In his new book A Farewell to Alms, Greg Clark, an economic historian at the University of California, Davis, contends that "[t]he New World after the Neolithic Revolution offered economic success to a different kind of agent than had been typical in hunter-gatherer society: Those with patience, who could wait to enjoy greater consumption in the future. Those who liked to work long hours. And those who could perform formal calculations in a world of many types of inputs and outputs...."

Clark also provides archival evidence that in medieval Britain (and to a lesser extent in China and Japan) the wealthy-who presumably had those "middle class" skills in abundance-raised more children than the average person. If you put these pieces together-a system that rewards a new set of abilities, plus greater reproductive success for those who have those abilities-then all you need to get some form of selection is one more link: A transmission mechanism. On the nature of the mechanism, Clark leaves the door wide open. Could be parent-to-child cultural transmission, could be genes, could be both.

While much of the discussion of Clark's book has focused on his "survival of the richest" hypothesis, Clark himself appears to be equally devoted to demolishing the widely-held view that economic institutions are the key to modern economic growth. He notes that the British people had solid property rights, limited government, and sound currency for centuries before they had their Industrial Revolution. Drawing on early work by Nobel Prize-winner Douglass North, he argues that economic institutions are largely endogenous and relatively efficient, at least when we're talking about time horizons lasting a century or more. If institutional change wasn't the driving force behind modern economic growth, then what was? In Clark's view, the driving force was change within human beings themselves.



1. In some early work, you wondered why workers in British cotton mills were so much more productive than workers in Indian cotton mills. You discuss this in the last chapter of A Farewell to Alms. You looked at a lot of the usual explanations-incentives, management, quality of the machines-and none of them really seemed to explain the big gap in productivity. Finally, you seemed to turn to the idea that it's differences between the British and Indian workers themselves-maybe their culture, maybe their genes-that explained the difference. How did you come to that conclusion?

Clark: I came to economics as an undergraduate expecting, as is the central view of economics, that the explanation for wealth and poverty would ultimately be located in social institutions and that people everywhere have basically the same aspirations and abilities.

But unlike most of my colleagues in economics I have always been interested in the mechanisms, and the fine details, of how things actually function. Much of modern economics is entirely theoretical, and even most empirical work in economics involves just looking at very high level correlations between variables such as income per person and education, or democracy, or the openness of trade.

When I set out in my PhD thesis to try and explain differences in income internationally in 1910 I found that asking simple questions like "Why could Indian textile mills not make much profit even though they were in a free trade association with England which had wages five times as high?" led to completely unexpected conclusions. You could show that the standard institutional explanation made no sense when you assembled detailed evidence from trade journals, factory reports, and the accounts of observers. Instead it was the puzzling behavior of the workers inside the factories that was the key.


2. Your book is clearly a call for a new research agenda in the fields of economic growth and economic history, one focusing less on institutions and more on what we might broadly call "labor quality." But your key hypotheses seem to turn on the question of how and why entire workforces change across the centuries, and involve questions of culture, child-rearing methods, and perhaps human genetics-fields quite outside the expertise of most economists. If you could command an army of, say, biologists, anthropologists, and neuroscientists to test your hypotheses about long-term changes in labor quality, what would you have them work on?

Clark: That is a great question. If, as is possible, the pre-industrial era changed people genetically to be better adapted to market economies, then a systematic comparison of the DNA of societies should find correlations between gene frequencies and the histories of these societies. If genetic change was also occurring in historical time, as opposed to the pre-historic era, then we would expect these changes to be incomplete even in societies with a long history of settled agriculture. In that case we would actually predict class differences genetically! The rich in these societies would differ genetically from the poor in certain systematic ways! All this should be testable at some point.

If the change was purely cultural, then we still might be able to discover systematic behavioral differences between poor and rich in modern capitalist society, such as over time preference rates, that correlate with differences between rich and poor societies.


