Saturday, November 27, 2010

Evolvability, speciation, and sex

Self-fertilization sure is convenient, but it spells doom in the long run.

One of the larger questions in evolutionary biology is about the level of natural selection. Dawkins leads the fundamentalists in saying that the level of selection is the gene. Nothing but the gene, ensconced within individuals which live or die by their individual genetic traits. Others, including Stephen J. Gould towards the end of his life, couldn't help but see a wider picture, where species and even genera had distinct high-level traits that are, over long periods of time, weeded out by natural selection.

I am very much in the group selection (also called multi-level selection) camp, seeing selection acting on many levels, from the single nucleotide to genera and kingdoms. The issue isn't whether DNA is the heritable material, (supplemented by culture to some degree among higher animals), and thus the ultimate locus of heritable selection, but whether selection can be thought of coherently as acting on higher levels such as groups whose members share some kind of selectable traits in common, and thus can be differentiated from other groups in the struggle for existence.

Perhaps this is merely a matter of perspective, were the gene fundamentalists emphasize that any change in population frequencies is due to the gain or loss of individuals, (and individual genes), whatever their traits might be that gain expression at higher organizational levels- such as altruism, herd instinct, exogamous mating, tendency to speciate, etc. Group selectionists, in contrast, emphasize the trait rather than the transmission mechanism, see group-level traits as irrelevant on the individual level, and thus see natural selection as irrelevant there also.

At any rate, a recent paper (and review) was a very nice demonstration of a species-level trait with serious consequences- self-fertilization versus self-incompatibility among plants. Most plants produce both male and female gametes (pollen and ovules). Some exceptions (dioecious) come in female and male versions, and example being the date palm. Buying such palms can be a tricky business at a young age, since only the females grow dates, and can't be sexed till they give fruit.

However, most plants produce both male and female gametes, often having anthers and ovules within the same flower. How do they ever manage to mate with other plants? Putting aside macro-physical mechanisms such as having gametes mature at different times, or putting them on different structures on the same plant, or the most glorious mechanism of all- using insects or birds for cross-pollination ... most such hermaphrodytic plants have molecular incompatibility systems, where the "self" pollen grains are recognized when they hit the pistil, and are summarily blocked from germinating or growing down into the ovule.

Molecular incompatibility systems are quite complicated, with proteins expressed on the pollen surface, other protein receptor proteins expressed in the stigma/pistil, multiple variants of each spread through the population, and close genetic linkage between the matching ligand/receptor gene pairs so that the host plant always rejects its own pollen. (Related paper on the intricate system in Petunia.) Such things are difficult to evolve, and easy to lose by mutation.

And lose them they do. This paper starts from the observation that such systems are frequently lost over evolutionary time, creating the fascinating question: why maintain such costly systems of outbreeding, much like the elaborate exogamous-marriage traditions common in tribal societies? The cost for plants is clear- a fortunate plant, dispersed by a helpful squirrel or jay, may find itself far away from its origin, ready to colonize new habitat. But it can't if no pollen wafts its way from a compatible partner. End of story. Some higher animals have developed parthenogenesis for similar reasons of convenience, but finding mating partners is generally easier for mobile animals than for plants, so the issue is less pressing and the trait much less common.

The problem, of course, is that sex is great- it promotes genetic diversity and recombination, allowing bad genes to be combined into loser individuals and good genes into winner individuals. Shuffling genes through all the individuals of a population releases variation rather than confining it to the clones of each self-fertilizing lineage, fated to live or die by the co-lineal sibling genes it is stuck with. Beneficial mutations arise far less frequently than harmful ones, making this clonal restriction a losing proposition. By promoting population-wide recombination and diversity, sex improves adaptation, which is where this paper hangs its hat.

The authors looked at 356 species of the Solanaceae family of plants, (nightshade, potato, tobacco, chili pepper, tomato, etc.), classifying them as self-incompatible or self-fertilizing. This family and its ancestors have maintained self-incompatibility systems with dozens of alleles for ~90 million years, yet continually gives rise to self-fertilizing species as well. These derivatives don't recover self-incompatibility, so this is a one-way street, a ratchet that tests whether there is something about self-incompatibility that is beneficial enough to withstand constant loss of species to the auto-sexual "dark side", as it were.

Looking at a phylogenetic tree of these species, constructed with help from molecular data, (from publicly reported chloroplast genes), the authors derive rates of speciation, and rates of extinction. Actually, a phylogenetic tree is built from extant organisms, so it isn't going to directly provide rates of extinction. The authors derive them by magical (err- mathematical) means via repeated modelling and simulation of similar trees, which I have neither the data nor expertise to assess.

