Two Cents About Grad School

Some months ago Felix Salmon wrote his excellent article with a cost-benefit analysis of getting an advanced degree in the humanities. This inspired me to summarize my own thoughts. I am not a graduate student in the humanities, but rather a medical student, and I just finished my first year. However, I did have a "real" job for 13 years before I went back to school. With that knowledge, weight my advice accordingly. I find that a lot of the same blind spots suffered by Salmon's hypothetical humanities student also afflict my younger classmates. However, I think there are several ways that students entering and studying in graduate programs, professional or otherwise, can avoid doing themselves a disservice.

1) Be sure to consider the economic future of your profession and your financial goals. You are not too good to worry about the mundane laws of supply and demand. They surely apply to you just as well as they apply to your mechanic. There's a difference between chasing dollars for their own sake, and being able to afford an apartment in a middle class neighborhood without a roommate when you're 49. You're choosing your lifestyle now, and you won't always be in your twenties or thirties. Think about that carefully.

2) Don't overspecialize or commit to an academia-only field. That ensures a lack of career options and mobility. Lack of control over your schedule and work location is one of the top factors damaging to happiness. Also, consider economics again. You're not special. Academia is not special. Do yourself a favor and free yourself of this bias.

3) Make sure to have frequent contact with people not in your program or university. Better living through induction! Talking face-to-face to people in bars or coffeehouses in other parts of town, and friends of parents, and people in any non-university-related social group - especially happy people - is absolutely invaluable. Get out into the great outdoors. Try something new that you're not good at. Don't be one of those people who lives for years in an interesting town or region of your country for years and barely leaves the academic ghetto. (I can't tell you how many Berkeley grads I know who have no idea about the amazing parks less than five miles from their doorsteps.) Having friends and activities in different social circles is another proven way to de-stress. The politics in your department and obstacles that you thought were all-important will suddenly seem really temporary and trivial, and you may just have an epiphany about what it is you're really trying to accomplish, in your project or your life.

4) Don't buy into the twenty-something myth that if you have interests outside of work and/or are usually happy, you aren't "serious about your career". This is just as true for twenty-somethings outside of grad school.

5) Don't go to grad school just to avoid the post-college depression. If you're on a career track that doesn't require a graduate degree, congratulations. Don't get one. When at age 23 you're suddenly for the first time not surrounded by age peers with whom you can socialize effortlessly, it's normal to get a little depressed. In fact I'm surprised "post-college depression" isn't a well-known institution of our culture by now. In 2010 it's probably a softer landing than it was in 1996 because technology makes it easier to stay in touch and meet people who share your interests, but it's still there. Be honest with yourself about your motives, and don't go back to college to be around other young people - you can do that for free.

The Bad Stripe Continues: Overall Well-Being

In an overall well-being survey, the Bad Stripe that jumps off of maps of the U.S. of well-being, health indicators, and economics is again unfortunately represented.

Read more about the Bad Stripe here, here and here. Looking at the reverse of the map above, the photonegative of the Bad Stripe stands out in this map of frequent mental distress (Kentucky comes up worst.) In addition to the relations there, the Bad Stripe is also the boundary between three geographical social networks built by Facebook users, and it also tracks the boundary between Baptists and Methodists judging by geography-associated tags on the internet. It's tempting to speculate about the link between being a cultural boundary zone and an emotionally depressed area and what the causality might be.

Even Now Athletes Are Rushing to Join North Korea's Sports Teams

After the 7-0 World Cup loss to Portugal, that can only be sarcastic. It's truly remarkable that more countries don't try to emulate the Dear Leader's management brilliance.

Will China Eat Our CleanTech Lunch?

That's the title of an article from Xconomy Boston. The worst position the U.S. could end up in is still being oil-dependent 50 years from now while China is not only weaning itself off oil, but developing and controlling the technology to do so.

Atlas Smirked

"We all lied on our timesheets. If I got lucky and finished three surveys in half an hour, I’d go home and get drunk in the afternoon and pretend I had spent four hours knocking on doors that no one answered. If I was too efficient in getting surveys filled out, I’d run out of work in my area and get let go, so I was really just following my rational self-interest like Ayn Rand would have told me to."

- ZING! A census worker describing his job in Viceland

The Iroquois Stickball Team and Real Sovereignty

They used Iroquois (Haudenosaunee) visas. To put it bluntly, countries like the U.S., Canada and South Africa that have "sovereign lands" arrangements with pre-European inhabitants are playing a game. We relax a few laws and call you a "sovereign" nation. It works fine, as long as there is no one involved besides the "sovereign" government and the surrounding, real government, and everyone plays the same game of pretend. It seems especially ridiculous when you consider that there are plenty of Native Americans who have no Federally recognized status as such just because they've never been "Federally recognized". That is, your Indian nation only exists if the U.S. government says it does. (In Northern California, Wintus are still not recognized, whereas the Feds did recognize some business partners who wanted to open a casino in San Pablo, CA.)