3. What do you think are the weakest links in the now-conventional "Institutions Matter" chain of reasoning?

Clark: The book challenges the modern orthodoxy of economics - that people are essentially the same everywhere, and with the right set of institutions, growth is inevitable - in three ways. First by showing that there were societies like medieval England where the institutional structure provided every incentive for growth, yet there was no growth. Second by pointing out that by objective measures the institutions of many highly successful modern economies, such as in Scandinavia, provide much poorer incentives to individuals than those of very poor economies. And lastly by showing that in the long run economic institutions that would prevent growth tend to get replaced endogenously by ones that are pro-growth.


4. You provide a variety of evidence that interest rates have fallen over the centuries; this is a fascinating set of data that we've discussed before at Gene Expression. Should economic historians still be searching for transaction cost stories to explain this fall in interest rates-e.g., lenders needed a high return in ancient Rome to compensate them for the high cost of searching for safe borrowers-or is that search likely to hit a dead end?

Clark: Interest rates on safe assets like houses and land fell from 25% or more in Ancient Babylon, to 10% in Ancient Greece, Roman Egypt and medieval Western Europe, to 4% in the eighteenth century in the Netherlands and England. Most economic historians assume this just represents transaction costs. But I can show in cases such as medieval England that transaction costs have nothing to do with this - the real return on investments as safe as modern Treasury Bonds was 10% or more. So I am confident that something much more fundamental was changing over these years.

5. You use data on British wills to argue that the British people of today are by and large the descendants not of peasants and not of the violent medieval aristocracy-both groups failed to reproduce themselves. Instead, the British people of today are largely the descendants of the bourgeoisie of the middle ages. Nowadays, that seems to be a testable hypothesis; have you run into genetic evidence bearing on what you call the "survival of the richest?"

Clark: I agree that, in principle, this is a completely testable hypothesis. If there was genetic change in the Malthusian era then we will find systematic differences in genes that influence behavior such as patience and propensity to violence between groups such as the British and those such as Australian Aboriginals that had no experience with settled agriculture.

However, as far as I am aware, the identification of genes that influence such behaviors is at a very early and tentative stage. The only such studies I have seen reported are those of differences across ethnic groups in variants of genes encoding monoamine oxidase enzymes.


6. How are economists reacting to the book? In particular, are there any misunderstandings that you'd like to address?


Clark: I expected a hostile and perhaps even dismissive reaction, given the controversy that the "survival of the richest" argument was bound to create, and given the attack on the modern orthodoxy amongst economists about institutions being the key to wealth and poverty. But economists who have read the book, even when they remain skeptical of the conclusions, have generally found it interesting and challenging. They have been surprised to learn in particular that the history of economies is not anything like the implicit assumptions they have, based on modern economic doctrine.


7. One implication of your model is that human populations that haven't been through the full Neolithic Revolution are going to fail miserably when they try to build a modern market-oriented society. If people turn out to as hard to change as they appear to be-if neither culture nor genes prove to be all that malleable in the medium-run-then how would you recommend improving the lives of these people? Do you think economists can design institutions that can help make these populations productive?

Clark: Anyone who reads history cannot fail to be impressed by the difficulties that hunter-gatherers, or societies with only limited experience of settled agriculture, have in successfully incorporating into the modern capitalist economy. I spent a week in Australia this summer, and the plight of Australian Aboriginals is very sad. The surviving Aboriginal communities have seen tremendous rates of poverty, alcoholism, drug use, violence and sexual assaults.

But an important point in the book is that while some of this cultural variation may be due to the long histories of societies, there is a lot of cultural variation within these constraints that produces dramatic differences in wealth in modern societies. So there is no ground for fatalism on the possibilities for any society. The problem is that measures to reform the cultures of societies seem difficult to devise. Look at the lack of success the Chinese Communist Party had in remaking Chinese Culture. China has emerged from a period of extreme ideological indoctrination seemingly with its pre-communist love of individual wealth and status completely intact.


8. You emphasize that "[t]he argument is not that agrarian life was making people smarter." But you also emphasize that agrarian life placed greater value on verbal and mathematical skills than hunter-gatherer life. Let's set aside for the moment the question of whether these skill changes were cultural, environmental, or genetic. Are you claiming that the rise in math and verbal skills was counterbalanced by an equal loss of some similarly valuable hunter-gatherer mental skills? In other words, were the mental effects of the Malthusian process zero-sum? If so, what process within your model would make that occur?

