On gene duplication and oppression, a reprise.

On gene duplication and oppression, a reprise.

Evolution depends upon the unnecessary.

Evolution is a process in which those organisms best suited to their environments – either because they persist longer than others or produce more progeny – become more abundant.  For a lineage to become better suited to an environment over time, the organisms have to change in a heritable way.

DNA polymerases aren’t perfect.  Whenever enzymes copy our genetic material, they make mistakes.  To be honest, these mistakes are rarely beneficial.  Sometimes they cause other enzymes to stop working.  Sometimes they turn a cell into cancer.  But that same imperfection – which changes genetic information from one generation to the next – gives rise to evolution.

The evolution of a particular species of bacteria has been carefully documented in biologist Richard Lenski’s laboratory.  These were allowed to compete inside a precisely-controlled environment over hundreds of thousands of generations, and some of the bacteria were frozen after every few hundred generations to keep track of all the genetic changes.

Zachary Blount and Richard Lenski horsing around with some of the Petri dishes from Blount’s work on the evolution of citrate utilization in one . Image from Wikimedia.

In this experiment, a single subpopulation gained the ability to metabolize a new nutrient, which gave it a huge competitive advantage and allowed it to conquer its tiny world.  But how?  After all, most of a bacteria’s genes are already important for something, and, when mutations occur, the most common outcome is for functions to be lost.  If you give a radio and a screwdriver to a toddler, you probably shouldn’t expect crisper reception come evening.  Chances are that your radio won’t work at all.

Gene duplication, as depicted by the National Human Genome Research Institute on Wikimedia Commons.

As it happens, a very rare event happened before this bacterial subpopulation “learned” to use the new energy source.  When the experiment was re-started with various frozen samples, most lineages never acquired this ability.  But in one set, there had been a “gene duplication event.”  During cell division, the enzyme that copies DNA had stuttered and accidentally included two copies of a gene that bacteria only need one copy of.  And these bacteria, recipients of that unnecessary second copy, would almost always gain the new metabolic function and swamp out the others.

Once there were two copies of the gene, the second copy was free to change.  A mutation in that copy wouldn’t cause the bacteria to grow weak or die, because they still had a fully-functional copy of the enzyme.  And eventually, through the rare happenstance of random error, bacteria would accumulate enough mutations in that second copy that it gained a new function.

In the beginning, this new function was pretty weak.  But once there was a faint glimmer, natural selection could refine it.  Without an unnecessary second copy of that gene, though, the bacteria never would’ve gained the new metabolic pathway.

You can look at human culture in a similar way.  Which isn’t to say that one culture is intrinsically better than another, and certainly doesn’t imply that we’re progressing toward some teleological goal.  Evolution is just a matter of statistics, after all.  The things that are, now, were probably descended from things that were good at being and producing.

An image from a 1902 engineering textbook from Wikimedia Commons.

For instance, cars make human life easier.  And so the traits that allow a culture to have cars, like a basic understanding of mathematics and a willingness to follow rules on roadways, seem to spread pretty easily.  Car cultures have swamped out non-car cultures all over the planet.  Walking is pretty great, and so are bikes, but any culture that has access to mechanical engineering textbooks seems to have a pretty huge advantage over those that don’t.

But if you’d dropped a mechanical engineering textbook into the lap of a Paleolithic hunter-gatherer, it’d seem pretty useless.

It took a lot of waste to reach a state when the textbook could matter.  Over many generations, there was excess and dead weight.  Many centuries of an oppressor class stealing from the mouths of the poor, really.

Somebody who is struggling every day to procure food doesn’t have the luxury to fiddle with mathematics.  That’s why so many of the early European scientists were members of the aristocracy.  They didn’t need to work to eat because they had serfs to steal food from, levying taxes for the use of land that was “theirs” because their ancestors had done a bang-up job of murdering other people’s ancestors.