Phylogentic tree of selected Solanaceae, (root starts at 36 million years ago), with self-incompatible (SI) species in purple, compatible (SC) species in blue/turquoise. C diagrams the model of transitions between SI and SC species, with lambda = speciation, mu = extinction, r = net diversification rate. A and B show the deduced relative rates for each process among the species classes. Rates are given in per million years.
To get a feel for what is going on, however, note in the figure that self-fertilizing plants (turquoise) are sprinkled throughout the tree (outside circle) quite evenly. Very few form deep roots that lead to large lineages devoid of self-incompatible species. This is not what you would expect from a frequent one-way process leading to evolutionarily successful self-fertilizing plants. But it is what you would expect from a process that frequently and from the very earliest times gives rise to self-fertilizing plants that then also die out relatively quickly.

Their statistical conclusions are displayed in the graphs (A, B), with lambda as the speciation rate, mu as the extinction rate, C standing for self-compatible, and I for self-incompatible. Lambda-C (yellow) is quite high. Self-fertilizing plants colonize new areas very well, and specialize quickly. However mu-C (grey-blue) is higher still, indicating that those novel self-fertilizing species can't manage to adapt well on the long term, probably because they can not utilize a population-wide reservoir of variation as efficiently as out-breeding plants can. The result (r: the net diversification rate, graph B) is that self-fertilizing species don't hang on for the long term: lower long-term net diversification. Disease might be a particularly difficult challenge, demanding ongoing diversity and recombination in the population to meet the constantly evolving threats from pathogens.

A Dawkensian could construct the finding that inbreeding species do worse on the species level in a gene-based narrative. Individuals in these species are becoming less fit as whatever beneficial mutations they build up are trapped in their parochial lineage, held hostage to whatever other problems that lineage might have. Their gene complements are not keeping up with those of out-crossing species that systematically recombine to join the best of local and even distant variation into better-optimized plants, whose greater accessible population variation likewise serves as a buffer against bad times and unforeseen conditions. In short, outbreeding plants evolve better, though not faster, than their inbreeding congeners.

While such a gene-centric construction would not be wrong and is important to appreciate for a micro-level analysis, outbreeding also seems to be an eminently species-level trait, as is extinction, making a group selection view appropriate as well. The divergent trends of species sharing either fertilization trait creates a conceptual species-level or higher rule that we can see as group trait, by which species live or die, on the very long term. Indeed, for the purposes of variation and adaptation, outbreeding populations form what could be thought of as super-organisms. So sex is good- very good for species, which is why individuals put so much effort into it, pumping out clouds of pollen, luring insects to their lush crevices, and making our world such a colorful and biologically networked place.

  • A bit of biological history, in New Zealand.
  • Overview episode of mid-empire economics from the outstanding History of Rome podcast.
  • Should we use deterrence to prevent crime?
  • Case for the carbon tax.
  • Get some vitamin D.
  • A paper on the cycles of economic history, and Abba Lerner.
"For Lerner inflation that occurred before 3 per cent unemployment was a product of faulty institutions, not a problem inherent in markets. Thus he refused to accept that the target level of unemployment should be raised to whatever level required to stop inflation."
  • In a related vein, some economic fallacies, by Vickrey.
"Government debt is thought of as a burden handed on from one generation to its children and grandchildren.
Reality: Quite the contrary, in generational terms, (as distinct from time slices) the debt is the means whereby the present working cohorts are enabled to earn more by fuller employment and invest in the increased supply of assets, of which the debt is a part, so as to provide for their own old age. In this way the children and grandchildren are relieved of the burden of providing for the retirement of the preceding generations, whether on a personal basis or through government programs."
Though I would hasten to add, this applies only in financial terms. In real terms, the older generation gets whatever it needs from the services of the younger, so the savings serve only to make the older generation financially able to demand the requisite services on the market, not magically able to provide directly for themselves. The "payback" is the share of future real production diverted to those who have previously saved into bonds and other assets.

Saturday, November 20, 2010

Unemployment is unnecessary

Imagine a world where unemployment is a dim and barbarous memory

Unemployment doesn't exist in primitive societies. Everyone has something to do, and at the same time, no one has a "job" or gets paid. Everyone helps to do what needs to be done, and gets a share of the results. Social tools as well as self-interest get everyone to pitch in, and in extremis, one who is not pulling his or her weight may be ostracized.