Clark: I wanted to emphasize in the book that I was not advocating any kind of Social Darwinism. The long Malthusian economy that preceded the Industrial Revolution changed people, but there is no evidence it made them "better" or "smarter." Indeed there is evidence that we did not become any happier as result of economic growth.

Anthropological accounts of forager societies suggest that people in these communities have strikingly developed powers of observation and memory (as well as an amazing ability to endure pain) - they are just not abilities that the modern market economy places much value upon.


9. Bowles, Camerer, and an interdisciplinary research team led a series of ultimatum-game studies in pre-modern societies; the found incredibly diverse outcomes. By contrast, across modern societies, ultimatum game play is much more similar, so it looks like the modern world really is a world of conformity, at least on this topic. How do you think their experimental evidence bears on your question of whether the "long Malthusian night," as you call it, selected for a certain set of behaviors and attitudes?

Clark: I have seen these results reported, but had not thought of relating them to the arguments of the book. I would have expected that pre-modern societies would have had a common response, but potentially a different response than in modern societies. So I do not think I could call this any kind of vindication of the hypothesis in the book.


10. What's the next project?

Clark: I always have several going at the same time. One is a follow up to the "survival of the richest" study for England reported in the book which will look more closely at the intergenerational transmission of economic success with a much larger set of data, and seek to show through examination of the effects of family size that the mechanism is indeed almost entirely the transmission of culture or genes. This study will also look over the whole period 1600-1914 and examine when and why richer men ceased to have more children than average and began to have less. I would love to use this data to try to tease out whether we have just cultural evolution as opposed to genetic - I just cannot think of any way to do that!

Labels: culture, Economics, History, human biodiversity

No, not that Haldane. His father. Seth Roberts points to several reviews of a new biography of JS Haldane. He was apparently quite the self-experimenter:

He survived concentrations of carbon monoxide in the blood that would, as his biographer notes, have looked entirely plausible as the 'cause of death' on a death certificate. 'Dry air,' Goodman writes, 'he could withstand to an astounding high of 300F, though if he moved about too much his hair began to singe.' Working in 99F 'dry bulb' heat, on one occasion, a colleague gave up after half an hour with a rectal temperature of 102.4F; Haldane went on for another 30 minutes. He spent hours and hours breathing toxic air and taking careful, methodical notes of its effects. He gassed himself with chlorine, methane, carbon dioxide, carbon monoxide, pure oxygen, nitrogen, mustard gas and god knows what else in various combinations... you name it, he turned blue and passed out on it. And, typically, no sooner had he come back round than he returned to the chamber to have another go.

Related: various posts on lil' Haldane

Over the last few years the British government has spent a good deal of taxpayers' money on educational activities for pre-school children, under the heading of 'Sure Start', aimed especially at those from 'disadvantaged backgrounds'.

If this sounds vaguely familiar to American readers, that should not be surprising, as the Sure Start scheme is partly inspired by the American Head Start scheme.

This week research by academics at the University of Durham has been published, showing that the Sure Start scheme has so far had no measurable effect on the abilities of children entering school.

In view of the Head Start precedent, this should not cause any great surprise. Even supporters of Head Start do not claim more than moderate benefits.

Predictably, parts of the educational establishment in Britain have jumped to the defence of Sure Start. According to Prof. Ted Melhuish, writing in the Guardian (where else?) "The effects won't show themselves for a couple of years yet and the really important effects won't show themselves until adolescence".

Are you sure, Ted? In most of the studies on the effects of Head Start, any educational benefits actually fade out after a year or two. Prof. Ted's optimism therefore seems to be a triumph of hope over experience.

Finns dominate mobile-chucking contest.

Labels: Finn baiting

As I have several times discussed the height of the Dutch (and other peoples) I was interested to come across a reference to this article. Unfortunately I don't at present have access to the full article (without paying $30), but the abstract says:

In the late-Middle Ages and at the onset of the early modern period, the Dutch population was taller than in the first half of the 19th century. This inference is partially based on skeletal evidence, mainly collected by the Dutch physical anthropologist George Maat and his co-workers. A spectacular increase in Dutch heights began in the second half of the 19th century and accelerated in the second half of the 20th century. At the end of the 20th century, the Dutch became tallest in the world.