In the generations after humans developed agriculture, the average quality of life plummeted.  If you were told to pick any year and your soul would be suddenly re-incarnated (pre-incarnated?) into a randomly-chosen Homo sapiens alive at that time, you’d probably be happier 20,000 years ago than at most times during the last few millennia.  20,000 years ago, nobody lived terribly well – there was scant medicine and a constant risk of famine – but the suffering and servitude experienced by the majority of humans later on was worse.

After farming, people worked harder, for more hours a day, to produce a less varied, less healthful diet than the hunter-gatherers had eaten.  They had even less access to medicine, and still endured the constant risk of famine.  Oh, and envy.  Because farmers, who had to live in place, could be conquered.

640px-Maler_der_Grabkammer_des_Sennudem_001Those conquered farmers could be taxed, charged rent, etc., with the proceeds used to feed an idle class.  Most of the idlers produced nothing of value.  They ate others’ food and lived in un-earned luxury (although their “luxury” would seem pretty shabby to us).  But a few of them – a very few – produced the cultural innovations (like mathematics, medicine, poetry, astronomy) that gave us the modern world.

It feels more than a little disconcerting that a gruesome history of violence and oppression allows me to type this essay on a laptop computer.

In the past, though, oppression was the only way for our world to have “excess” people, those who could be free to devote their time and energy toward changing things.  Now, however, food production (and many other things) has been heavily automated.  We could have a much larger excess population, which could increase the rate of cultural evolution.  A luxurious lifestyle could be had by all using the essential (food- and shelter-producing) efforts of a smaller number of people than ever before.

With a guaranteed basic income – which could be funded by taxing wealth at a very low rate, maybe a percent or two – nearly all people could effectively become aristocracy.  People could follow their passions and curiosities.  Most, as ever, wouldn’t change the world. That’s how evolution works.  Chaotic tinkering with things that are pretty good rarely improves things.  But with billions of tinkerers, the odds that something works out are better.

It’s easily within reach.  Instead we’ve stuck with the same system of celebrating historical violence that was used to oppress people before.  Maybe it was necessary, all that cruelty, to get from our past to here.  But it certainly isn’t needed now.

Featured image: DNA duplication diagram by Madeline Price Ball on Wikipedia.

On Sci-Hub, the Napster of science.

On Sci-Hub, the Napster of science.

Here’s a story you’ve probably heard: the music industry was great until Napster came along and complete strangers could “share” their collections online and profits tanked.  Metallica went berserk suing their fans.  It was too late.  The industry has never been the same.napster

Sci-Hub has been called a Napster equivalent for scientific research papers, and the major publishing companies are suing to shut it down.  The neuroscience grad student who created it faces financial ruin.  The original website was quickly shuttered by a legal injunction, but the internet is a slippery place.  Now the same service is hosted outside U.S. jurisdiction.

[Note: between writing and posting this essay, Sci-Hub has lost another lawsuit requesting all such sites to be blocked by internet service providers.]

The outcomes of these lawsuits are a big deal.  Not just for the idealistic Kazakhstani grad student charged with millions in damages.  Academic publishers will do all they can to accentuate the parallels between Sci-Hub and Napster – and, look, nearly a quarter of my living relatives are professional musicians, so I realize how much damage was wrought by Napster’s culture of theft – but comparing research papers to pop songs is a rotten analogy.  Even if you’ve never wanted to read original research yet … even if you think – reasonably – that content producers should be paid, you should care about the open access movement.  Of which Sci-Hub is the most dramatic foray.

My own perspective changed after I did some ghostwriting for a pop medicine book.  Maybe you know the type: “Do you have SCARY DISEASE X?  It’ll get better if you take these nutritional supplements and do this type of yoga and buy these experimental home-use medical devices!”  Total hokum.  And yet, people buy these books.  So there I was, unhelpfully – quite possibly unethically – collaborating with a friend who’d been hired to ghostwrite a new one.

