Tuesday, December 28, 2010

Top 10 ABBA songs

So, the year is almost over, which means it's all top-ten lists all the time. Lost in Transcription is no different. Do we really need a top-ten ABBA song list, you ask? I mean, aren't they dead – and Swedish?

Do we need an electric spin-the-bottle game? A motorized ice-cream cone? A combination fork and pizza cutter?

Yes, yes, and yes.

Let's get started.

10. Lovers (Live a Little Longer)
     The premise in this one is that a woman reads in the paper about a scientific study finding that romance increases lifespan. The science writing apparently moves her to burst into song. The high point is the sassy emphasis on she, indicating that the lead scientist on the study was a womyn.

9. Hey, Hey Helen
     Half feminist anthem, half catty anti-feminist anthem. She's a single mother, making it on her own, but her children are becoming irrevocably twisted by the absence of a male role model, and will probably wind up being serial killers. Was it worth it? Well, was it?

8. Love Isn't Easy (But it Sure is Hard Enough)
     Um, what?

7. Kisses of Fire
     Kisses of fire, burnin' burnin'
     I'm at the point of no returnin'

6. When I Kissed the Teacher
     Companion song to Don't Stand So Close to Me by the Police. That teacher is SO fired!

5. Bang-a-Boomerang
    Bang a boom a boomerang 
    Dum de dum dum de dum de dum dum
    Bang a boom a boomerang
    Love is a tune you hum de hum hum

4. King Kong Song
     A song about a guy writing a song about watching a King Kong movie. It's just like Inception. My mind is, like, totally blown.

3. I Do, I Do, I Do, I Do, I Do
     Awesome in part because this is actually the title, with five "I"s, five "Do"s and four commas, and in part because this was the song that my wife and I went back down the aisle to at our wedding.

2. So Long
     In which the narrator repeatedly asserts that she is NOT a prostitute.

1. Waterloo
     Extended "love is war: metaphor. You see, she is defeated utterly and completely by his romantic advances, just like Napoleon was defeated utterly and completely at Waterloo. Then, just like Napoleon, she contracts syphilis and dies alone on an island in the middle of the ocean.

Where are Chiquitita and Dancing Queen, you ask? Yeah, well, where are your mom and the – um – guy – um – who's not your dad?

Sunday, December 26, 2010

Douchebilly of the Magi

So, for Christmas my wife got me an Urban Dictionary mug with the definition of "douchebilly" on it:

A combination of a douchebag and a hillbilly. Not just a douchebag and not just a hillbilly but both! A Douchebilly! 
My ex-husband is a real douchebilly

Why, you ask? Two reasons. First, my wife is AWESOME! Second, this is a word that I made up at a bar, and a friend contributed to Urban Dictionary. It had its origin in an unbearably precious conversation about which Ivy League school was the douchiest. (If it occurs to you to ask, the answer is, "Whichever one you went to.") I suggested "douchebilly" as the answer posed to the question (asked in reference to me), "What do you call someone with two degrees from Harvard who wears old jeans and cowboy boots?"

I'm telling you this because I hope that you will start using this word all the time, and that you will mail me a nickel every time you do.

You might be wondering, do we really need more words, especially one like "douchebilly"? If the only use for "douchebilly" was to describe me at a bar, well, then you could argue it either way. But I also think that there's a real need for this word in American political discourse.

For reasons I do not fully understand, American politicians have to downplay their education, upbringing, and accomplishments, at least in certain contexts. If they are not able to do so, they risk losing the votes of people for whom it is critically important that their leaders be "like them." Bill Clinton grew up poor in Arkansas. He went on to tremendous academic achievements, but maintained a folksy, southern manner that was critical to his political success. I suspect that this was a calculated decision on his part. George Bush was a fifth-generation Yalie. Sure, he grew up partly in Texas, but in incredibly privileged circumstances, and finished high school at Phillips Adademy before going to Yale. The only way he talks like that is through deliberate construction. Even Barack Obama, while running for president, would periodically slide into this vaguely southern accent. Obama did not grow up in privileged circumstances, but the guy is from Hawaii, went to Columbia and Harvard, then moved to Chicago. What's up with that intermittent accent, then?

And when I say, "I do not fully understand," what I mean is that I am completely and utterly baffled by this. I don't want the people in charge of running the country to be like me. I want them to be better than me in every possible way. Maybe if we started referring to politicians as "douchebillies" whenever they actively misrepresent their educational and economic status, we could encourage them to portray themselves more honestly.

Don't misunderstand me. I am a linguistic relativist, and there is absolutely nothing wrong with a southern, Texas, or any other sort of accent. There is nothing inherent in any accent or dialect that indicates intelligence, or education, or the ability to ably lead. I am also sympathetic to the idea (although I don't personally feel this way) of having the country run by people who are truly representative of the overall population. The fact is, however, that accents in America are not just regional, but correlate strongly with education level and socio-economic status.

What bothers me is that we have a system ]stocked with a lot of "elites," as Fox News likes to say, but elites who pander to the public by pretending to be un-elite. Some are self-made, but many were born into privilege. I would love to see more people in government who are intelligent and hard-working, but who are not obscenely wealthy, and do not come from privileged backgrounds. There also seems to be a desire among the electorate to vote for such people. I'm not sure we're going to get a lot of them, though, so long as all you have to do to come off as a "man of the people" is drawl a little bit.

Like any good American, I have only a passing familiarity with the politics of other countries, so I do not know how wide-spread this phenomenon is. I am heartened, however, by the recent election in Brazil of Tiririca, a 45-year old television clown. Not television clown like Glenn Beck, but television clown like Bozo. He ran on a campaign with slogans like: "What does a federal deputy do? Truly, I don't know. But vote for me and I will find out for you." After being elected to congress, Tiririca had to take a literacy test, which he passed after displaying "a minimum of intellect concerning the content of a text despite difficulties in writing."

Tiririca – NOT a douchebilly – Just awesome.

Tuesday, December 21, 2010

From Friendster to Wikileaks: In Defense of Oversharing

So, I assume that by now you've heard about how Wikileaks is run by traitorous, anarchist terrorists who hate freedom. This is not going to be a post about how the US government's knee-jerk overreaction, its moronically overinflated rhetoric, or its Orwellian attempts to control what government employees can do in their own homes. You can probably guess my opinions, and others have written on the subject more knowledgeably and compellingly than I would.

I want to write about oversharing more generally.

I'm part of the generation that has spent much of the past five years hand-wringing and tooth-gnashing about how kids these days are posting pictures and videos of themselves drunk and naked, or with their mouths on things that – if only for hygienic reasons – mouths really shouldn't be on. We worry in print about these kids' futures. What will happen when a prospective employer or prospective spouse types their name into google twenty years from now? We worry that they fail to understand the consequences of youthful indiscretion in an age where every action is recorded and broadcast.

Don't get me wrong. I love my generation. Someday, when Ryan Seacrest is the NBC news anchor, he will hire James Frey to ghost-write a book about us called The Most Greatest Generation Ever! But somehow I feel that history will look back on us like the people who fretted about blue jeans, rock and roll music, and comic books. At least, I hope that is true.

I hope that the next generation, immersed as it is in oversharing, learns to admit that people are, well, human. The thing is, everyone does and says stupid things. Everyone always has. Yet, somehow, we've painted ourselves into this corner where we all have to pretend to be perfect (at least along certain, critical axes) in our public personas. People who aspire to politics carefully guard what they say for years, so as not to create a sound byte that can be used by their opponents. And somehow, we and the media jump on the bandwagon to vilify people for past indiscretions – even for things that we've done ourselves.

The result is that we have a country run predominantly by two sets of people: those who efficiently and ruthlessly fictionalize their own pasts, and those who have lived so carefully that you begin to question the extent to which they have lived at all.

I have done and said stupid and offensive and hurtful things. Am I proud of them? Of course not. But I hope that I have become smarter and better and kinder, and I hope to continue to become smarter and better and kinder in the future. Maybe if everyone's flaws and mistakes are cataloged on the internet, we can recognize that people are complicated and dynamic. Maybe we can learn to judge people based more on who they are and who they may become, rather than on random, isolated snapshots of who they were at some point in the past.