John Hawks follows up the monkey hybridization story, providing some important ecological context:

[T]he primary difference between the two species is cold tolerance: A. pigra can and does live at higher altitudes than A. palliata, ranging high enough that it must tolerate freezing temperatures
...
Larger monkeys with larger, more complex molars, differences in throat anatomy, and greater cold tolerance, in contrast to a smaller, more cosmopolitan species, with the opportunity for gene flow during interglacials. They sound like Neanderhowlers.

Labels: Genetics

The Economist has a long piece about the impact that ubiquitous genetic testing will have on health insurance, especially in the United States. This part is crucial:

...If that is the consequence, then other ways of paying will have to be devised. Carol McCall of Humana, a big American health-care provider, thinks a move toward some sort of compulsory, universal coverage is inevitable, even in America. That need not necessarily mean a scheme financed mainly out of taxation, of the sort found in most other rich countries. However, social outrage over a rising class of uninsurables may make the government an insurer of last resort-particularly, as Dr Cecchetti observes, when some rich and powerful people discover that they, too, are not immune from the genetic lottery. He reckons testing will lead to individuals receiving a health score akin to today's personal credit score. Those whose files come on screen to the accompaniment of flashing red lights will not find it easy to obtain cover for much less than the cost of paying for their treatment themselves.

Actually I think the key here is family. Just as surveys have found that having a friend or family member who is gay tends to change how one perceives attitudes toward gay rights, my own hunch is that genetic predispositions found among the circle of family and friends will tend have more of an impact than we might think. The distribution of mutational load being what it is it seems likely that uninsurables will be found across all classes and socioeconomic clusters, as opposed to the current population of uninsured which is disproportionately young, poor or marginalized in some way.

Labels: Genetics

It seems that a coalition of non-Open Access journals, Partnership in Research Integrity in Science & Medicine, is out to take down journals like PLOS. I know people have to put bread on the table, but really there isn't an open-ended guarantee that you can milk your business model forever. In any case, Blog Around the Clock has links to many comments around the web in regards to this issue.

Labels: science

Just wanted put a note here that I have two posts, here and here about a new incarnation of the "redheads are going to go extinct" meme. The current culprit is National Geographic Magazine. The only reason that I know about this is that there was a spike of traffic from message boards on my other blog attempting to debunk the story using some stuff I'd posted earlier.

Labels: Genetics

I tend to assume that all people of taste and intelligence (e.g. readers of Gene Expression) will regularly check out John Derbyshire's site, but in case they don't, here is his brilliant review of a book by Robert Spencer.

Check out this new interview with Steven Pinker. It ostensibly focuses on his new book, The Stuff of Thought, though it covers a lot of ground. My own feeling is that the interviewer should have let the focus be more on Pinker than his own pet theories, but there's a lot of good stuff in there.

Labels: Blog

Alice Dreger's account of the Bailey story is available here [pdf]. It's a dizzying trip through the looking glass-- there are plastic vulvas, Stalinist purges of the transexual ranks, and, of course, a neo-conservative conspiracy. If you don't want to read the whole thing, just imagine an Almodovar movie gone horribly, horribly wrong.

I'm reading When Baghdad Ruled the Muslim World: The Rise And Fall of Islam's Greatest Dynasty, a history of the Abbasids. This on page 169 caught my attention:

...the caliph called for wine. A golden goblet was brought and the drink was poured into it. Ma'mum drank and handed it to Hasan....Hasan, a good Muslim had never drunk wine, yet to refuse could be seen as an insult to the caliph...'Commander of the Faithful,' he said, 'I will drink it with your permission and following your order,' for if the caliph himself had commanded him to do it, how could it conflict with Islam? The caliph replied that if it had not been his order, he would not have held out the goblet to him. So the tension was relaxed and they drank together

There are many references in this book to the consumption of wine at the court of the Abbasids, and even the patronage of a genre of poetry focused upon wine. I knew the general outline of this, and amongst Muslim rulers alcohol consumption doesn't seem that rare. I recall that the Mughal ruler Jehangir was an alcoholic, as was Saud bin Abdul Aziz, the king of Saudi Arabia in the 1950s and early 1960s (his problems with alcohol were one of the reasons that he was forced to abdicate by his brothers). Of course, Islam prohibits the consumption of alcohol, and yet here you have the titular spiritual leaders of the Islamic world, the caliphs, making it a normal part of their lifestyle. What's going on here?