Central_core_disease_NADH_stainI read huge numbers of research papers and wrote chapters about treating this particular SCARY DISEASE with different foods, nutritional supplements, and off-label pharmaceuticals.  My sentences were riddled with un-truths.  The foods and drugs I described are exceedingly unlikely to benefit patients in any way.

Still, I found research papers purporting to have found benefits.  I dutifully described the results.  I focused on the sort of semi-farcical study that concludes, for instance, that cancer patients who drink sufficient quantities of green tea have reduced tumor growth, at which point newspapers announce that green tea is a “superfood” that cures cancer, at which point spurious claims get slathered all over the packaging.

Maybe nobody has written a paper (yet!) claiming that green tea ameliorates your particular SCARY DISEASE.  But there’s also turmeric, kale, fish oil, bittermelon, cranberries… I’m not sure any ingredient is so mundane that it won’t eventually be declared a superfood.  Toxoplasma gondii has been linked to schizophrenia, but low-level schizophrenia has been linked to creativity: will it be long before cat excrement is marketed as a superfood for budding artists?

cat-shit-2-flat-1.jpgAs it happens, enough people suffer from our book’s SCARY DISEASE that many low-quality studies exist.  I was able to write those chapters.  And then felt grim.  The things I’d written about food weren’t so bad, because although turmeric, coconut oil, and carpaccio won’t cure anybody, they won’t cause much harm either.  But the drugs?  They won’t help, and most have nasty side effects.

My words might mislead people into wasting money on unnecessary dietary supplements or, worse, causing serious damage with self-prescribed pharmaceuticals.  Patients might follow the book’s rotten advice instead of consulting with a trained medical professional.  I’d like to think that nobody would be foolish enough to trust that book – the ostensible author is probably even less qualified to have written that book than I am, because at least I have a Ph.D. in biochemistry from Stanford – but, based on the money being thrown around, somebody thinks it’ll sell.

And I helped.

Whoops.  Mea culpa, and all of that.

But I didn’t perpetrate my sins alone.  And I’m not just blaming the book’s publishers here.  After all, the spurious results I described came from real research papers, often written by professors at major universities, often published in legitimate scientific journals.

It’s crummy to concentrate all that slop in a slim pop medicine book, I agree, but isn’t it also crummy for all those spurious research papers to exist at all?

Maybe you’ve heard that various scientific fields suffer from a “replication crisis.”  There’s been coverage on John Oliver’s Last Week Tonight and in the New York Times about major failures in psychology and medicine.  Scientists write a paper claiming something happens, but that thing doesn’t happen in anyone else’s hands.  That’s if anyone even bothers to check.  Most of the time, nobody does.  Verifying someone else’s results won’t help researchers win grants, so it’s generally seen as a waste of time and money.

Still, the news coverage I’ve seen hasn’t stated the problem sufficiently bluntly.  Modern academic science is designed to be false.

This is tragic.  It’s part of why I chose not to stop working in the field.  I became a writer.  Of course, this led to my stint of ghostwriting, which… well, whoops.

Here’s how modern science works: most research is publishable only if it is “statistically significant.”  This means comparing any result to a “null hypothesis” – if you’re investigating the effect of green tea on cancer, the null hypothesis is simply “green tea does nothing” – then throwing out your results if you had more than a one in twenty chance to see what you did if the null hypothesis were true.

If you have a hundred patients, some of their tumors will shrink no matter what you do.  If you give everybody buckets of green tea and see the usual number of people improve, you shouldn’t claim that green tea saved them.

Here’s a graphic from Wikipedia to help:


Logical enough.  But bad.  Why?  Because cancer is a SCARY DISEASE.  Far more than twenty people are studying it.  If twenty scientists each decide to test whether green tea reduces tumors, the “one in twenty” statistical test means that somebody from that set of scientists will probably see an above-average number of patients improve.  When you’re dealing with random chance, there are always flukes.  If twenty researchers all decided to flip four coins in a row, somebody would probably see all four come up heads – doesn’t mean that researcher did anything special.