This is not a relativist argument. I believe that there are good people and bad people. I just think that we would all do a better job of identifying them if we did not have to place so much weight on the little slivers that leak out of the carefully constructed public shells.

The same argument goes for Wikileaks. The US government was embarrassed by the leaking of documents from the state department. Why? I honestly have no idea. Was anyone really surprised that internal memos spoke in frank terms about goals and objectives, about other countries and leaders? Was anyone really surprised to learn that the US uses its political muscle to promote the agendas of US corporations? Does anyone doubt that most of this is fairly vanilla behavior in the world of international diplomacy?

In a world filled with classified documents, fictions develop and take on a life of their own, spinning off their own morality. Governments pretend to be high-minded and moral, which turns out to be somewhat inconsistent with many of the things that real governments need to do in the real world. Then, something leaks out about some government activity, everyone pretends to be surprised and outraged, no matter how trivial or justifiable the infraction. Sometimes the infraction is only against this weird, artificial, fictional morality. But when the response is to enhance secrecy, to reinforce the fiction, it creates the opportunity for the government to do things that truly are horrific.

I have not spent a lot of time looking through the the latest Wikileaks documents, in part because most of them seem dreadfully boring. I'm glad that there are people who are reading these documents, pulling out the interesting bits, and cataloging them. It is conceivable to me that there will be pieces of information here and there that demand immediate action. However, my greater hope is that Wikileaks and its successors will allow us to make our peace with the messiness of government and diplomacy, so that we can focus our outrage on the big infractions.

Some of the Afghan leaks revealed certain atrocities, like the killing of civilians. Most of the reactions that I saw were some version of "It's just a few bad apples," "Leaking this will ruin our relationship with the Afghans," or "America is evil," all of which miss the point. I believe that the point should be that when you take tens of thousands of kids, some just barely out of high school, and put them halfway around the world in hellish conditions, bad things are going to happen. At some frequency, civilians, including children, are going to be killed. We need to focus on training and policies that keep those incidents to an absolute minimum. AND, we need to understand that this is a part of war, and part of the reason that military intervention needs to be the option of last resort. Secrecy leads to the romanticization of war. Currently, it seems that each generation has to rediscover the horrors of war for itself. Maybe additional transparency would let us hang on to those lessons for longer.

I was not in favor of Rand Paul (although his election has the silver lining of future comic potential), but I would have liked to see the media coverage focus more on his opposition to civil-rights legislation, and less on college pranks involving the "Aqua Bhudda." Maybe the future will contain copious footage of every Senate candidate being young, naked, and drunk. If we become desensitized to the salaciousness of it all, perhaps the media will cover the substantive philosophical and policy issues that distinguish the candidates.

The future that I am hoping for is not an entirely comfortable one, especially for those of us who came of age before the camera-phone panopticon. But, I want to trust the next generation to turn overshared lemons into lemonade.

In Arthur Miller's A View from the Bridge, the protagonist, Eddie Carbone lives with his wife, Beatrice, and his niece, Catherine. They house two of Beatrice's cousins, who are are in the country illegally for work. When Catherine falls in love with one of the cousins, Rodolpho, Eddie's romantic desires toward his own niece are revealed, and, acting out of jealousy, he turns the cousins over to immigration. The other cousin, Marco, has a starving family back in Italy, and deportation spells disaster for him. Eddie's betrayal of the cousins ruins him in his community and his family. In the end, Eddie and Marco fight in the street. Eddie pulls a knife, but dies after then knife is turned on him.

The family lawyer and narrator, Alfieri, closes with this:
Most of the time we settle for half and I like it better. But the truth is holy, and even as I know how wrong he was, and his death useless, I tremble, for I confess that something perversely pure calls to me from his memory – not purely good, but himself purely, for he allowed himself to be wholly known and for that I think I will love him more than all my sensible clients. And yet, it is better to settle for half, it must be! And so I mourn him – I admit it – with a certain . . . alarm.

Saturday, December 18, 2010

State-by-State FST(ish) Values: The Structure of Racial Diversity in America

So, in the world of population genetics, as in the real world, people are often interested in diversity, and in how that diversity is distributed. In biological contexts, quantifying these things is important because it gives us insight into the processes – like reproduction, migration, selection, etc. – responsible for generating the observed patterns of diversity.

Here I look at how racial diversity is apportioned among counties (or county equivalents) in each of the 50 states, using two different statistics derived from the population genetics and ecology literature. Hit the jump for the analysis, and scroll down to skip the introduction and go straight to the maps.

Monday, December 13, 2010

Where stalkers become friends: Geo-tagging on Flickr

So, you probably remember this from the most recent episode of The Mentalist / Bones / Castle / Criminal Minds / Numb3rs:

SASSY JUNIOR DETECTIVE: Nothing. All of our leads have dried up like Cher's ovaries.
GRUFF SENIOR LAW ENFORCEMENT OFFICIAL: We've got to wrap this thing up. I've got the mayor breathing down my neck.
MAYOR: Hhhhhhhhhh. Hhhhhhhhhh.
G.S.L.E.O.: And now he's drooling.
S.Y.P.D.: We'll keep after it, but we're a bit short-handed after half of the department was beheaded and, ironically, eaten by The Vegan Killer.
G.S.L.E.O.: I don't want excuses. I want someone behind bars.
S.J.D.: You and my alcoholic ex wife.
SOCIALLY INAPPROPRIATE GENIUS: Actually, we know that the comptroller picked up his dry-cleaning on Wednesday. The same Wednesday that the chimney sweep showed up at the wedding in a curiously un-besooted pair of dungarees. Thus, the heiress was murdered by the delivery man who brought the Martinizing agents to the dry cleaners, also on Wednesday. Also, he was her half brother.
And, scene.

Thanks to research just published in PNAS by a group out of Cornell, we are now one step closer to living in a dystopian panopticon in which our associations can be inferred by any monkey with a laptop. Soon, Patrick Jane will be back to doing parlor tricks, Richard Castle will be back to making a living as an imaginary writer, and everyone else will be in prison for consorting with each other.

More specifically, the authors investigate whether they can infer a social connection between two people on the basis of their having been at the same place at the same time on multiple occasions, using data from Flickr. They look at 38 million pictures that contain both a timestamp and a geo-tag, indicating the time, latitude, and longitude at which the picture was taken. They define a co-occurrence of two Flickr users as having pictures taken within a time t of each other and within the same geographic region: a square(ish) region of length s latitude or longitude degrees on each side. The social dimension of the data comes from Flickr's networking functions, which allow users to specify their links to others. 

They find that the greater the number of co-occurrences for a pair of users, the more likely it is that they are friends. This is not particularly surprising, although the magnitude of the effects are quite striking. For example, here is one graph from the paper:

Part of Figure 2D from the paper. In this case, the spatial range for co-occurrence is defined by s = 1.0 degrees (about 55 miles by 65 miles where I live). The different curves correspond to different time windows.
The probability that two randomly selected Flickr users are friends is less than 1 in 7000 [Corrected. Original post said 1 in 700]. However, if two users have uploaded pictures from the same 1 degree by 1 degree region within a day of each other on five different occasions, there is nearly a 60% chance that they are friends. If they have done it more than eight times, the chance is more than 90%.

In other words, if you and your accomplice both upload photos from the same dry cleaner every Wednesday, even a non-genius will be able to figure out that you know each other. This is how Strangers on a Train will end in the 2032 remake starring Freddie Highmore and Abigail Breslin.

For those interested in looking at more pretty graphs, the article is Open Access, and can be found here.

For those interested in mounting a futile defense against the Orwellian State, more information about geo-tagging and privacy can be found here, including ways in which you may inadvertently be sharing location information without meaning to.

Crandall, D., Backstrom, L., Cosley, D., Suri, S., Huttenlocher, D., & Kleinberg, J. (2010). Inferring social ties from geographic coincidences Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1006155107

Saturday, December 11, 2010

You and I are going to the top of the charts!

So, a "supergroup" in the UK provided the latest British entry in the ongoing spectacle that I like to call, "What's Up with People?" This, from the guardian, via Boing Boing:

Later today, Pete Doherty, the Kooks, Billy Bragg, Imogen Heap, Orbital and many more will gather in a London studio, collaborating in a bid for this year's Christmas No 1. But the strangest bit is not the team-up: it's that they are not recording a single note. The ad hoc supergroup is assembling in support of Cage Against the Machine, a charity campaign to take John Cage's infamous 4'33" – a composition of pure silence – to the top of the Yuletide charts.