With the rise of money, capitalism, and technology, humanity gained huge productive powers, allowing each person to exchange his, (or now her), expertise for the infinitely various products of others. An ironic problem with this world, however, is that it is too productive. It is possible for the entire population to survive based on the work of only half, or less. Indeed, agriculture takes up only 3% of the workforce in the US. What are the rest of us to do? Ideally, most of us might lie back in leisure, with Mai Tais supplied by the employed workforce.

Unfortunately, deciding who should be among the slackers isn't an easy problem, and unless one is the beneficiary of unusual inherited wealth, each of us needs income, based on our contributions to the community, in order to get a share in return, not just of Mai Tais, but of absolute necessities. In short, one needs a job. Conversely, society at large does not need any specific person to have a job. It can get along fine either way.

In positive economic times, this is not a problem, as jobs can be made of all sorts of pursuits. Musicians, mimes, bankers, buskers .. whatever can attract a buck is a job (just not blogging!). But sometimes there aren't enough bucks to go around. The current crisis is a classic case of financial collapse, with plunging investment and rising savings, leading to contraction of economic demand ... which is less bucks being spent, and thus fewer jobs.

In the lala land of conservative economists, (Chicago and Austrian schools), the labor market is always perfect, and anyone out of work just doesn't want a job at the going rate. They are lazy slackers. But that ignores the vast assymmetry of the labor market, best indicated by the seeker-offer ratio, now officially at five job seekers per job on offer. And this is a conservative estimate, since the official unemployment rate of ~9.5% misses significant classes of workers who either are so discouraged that they are not even looking anymore, or who have part-time work and would like full time work. With these classes, the unemployment rate is more like 16% and the ratio more like eight to one. Clearly, these are impossible odds, taunting seven of those ex-workers, day after day, month after month. They will be doing unpaid work (laundry, dog-walking, thumb-twiddling) for some time to come.

Unemployment rates, with U6 including discouraged, and part-time wanting full time work.
So the money economy drives everyone to participate to get money, but at the same time does not necessarily supply enough jobs to all who want them. Underemployment can be a stable condition, since the unemployed do not create the economic demand that leads the private system to invest in more productive capacity that creates more jobs. Thus the classic Keynesian policy of government picking up the slack by spending the missing amount (fiscal spending) to create that demand when demand is short of aggregate economic capacity, which can be conveniently defined as the existence of unemployment.

The second classic Keynesian idea is to create "automatic stabilizers", such as unemployment insurance and other safety net programs, so that when the business cycle hits a pothole, the federal government automatically (no legislation needed- no hands!) spends more into the economy on assistance programs while it simultaneously takes in less revenue in taxes. These work well as counter-cyclical policy, (except when economically illiterate legislators enter a state of deficit hysteria at the bottom of a cycle), but in the US, they are relatively weak. Unemployment insurance amounts to ~$1200 per month, on average, and has a limited term which has been only grudgingly extended in the current downturn on an ad hoc basis.

Other countries, such as Germany and Australia, have stronger insurance and other programs which help their economies (and workers) weather economic storms with much less disruption. (pdf, and see here.)
But obviously, there are problems with paying people to not work. Even if one takes the liberal-left view that people on average want to work and contribute to the greater good, incentives are important. That is why the economists I have been reading of late promote the idea of putting the unemployed directly to work on public projects.

This idea is typically called the "Job Guarantee" (JG) concept in the MMT literature. But to me that sounds like a political loser, so I will instead call it the Everyone Works concept (EW). The basic idea is that the Federal government funds, and local governments offer, jobs to anyone who wants one, at a basic civilized salary. For able-bodied workers, the government would no longer simply send money to those out of work, but would rather put them to work on local projects of a public nature, from litter collection to ESL instruction to road construction. Looking around, I see no shortage of public needs going unfilled, and it is really a crime to let the unemployed fester psychologically while not using their labor for beneficent ends.

Obviously the devil is in the details- how much are they paid, who hires them, who fires them, what do they do, and so on. The pay would be a living wage, which in my book would be 1.5 times the poverty level, or ~$30,000 per year / $2,500 per month, plus benefits. These jobs are on-going, depending on the mutual desires of the worker and employer. All EW workers would be paid the same, and naturally at this level, a strong incentive remains to find a private sector job at higher pay. This level would also set an effective minimum wage policy, obviating the need for continued legislation on that front. Youth might enter the workforce through this kind of program as a matter of course, resembling in some degree the national service ideas the come up in other contexts.