Or, did you hear the news that high folate might be correlated with autism?  This study probably sounds legitimate – the lead scientist is a professor at Johns Hopkins, after all – but the result is quite unlikely to be real.  That scientist hasn’t written about folate previously, so my best guess (this new study is currently unpublished) is that pregnant women were tested for many different biomarkers, things like folate, iron, testosterone, and more, and then tracked to see whose children would develop autism.  If the researchers tested the concentrations of twenty different nutrients and hormones, of course they’d see one that appeared to correlate with autism.

[Edit: these findings were recently published.  Indeed, the data appear rather unconvincing, and the measurements for folate were made after the fact, using blood samples – it’s quite possible that other data was gathered but excluded from the published version of the study.]

This is not science.  But if you neglect to mention how many biomarkers you studied, and you retroactively concoct a conspiracy theory-esque narrative explaining why you were concerned about folate, it can do a fine job of masquerading as science.  At least long enough to win the next grant.

Which means that, even though the results of many of these studies are false, they get published.  When somebody checks twenty nutrients, one might appear to cause autism.  When twenty scientists study green tea and cancer, somebody might get results suggesting green tea does work.  Even if it doesn’t do a thing.

In our current system, though, only the mistaken researcher’s results get published.  Nobody knows that there were twenty tests.  The nineteen other biomarkers that were measured get left out of the final paper.  The nineteen researchers who found that green tea does nothing don’t publish anything.  Showing that a food doesn’t cure cancer?  How mundane.  Nobody wants to read that; publishers don’t want it in their journals.  But the single spurious result showing that green tea is a tumor-busting superfood?  That is exciting.  That study lands in a fancy journal and gets described in even briefer, more flattering language in the popular press.  Soon big-name computer CEOs are guzzling green tea instead of risking surgery or chemo.

I generally assume that the conclusions of research studies using this type of statistical testing are false.  And there’s more.  Data are often presented misleadingly.  Plenty of scientists are willing to test a pet theory many ways and report only the approach that “works,” not necessarily because they want to lie to people, but because it’s so easy to rationalize why the test you tried first (and second, and third…) was not quite right.  I worked in many laboratories over a decade and there were often results that everybody in the lab knew weren’t true.  Both professors I worked under at Stanford published studies that I know weren’t done correctly.  Sadly, they know it too.

This subterfuge can be hard for outsiders to notice.  But sometimes the flaws are things that anybody could be taught to identify.  With just a little bit of guidance, anybody foolish enough to purchase the pop medicine book I worked on would be able to look up the original research papers and read them and realize that they’re garbage.

There’s a catch: most of those papers cost between twenty and thirty dollars a pop.  The chapters I wrote cite nearly a hundred articles.  I’d describe a few studies about the off-label use of this drug, a few about that one, on and on, “so that our readers feel empowered to make their own decisions instead of being held at the paternalistic mercy of their healthcare professionals.”  A noble goal.  But I’m not sure that recommending patients dabble with ineffectual, oft-risky alternative medicines is the best way to pursue it.  Especially when the book publisher was discussing revenue sharing agreements with sellers of some of the weird stuff we shilled.

So, those hundred citations?  You could spend three thousand dollars figuring out that the chapters I wrote are crap.  The situation is slowly getting better – the National Institute of Health has mandated that taxpayer-funded studies be made available after a year, but this doesn’t apply to anything published before 2008, and I’m not sure how keen sick patients will be to twiddle their thumbs for a year before learning the latest information about their diseases.  Plus, there are many granting organizations out there.  Researchers who get their money elsewhere aren’t bound by this requirement.  If somebody asks you, “Would you like to donate money to fight childhood cancer?” and you chip in a buck, you’re actually contributing to the problem.

Photo by diylibrarian on Flickr.