Where the rubber meets the road is when something happens that requires a foreign government not playing this game to recognize their sovereignty - as happened here. This would be bad enough even if people hadn't previously entered the U.K. using a Star Trek Federation visa (if you have the link, send it.)

That being the case, if American Indian reservations want to be recognized internationally, they have to start behaving like actual sovereign nations, and this means (for one thing) if you want to use your own travel documents, establish the relationship ahead of time, instead of assuming that the U.S. will do it for you. I've often wondered why Indian reservations in the U.S. don't push the issue more, and experiment with more than just gambling laws. Anecdotally, it certainly seems to me that gambling on rural reservations isn't contributing positively to the trade balance with the outside world; it seems that the vast majority of people gambling are from the rez, and the only wealth movement (not creation) is going from the pockets of people on the rez to the few people on the rez that own the casinos. I recall a case in the 80s or 90s of a reservation in Oklahoma that was pissing off the Federal government by offering wacky interest rates on loans and bank accounts, though I don't remember the details and can't find it now.

The real reason to support reservations pushing the issue with the Federal government is not to create anarchy but because it would provide a great opportunity to improve our democracy; there would be pressure on Federal institutions, and the closest thing to competition that government has. Why not more and more dramatic experiments than just gambling? Drug decriminalization is an obvious one, but what about foreign relations (begin relations with China and see how the Feds like that), medical research, numbered bank accounts, various internet safe-havens? It would be pretty awesome if the Navajo Nation offered its own Phase I drug research facilities. If that sounds potentially exploitive, you can mandate a certain level of investment in the local economy or a certain number of local employees like Thailand did when every corporation and his brother started doing HIV research there. And I'm sure lots of people (especially foreign pharmaceutical personnel with lots of currency!) certainly wouldn't mind a work-related excuse to be in the proximity of Canyon de Chelly and Monument Valley.

Other Primates Have Developed Other Forms of Political Satire

Read about them here, hat tip Tyler at Marginal Rev. On the whole I prefer Jon Stewart, but then again I'm human.

One Way to Tell Your Workplace Has a Toxic Environment

I consulted at a number of biotech companies in my pre-med-school life and I was fortunate that most of them were great places to work with good people. Two in particular were not. The distasteful reality I noticed at both of them was that it wasn't possible to get anything done without being a member of political alliances. That alone is not uncommon at companies (sadly enough) but the important feature here is that at a truly toxic company, these alliances are based on blood relations or shared ethnic background. Ugly, but unfortunately real - and it unfortunately makes sense. In a company that lacks the corporate equivalent of rule-of-law, life is unpredictable, and the only relationships with any degree of trust are those deeply-imprinted connections of family or culture, because they're not within your power to consciously opt out of.

Needless to say, I didn't spend much time at either company, and neither did very well. One no longer exists, and the other is about to de-list from its exchange.

Reporting Live from the Oakland Riots

If you're unfamiliar with the New Year's Eve police shooting of Oscar Grant in Oakland and the verdict which just came out yesterday, you can go here to read about it. Note well that there has appeared a fine tradition of participation in the subsequent riots by people who are best characterized as frat boys who like to break stuff but who think they're activists because they can parrot a few lines from that radical political theory class they had to take to graduate (and in which they got a pity C.) Here is some of the representative graffiti I saw this morning:

"Say no to work, say yes to looting"

"Tonight Oakland is our amusement park"

Clearly, these are people grieving for Oscar Grant. These are clearly people who spend their lives fighting for justice.

Also of note is that the silliness was confined to a few blocks of Broadway. Of course in the greater San Francisco metropolitan area there's a sense that all of Oakland is convulsed in flame that the media does nothing to dispel because it keeps people glued to their TVs. People were terrified to get within 50 miles of Oakland. A friend of mine in Vallejo wouldn't even drive through Oakland to get to San Francisco. I'm sitting a mile from the riot zone and last night seemed exactly like a normal Thursday night.

Interesting Timing on Wikipedia Down-Time

The 2009 Urumqi Riots are selected as the cover article for today, and suddenly people are having trouble getting to Wikipedia. Touchy Han nationalists perhaps?

Do Small Biotechs Really Produce More AND BETTER Drug Candidates?

...and if so, why?

This is a crucial question for the U.S. economy since (until recently anyway) pharmaceuticals were one area where the U.S. wasn't running a massive trade deficit.