The EW program would have strongly competitive aspects, since the public need for work varies widely, from menial to artistic, technical, and beyond. Workers would apply & compete for jobs suiting their interests and talents. While local agencies would be obliged to hire each applicant for some kind of work, that may be as menial as litter removal or ecological restoration. Workers could likewise be fired from jobs if they didn't perform well, ultimately ending up on litter removal detail if otherwise unwilling to work at a higher level. If still not conforming to public needs, a worker could be completely fired and handed over to the deeper social safety net for psychological evaluation, counseling, etc. as needed. But this safety net would be much reduced, since the major pathologies of chronic unemployment would be a historical curiosity.

The WPA and CCC during the depression were inspiring examples of such programs, still paying dividends today in their physical and artistic achievements. Hoover Dam was built by an army of the unemployed in a public works project lasting only five years during the depths of the Great Depression. At a time when our infrastructure is crumbling, other public goods are rotting for lack of maintenance, and workers are going begging for jobs, a wide-ranging work program could usher in a new age of economic stability as well as improved public amenities.

A more modern example exists in Argentina, where an economic crisis prompted the government to start an EW-type program called Jefes de Hogar (Heads of Households), offering half-time community work and half-time schooling or training to all comers. This has been very successful in reducing poverty, stabilizing the economy, and enhancing development, especially in rural areas, at a cost of 1% of GDP. (See here and here for pdf reviews.) It has also pulled people out of the informal economy and employs many who had previously not sought employment at all.

Workers in this program would be trained as needed for new skills, and would also facilitate their search for private sector jobs by having their current work situations open to private employers, with job search components integrated, to a limited extent. Private poaching would be welcomed, and private employers would be assured of workers in better psychological condition, and often with extra skills, compared to those currently coming from the army of the unemployed sitting on couches and twiddling their thumbs.

Clearly, this kind of program would seem to be more geared towards low skill workers whose efforts are more easily fungible and usable for basic public service projects, whose private sector work tends to be more sporadic, and whose pay would be in the range of the EW wage. But I think all sorts of professional and skilled workers could find quite useful roles to play in a sufficiently open program, especially if they had a role in identifying and bidding for public needs. The program could use and enhance intellectual flexibility.

Who would pay for it? Under current conditions, the budget for 16% of the labor force of about 160 million in the US would be $770 billion dollars, roughly the proper scale of stimulus spending we need yearly till the economy gets back on its feet. If the US resumed a serious commitment to full employment, with unemployment rates of 2-3%, as existed fifty years ago, the needed funds would decline to $120 billion per year, easily affordable on an ongoing basis in view of the widely positive effects. For comparison, unemployment insurance, welfare, foodstamps, and EIC currently make up, very roughly, $200 billion in average years like 2006.

Can we afford it? The cost of EW hardly exceeds the sort of non-work programs which it would largely replace. So yes, we can afford it. During recessions, extra spending channelled through EW  would have positive effects on aggregate demand and the revival of the private economy, on the health of the labor market, and on the morale of workers involved, not to mention local public amenities, infrastructure & services. As the private economy revived, EW jobs would evaporate and localities would return to lower levels of federal support. One of the most pernicious aspects of the current downturn is that state and local governments have had to cut disastrously at exactly the time when needs are greatest. An EW program would allow the power of federal counter-cyclical spending to reach down to these lower levels in a stronger and systematic way.

Shouldn't unemployed people go the entrepreneurial route, making small businesses and creating jobs? In an ideal world, unemployed people would pull themselves up by their bootstraps, start bakeries, manicure shops, delivery services... anything that could bring in a piece of that economic pie. But even if the initiative and skills were there, it still wouldn't work from a macroeconomic perspective, since the pie just shrank. Just as there are fewer jobs than applicants, there is less spending (aggregate demand) than people who need that spending, whether through large or small businesses. So here again, someone (the government) needs to step in to the breach with counter-cyclical spending.

Would EW public work programs be boondoggles and make-work? Localities would have substantial incentives to make good use of this labor, it being at their disposal for projects of their choice, for their constituents. One could imagine a worker-initiated proposal system for projects, reviewed by local experts or elected officials. Localities may also wish to compete for workers from other places, based on quality of work offered, though the primary focus would be on local labor that is temporarily unemployed.