I was only able to write my chapters of that book because I live next to a big university.  I could stroll to the library and use their permissions to access the papers I’d need.  Sometimes, though, that wasn’t enough.  Each obscure journal, of which there are legion, can cost a university several thousand dollars a year for a subscription.  A few studies I cited were published in specialty journals too narrowly focused for Indiana University to subscribe, so I’d send an email to a buddy still working at Stanford and ask him to send me a copy.

If you get sick and worry yourself into looking for the truth, you’ll probably be out of luck.  Even doing your research at a big state university library might not be enough.

That’s if you keep your research legal.

Or you could search for the papers you need on Sci-Hub.  Then you’d just type the title, complete a CAPTCHA on a page with instructions in Cyrillic (on what was until recently http://www.sci-hub.cc, at least), and, bam!  You have it!  You can spend your thirty dollars on something else.  Food, maybe, or rent.

Of course, this means you are a thief.  The publisher didn’t get the thirty dollars they charge for access to a paper.  And those academic publishers would like for you to feel the same ethical qualms that we’re retraining people to feel when they pirate music or movies.  If you steal, content producers won’t be paid, they’ll starve, and we’ll staunch the flow of beautiful art to which we’ve become accustomed.

The comparison between Napster and Sci-Hub is a false analogy.  Slate correspondent Justin Peters described the perverse economics of academic publishing, in particular the inelastic demand – nobody reads research journals for fun.

With music and movies, purchasing legitimate access funds creators.  Not so in academia.  My laboratory had to pay a journal to publish my thesis work; this is standard practice.  It costs the authors a lot of money to publish a research article, and “content producers” only do it, as opposed to slapping their work up on a personal website for everyone to read free, because they need publication credits on their CVs to keep winning grants.

With music and movies, stealing electronic copies makes content producers sad.  With research articles, it makes them happy.

In fact, almost everyone believes research articles should be free.  At the European Union’s recent Competitiveness Council, the member states agreed that all scientific papers should be freely available by 2020 – these  are the governments whose enforcement is necessary to maintain the current copyright system!  The only people making statements in favor of the status quo are employed by the academic publishers themselves.  Their ideological positions may be swayed somewhat by the $2 billion plus profit margins major publishers are able to extract from their current racket.

Academic publishers would argue that they serve an important role as curators of the myriad discoveries made daily.  This doesn’t persuade me.  The “referees” they rely on to assess whether each study is sound are all unpaid volunteers.  Plus, if the journals were curating well, wouldn’t it have been harder for me to fill that pop medicine book with so much legitimate-looking crap?

Most importantly, by availing yourself of Sci-Hub’s pirated material, you the thief no longer live in ignorance.  With our current healthcare model, ignorance is deadly.  The United States is moving toward an a la carte method of delivering treatment, where sick people are expected to be knowledgeable, price-sensitive consumers rather than patients who place their trust in a physician.  Most sick people no longer have a primary care physician who knows much about their personal lives – instead, doctors are forced for financial reasons to join large corporate conglomerates.  Doctors try their best moment by moment, but they might never see someone a second time.  It’s more important than ever for patients to stay well-informed.

Unless Sci-Hub wins its lawsuit, you probably can’t afford to.

On theft and bullying.

On theft and bullying.

We aren’t born equal.

We never have been, not humans or any other animals.  Among species that birth in litters, the baby that leaves the womb largest has a lifelong advantage.  In the modern world, where a baby happens to be born dictates its future prospects to a huge degree.  Maybe it’ll be born in the United States, instantly reaping the benefits of citizenship.  Or maybe it’ll be born into a war-torn nation, amidst strife caused by climate change… which was itself caused by the creation of wealth and prosperity for all those U.S. babies.

And we use our initial advantages to further tilt the scales.  The largest mammal in a litter pushes the others aside and takes the most milk.  The rich get richer.