One of the main reasons that I have generally turned a skeptical eye toward explanations of religious constraint upon behavior are these sorts of examples. From an atheist perspective I had always tended to view religions as clear and distinct sets of axioms; but operationally the practice seems far more subject to social consensus and individual rationalization. This isn't only an issue with religions, I have known of environmentalists who drive SUVs, self-proclaimed social conservatives who are heavy users of drugs and indulge in non-standard sexual practices, and so on. I'm sure most people can repeat such examples. Years ago when I found out that George H.W. Bush had switched from being pro-choice to pro-life, as had Ronald Reagan to some extent (Reagan's pro-choice period was more that he simply signed laws decriminalizing abortion in California as governor), I assumed this was conscious political opportunism. The same for Al Gore or Jesse Jackson, who made the inverted transition. And surely some aspect of political calculation was at work here on the ultimate level, but what about the proximate cognitive processes? Humans are good at rationalization, and I'm not sure anymore that the elder Bush or Reagan were insincere in their rather fortuitous conversions. Or, at least part of their minds were pretty convinced that their change in opinion had more to do with reflective shifts in the underlying assumptions and values and not an exogenous push due to circumstance.

In short, humans beings perceive themselves to be reflective beings shaped by essential axioms open to conscious inspection. But the reality is that human behavior and psychology seems to exhibit a great deal of contextual contingency which shape a host of cognitive processes insulated from conscious inspection. We regularly seem to make up, and believe in, stories which reinforce our self-perception that we are rational beings with free will who make decisions and form beliefs by carefully taking into account data filtered via our avowed norms. But cognitive psychology shows that humans can be easily influenced by priming inputs which they are not conscious of in regards to the choices they make, all the while happily regaling researchers with their theories that sketch out the underlying causal factors behind their behavior. Yet it seems here that as in the case above the reason is posterior to the act; constructed post facto to give intellectual support to decisions made via other means.

Surely there is a method to the madness, and the outline of human behavior is constrained by a host of concrete parameters (biology, sociology, history, even rational calculation!). But, the biases which serve as weighted parameters in the function that generates the distribution of human behavior are likely more complex, contingent and opaque to the naked eye then we might have hoped for. Just as "friction," "bounded rationality" and "behavioral economics" are emerging as necessary and essential tools in economics, so broad brush histories and anthropologies must take into account the multi-dimensional nature of human psychology and the disjunction between the stories we tell and the dynamics which drive us.

Labels: Cognitive Science, Religion

From an article in Genetics:

Well-documented cases of natural hybridization among primates are not common. In New World primates, natural hybridization has been reported only for small-bodied species, but no genotypic data have ever been gathered that confirm these reports. Here we present genetic evidence of hybridization of two large-bodied species of neotropical primates that diverged ~3 MYA. We used species-diagnostic mitochondrial and microsatellite loci and the Y chromosome Sry gene to determine the hybrid status of 36 individuals collected from an area of sympatry in Tabasco, Mexico. Thirteen individuals were hybrids. We show that hybridization and subsequent backcrosses are directionally biased and that the only likely cross between parental species produces fertile hybrid females, but fails to produce viable or fertile males. This system can be used as a model to study gene interchange between primate species that have not achieved complete reproductive isolation.

The fact that the species (two species of howler monkey) diverged about 3 million years ago is pretty striking-- the divergence time of humans and chimps is "only" one or two million years more than that, but creating a humanzee doesn't seem to be possible. Humans and Neandertals, though, only split a few hundred thousand years ago.