Of more worry, perhaps, is the possibility of EW workers displacing regular government or contract workers with competing skill sets, since people from all sorts of professions would participate. The local government would have an interest in keeping its permanent skill sets and loyal workers. But at the same time, the public employment sphere has become remarkably bloated and could perhaps use some novel competition of this kind, from talented people temporarily out of private work.

If this competition is too much for local governments to bear, despite their professed dedication to the public's welfare, they could contract with NGOs and philanthropies for projects that fulfill a public goods mandate, well away from the duties of regular civil servants. Remember that even if the work is of no significance whatsoever, half of the program goals are still achieved, which are macroeconomic stabilization and civilized income support for the unemployed. As Keynes said, paying people to bury fiscal dollars and then unleash others to dig them up again would be rational policy in recession conditions. Creating public goods is a highly desirable goal, but not the only one.

When all is said and done, this kind of program is a way to improve the standing of labor in the US, forming a more useful and helpful safety net with positive macroeconomic and cultural benefits. A typical countervailing argument, presented in one of the above-linked analyses of the Argentine program, is that such programs "reduce job search intensity", while increasing the quality of private sector jobs the workers ultimately take. In short, they make labor less desperate. Personally, I would regard that as a good thing. It is time for employers to do a little work in the labor market!

  • Kristoff compares the US with Argentina.
  • A fellow blogger covers unemployment trends.
  • The unemployed are pariahs, to pampered employers who have jobs.
  • In the black community, the unemployment fire is out of control.
  • Predatory loans and business corruption- at the root of the financial crisis.
  • The contest of wills goes on in Afghanistan.
  • Our bodies, our religions.
  • GOP congressman: gimme my free healthcare now!
  • Occasional Republican appalled at colleague's climate change corruption.
  • Bill Mitchell quote of the week, courtesy of Chicago-school ├╝ber-economist Robert Lucas in 2003, saying that the business cycle is dead:
"My thesis in this lecture is that macroeconomics in this original sense has succeeded: Its central problem of depression-prevention has been solved, for all practical purposes, and has in fact been solved for many decades. There remain important gains in welfare from better fiscal policies, but I argue that these are gains from providing people with better incentives to work and to save, not from better fine tuning of spending flows. Taking U.S. performance over the past 50 years as a benchmark, the potential for welfare gains from better long-run, supply side policies exceeds by far the potential from further improvements in short-run demand management."
At this late date, Ben Bernanke, who comes from the same perspective and is also critiqued in Bill's post, is trying desperately to perform monetary miracles without calling for more fiscal spending, which to his school (the supply-side, give money to the rich and wait for it to trickle down, school), is anathema. So interest rates are beaten down to zero at all terms, banks are given vast liquidity, and we wait for their animal spirits to revive. But it is spending that creates demand that calls forth investment, hiring, and further economic activity. Bernanke is gingerly and reluctantly stepping in that direction, having the decency to say that current unemployment is "unacceptable". To congressional Republicans, it seems to be quite acceptable, even desirable, if it weakens Obama.

Saturday, November 13, 2010

Did we screw up Afghanistan?

Conventional wisdom is that the US "deserted" Afghanistan after the Soviet withdrawal in the 90's, so everything afterwards was our fault.

Mired as we are in a decade-long nation-building and counter-insurgency project in Afghanistan, I keep thinking about its antecedents and background. A frequent narrative is that the US, after supporting the Mujahideen (jihadists) operating out of Pakistan through the 80's against Soviet occupation, dropped them like hot potatoes and was therefore derelict in its humanitarian, moral, and strategic duties in rebuilding Afghanistan.

It is surely a complicated issue, but I'd like to suggest that this narrative is wrong, and that the US was holding to its principles in leaving Afghans to their own devices, and doing very much the right thing. It seems deeply patronizing to say that without our "adult" supervision, the many fighters who had made the Soviet military machine cry uncle couldn't come up with a viable political structure for their own country. The natural presumption had to be that the Afghans, after so much sacrifice, had earned the right to direct their own affairs and form a government to their own liking.

In the first place, the analogy to our own revolution comes to mind. Would we have wanted France to "assist" us in setting up a new government, perhaps supervising our constitutional conventions or installing a temporary king? Clearly not. We muddled through with the Articles of Confederation for a decade, without any serious interference from Europe, and were glad of their neglect. After a decade or more of valiant war, the Afghans would hardly have wanted to exchange one colonizer for another, however well-meaning. Even now, after their own political system melted down further through chaos, civil war, and through to Taliban tyranny, it would be hard to say that the majority of Afghans want us there. Nor would Russia or the international community have seen us as terribly benevolent in taking advantage of the sudden collapse of the Soviet system by rushing into a former client.