So many things.

First, referring to a collection of musicians as a "supergroup," when the headliners are Imogen Heap and the Kooks is like referring to the Pittsburgh Pirates' "All-Star lineup."

Second, doesn't a charity campaign to take a single to the top of the charts sound a bit like a McDonald's "charity" campaign to sell a lot of Happy Meals?

Third, am I going to be listed in the credits for my performance on the Jingjingler? Are you going to receive royalty payments for your performance on the Floofloober?

Fourth, WTF?

Okay, to be fair, it seems that the proceeds from the record will be going to actual charities. And, also to be fair, I did not actually stand in the studio not playing my Jingjingler for four and a half minutes. I have no information on the whereabouts of you and your Floofloober on Monday.

If you're like me – and my particular personality disorder makes me assume that you are – you have no idea what is going on here. If you're in the UK, you're probably familiar with the backstory, but if not, here is my understanding of the situation. There is a TV program called X Factor, which is the Simon Cowell's replacement for Pop Idol, which is the off of which American Idol was spun, along with a host of other things. Apparently, for three or four years running, the winner of X Factor would release their record, and it would shoot to the top of the downloads chart around Christmas.

Eventually, some people got fed up, and last year there was a campaign to get people to buy the profanity-heavy "Killing in the Name" by Rage Against the Machine in late December, specifically to keep X Factor winner Joe McElderry out of the top Christmas song spot. And it worked, by something like a factor of 10.

So, this year, there are multiple copy-cat campaigns designed to keep this year's X Factor winner out of the top spot, including Cage Against the Machine, as well as an apparently much more popular one focused on the 1963 hit "Surfin' Bird." In addition to being derivative of last year's "Killing in the Name" campaign, Cage Against the Machine is also highly reminiscent of a drive from just a couple of months ago to sell copies of "2 minute silence," a track containing two minutes of silence, a reference to two minutes of silence observed on Remembrance Sunday (think "Veterans' Day). Apparently the dance group Orbital (think "Neifi Perez"), which is part of the Cage Against the Machine group, released a remix of one of their tracks back in 1994 that consisted entirely of four minutes of silence.

An excerpt from my new novel, 947 Pages. I will be starting a 501(c)3 dedicated to getting onto the New York Times bestsellers list in time for Intergalactic Tutu Day.
Let me be clear. I am 100% behind loosely organized groups of people doing things that are snarky and pointless. And I'm not questioning that the money Cage Against the Machine donates to the British Tinnitus Association will be well spent. I guess. Also, this is not a complaint against conceptual art.

What this is a complaint about is the smug recycling of conceptual art that, in my view, completely misses the point. When Duchamp calls a toilet a fountain, it is a statement – or a question – about what constitutes art. It is a big moment, and one that contributed substantially to a change in our collective perceptions. If I come along 90 years later, take a toilet and call it a fountain, it is just a lazy attempt to embezzle some cultural capital.

From xkcd:

Ni, Mr. Cage., Ni.

Thursday, December 2, 2010

The Distribution of Dominance

So, as you have no doubt surmised from the title of this post, the cash-strapped Republican Party is going to start using their abundant frequent "flyer" points to pay their debts.

I'm kidding, of course. The GOP doesn't pay its debts!

Actually, we're going to talk about a paper just out in Genetics by Aneil Agarwal and Michael Whitlock. They provide a very thorough analysis of data on the fitness effects of homozygous and heterozygous gene deletions in yeast.

But let's back up for a minute first.

The authors are interested in understanding the distribution of dominance, in the population-genetic sense. Traditionally, the dominance is represented by h, and the strength of selection by s. Usually, we define the fitness of the wild-type (hypothetically not carrying any mutations) as 1. Then, we consider the fitness effect of a mutation in a particular gene. In this case, we're going to focus on deleterious, or harmful mutations, which reduce fitness. If an individual carries two copies of the deleterious mutation, they have a fitness of 1-s, so that small values of s mean weak selection, and large values of s mean strong selection. The dominance refers to the relative fitness of an individual carrying only one copy of the deleterious mutation. This heterozygous fitness is 1-hs. If h equals 1, the deleterious mutation is completely dominant, meaning that having one copy of it is just as bad as having two. If h equals 0, the deleterious mutation is completely recessive, and having one defective copy of the gene is just as good as having two functional copies.

So, what is a typical value of h? Does it depend on s? How much does it vary from gene to gene? The conventional wisdom is that most deleterious mutations are recessive. This is why you should not have children with close relatives. I carry a bunch of recessive mutations, as does my wife. As long as we have different ones, our son inherits a bunch of mutations – but only one copy of each – so they're recessive in him as well. If we were closely related, we would carry many of the same mutations, and there would be a decent chance that our son would inherit two defective copies of the same gene, which could have various health consequences.

Charles Darwin and his first cousin Emma Wedgwood were married in 1839. 170 years later, they were portrayed by real-life-non-first-cousin couple Paul Bettany and Jennifer Connelly (not pictured).

However, population geneticists don't care about things like this just because of the implications for human disease. Dominance has a major impact on the eventual fates of individual mutations, and can influence other evolutionary processes, like speciation. Often, in order to model some other process, we have to make some sort of assumption about the distribution of fitness effects of mutations. Traditionally, a researcher would pull this distribution out of his or her asc. This is one of the biggest contributions that this paper will make to the field. It provides a nice, empirically based distribution of dominance effects that can feed into other evolutionary studies.

The results also confirmed (with much greater confidence than was previously the case) the relationship between h and s which had been suggested by some previous studies. They find that larger values of s tend to go with smaller values of h. Consistent with the conventional wisdom about not marrying your cousin, strongly deleterious genes tend to be pretty recessive. More surprisingly, most mildly deleterious mutations had fairly high h values. In fact, the mean value of h over all deleterious mutations was 0.8 – quite dominant. However, when the average is weighted by the fitness effect s, it drops to 0.2.

The authors also point out that this negative relationship between h and s has implications for the evolution of dominance. This pattern is most consistent with theories in which dominance is shaped by indirect selection. For example, deleterious mutations might be recessive if the protein produced by the gene were selected for overexpression to enhance a metabolic pathway, or to buffer the performance of that pathway in certain environments. Then, loss of one copy of the gene encoding that protein might not have a major effect on function (half of too much being still enough). Alternatively, recessiveness could come from feedback mechanisms that upregulate the functional copy of the gene when not enough of the gene product is being made.

The point is that in either of these cases (among others), recessiveness is driven by selection to maintain the function of the gene. The more important the gene is (the larger the value of s associated with it), the stronger this selection will be, and the more recessive deleterious mutations will become. Therefore, mechanisms like these predict the observed negative relationship between h and s.

On a historical note, this type of buffering process was proposed by one of the giants of population genetics, J. B. S. Haldane way back in 1930. Haldane passed away on December 1, 1964.

R. I. P., J. B. S.

Agrawal, A., & Whitlock, M. (2010). Inferences About the Distribution of Dominance Drawn from Yeast Gene Knockout Data Genetics DOI: 10.1534/genetics.110.124560

Tuesday, November 30, 2010

Concerning a Way for the Prolongation of Humane Life

So, Deare Readers of this Blogue, I hope that you will indulge me in reporting on an Interesting Idea published by the Royal Society in their Philosophical Transactions. I hope, Deare Reader, that you may also see fit to join me in Lauding said Society for having made their entyre back catalogue freely available to the publick this Month of November.

The Publication in Question, titled An Extract of a Letter Written by Monsieur de Martel of Montauban to the Publisher, Concerning a Way for the Prolongation of Humane Life, together with Some Observations Made in the Southern Parts of France, English'd as Follows, contains the author's reflections on the Causes of the Debilitation of Nature's strength in the course of man's life, and how these Causes might be Ameliorated, leading, naturally, to a means of achieving Eternal Youth through Medical Science.