The same principal holds true in astrophysics.  The more dense a black hole, the better it will be at grabbing additional matter.  Densely-arrayed galaxies will keep their neighbors longest: because empty space expands, the rate at which stars drift away from each other depends upon their initial separation.  The farther away you are, the faster you will recede.  The lonely become lonelier.

But we are blessed.  Through the vagaries of evolution, humans stumbled into complex language.  We can sit and contemplate the world; we can consciously strive to be better than nature.

We can read Calvin and Hobbes and think, “Hey, that’s not fair!”

calvin 9 - 11.png

It is perfectly natural for Moe to get the truck.  He is bigger, after all.  He is stronger.  In the world’s initial inequalities of distribution, physical prowess determined who would reap plenty and who would starve.  After all, not all territories are equivalently bountiful for hunters or gatherers.  Now we have sheets of paper that ostensibly carve up the world amongst us, but in past eras raw violence would’ve staked claims.  Human mythology brims with accounts of battle to gain access to the best resources… and we humans still slaughter each other whenever insufficient strength seems to back the legitimacy of those papers.

When the threat of contract-enforcing state violence in Syria waned, local murder began.  And we lack an international state threatening violence against individual nations – inspired partly by the desire for resources, George W. Bush initiated a campaign of murder against Iraq.

Except when we’ve banded together to suppress individual violence (the state as Voltron), the strong take from the weak.

At least we know it’s wrong.

We’ve allowed other forms of bullying and theft to slip by.  After all, differing physical prowess is only one of the many ways in which we are born unequal.  If it is wrong for the strongest individual to steal from others, is it also wrong for the most clever to do the same?

weaponsofmathdestructionFrom Cathy O’Neil’s Weapons of Math Destruction:

But the real problem came from a nasty feeling I started to have in my stomach.  I had grown accustomed to playing in these oceans of currency, bonds, and equities, the trillions of dollars flowing through international markets.  But unlike the numbers in my academic models, the figures in my models at the hedge fund stood for something.  They were people’s retirement funds and mortgages.  In retrospect, this seems blindingly obvious.  And of course, I knew it all along, but I hadn’t truly appreciated the nature of the nickels, dimes, and quarters that we pried loose with our mathematical tools.  It wasn’t found money, like nuggets from a mine or coins from a sunken Spanish galleon.  This wealth was coming out of people’s pockets.  For hedge funds, the smuggest of the players on Wall Street, this was “dumb money.”

the math was directed against the consumer as a smoke screen.  Its purpose was only to optimize short-term profits for the sellers.  And those sellers trusted that they’d manage to unload the securities before they exploded.  Smart people would win.  And dumber people, the providers of dumb money, would wind up holding billions (or trillions) of unpayable IOUs. … Very few people had the expertise and the information required to know what was actually going on statistically, and most of the people who did lacked the integrity to speak up.

O’Neil was right to feel queasy – after all, she had become Moe.  All the high-frequency traders – who are lauded as brilliant despite often doing no more than intercepting others’ orders, buying desired products a millisecond before anyone else can, and re-selling them at a profit – are simply thieves.  Sometimes they are stealing because they are more clever.  Other times, they are stealing because their pre-existing wealth allows them to buy access to lower-latency computer servers than anyone else.

In any case, Calvin would disapprove.

calvin 9 - 20.png

Thankfully, O’Neil quit stealing (although she doesn’t mention returning her prior spoils).  After all, that is part of our blessing – we cannot change the past, but…

… and here it’s worth mentioning that Ludwig Wittgenstein was clearly incorrect when he wrote that “One can mistrust one’s own senses, but not one’s own belief.  If there were a verb meaning ‘to believe falsely’, it would not have any significant first person present indicative.”  Most physicists believe in free will and the mutability of the future, despite also knowing that, according to the laws of physics, their beliefs should be false…

… we can always fix the future.

(As a special treat – here is one of the most beautiful comic strips about opening your eyes to change.)