Review: The Remedy: Robert Koch, Arthur Conan Doyle, and the Quest to Cure Tuberculosis (Thomas Goetz)

I love this book so much I gave it to my cats to cuddle, which would have made a more impressive visual if I hadn't gotten the kindle version.
I love this book so much I gave it to my cats to cuddle, which would have made a more impressive visual if I hadn’t gotten the kindle version.

I don’t even know where to start.  This book was fun to read and I felt like I learned a lot.  It covered both the specific facts of Robert Koch’s quest to prove germ theory and cure tuberculosis, and provided a good general sense of how science and medicine move forward and don’t.

A couple of specifically interesting points: doctors fought germ theory tooth and nail.  They also rejected stethoscopes as technological interlopers to be disposed of because they threatened the doctors importance, while using so many leaches prosperous countries had to import them.  The naive interpretation is “doctors are idiots, their reluctant to use quantified self data is proof they haven’t changed.”  This is the first time I’ve seen any hint as to why they found germ theory so implausible.  In the particular case of tuberculosis, everyone was exposed all the time, and it took the infection years to become symptomatic.  Preventing any one exposure wouldn’t have had noticeable results.  Another early-identified bacteria was Anthrax, which didn’t follow a typical exposure pattern either.  The doctors still come out looking pretty bad for refusing to wash their hands between autopsies and childbirth, but marginally less than they might have.

I knew this already, but it was good to have a reminder that the first person to suggest the germ theory of disease, Ignez Summelweis, died in an insane asylum.  This either means that people with truly visionary ideas can be broken when we reject them, or germ theory was so crazy it took a crazy person to see it.  Goetz doesn’t mention it but according to my dad Summelweis was also an asshole, which I try to remind myself every time someone mean says something I disagree with.

Remember last week when I suggested using microchips to force people to finish their antibiotics?  Several friends seriously questioned the effect of that, since they didn’t estimate the contribution of unfinished antibiotics to antibiotic resistance as very high.  The Remedy says that the current protocol for drug resistant TB is to have a medic visit a patient every day for 6 -24 months to observe them taking their pills, because drug resistant TB is that big a problem and the pills are that unpleasant.  So at least in that situation swallowable microchips would be an enormous improvement.

Apparently syphilis is always the [nationality] disease, where the nationality is not the speaker’s.  French is the most popular, but far from the only

I’ve always found the methods section the most boring of any paper or textbook.  I want to know what we learned, not how.  But The Remedy (and to a lesser extent Neanderthal Man, which I reviewed last week) made it seem interesting.  I’m still not terribly interested in microscopy, but it was deeply interesting to see how advances in technology enabled scientific advances.  Using or inventing new technology is how you move the world forward.  And when I thought about it, the modern field that most reminds me of the wide-open-ness of microbiology in the mid 1800s is programming.  That is where I get the most sense of possibility.  I still really care about translational health (in fact this book taught me that that is the word for what I am trying to do with this blog) and mental health, but I am feeling more and more like staying in programming would be the best way to accomplish that.

What We Talk About When We Talk About Effectiveness

The biological/scientific definitions of heredity and heritable differ slightly from the popular usage.  Lay people tend use it  to mean “how much is this caused by genes?”  In science, heredity is how closely people resemble their parents, divided by the total variation in the population.  Biological sex has almost zero heritability because knowing someone’s parents sex does not allow you to predict their own sex.*  Number of arms is barely heritable, because there’s almost no variation in number of arms among humans, and what variation exists is overwhelmingly caused by environment, not genetics.

A corollary to this is that a measure of heredity is only valid for the exact environment you measured it in.  If you plant a variety of seeds in identical pots and give them identical water and supplements, most variation will be due to genetics, and a small amount to chance (which will be counted as environment), so traits like height and time to flower will be highly heritable.  If you plant those same seeds in widely varying pots and vary the water and nutrients they get, a lot of the variation will be due to environment, and the heredity values of the same traits will be much lower.  Skin color in Norway is more heritable in the winter than in the summer, because teenagers deliberately tan more than their parents.