The author agrees with the illustrious Messrs. Bacon and Sanctorius that the extinction of the natural heat and dessication of the Radical humour, as previously understood by Philosophers, seem not sufficient explanation for the causes of Age. However, Monsieur de Martel disagrees with Sanctorius's assertion that "the Fibres do dry up, that they can no more be renew'd," noting that even old Oxen have at certain times more or less marrow (though not, he is quick to point out, owing to the cycles of the moon).

Blood, claims Monsieur de Martel, is the Principle of Life, but notes that a Man typically has no Shortage of Blood when he dies. What causes this man to age, then, is that the Veins and Arteries which inclose the Blood, much like the Chymists Furnace, develop apertures, which, being insufficiently repair'd, do ease the dissipation of the igneous particles, such that they abandon the Blood. He reasons, then
 As in Stuffs and Cloth (whose woof is in manner like that of the Tunicles) the Threds by wearing do loosen and break, insomuch that many holes are made in it as in a Sieve. So that, if we had the Art to reinforce and to strengthen anew those Coats and Membranes, that they might not let slip what maketh the blood vital, the life would be preserved perpetually. . . . There is no reason to despair of finding out such Medicins, or Ailments, as are proper to strengthen the Coats and Membranes of the Vessels, so that they may at all times retain the fiery and spirituous corpuscules of the blood, as well as in the time of Youth.
The author also reports on the method of making Muscadin Wine in Frontignac.

For those wishing further to pursue Monsieur de Martel's ideas on the Acquisition of Eternal Youth through preservation of the blood's vital igneous particles, or those wishing to instruct their Slaves on how best to produce a nice Muscadin, the citation information is:

de Martel, M. (1670). An Extract of a Letter Written by Monsieur de Martel of Montauban to the Publisher, Concerning a Way for the Prolongation of Humane Life, together with Some Observations Made in the Southern Parts of France, English'd as Follows Philosophical Transactions of the Royal Society of London, 5 (57-68), 1179-1184 DOI: 10.1098/rstl.1670.0020

Wednesday, November 24, 2010

Irony Alert: Marc Hauser on moral judgments

So, PNAS has just published a brief exchange on the nature of moral judgments, including a letter where one of the coauthors is the man who put the a** in a**ertainment bias.

Marc Hauser is a Professor in the Psychology Department at Harvard. He made a name for himself publishing a variety of behavioral and cognitive studies on both humans and non-human primates, with the goal of understanding the evolutionary origins of human cognition, including complex traits such as language, economic decision-making, and moral judgments. More recently, he has made a name for himself by allegedly falsifying data and allegedly bullying the people in his lab who naively thought that the data published by the group should be . . . I don't know . . . NOT falsified. I won't repeat what this more recent name that he's made for himself is, as it would violate the norms of internet civility. Over his career, Hauser has published something like 200 articles and 6 books, many of which probably contain certain things that are not entirely false. At the moment, he is on leave from Harvard, following an investigation's finding him solely responsible for 8 counts of scientific misconduct. Presumably, he is working on his next book, allegedly titled Evilicious: Explaining Our Evolved Taste for Being Bad.

Snarking aside, the two letters that were just published follow from an interesting article published in PNAS earlier this year, where Hauser is the third of four co-authors. For those not familiar with authorship conventions in biology and related fields, here is what is typically implied by the order of authorship on a four-author paper. The first author probably did all of the experiments. The second author helped with some of the experiments, and/or some of the data analysis. The third author probably didn't directly participate, but contributed ideas and/or reagents and/or equipment. The last author probably runs the lab where the experiments were done. In fact, the other three authors are all at the other Cambridge, in England, where the experiments were actually done. I point all this out just because I don't want to leave the impression that we should be suspect of the results in the paper just because Hauser's name is on it.

The original paper, which can be found and freely downloaded here, tests the effect of enhancing serotonin activity on a variety of tasks or decisions, some of which had a moral flavor. Serotonin enhancement was achieved by giving some of the subjects the drug citalopram, which is a selective serotonin reuptake inhibitor (SSRI), like Prozac or Zoloft. The finding was that enhancing serotonin made subjects less willing to take an action that required them to inflict harm on another individual in an emotionally salient context.

This work fits in with a substantial literature on moral dilemmas. I'll just briefly outline the gist of that literature here in the context of one particular dilemma that often makes an appearance in these studies. The scenario is this: there are five people tied to a train track, and there is a train rushing towards them. You have the opportunity to save them, by stopping the train or switching it to a different track, but the only way to do it involves killing one person. What do you do?

Most people find that they have two conflicting impulses. On the one hand, killing one person to save five makes sense from a utilitarian perspective. That's four fewer dead people. On the other hand, you are the one who has to kill the one person, and most people feel a moral repulsion to killing someone, even if it is for the greater good.

In these studies, which of the two impulses seems to win depends on how personal the killing is. If all you have to do is pull a switch, and the train will go on another track, which, for unknown reasons, has one person tied to it, the killing is fairly impersonal, and many people will choose this utilitarian, four-fewer-dead-people option. On the other hand, if the only way to stop the train is to chop off someone's head and throw it through a magical basketball net woven of human entrails (I'm making this up), many people will find this too emotionally and morally problematic, and will let the train go on its merry five-corpse-making way. Researchers have mapped out a whole continuum between these two extremes: pushing someone off a bridge with your hands is more emotionally salient (and therefore less morally acceptable) than pushing someone off a bridge with a stick, and so forth.

What the original paper finds is that giving someone an SSRI does not have much effect on decisions that are morally neutral, or where the harm that must be inflicted is impersonal (like throwing a switch to divert the train). However, in cases where one decision would require the subject to harm someone in a personal and emotionally salient way (like pushing them off the bridge with their bare hands), the SSRI seems to enhance the emotional/moral aversion to taking that action.

So, in addition to nausea, insomnia, and diarrhea, add to the list of possible side effects of antidepressants: "may reduce willingness to harm others in emotionally charged situations." Maybe Charlie Sheen should be on one of these.

The letters commenting on the original paper can be found here and here, but require a subscription to PNAS to access. I wouldn't go to great lengths to get them, however. There is some quibbling about terminology – driven more by a commentary on the original article than by the article itself – and some tiresome academic "Get off my lawn!" moments, but probably nothing of interest to most of the reader(s) of this blog.

Crockett MJ, Clark L, Hauser MD, & Robbins TW (2010). Serotonin selectively influences moral judgment and behavior through effects on harm aversion. Proceedings of the National Academy of Sciences of the United States of America, 107 (40), 17433-8 PMID: 20876101

Monday, November 22, 2010

Neural compensation and autism

So, a study just published in the Proceedings of the National Academy of Sciences uses fMRI to compare the neural response to biological motion in three groups of subjects: people with autism, unaffected siblings of people with autism, and a control group, who have neither autism nor family members with autism. This is a fairly standard sort of thing to do when people study disorders that, like autism, have high heritability, and therefore presumably a significant genetic component. There were some interesting findings in this paper, though, that make it stand out. In particular, the authors identify a set of brain regions that show elevated activity specifically in the group of unaffected siblings, and call these "compensatory" regions.

The idea is this. People with autism have a set of genetic variants that give them a predisposition for developing autism. Straightforward, right? Presumably, the siblings of people with autism carry many of these same genetic variants, but there is some reason why they don't develop the disorder. Of course, one possibility is that they do not, in fact, carry the autism-causing genetic variants. Another possibility, raised by this paper, is that they do have genes that predispose them to autism, but that some compensatory mechanism has maintained normal neural development in the face of this genetic predisposition. This compensation could be developmental – in that some sort of canalization mechanism sets in when it somehow senses that brain development is going off track. Or, it could be genetic, in that the unaffected siblings also possess genetic variants (presumably at other genetic loci) that shift them back towards normal development.

Here's Figure 3 from the paper. The top panel shows the "state" regions. Those are brain regions that show differential activation in the autism group (reduced activity in response to viewing biological motion). The middle panel shows the "trait" regions, which are the regions with reduced activity in both the autism group and the group of unaffected siblings. The bottom panel shows the "compensatory" regions, which show elevated activity specifically in the group of unaffected siblings.

The brain regions identified as "state" regions are those that are typically identified as regions of reduced activity in autism – a nice validation. The two "compensatory" regions are the right posterior superior temporal sulcus (pSTS) and ventromedial prefrontal cortex (vmPFC). Both of these regions have been associated with social perception and cognition. Note that both of these regions also appear in the "state" category.

