a half ago for various reasons, some of which will become obvious later in this post.  Last week I casually sparred with an old training partner. I went in knowing he would, by any objective measure, be the winner of a fight between us. He’s bigger, preternaturally talented, won every fight back when I was training actively, and has been training very seriously since. But I didn’t care, and the sparing exceeded my expectations- I got a few shots in, I took hits well, and it turns out most of his growth in the last 1.5 years was in control and teaching, so in many ways I actually felt like my actions had a bigger impact on the outcome of our fight than I did before. It was a huge success.

Off the mat, a bystander (not affiliated with my old dojo), complimented me, which was kind of him. I forget exactly what I said, but I referred to my friend as “better.”. The bystander cut me off.

“Don’t say that. If you think it it will always be true.”

Ugh.

I know this is well meant. And I know that perception can affect outcome. But American martial arts have such a strain of bullshit around this that I want to wash myself of the whole thing. There’s no shame in being worse at something than someone. There’s no shame in being worse than a particular person at a lot of different things. It would, in fact, not be the end of the world if my own pessimism led me to perform slightly worse at a hobby I no longer pursue, whose benefits were never skill acquisition.

I resent the suggestion that I could be a ninja if only I just imagined it. Or as my ex-dojo would say, committed to it. It was used to excuse people who hit way too hard or otherwise violated safety norms- “it only hurts so much because you’re afraid of it.” It may be true that it would hurt slightly less if I had less fear- but that’s not the same as saying it wouldn’t hurt, or that the pain/physical risk would be low enough to be acceptable to me.

Top Dog says that people work harder (and learn more) when put in competitions where victory is imaginable, but far from certain. I suspect that people who say these things are trying to induce me to work harder by suggesting victory is achievable. It doesn’t work on me in this case, because I’m convinced I have logic on my side. Even if I’m wrong, their attempts to negate the belief reinforce it, in mechanisms very similar to the one they claim is holding me back. It is, at best, trying to tear down the master’s house with the master’s tools.

What I would prefer is to find ways to be able to give my all (or whatever amount of effort and attention I deem optimal) regardless of my perceived chance of success. That strikes me as a much more worthy, and sustainable, endeavor.

While I’m on the subject, I am also tired of medium-to-large men telling me any strength differential can be overcome by sufficient skill. It’s technically true for a broad enough definition of the word “skill”

[here, skill is defined as bringing a gun to a sword fight]

but it still lowers my estimation of what the speaker could teach me.

Book Review: Top Dog

A popular science writer has two choices: be vague when explaining the specific experiments behind their explanations, thus leaving themselves open to criticism about not sufficiently proving their supposition, or be exhaustive, which is boring.  It is impossible to be both truly rigorous and readable by mainstream publishing standards.

Reading Top Dog, I had an urge to make myself feel smart/assert dominance by criticizing their science.  Those of you who follow me on twitter got a taste of that.  But I stopped because I realized the criticism was a net drain on the universe.  While every study and experiment they cited could be criticized, that  is the nature of research: you can only prove so much in any given run.  You have to draw conclusions from the body of applicable research as a whole.  And in that context, I think it’s a pretty good book.  It explained  biochemistry in a way I found understandable but rigorous,* and I think their overall conclusions  are merited and well supported.  Some of them will be proven incorrect tomorrow, but that is the nature of science.

If you are looking for science writing for the sake of science writing, I would recommend the authors’ previous work, Nurture Shock.  But if you are looking for something specifically on the science of competition and, more broadly, stress, seriously consider Top Dog.

* This is a compliment.  I nearly ran on stage last week when a play’s key plot point depended on a faulty understanding of sickle cell anemia.