I have struggled before to make effectiveness estimates when the intervention’s usefulness depends on multiple factors.  Blood for car accident victims is only helpful in the context of emergency rooms and medical schools and sterile gauze.  Suicide hotlines require phones and electricity and suicidal people at a bare minimum, and active rescues require police and mental hospitals and often pharmaceutical research.  I think I’m just going to have to put effectiveness in the same category as heredity: the quantification is only valid for the environment in which it is measured.

I’ve worried before about Effective Altruism’s tendency to take the existing system as a given.  That was a reasonable simplification when the movement was first starting, and there was plenty of low hanging fruit that didn’t require more sophisticated analysis.  But I’m really happy to see organizations like the Open Philanthropy Project branch into studying how to change systems and how to measure the effectiveness of attempts to do so.

*Intersexuality confounds this a little but my impression is it’s mostly not a genetic issue, in part because intersex people generally have difficulty reproducing.

The Science of Blood Types

Yesterday I made an offhand remark that the Red Cross was so persistent in stalking me because I was O-.  Here’s why that’s important:

Your red blood cells can have two different proteins on them (A or B), or both, or neither.  If you receive a transfusion with red blood cells with a protein you don’t have, your immune system will mark it as a foreign invader and attack it.  If you get too much of these cells, you will die.  Parallel to this is another protein Rh factor, which you either have (Rh+) or you don’t (Rh-).  A- means you have A proteins, but not B or Rh factor.  If you are Rh- and receive Rh+ red blood cells, same problem.

foxindogs
You cannot bluff the immune sytem.

O- red blood cells have no immune-triggering proteins on it, and so can be given to anyone.  That makes O- blood extremely useful when you don’t have time to type a patient, or have limited carrying capacity.  Moreover, O- red blood cells are the only type O- patients can accept.  So O- is often the first to run out.

You might think this makes donations from AB+ people pointless, but that is not the case.  Their red blood cells are of limited use, but their blood plasma (which is the part that contains the antigens that trigger attacks on foreign matter) contains no antigens to any blood type.  Meanwhile everything looks like an invader to my O- plasma, and it will react accordingly.  This also means you can only do whole blood donations between complete type matches.  A B+ person can take my red blood cells, but would need plasma from someone else.

And that is why typed-matched blood is preferred and donations of all types are necessary.

Is Blood Donation Effective? (Yes)

Seattle is apparently not the only Effective Altruism group to talk about doing volunteering meetings, only to remember that the traits that make volunteering useful are almost antithetical to the traits that make it fun and doable to for a group on a drop-in basis.  I am kind of hoping that blood donation can bridge that gap.  So here’s my math on how effective donating blood is.  The Red Cross estimates a single donation can save three people, but what they mean is “a single donation can go to three different people.”  To get the actual value we need to see how many units of blood were donated and how many deaths they prevented.

The most recent data I could find was the 2011 National blood Collection and Utilization Survey Report (PDF), which couldn’t make it harder to do this kind of calculation if it tried.  They were extremely loose with what “unit” referred to, so I’m going to stick with the whole and red blood cell transfusions, so my numbers are consistent.  There were 15,721,000 units collected, of which 14,589,000 were deemed usable.  13,785,000 were used, of which 37,000 were directed to a specific patient, and 65,000 were self-donations, which are less effective for various reasons.  The collections numbers don’t call out general vs. specific donations and the numbers are small, so I’ll just use the total number used.  If some blood donations are also generating plasma and white cells in addition to the red blood cells counted here, that would only increase effectiveness.

A single donation is one pint.  Health and Human Services fails to define what they mean by unit, but it appears to mean “whatever you get from one donation after some filtering“, so let’s assume it’s 1:1.  The average recipient receives 2.75 units.  If you assume each person who received a transplant would otherwise die (supported by this sourceless FAQ), that means each donation saves ~1/3 of a life (discounting for donations that are rejected).  Using GiveWell’s $5,000/life number, that’s still equivalent to donating $1,667.   That is overstating the case, because some portion of recipients (I can’t find out how many) have diseases like sickle cell anemia that require chronic transfusions, and the fair thing is to count their lifetime transfusion count, not their per treatment count.  To get an upper bound I’ll use the Red Cross’s number that a car accident victim can use up to a 100 pints of blood, which means each donor saves 1% of that life, which is equivalent to $50 to an extremely effective charity.