Secondly, Islam presents itself as the ultimate political structuring ideology. It is a complete solution- a "government in a box", if you will, encompassing the spiritual system, social system, and political system. We had our Founders and our enlightenment principles, leading to durable social and political structures. Islam has its thorough compendium of Koran, hadith, sharia, and other legal structures, expressed to various extents in current Muslim states. Pakistan calls itself an Islamic republic, and Afghanistan just as much views itself as an Islamic state, whatever the vagaries of local tradition. Both should have been able to cooperate as friends and allies to bring the Islamic political vision to pass for the Afghan people.

Now of course I write with my tongue partly in cheek, since the empirically speaking, Western enlightenment principles of government are far superior to what Islam has been capable of, mired as it is in frankly medieval political theory with huge gaps where rational government, personal freedom, and popular legitimacy would otherwise be (though ironically, Islamic government during its golden age, a millennium ago, wasn't so bad). One solution is that of Turkey a century ago, which threw the whole Islamic edifice out the window and started from scratch on a Western model. And cancelled the caliphate for good measure. Egypt, Jordan, Syria, Saudi Arabia, Indonesia, and other Muslim countries have all tried to find middle ways, none very good to Western eyes. But who are we to criticize? If another country can keep itself together and not trouble its neighbors, that should be well enough. Right?

So one question is how capable the Mujahideen were of founding a decent Afghan state. We knew they were no Jeffersons and Madisons, but still, we had little right to meddle in their post-war arrangements. In fact, many had been brutalized through the Soviet war and related internecine wars, to the point that they could hardly conceive of a government not imposed at the tip of an RPG launcher. They also continued the age-old fissiparous traditions of Afghan tribalism which saw little need for a central government at all, but rather an unending small-bore contest of charismatic personalities and ad-hoc militias, harkening back to ancient Greece and before. But that again would not be a huge issue for us on the outside, as long as some internal arrangement arose, however decentralized.

This is one reason why Ahmad Shah Massoud, the Panjshir warlord most resistant to the Soviets and the Taliban, remains so revered in Afghanistan. He seems to have been the one person closest to a founding father, among all the parochial warlords and mafia figures, who towards the end of the Taliban era was broadcasting a broad vision of a unified and civil Afghanistan, before being assassinated by Al Qaeda. He was the only major leader not coopted by Pakistan, Iran, Russia, or other foreign powers, as well as not being Pashtun and thus particularly interested in a non-sectarian vision of Afghan unity. Now the country limps along under the tutelage of Hamid Karzai, originally thought to be a similarly unifying figure, but as it turns out, one with a much smaller vision, with deep problems of corruption and nepotism, who has been seriously undermined by our own failures and lack of understanding.

Another large question is the influence of Pakistan. After supporting Afghan nationalism for so many years, it was hard to believe (for a naive person, perhaps) that the Pakistanis would so thoroughly abdicate their brotherly and Islamic role in Afghanistan's postwar future by promoting the most vicious civil war, continuing instability, and ultimately, the rule of astoundingly regressive Islamists orginating from the madrasahs of Pakistan (the "students", or Taliban). But that is what happened.

Of course, the Pakistanis have little to crow about in their own governance or neighborhood relations, so this also would have been less surprising to experienced US policy makers. All the same, the malign influence of Pakistan, even if fully recognized, was hardly reason for us to enter the treacherous Afghan political scene in a more direct way, especially as we had let Pakistan control our aid to the mujahideen for years. Even now, when Pakistan remains the bulwark of Al Qaeda and Taliban resistance to Afghan and US interests, we are, of all things, giving them arms and calling them our "allies".

So we were honestly and rightly reluctant to have any deep role in Afghanistan after the Soviet era. Should we have given more aid? Perhaps, though it is hard to see to whom that aid should have gone. Should we have watched developments carefully and nurtured our own intelligence and language capabilities for Afghanistan? Of course. Should we have put the screws on Pakistan to turn off their spigot of arms and not play strategic games with their neighbor, poor and weak as it was? Sure, that would have been nice, but ineffective in light of our current influence on their perpetually self-defeating policies. By the late 90's, we had put Pakistan in the deep freeze anyway over their nuclear testing.