So what does that mean? Well, that means that there are certain regions within these two structures that show reduced activity in cases of autism. There are other regions within the same two structures that are not impaired in autism, but show enhanced activity in unaffected siblings.

Like much of the most interesting science, this paper raises more questions than it answers, and there are many conceivable explanations of these patterns. The results suggest a number of interesting avenues for future research, however.

The paper can be found here. It is an open-access article, so you don't need a subscription to PNAS to get it.

Update: Full citation

Kaiser MD, Hudac CM, Shultz S, Lee SM, Cheung C, Berken AM, Deen B, Pitskel NB, Sugrue DR, Voos AC, Saulnier CA, Ventola P, Wolf JM, Klin A, Vander Wyk BC, & Pelphrey KA (2010). Neural signatures of autism. Proceedings of the National Academy of Sciences of the United States of America PMID: 21078973

Thursday, November 18, 2010

Snake parthenogenesis III: The final chapter

So, I really had no intention of doing three separate posts on virgin birth in snakes, and I sincerely hope – for your sake as well as mine – that this finishes off the topic for the time being. In the first installment, we talked about this Boa constrictor that had given parthenogenetic birth to 22 babies, and some of the interesting genetics raised by that observation. In the second installment, we noted some species that undergo paternal genome exclusion, which seems like a similar phenomenon.

I was then pointed toward the case of the whip-tail lizard in a note from John Wilkins, who not only has an AWESOME name, but also runs possibly the best blog out there on philosophy and evolution. If you're not already reading his blog, I highly recommend it.

The phenomenon of non-virgin virgin birth may not be all that rare or unexpected among herps (amphibians and reptiles). For example, in the case of the whip-tail lizards, some species consist only of females, all of whom reproduce parthenogenetically. The interesting thing is that mating is required in order to trigger this parthenogenetic developmental process. So, how does that work, if there are no males? What happens is that these females will mate with males of another species, and it is likely that the diploid, parthenogenetic egg starts developing only when it receives a biochemical signal that depends on physical contact with the sperm.

I spoke about this with Andrew Singson, who studies cell-cell interactions, particularly between gametes. He noted that the requirement for physical stimulation of the egg by sperm is actually quite widespread. In many birds, for example, polyspermy, where more than one sperm interacts with the egg, is required. Only one of these sperm fuses with the egg and contributes genetic material to the offspring. However, that single sperm may not provide enough of a signal to flip the egg's developmental switch. Before the process of embryonic development can start, many other sperm have to physically interact with the egg in a sort of wing-man role. Opportunities for analogy abound, but fortunately – for your sake as well as mine – other demands prohibit me from plumbing their depths at the moment.

Saturday, November 13, 2010

Snake parthenogenesis II: Non-virgin virgin birth

So, in the last post, we went through some of the strange and interesting things associated with the Boa constrictor that gave parthenogenetic birth to 22 baby Boas. It turns out there's yet another crazy thing going on here. Etymologically speaking, parthenogenesis means "virgin birth." It is a combination of parthenos (παρθένος), meaning "virgin," like the parthenon, and genesis (γένεσις), meaning, well, genesis.

The thing is, though, while it seems clear that the baby Boas' genetic material comes entirely from the mother, she's likely not really a virgin. I don't mean that she's a born-again virgin who had some had some wild times back in snake college, repented, then ran for Senate. Instead, it appears that she only gave birth after being housed with a male snake. Of course, it's only two litters, so it could well be a coincidence. On the other hand, it could be that fertilization was required to initiate development of the diploid eggs produced by the female.

There is a somewhat related phenomenon of paternal genome loss that has been identified in several different species of creepy crawlies, including at least some species of Phytoseiid mites (click here for non-English text, but drawings of them preying on other mite species), scale insects, and sciarid flies. Typically, paternal genome exclusion is limited to males, which start of diploid, but then lose their paternally inherited genome at some point during development, often living much of their lives in a haploid state. These and related phenomena are nicely covered in chapter 10 of Genes in Conflict by Austin Burt and Robert Trivers. Of course, the difference here is that the snakes have two full maternal genomes. Also, we don't really know if they received, and then jettisoned paternal genes, or never got them in the first place.

It also bears some similarities to one of the mechanisms by which uniparental disomies arise in humans (among others). Normally, meiosis results in one copy of each chromosome going into each gamete. With some frequency, though, they don't sort out correctly, and two aneuploid gametes wind up being produced, one with an extra copy of one chromosome, and one that is missing that chromosome altogether. If one of these gametes winds up contributing to the offspring, that offspring may wind up missing one copy of a chromosome (e.g., the X chromosome in Turner's syndrome), or with an extra copy of a chromosome (e.g., the X chromosome in Kleinfelter's syndrome, or chromosome 21 in Down syndrome). Another possible outcome for the extra chromosome case is "trisomy rescue," where the zygote somehow recognizes the presence of the extra chromosome and kicks out one of the three copies.

There are a couple of different ways that this trisomy rescue can happen. Let's say the extra chromosome came in with the egg. If one of the two maternal copies is kicked out, you wind up back at the standard diploid genome. On the other hand, if the paternal copy gets kicked out, you have the standard number of chromosomes, but a uniparental disomy. If the chromosome contains one or more imprinted genes, this can have various developmental consequences.

So, one possibility is that this female snake, for whatever reason, produces diploid eggs. Fertilization triggers development, but then a triploid rescue mechanism kicks in. The key thing is that it would need to be kicking in before fusion of the maternal and paternal pronuclei, since it seems to be the paternal genome that goes missing in every case.

Or this could all be related to the fact that the males snakes housed with this female in 2009 and 2010 were all huge General Ripper fans.

Update: One more follow-up post here.

Wednesday, November 10, 2010

Parthenogenesis: now in snakes!

So, as if my friends on the religious right needed more reasons to be afraid of snakes, now they are threatening to undermine the nuclear family, which is clearly defined in the Bible as a mommy, a daddy, and two overachieving children. A recent paper in Biology Letters has studied two litters of offspring from a female Boa constrictor, totaling 22 baby snakes. All of the babies are female, and all of them have a rare, recessive color trait that is exhibited by the mother, but by none of the possible fathers.

What the researchers were able to demonstrate was that these baby snakes do not have a father at all. Rather, they are all parthenogenetic products of the mother. The researchers typed the offspring at eight microsatellite loci, and all the daughters were homozygous at all of the loci, matching in each case one of the two maternal alleles.

Note to self: No Boa constrictors on the island!

Several interesting things here. First, the implication is that these daughters are genome-wide homozygotes. This suggests a complete absence of lethal recessive mutations in the mother's genome. This seems surprising, but let's do a quick back of the envelope calculation. Let's assume there are about 10,000 genes in the snake where a loss-of-function mutation is lethal. Say the coding region for each gene is about 1000 nucleotides long, and that, say 1/10 of those nucleotides are fixed, in the sense that a mutation obliterates the gene's function. That would be a lethal mutational target of 100 nucleotides for each gene. Assuming a mutation rate of 10-9, mutation-selection balance at each locus would have loss-of-function mutations circulating at a frequency of about 1 in 3000. So, we would expect each maternal half-genome to contain, on average, about 3 lethal recessive mutations. Assuming that those mutations are Poisson distributed, there is about a 5% chance that it would contain no such mutations. So, not super likely, but not out of the question either. And, that probability would be higher if the mutational target is smaller, or if the Boa population has undergone significant inbreeding, which would have driven the frequency down.

Second, there's a weirdness with the sex chromosomes. Now, in mammals, sex is determined by whether you have two X chromosomes, in which case you are a female, or an X chromosome and a Y chromosome, in which case you are a male. Everyone inherits an X chromosome from their mother, and you inherit either an X or a Y from your father. So, if you don't have any sons, it's not your wife's fault. Snakes also have chromosomal sex determination, but use a ZW system. Males have two Z chromosomes, while females have a W and a Z. It turns out that every one of the parthenogenetic daughter snakes is actually WW. That's some serious weirdness on which I have little insight. The one thing we can say is that you would never see a YY male. The Y chromosome is a shriveled little thing that does not do much other than tell you to be male, while the X does all the work. The snake W chromosome, on the other hand, is a real chromosome, that is, in fact, impossible to distinguish from the Z under the microscope.