Labels: Genetics

The UK Times today has a short report into some surprising research findings. The main text is as follows:

A study into the mysterious changing skull shape of medieval man casts serious doubt on current theories.

The peculiar shift from long narrow heads to those of a rounder shape, and back again, which took place between the 11th and 13th centuries, has been noted at sites throughout western Europe. But a study of skulls found at the deserted village of Wharram Percy, near Malton, North Yorkshire, suggests that the anatomical blip was not down to an influx of Norman immigrants, or climate change, English Heritage has said.

It examined nearly 700 skeletons recovered from the village. Unlike other research, data from the Wharram site traces the change to a single, indigenous community which has been radiocarbon-dated.

Simon Mays, a skeletal biologist, said: "Our work has yielded few clues on why skulls changed, but we have cast serious doubt on some of the current theories. Despite the best efforts of science, we're still in the dark to explain why it happened."

Another report, in the Guardian, has more detail, including the important point that the changes are only found in male skulls.

And yet another report is here.

It's all very mysterious. I was aware that archeologists had found some changes in the shape of English skulls over the last thousand years, but I didn't know it was a change found elsewhere in Western Europe, or that skulls had changed in one direction and then back again in a few centuries.

And before anyone says 'Black Death', and has me chewing the carpet, I must point out that the change between the 11th and 13th centuries precedes the Black Death.

John Hawks has put up an inaugural post in a series on natural selection. His background as an English major shows (in a good way). It is interesting to note that John alludes to the Malthusian background of natural selection, since Greg Clark's work presupposes exactly this dynamic up until the 19th century for our species (Clark notes we were subject to the same dynamics as any other animal, though I would add that more or less we still are).

Labels: Evolution

Read all about it in Spiegel Online (who knew that Yoda wrote for a German audience?). Here is the original post by "Tyler Cowen."

Labels: German baiting

Pardon the interruption, but if anyone has successfully used Parallels with a Windows XP partition in Boot Camp that is FAT 32 configured would you please drop a line (clicking the name "amnestic" above will result in a pop-up window with a contact box)? I have been combing through the knowledge bases, blog entries, and forums for a couple days and I am still stuck with "Unable to open disk image Boot Camp!" Frustration mounts.

There's a new paper which uses fMRI to localize an area of the brain which seems to be involved in preventing impulsive actions. I can't but help think that something like this, which might vary from person to person, could be one of the upstream factors which shapes individual time preference. This is on my mind because I just finished Farewell to Alms by Greg Clark, and change in mean time preference is at the root of a shift in behavior which he believes primed the English (among others) for their breakout from the Malthusian trap. But it is one thing to posit a behavior whose distribution is governed by selective forces of a quantitative genetic nature, the case for any such arguments gains a boost if one could tunnel down to the level of biophysical specificity so as to assess variation across individuals and populations.

In other news, watch this space. Our own Herrick has a "10 questions" with Clark pending, so keep an eye out (that means you Ambrosini Critique).

Labels: Neuroscience

One of my favorite recent ideas wondering through the literature is that of an RNA regulon or post-transcriptional operon. Operons in prokaryotes are groups of genes whose protein products all function in the same biochemical pathway. The genes are coordinated by sticking them all next to each other and transcribing all when you transcribe one. The post-transcriptional operon idea is that RNA motifs allow proteins in the same biochemical pathway to be regulated at the translation step instead. If several proteins were needed, for instance, to build some new architecture sticking off a cell at a specific location far from the nucleus, it wouldn't do to have to coordinate them way back there. Instead, you just throw in an RNA motif, say AUUUA. Then produce an RNA binding protein that is specific for that motif. Now traffic that protein to the location of interest. All of the RNAs will be localized to the right spot.