Now, two decades on, we are very much in Afghanistan, and need to be clear on the vast scope of what we are trying to do. Which is, to reshape the political culture of Afghanistan from top to bottom, easing Afghans out of a civil war mindset, sidelining Pakistan's influence, and protecting nascent civil life and political institutions, patterned partly on Western models, from the constant assaults of insurgent violence and islamist ideology. It is an enormous job, and not one we would have willingly gotten into without the absolute necessity of "fixing" a nexus of failed governance and playpen of global jihadery.

Can we fix it? That we pulled the bacon out of the fire in Iraq is promising as a model, but the problems of Afghanistan are less tractable- especially the influence of Pakistan and the Afghan's own lack of experience in state structures vs tribalism. We are perpetuating the civil war as participants, so it is hard to say that our influence is entirely good and pacific. Nevertheless, the main need is time, since the core of the job is a slow process of cultural change. Afghan minds are turning from internecine warfare to democratic political contests and quality of government issues at all levels. The deal is that we will leave once enough Afghans have turned the corner and once the middle tier of warlords and mafiosi has been disempowered, replaced by public servants. The US and NATO, as representatives of, let us just say- empirically superior Western governing practices, are protecting and teaching, but it is up the Afghans to listen and hear.

"The current state of affairs – with appallingly high unemployment and low activity levels – can be considered an equilibrium in the sense that there are no dynamics present that will change the situation. Firms are producing and hiring at levels that are consistent with their sales. The unemployed clearly desire higher consumption and would buy more goods and services if they were working but that latent demand is “notional” and not effective (backed by cash). The market fails to receive any signal from the unemployed and so firms cannot respond with higher production."
..."My own profession should hang its head in shame for being instruments of this religious persecution of the disadvantaged."

Saturday, November 6, 2010

The genomics revolution will not be televised

The genomics revolution has happened.. on the scientist's bench, but not in the doctor's office.

Scientific American had a very good article on the genomics revolution, ten years after the first human genome was fully sequenced. That sequence was a signal event in the progress of human knowledge, as was the prefiguring discovery of DNA's structure fifty years before. But who has benefitted? There is no comfortable way to say this ... biologists have made out like bandits so far. They (especially Francis Collins) promised a transformation of medicine resulting from the knowledge gained through this sequence, but that train has hardly pulled out of the station ... yet.

Biologists have seen their field transformed by this new knowledge and associated technologies, which have multiplied their power to ask questions of organisms. Where they were happy to know how one or two genes responded to a drug or other condition, now they measure the response of every gene in an organism. Where they spent years mapping the mutation and gene responsible for an interesting phenotype or disease, now it may take only days to figure out the gene's location.

What's the slowdown? Obviously, it has to do with complexity. Even with the genome in hand and with accelerating technical capacities, understanding doesn't come as rapidly. The blueprint metaphor for the DNA code doesn't quite work because it is not actually a scale model or drawing of the organism's morphology, or a neat drawing of its chemistry either. Instead, the DNA is a digital code for rune-like protein sequences that assemble themselves into dynamic animated super-heroes that fly around the cell doing difficult-to-understand jobs, controlled not by a single mastermind, evil or not, but by a bogglingly complex network of whatever happened to crop up during evolution. Perhaps a sprinkle of protein phosphorylation here, a location-specific DNA controller there, and indirectly regulated protein degradation as well. It all goes into the pot of what makes our biology go.

Integrating all this action and re-action conceptually, as the cell does in the flesh, has been an enormous problem that has made computer sciences particularly important in biology. But success in that kind of modelling remains tantalizingly far off. Biology is in essence an alien technology, perhaps the most alien technology we will ever encounter, having nothing to do with our macroscopic technologies of carpentry, stone-hewing, metal-working, etc. Its principles are completely different, and not simple.

Another issue is about what is even possible with respect to medicine. Not every malady will ever be addressable by a drug in the current paradigm, which is making drugs that interfere or help the function of proteins. Only when we gain the capability of using drugs to directly control and change genes throughout the body's DNA will our pharmacological powers truly be omnipotent, something still quite far off, and of course full of ethical conundrums as well.

But back down to earth... the most interesting point made in the article was about a push over the last decade to map common variants in the human genome, among people and populations, in hopes of identifying the most important disease-causing genes and pathways. (One example is the HapMap project.) Because sequencing one genome was of course not enough- we had to sequence lots of genomes and compare them to figure out how people differ, in all those interesting ways that make us happy or unhappy. Eventually, every person will have their genome sequenced, which will be a rich and central part of the individual and collective medical record.