But the question isn’t “what is the average value of donated blood?” but “what is the marginal value of your potential donation?”  I can’t find any direct numbers for this, but we have the following evidence:

  • Very little blood is thrown out.
  • People are spending lots of time and money developing artificial blood substitutes.  Despite this there are no generally accept substitutes for blood’s oxygen-carrying capacity.
  • The Red Cross spends a lot of time and money harassing people to donate.  They called my parents’ house for years after my one donation (I’m O-).
  • Some blood is able to reach the “too old” state, but then used to ill effect, indicating lumpy supply or demand.  Unless you can predict demand spikes you should use the average efficacy.  If you can predict demand spikes, there are probably more effective things to do with that power.

So I’m just going to use the average effectiveness as the marginal effectiveness for now.

What are the costs to the donor of donating?  The one time I donated it was high because I slept for the next two days.  If you’re my friend Elena who went into shock after donating, it cost you days and several thousand dollars in ER visits.  So it is probably not worth it for either of us to donate.  But for a typical person with no side effects, it’s plausibly useful.  If it’s replacing work time, then effectiveness depends on their hourly wage.  Multiple websites list the time to donate as 60-90 minutes, which translates to a minimum psuedowage of $33/hour and a maximum of $1667.  The average hourly American wage is $24/hour, although I would estimate the average wage of people earning to give as somewhat higher than that.  So that’s extremely plausible on its face.  But if the time isn’t coming out of work, and is made rewarding to the participant, blood donation is hugely effective.  This suggestions that an event that induced people to donate without replacing work would be effective, more so if it could be made into a positive experience.  So a blood donation event could be a huge win for an EA event.

[Side note: if you decide to do this yourself, I would recommend donating anywhere but the Red Cross if at all possible.  I’m going to try for Bloodworks NW, because if I get enough people they will send a truck and we can make it an actual party]

Bloody cupcakes
Do not GIS “blood donation party” with safesearch off

How Tests Improve Code Structure pt 2

I’ve always admired Test Driven Development and longed for it from afar, but never had a chance to use it until I was on my own project.  Most times when you crave something this intently it’s a let down, but no, this is every bit as fun as I thought it would be and more.  It’s so relaxing, and it takes so much less mental RAM.  I won’t go back to any other way.

I keep trying to explain why it is better and exactly how it made it obvious what I needed to do, but everything I write comes out boring and I don’t think it explained it anyway.  Let’s try an analogy.  You know how when you attempt a big cleaning project the middle looks worse than if you’d never started?  And if you misjudge your energy level it stays that way, and then gets worse because you’re still living your life?  Or maybe you misjudged the amount of space something required and your plan becomes unworkable, at which point you can improvise or revert?  That’s what regular coding feels like to me.  You don’t know if something’s working until it’s all working.

I’ve been cleaning up my apartment lately, including getting rid of things I don’t want and rearranging things I have so they are more accessible/easier to find/take less space.  And I am being very careful not to do that.  I pick tasks that can be done incrementally.  If I want to move things from cabinet A to cabinet B, things in cabinet B get moved to cabinet C first.  But cabinet C doesn’t have to be their permanent home, just a pareto improvement over the old one.  I have consolidated three dressers into 1 + some other storage bins.  I will probably rearrange those storage bins and the remaining dresser as I learn more about how the current arrangement works, but I was never going to be able to plan that out ahead of time anyway.    This way I never get stuck halfway through, out of energy or realizing my plan is unworkable.

That is what TDD feels like to me.  You might technically be writing and erasing a lot more code, but the mental effort is so much less.  Every step leaves you a little bit better off, and you can concentrate your efforts on one problem at a time.

I was really unimpressed with the android tutorials I saw.  I did Udacity’s, which is officially recommended by Google, but didn’t provide reference code or a way to check your project, so if something didn’t work you didn’t know where the error was. That’s bad enough when it’s a technology you’re well versed in, but with a new tech you don’t have any debugging tools.  It’s like trying to learn a foreign grammar by having it explained to you in its own language, when you don’t even have any vocabulary yet, except your brain hasn’t been crafted by millions of years of evolution to do it.  There are other tutorials, but most of them were written for the now-deprecated Eclipse IDE.  Translating from one IDE or build system is not a big deal when you’re familiar with at least one of them, but at the beginning you don’t even know what to Google.  That’s why you’re doing a tutorial. It’s even more fun with Android because it uses a bunch of very common Java tools but requires slightly different usage than everything else.