Finally – and this is the reason I'm writing about this here – this tells us something about genomic imprinting. In mammals, there appear to be at least 50-100, possibly as many as 1000 imprinted genes, which are expressed from only one of the two copies. So, if there are 200 imprinted genes, there will be, say, 100 of them that are expressed only from the paternally inherited copy. If you produce parthenogenetic offspring, they will inherit two maternally derived alleles at each of these loci, which will be like having 100 of your genes knocked out, and is almost guaranteed to be lethal. In fact there are a number of genetic disorders in humans that result from uniparental inheritance of just a small subset of imprinted genes, and these produce fairly severe phenotypes. So, the fact that these parthenogenetic snakes appear to be perfectly viable implies that there are few – or quite possibly no – imprinted genes in this species.

Booth, W., Johnson, D., Moore, S., Schal, C., & Vargo, E. (2010). Evidence for viable, non-clonal but fatherless Boa constrictors Biology Letters DOI: 10.1098/rsbl.2010.0793

Update: Two follow-up posts here and here.

Sunday, November 7, 2010

The flux capacitor in your brain

So, you already know that Friday was the 55th anniversary of Doc Emmett Brown's falling off his toilet, hitting his head, falling unconscious, and coming up with the flux capacitor, which not only allowed Teen Wolf to make out with Caroline in the City, but is singlehandedly responsible for the fact that anyone still remembers what a DeLorean is. How do I know you know? Because you spent all week baking this cake.

It took the good doctor thirty more years to get his idea working, so that time travel first became practical in 1985. However, it turns out that, as usual, natural selection got there first. There is an article in press in the Journal of Personality and Social Psychology that presents experimental evidence for precognition or time-reversed instances of causation. The preprint is available here, from the website of the author, Daryl Bem.

Bem is fairly well known, particularly for his early work in social psychology on the "self-perception theory of attitude change," which is basically that we learn about ourselves in much the same way that someone else might. For instance, say I hate peanut butter sandwiches. But then I eat a peanut butter sandwich every day for a month. I then look at myself, and say, "Hey, that handsome fellow really seems to like peanut butter sandwiches." This is the academic basis of that damn Stuart Smalley sketch. He is also responsible for the "Exotic becomes erotic" theory of the formation of sexual orientation.

The paper presents the results of nine experiments, each of which tested for awareness of future events. In the first experiment, subjects were told that there was a picture behind one of two (virtual) curtains, and they were supposed to guess which one. When the picture was just a picture, they picked the right curtain 49.8% of the time, which was not significantly different from the expected 1/2. But, when it was an EROTIC picture, they picked the right picture 53.1% of the time, which, while not particularly overwhelming, is apparently statistically significant at the p=0.011 level. There are eight more experiments on retroactive priming, precognitive avoidance of negative stimuli, and retroactive habituation and induction of boredom. The article also includes discussions of random number generators, pseudorandom number generators, quantum mechanics, and Alice in Wonderland.

So, if you read to the end of this blog post in the hopes that I would tell you what the hell is going on here, I'm afraid I'm going to leave you disappointed. Although, to be fair, your precognitive boredom should have known that I would have nothing intelligent to say sometime around the slash-fic link, in which case you've long since moved on. I'll just lay out the obvious candidates. First, it's pure chance, although getting consistent results across nine experiments makes this seem not terribly likely. Second, these are nine of a much larger number of experiments, most of which did not conform with the experimenter's expectations, and were therefore viewed as flawed and discarded. Third, there is actual manipulation of the experiments and/or data, either consciously or unconsciously. Fourth, there is some small possibility of some crazy-cool, Dune-esque, Jedi stuff going on here that is someday going to completely revolutionize how we understand cognition, causation, and time.

Personally, my money is on some combination of options two and three. Even without any type of fraud going on, I think it is incredibly easy for us as scientists to be so convinced that we know what the outcome of an experiment is going to be, that we can massage things around the margins. Keep in mind that these effects are only a couple of percent. On the other hand, even the smallest possibility of number for justifies, to me, the entire institution of tenure. This is exactly the sort of nut-bag research program that you can only pursue if you have absolute job security. I wish that more tenured faculty pursued research like this.

Thursday, November 4, 2010

What's the Swedish internet made of?

So, if you've never played with Google Analytics, I highly recommend it. It is awesome. You can see who came to your website, where they came from, and what they were actually trying to find when they fell victim to your amateurish attempts at search engine optimization ("Sexy Megan Fox bikini pix!! Sexy Megan Fox bikini pix!!"). You can sort them by operating system, web browser, social security number, or alphabetically by password. It's the second best way to waste huge amounts of time on your computer – the best if you work at a place with content filtering.

For example, last week, I got a hit from Georgia. Not the Coca Cola and Peaches one; the Stalin and fighting-with-Chechens one. This person got to the site by searching for "ჯონ ვილკინს" on Google, which I can only assume is Kartuli for "People's 2010 rankings of the top 100 sexiest evolutionary biologists." It's an incredibly efficient language.

A couple of days ago, I got a hit from Sweden. Yes, the ABBA and Volvo one. In this case, the interesting thing was the service provider: "handelshogskolan." Now, we know that the American internet is a series of tubes. Well, apparently so is the Swedish internet, but their tubes are made out of pig intestines. Sadly, that means that from now on, when I hand my e-mails to my hamster, Hedwig, and send her off, I'm going to have to mentally revisit that whole Richard Gere thing.

Wednesday, November 3, 2010

Democrats investing in kleenex, socks in wake of midterm elections

So, yesterday's election turned out rather poorly for Democrats.

On a completely unrelated note, I wanted to draw attention to a paper published in Biology Letters that investigates the ejaculatory strategies of male flour beetles of the species Gnatocerus cornutus. As in many species, G. cornutus males engage in pre-copulatory sexual selection, where males fight, and the winners get privileged access to mates. The researchers, at Okayama University, find that the losers of these fights appear to shift to a strategy that focuses more on sperm competition, through increased "ejaculatory investment." Winning a fight has no effect on the number of sperm "transferred" during a copulatory event. However, losers show two effects that indicate a strategic shift: they are less aggressive towards other males, and they increase their sperm transfer by nearly two-fold.

By the fifth day after losing the fight, both aggressiveness and sperm-transfer levels return to normal, so we can expect a return to Republican levels of "transfer" sometime this weekend.

Saturday, October 16, 2010

Genomic Imprinting II: Inclusive Fitness and Conflict

So, as we discussed previously, genomic imprinting is the phenomenon where the pattern of expression of an allele differs depending on whether that allele was inherited from your mother or your father. This difference in expression does not depend on differences in the DNA sequence of the two alleles. Your two alleles might have identical DNA sequences, but function completely differently.

For example, one of the two alleles might be epigenetically silenced. That is, because of reversible chemical modifications to the DNA, or to proteins that are closely associated with the DNA, that allele would be inactive. The other allele, with an identical DNA sequence, but different modifications, would be happily chugging along producing its gene product(s). Today's question is, "That seems crazy! Why would you do something like that?"

One of interesting (and by "interesting" I mean "sad") things about evolutionary biologists is that whenever something genuinely new and surprising is found in the world, everyone feels the need to propose an evolutionary explanation for it, whether new explanations are needed or not. So, many attempts to explain the origins of imprinting have been proposed, most of which are consistent with at least some of the data, and a few of which actually make sense. There is one explanation, however, that is far and away the most successful in explaining the distribution and nature of imprinted genes: the "Kinship" or "conflict" theory of imprinting. This theory owes its creation and early development primarily to David Haig (who laid out the theory originally in papers with Mark Westoby and Tom Moore).

The basic idea of the Kinship Theory is that natural selection favors different expression behaviors for maternally and paternally inherited alleles. That is, the optimal level of expression for an allele that is maternally inherited is different from the optimal level for a paternally inherited allele. Now, if you think about that for a minute, it probably seems strange. I mean, if I survive and reproduce, that's equally good for any of my genes, independent of where I got them from, right? Right?