But the logic of this first variant hunt was fatally flawed, for eminently Darwinian reasons. The idea behind it was that many traits, like hypertension or diabetes, are common. Thus the genetic variants that cause them should be common as well, making them easy to detect with the modest sequencing technology of the day. But actually, this was like looking under the street light just because you can, rather than because the keys are there. Genetic variants become common in a population precisely because they are inoffensive, perhaps even fitness-enhancing, not because they are the primary causes of the diseases that doctors and geneticists were hunting around for.

What the researchers found, at the cost of about $100 million, were lots of variants, but precious few with any effect on disease, and those with only tiny effects. They were essentially useless either for diagnosis or for the important work of studying genetic networks/pathways of disease. This led to a lot of papers (and news reports) about gene X linked to, say, alzheimers, which later turned out to be insignificant. It turns out that rare variants are the ones that are far more influential for diseases with genetic components. We all have lots of variants, and the ones that kill us are likely to be quite rare in the population, understandably enough. But more always come along, to be sifted out again and again via selection.

A similar story has happened with the specific condition of autism, which has been found to be related to variants in a stunning number of genes- dozens, if not hundreds. It looks like autism arises from defects in a broad developmental process in the brain that can be derailed into some characteristic groove by many genetic defects, each of which are naturally weeded out during evolution and thus never become common in the population.

So, sadly, ironically, but perhaps not surprisingly, molecular biologists had a weak understanding of evolutionary biology, were smitten by their new sequencing toys, and thought that the most accessible data (common variations) would be informative, or at least were able to convince their peers/funding agencies to that effect. The common variations have certainly been useful in some ways, however, such as tracing human ancestry over time and geography. And, now that we know the forces involved, in setting a baseline of sorts for low-impact genetic variation.

Now that rare variations are far more accessible as sequencing technology advances, researchers have been increasingly successful in finding genetic links to diseases. But what of it? One dream in the field was that genetic testing would be able to help us predict disease propensity with great accuracy. But if the disease-causing genetic variants are rare if not novel, and, in scientific terms, uncharacterized, they can't be used for a reliable prognostic test. This dream remains essentially unrealized. On the other hand, finding genes with stronger ties to diseases, by directly sequencing affected people and their families, helps the research enterprise tremendously, finally filling in some of the nodes in the networks that break down or go haywire in disease.

One example is a recent paper in Science by researchers who sequenced all the protein-coding genes of tumor cells from eight different human ovarian tumors. Amongst the scattershot mutations common in cancer cells, (these were not inherited germline mutations, but somatic mutations that arose during tumor development), they found four genes that had been hit more frequently. These four where then resequenced in a panel of 42 ovarian cancer tumors, 24 of which showed mutations in one gene whose product regulates chromatin accessibility. This gene had never before been thought of as a tumor suppressing gene, but its super-high rate of co-involvement here showed it to be one. Thus one more piece is added to our knowledge of how one kind of cancer can escape normal cellular controls. But knowing that this gene's inactivation can contribute strongly to cancer brings us little closer to a medical treatment, unless we have a way to replace its function ... i.e., to do gene therapy.

  • Unlike basic science research, medical studies are a minefield of error as well as waste.
  • You know it's hot when Ms magazine complains that not enough new atheists are women.
  • Black and godless.
  • Obama's unrequited good work.
  • BofA and its MMT accusers discuss its fraud. Quite illuminating.
  • Bill Mitchell quote of the week, quoting Joseph Stiglitz:
"JOSEPH STIGLITZ: My view is we cannot afford not to stimulate the economy. So, you know, anybody that says we should go back to austerity or we should not have a second-round stimulus just doesn’t understand economics. And let me be very clear about this. If we don’t stimulate the economy, the economy is going to get weaker. When the economy gets weaker, tax revenues go down and expenditures go up. Already, more than 40 million Americans are on food stamps. Number of people on Medicaid is reaching record levels. So, revenues go down, expenditures go up, deficits get worse. If you stimulate the economy, then people get jobs, they spend money, tax revenues go up. Now, if we spend the money on investments—investments in education, technology, infrastructure—you grow the economy in the short run from the stimulus, you grow the economy in the long term because of the returns that you get on these investments."
Bonus quote of the week, from Rand Paul: 
"There are no rich. There are no middle class. There are no poor. We all are interconnected in the economy. You remember a few years ago, when they tried to tax the yachts, that didn’t work. You know who lost their jobs? The people making the boats, the guys making 50,000 and 60,000 dollars a year lost their jobs. We all either work for rich people or we sell stuff to rich people."