So what I actually did was do Udacity long enough to know how to make baby’s first project, come up with a concept that I was pretty sure I could subdivide into google-able problems, and then did so, one at a time.  I learned testing basically from scratch, because the two tutorials that covered it required me to know a ton of abstract android architecture, and none of it was explained well enough to mean anything unless you had already coded.  “Make minor changes until you understand the permutations” is how every programmer I know learns, and yet no class teaches this way.

All of which leads me to believe a test-driven tutorial could be really useful.  I’m picturing a project with a few very simple UI elements, and a series of commented out tests.  Users would uncomment the tests one at a time, in order.  The test would fail. The error message would be informative, maybe there would be a few suggestions for how to solve it.  Then they would research on their own until they found a solution.  They would know they had done it right because the test would be passing. Plus they’d learn testing tools at the same time, and those are extremely useful.  This may be my next project.

TDD got me all of the features I wanted in HungerTracker 0.2 except notifications.  I’m still poking at it, but notifications require a deep understanding of several concepts I’ve entirely ignored until now, and need several moving parts to work together to verify any of them.  So here’s version 0.2, which has a greatly improved button layout and a scrollable list that shows as many or as few entries as actually exist.

Review: Neanderthal Man

As a narrative about how science works, this is pretty strong.  I got it as part of my new policy of not reading emotionally intense books right before bed, and while it didn’t produce the post reading anxiety that, say, that book about slavery did, it was pretty exciting and pushed my bedtime back quite a bit.

The actual science, I’m not sure about.  He’s doing molecular biology without any background in basic bio, so he says things like “I didn’t know insects were animals.” on his first day as a zoology professor (he’s since realized his error) or “Can we really say they’re the same species just because they fertily interbreed.” in his book, on biology, that people paid him actual money to publish.  Yes, we can say that because that is exactly what species means.

I’m also a little confused by how they determined humans and neanderthals interbred.  It seems like they’re using the same data to calibrate the technique they’re using to sequence the DNA, the degradation rate of DNA, the contamination rate of the sample, when humans and neanderthals diverged, and when/how much they interbred.  He also doesn’t make a good distinction between when he’s talking about junk DNA (which is not subject to selection pressure, so is a pretty good molecular clock) and when he’s talking about genes (which is, and so it’s difficult to distinguish inheritance from the same source, interbreeding, and convergent evolution).

Lots of very smart people with much more information and training in this area than I have seem to be okay with his conclusions, so I assume this is one of those things where he is simplifying, and I know enough to know that he is missing something but not enough to fill in the gaps myself.  But if you are not in that uncanncy valley, it’s very well written and entertaining.

Being a cyborg proves more boring than anticipated.

Barack Obama recently announced doubling funding to fight antibiotic resistance, which would be more impressive if there wasn’t a significant step that cost the government nothing: ban use of antibiotics for livestock, which currently account for 80% of antibiotics produced.  Hell, taxing use of antibiotics in livestock would reduce the problem and generate revenue.  Representative Louise Slaughter has introduced a bill to (more or less) do this for five years running and it has gone absolutely no where.  So this feels a little like California introducing water restrictions on people while saying nothing about agricultural use, which coincidentally is 80% of their water use.

But maybe Obama’s new money will go to one of the lesser contributors towards antibiotic resistance: people who don’t finish their prescriptions.  Researchers are studying a new microchip that sends a signal when it is being digested.  They’re using it for severely mentally ill patients, who for various reasons sometimes have trouble staying on their meds (good luck to the first schizophrenic to explain to their new doctor that their old doctor tracked their medication by making them swallow computer chips), but what if we used them for antibiotics?

This isn’t a simple solution.  To have it do any good you have to either punish people for not finishing them (which is extremely hard on low income people) or pay them for finishing (hello terrible incentives).  People who split prescriptions are often trying to save themselves the doctor’s visit more than the cost of the medication itself, and this doesn’t address that.  But it seems like we ought to be able to do something with this.