The key is recognizing that natural selection favors allele that pass on the largest number of copies to future generations. ("Isn't that what I just said?") AND, that it doesn't matter whether those copies are passed on directly by my having children, or if they are passed on because because one of my relatives, who has inherited an identical copy of that allele, has children. There are different ways to represent this (which are all mathematically equivalent if you do them right), but the one that I find most intuitive is the idea of "inclusive fitness." Basically, we can think of natural selection as maximizing the inclusive fitness of an allele, which is the fitness of every individual in the population, weighted by the probability that they carry the allele. In the simplest model, this probability is 1 for me, 1/2 for a sibling, 1/8 for a cousin, and so on.

Now, think about your relatives. With the exception of your descendants, your full siblings, and their descendants, all of your relatives are related to you either through your mother or your father. That means that, in general, this inclusive fitness calculation will be different for maternally and paternally derived alleles. Therefore, there will be a conflict, where the phenotype that would maximize the inclusive fitness of your maternally inherited allele will be different from the one that would maximize the inclusive fitness of your paternally inherited allele. If this difference is large enough, it can actually drive alleles to take on two different conditional expression strategies, and, voila, imprinting.

Granted, even in the most extreme cases, this difference is likely to be pretty subtle, which might make it seem strange that this could explain a situation where one of the two alleles is completely turned off, while the other one is cranking away. This phenomenon, where a little conflict leads to a big effect, will be the subject of the next installment.

Saturday, September 18, 2010

On sex and singles

So, the post title is clearly designed to pump up pageviews, but those of you who have come here hoping to see photos of me with dollar bills hanging out of my G-string are going to be sadly disappointed. The good news is the money you'll save having your corneas scraped.

This post is actually about the evolution of sex, or "recombination," as the biologists like to call it. The question is, why does sex exist? Or, at a genetic level, why would an organism do something that passes on only half of its genes (by mating with something that donates another half), rather than simply making a genetic copy of itself. This is often referred to as the "two-fold cost of sex." Presumably, there must be an evolutionary benefit to sex that is great enough to overcome this two-fold cost.

As with everything in evolutionary biology, there are an enormous number of theories that have been proposed to explain the evolution of sex, but there are two major arguments. One is that sex allows beneficial mutations that arise on different backgrounds to be recombined onto a single genetic background. This allows adaptive evolution to occur at a faster rate. The other (which is really sort of another side of the same coin) is that sex permits more efficient purging of deleterious mutations.

Let me use an analogy that requires us to take a walk down memory lane. You kids may not know this, but a long time ago, music came on albums, which contained a bunch of songs. The problem with the album system was that most bands would put out one good song, and then fill the rest of their album up with crap. So, to get a collection of good songs, you had to buy a whole bunch of other songs that you didn't actually want. Sure, you could buy the 45, but who did that, seriously?

So, in this analogy, the first theory, the one about beneficial mutations, is like how you would take all of your albums and put the best songs together on a mix tape that you give to a girl you're trying to impress. Yes, back then, this was done non-ironically by people who were not hipsters. She would then listen to the first few songs out of a sense of politeness, make some awkward comment about how knowledgeable you are, and then mysteriously change her phone number.

One of the great things about the advent of mp3s and digital music sales is that it is easier to hide your embarrassing musical taste. It used to be that your friends would always pull out your Night Ranger album and make fun of you. Now you can rock out to Ke$ha and just close your computer when someone knocks on your office door.

Also, and more relevantly, it is easier and more natural now to buy individual songs. So, you don't ever wind up owning a whole pile of non-I'm-Gonna-Be-(500-Miles) Proclaimers songs. Music has undergone a transition to where it is more like our second theory, where recombination permits the elimination (through failure to purchase) of deleterious mu(sic)tations.

I'd write more, but there's a pile of cash on the dresser that I need to count.

Monday, September 6, 2010

On evolution and sequels

So, there are a lot of things in evolution that seem like they are moving in one direction, when actually they are moving the opposite way. Or maybe it's the other way around – I forget. For instance, one of the things that we know is that the vast majority of naturally occurring mutations are deleterious. That is, just like your crotchety old grandfather always said, children are, on average, a little bit worse than their parents (and the music they listen to is A LOT worse). Yet, somehow, evolution is able to maintain a level of function in the face of these deleterious mutations, and even to create new adaptations.

The reason is natural selection. Children will be worse than their parents on average, but there will be variation. Some will be a lot worse, and some only a little worse. Some may even be a bit better. The key is that the better children will, on average, produce more grandchildren than the worse children will (so your nagging mother was also right). It's a bit like walking the wrong way on one of those people-movers at the airport.

Of course, there is also noise in the system. Sometimes a big rock falls on the "fittest" individual in a way that has little to do with that individual's genotype. And sometimes an individual carrying a lot of deleterious mutations starts a polygamous cult and has about a hundred kids. But on average, the filtering effects of selection seem to counterbalance, or even outweigh the effect of those deleterious mutations.

This got me wondering if there was maybe something similar going on with movie sequels. The conventional wisdom in most quarters is the movie sequels suck. Sure, there is the occasional Godfather II, but for every one of those, it seems like there are a hundred films that are closer to Highlander II. So, I did a little study [1], in which I compared three classes of films: movies that got sequels, movies that are sequels, and random movies. Two scores from Rotten Tomatoes were collected for each movie: the "tomatometer" score, which is the percentage of reviews of the movie that were positive, and the user score, which is the average rating (out of 10) by users of the site.

The average scores are:

Movies with sequels: 59.2% positive 5.92 average (coincidence, or Illuminati plot?)
Movies that are sequels: 44.8% positive 5.16 average
Random movies: 45.7% positive 5.21 average

So, what's our conclusion here? Well, it seems like sequels are, on average, pretty darn similar in quality to the random sample of movies. The outlier is the set of movies that get sequels made. So, maybe we think that sequels suck because we tend to mentally compare them with the originals, and, like our high-school sports careers, they fail to live up to expectations. Maybe sequels suck because movies suck, and a sequel is no more or less likely to suck than anything else. Or is there something about sequelness in itself?

We can drill a little deeper by dividing our movies into five quintiles (with ten movies each) based on the tomatometer scores of the originals:

Bottom quintile:
Movies with sequels: 17% positive 3.6 average
Sequels of movies: 15% positive 3.6 average

Second quintile:
Movies with sequels: 45% positive 5.2 average
Sequels of movies: 22% positive 4.0 average

Third quintile:
Movies with sequels: 58% positive 5.9 average
Sequels of movies: 49% positive 5.3 average

Fourth quintile:
Movies with sequels: 82% positive 7.0 average
Sequels of movies: 64% positive 6.1 average

Top quintile:
Movies with sequels: 94% positive 7.9 average
Sequels of movies: 74% positive 6.8 average

What this makes it look like is that there really is something about making a sequel that makes your movie suck more than the original. For the most part, you can expect a 15-20% drop in the number of favorable reviews going from the original to the sequel, even if the sequel was only average to begin with. The one exception is the bottom quintile, where you can expect your sequel to suck just about as much as the original did. This may be a boundary effect, as the average number of positive reviews is bounded at zero. This is the great thing about making "Baby Geniuses 2" is that it is virtually impossible to underperform "Baby Geniuses." On the other hand, with a tomatometer score dropping from 2% to 0%, the baby geniuses somehow managed it.


[1] Not-very-scientific study methodology:

In order to collect a sample of sequels, I went to Rotten Tomatoes, and searched for "2" and "II," discarding anything that was obviously not a sequel, or for which there was no rating information available. This yielded a list of 50 movies, including "2 Fast 2 Furious," but not "Aliens." For each of these, I got the "tomatometer" score and the average user rating for that movie and for the movie of which it was the sequel.

For the random sample, I went to The Movie Insider, and used their list of January-June 2009 releases. I discarded anything that was a foreign film or documentary that had an initial release date prior to 2009. The rationale here was that if a documentary is shown at film festivals in 2007, and then gets a major theatrical release in 2009, this is not a random movie. It is a movie that has already undergone a fairly intense selection process. In the end, this list had 75 movies in it.

The study was not double-blind or vetted by anyone else, and undoubtedly contains errors in both transcription and judgment. However, hopefully it is close enough for analogic use.

Sunday, August 29, 2010

Why "Lost in Transcription"?