Of course, localizaton is just one way this could work. Any process better controlled faster or farther away from the nucleus could use an RNA regulon. One notable case is that of the Pumilio family (Puf) RNA-binding proteins in yeast. Melissa J. Moore explains it here:

... each Puf protein exhibited a highly skewed distribution of bound mRNAs: Puf1p and Puf2p bound mostly mRNAs encoding membrane-associated proteins, Puf3p almost exclusively targeted messages for nuclear-encoded mitochondrial proteins, and Puf4p and Puf5p associated primarily with transcripts encoding proteins bound for the nucleus. In several cases, a majority of the subunits comprising a particular multiprotein machine, such as the mitochondrial ribosome and a number of nuclear chromatin modification complexes, were encoded by mRNAs "tagged" by a single Puf protein. Together with earlier data (12), these new results (16) strongly support the idea that the expression of proteins with common functional themes or subcellular distributions is coordinated by large-scale regulatory networks operating at the mRNP level.

Many other examples can be found in this review by Jack Keene. I don't think I've seen an example of this yet, but given the slight wobble in microRNA specificity, one could imagine a single microRNA regulating a whole set of genes. Also, most interesting for my neuro-tastes is the recent report from the Moore lab showing that the immediate-early gene implicated in neuronal homeostasis, Arc, may be part of a regulon defined by introns in the 3'UTR. The mechanism is just too clever but requires an explication on the "pioneer round" of translation. Basically the cell tricks itself into thinking it made a funky RNA and destroys it after one round of synthesis. The other RNAs regulated in this path in neurons must have opposing effects to Arc though because knocking down this negative regulation pathway led to increased excitability (increased Arc reduces neuronal excitability). This raises a more general question. The idea of RNA regulons is nice, but how much can you predict knowing that your gene of interest is part of one? RNAs associate with multiple complexes throughout their lifespan, and complexes gain and lose factors dynamically. Also, how promiscuous are RNA binding proteins for cellular processes? For instance, I originally became aware of the Hu proteins as positive regulators of the pre-synaptic calcium-buffering protein GAP-43, but it turns out that they also regulate proteins involved in immune function. Maybe I am just thinking at too high a level of cellular organization. Perhaps all of those proteins respond to calcium in some way. At any rate, I'm expecting that RNA regulons will be increasingly important in understanding the translational regulation that must take place in dendrites to produce persistent memories. Looking forward to more on that in the next year or so.

Labels: RNA, translation

I recently finished Uri Alon's An Introduction to Systems Biology: Design Principles of Biological Circuits, which I concluded about halfway through was one of the greatest textbooks I've ever read. No joke. It's simply excellent. If you're a biologist with any interest in gene regulation, read this book. If you're a physicist or engineer with any interest in biology, read this book. If your eyes don't glaze over when you read my more technical posts, read this book. Here are a few reasons:

1. The organization of the book itself, and the narration within, is spectacular. Alon takes a classic reductionist look at biological networks-- the whole can be understood by considering the parts. Though the parts, in this case, are not individual genes themselves, but the recurring types of regulatory interactions-- "motifs"-- that are seen in different types of network, biological or otherwise. As he points out multiple times, it didn't have to be this way-- in principle, evolution could have stumbled on incredibly complex network architectures, but that isn't the case. A simple mathematical analysis of two or three node circuits reveals subtle behaviors that are seen over and over again-- it's truly sublime.

2. This is not a laundry list of experiments, tools, and results. Each example is fully explored, both using mathematical models and, where available, experimental results. This leads to a nice fully picture of a mathematical model and its application. And note the math itself is completely accessible to anyone with some exposure to calculus and differential equations.

3. Alon doesn't stop at describing biological networks and their architecture, though he could have stopped there and had an excellent text (the retrospectively obvious points he makes about the different time scales of reaction times in different networks, and the impact that has on network organization, was worth the price of the book alone). He goes on to ask the evolutionary questions: why are certain genes regulated by activators, and others by repressors? In what situations is a certain type of network motif favored, and in which situations is it disfavored or neutral? He closes the book with a quote from Michael Savagaeu that very much resonated with me:

Differences in biochemical details might be the result of historical accidents that are functionally neutral, or they might be governed by additional rules that have yet to be determined. One can always assume that certain differences are the result of historical accident, but such an explanation has no predictive power and tends to stifle the search for alternative hypotheses. It generally tends to be more productive if one starts with the working hypothesis that there are rules. One may end up attributing differences to historical accident, but in my opinion it is a mistake to start there.

Again, read this book.

Labels: Systems biology