So, I like to imagine that people are reading this blog, that they are intrigued by its content, and it's got them wondering, "Why is this blog called 'Lost in Transcription'?" As I noted in the pilot, the aim here is to talk about poetry and science, particularly those parts of science that are related to my own research, where I can claim some degree of expertise. The title is meant to bridge between these two worlds.

First, in the literary domain, it is a play off of the phrase "lost in translation," which appears any time there is a discussion of either literature, of cultural differences, or of Scarlett Johansson that goes on for longer than ten minutes. Within poetry, its two most famous appearances are as the title of a James Merrill poem (perhaps the best poem ever written about working a jigsaw puzzle), and in a quotation attributed to Robert Frost, that "Poetry is what gets lost in translation."

Within genetics, translation refers to the process by which an RNA sequence is read to generate an amino acid sequence. In a related process called transcription, DNA serves as a template for the synthesis of RNA. One of the topics that I work on is genomic imprinting, where one of the two gene copies in a cell has its transcription silenced. So, in a strictly literal sense, a better title would have been something like "loss of transcription," but if you are willing to stretch with me, we could imagine that at a genetic locus that is subject to genomic imprinting, the genetic information from one of your two parents is Lost in Transcription.

On aging, conservatism, and experimental economics

So, it is standard conventional wisdom that people are liberal when they're young, and conservative when they're old. To the extent that we interpret "liberal" as "eager for change" and "conservative" as "against change," this trajectory is only natural. Especially in the modern world, where things are changing all the time, it may simply come down to a difference in experience: you're less likely to pine for the way the world was thirty years ago if you weren't alive thirty years ago.

But what I am really interested in here is the apparent trend where people become more conservative with respect to economic policies. In this context, the argument about familiarity does not seem to hold. In the United States, the government's economic policies have been trending more conservative for decades, and the familiarity argument would predict that older people should be, on average, more liberal. However, there is a different aspect of familiarity that may be relevant, as it pertains to our beliefs about human nature.

A key aspect of the economic debate between liberals and conservatives is a difference in the assumptions they make about how people will behave when left to their own devices. If you will forgive me for painting complex things with a simple brush, the cartoon versions of these are something like this. Conservatives believe that people are inherently self-serving and lazy, and will work hard only if they are given tangible incentive to do so. From this perspective, progressive tax structures and government programs like welfare and social security are problematic because they take away the incentive to earn money. Liberals, by contrast, believe that everyone is trying hard, that inequality comes largely from societal structures that are beyond individuals' control, and that people should not be punished for the inherent unfairness of society (except maybe those at the top of the pay scale, who have benefitted most from those inequalities).

Now, the most obvious difference between young people and old people is that old people have a lot more experience with other people than young people do. That is, we tend to start out with positive views about human nature, but over time we interact with more and more people, they disappoint us, and we become progressively more cynical. Many conservatives see this as evidence in favor of their position: we start naive, and become conservative when we learn what people are actually like. However, I want to suggest a different explanation, having to do with asymmetries in how we perceive positive and negative deviations from our expectation. Intuitively, this comes down to the fact that we notice whenever we get stopped by a red light, but often don't notice when we hit a green light. Therefore, we perceive that stoplights are red more often than they actually are.

This also happens in the economic domain, as has been extensively documented by experimental economists in a variety of "public goods" games. The basic structure of these games is as follows. You have a group of people, say 10, and you give each of them some money, say $10. Each person can then contribute a fraction of their $10 to the "pot." The money in the pot is the multiplied by some factor, say 5, and then distributed equally among the ten players. So, if no one contributes anything, everyone gets to keep the $10 they were given at the beginning. If everyone contributes the full $10, the pot has $100, which is multiplied by 5 to give $500, which is distributed back to the players, and everyone walks away with $50.

The ideal thing for the group as a whole is for everyone to contribute the maximal amount. However, the ideal thing for the individual is to contribute nothing (and to hope that everyone else contributes the maximum). For example, if I contribute nothing, and everyone else contributes $10, I walk away with $55, and everyone else walks away with $45. If I contribute $10, and no one else contributes anything, I'll get $5, and everyone else will get $15. From an "economic rationality," "Nash equilibrium" perspective, the thing to do is contribute nothing. However, this is not what happens in practice.

In a wide variety of experimental setups, what people actually do is contribute about 50% of what they are initially given. So, the typical outcome in our experiment would be that everyone contributes about $5, which makes $50 in the pot, which is multiplied to $250, and everyone walks away with $30 (the $5 they kept plus $25 from the pot). Across a broad range of cultures, ages, quantities of money, etc., people come into these experiments with a somewhat liberal perspective, as they seem to both trust the good will of the other players, and care about the results for the group as a whole.

However, if we play the game over and over again, an interesting thing happens: the average contribution gradually declines, until eventually, no one is contributing anything to the pot. Based on interviews with the participants in these games, economists believe that they understand this trend. Let's say that one person contributes $5, which is the average among the group, but some people contribute $4, and some $6. This person will not really think about the people who gave $5 of $6, but will think a lot about the people who gave $4, get pissed off, and reduce their contribution in the next round. While it is mathematically trivial that people, on average, contribute the average amount to the pot, it seems to be psychologically true that people perceive themselves on average as having made an above-average contribution.

What I think is that something analogous happens over the course of the lifetime of an individual. We meet some people who are hard working, and some who are lazy, but there is this perceptual bias that means that the lazy, selfish people we meet weigh more heavily in our developing opinions about "what people are like."

The other interesting finding from these experiments is that it is remarkably easy to reset the spiral of cynicism. If you take the participants out of the room, give them a cup of coffee, and let them use the bathroom, when they go back in, they often go right back to contributing 50% on average. So, note to Democratic lawmakers, if you can figure out how to let the country drink a collective cup of coffee and use the collective bathroom, you may find a dramatic increase in support for social programs and a progressive tax structure.

Sunday, August 8, 2010

Genomic Imprinting I

So, one of the things that I study is genomic imprinting. What is that, exactly?

Even if you're not a biologist, you are probably familiar with the fact that, for most of your genes, we carry two different copies, or alleles. You get one of those alleles from your mom, and one from your dad. Those two alleles could be the same (have identical DNA sequences) or different (usually only at a small number of positions within DNA sequence). If they are different, then the consequences of those alleles on your traits, like how tall you are or what color your eyes are, are determined by the dominance relationship between those two alleles. For example, the main allele responsible for red hair (at the MC1R locus) is recessive in relationship to alleles for brown or black hair. So, if you have only one copy of the red-hair allele, you will probably have dark hair. Importantly, in terms of what follows, it does not depend whether the recessive red-hair allele you have came from your mother or father.

If you are a biologist, you already knew all of that, but you may or may not be familiar with imprinted genes. About one percent (or possibly more) of our genes are imprinted. For these genes, it does matter which allele came from your mother and which one came from your father. That's because imprinted genes retain a chemical memory of which parent they came from, and function differently depending on their parental origin. More specifically, at an imprinted locus, alleles are subjected to epigenetic modifications in the germ lines (ovaries or testes). These epigenetic modifications can be chemical modifications applied directly to the DNA itself, or modifications to proteins that are closely associated with the DNA. These modifications alter how the allele functions, without modifying the DNA sequence itself. The key thing is that, for imprinted genes, the epigenetic modifications that are established in the male germ line are different from those established in the female germ line. So the allele that came from your father will function differently from the allele that came from your mother, even if the DNA sequences are identical.

In the simplest cases, one of the two alleles is inactivated, or turned off. The effect of that gene on a given trait, then, depends only on the active allele. To return to the red-hair example, imagine that the MC1R locus was imprinted (which it is not, as far as we know), and that only the paternally inherited copy was expressed. Now, if you had one copy of the red-hair allele, and one of the more common dark hair allele, you would not necessarily have dark hair. Your hair would be dark if your red-hair allele came from your mom, but if it came from your dad, your hair would be red.

Of course, as with all things in biology, once you start looking at the details, everything becomes a lot messier and more confusing. But, that is the basic gist.

Genomic imprinting was one of the biggest surprises to come out of molecular biology in the past few decades. Both the origins of imprinting of particular genes, and the effect of imprinting on the evolution of those genes, are interesting questions that we will return to in future posts. At some point along the way, we will get deeper into those messy and confusing details.