It's a cliche that Big Pharma can't find its own leads and has bought its pipeline from biotech for the past 10-15 years, which serves effectively as free-range R&D (until the eventual round-up.) Having spent most of my time before medical school consulting at smaller biotech companies, and several times finding myself with unexpected free time because one of those companies was bought for its portfolio and closed, I've spent my fair share of time wondering about this question. However I actually can't recall seeing an analysis of biotech vs big pharma output, or in particular, of the quality of drug candidates judging by ROI or absolute annual sales. But let's assume that the disparity is real. Big pharmas certainly assumes the disparity is real - they sometimes try to duplicate the perceived success of small biotechs by putting together small entrepreneur-like groups, like Glaxo. So what is it, exactly, that is more productive about small biotechs?

1) The most obvious: small biotechs have a much greater incentive to get their (usually lone) drugs into clinical trials - if they don't, they disappear. Big pharma management is not so incentivized, and timelines of individual drugs are sometimes adjusted to fit the portfolio. What's being maximized is completely different for a start-up biotech and a multi-drug big pharma. Overall sales is what's being maximized in big pharma, while speed to first-in-human and to market is being maximized in biotech (it equates to survival and therefore financial incentive.)

2) Small biotechs may produce more candidates, but on average lower quality candidates. Because of money and therefore time limitations, they're willing to push through the first lead where the Glaxos of the world have the cash to keep tweaking the skeleton. You would think this would necessarily mean that the big pharmas then wouldn't be interested in these low-quality candidates, but a) not all decisions are rational, and hype and groupthink have effects in the real world ("We have to buy them to get the first XYZ inhibitor!") and b) the first-in-humans candidate of a given class is often "lower quality" than what might have been the second-in-humans candidate, which as mentioned above the biotech won't wait around to discover. The perception and impact of candidate quality difference is highly context-dependent in this regard.

3) At biotech start-ups, scientists have the greatest influence on senior management or are senior management. At companies in general, typically the management of the group closest to revenue generation is the one that has the most influence over the CEO. In contrast to biotechs, at big pharmas, this means sales, not drug discovery. In a company that doesn't yet have any sales, this means clinical, or (if even earlier in the cycle) chemists and biologists. Once sales obtains this position, the amount of time the CEO spends thinking about new drug candidates decreases and development plans tend to be de-emphasized (until everyone panics and it's too late.) I had long suspected that Genentech owes its productiveness to keeping its scientists in key decision-making positions (including at the very top) and after having consulted there I'm more convinced that this is the case.

4) There are scale-dependent effects that would be present in any organization but are exacerbated by the uniquely long product development cycle in pharmaceuticals. Amplifying this is the level of government oversight in the industry and the consequences of regulatory transgressions, leading to what are referred to in politics as Olsonian veto blocs inside the company, large groups of people who have a say in the process and have nothing to lose by saying "no" but everything to lose by saying "yes" at an inappropriate time. In the pharmaceutical world this is legal, regulatory, and QC - absolutely necessary to the industry, but their influence on timelines seems to be strongly scale dependent. In my own experience in the industry, some of the most focused "how do we get this done" people I've worked with were in QC at the biotech level. Some of the most obstructionist were in QC at the big pharma level. In general a company with a large revenue stream should be expected to be much more risk-averse than a company with no profits. In the same vein, once a drug is approved, any new investigations could potentially yield a new indication that would either provide some new revenues for one indication, or new safety findings that would diminish revenues across the board for the whole molecule, for all indications. Consequently post-marketing investigations are usually done with kid gloves.

5) Free-riders are proportional to company size (again we see scale-dependent effects.) At a smaller company, free-riding is obvious to all, more immediately detrimental to the future of the entire company, and more quickly punished. This is not the case at large companies with deeper pockets, many of the employees of which seem to be benefiting from a kind of corporate welfare state. This situation often arises at low surface-area-to-volume companies, where a greater fraction of employees interacts only with other employees rather than with customers, vendors, or industry contacts outside the company. It would be worth seeing whether there's a sweet spot for company size in terms of a relationship between number of personnel vs. first-in-human clinical trials per person*year, including outlicensed compounds. (My prediction is that this drops with increasing company size, with a curve that steepens around 250 head count and starts leveling out a little at a thousand.) Anecdotally, I have also noticed an odd scale-dependent increase in the proportion of employees at a company who have ever worked in government - not from related agencies like FDA, but from local governments or other areas. Larger companies are more government-like.

[Story time - and if you know me personally, you know which company I'm talking about. I couldn't help but reflect that the strategy of employees of one big pharma subsidiary company where I worked was exactly that of a parasite in the gut of a large, warm mammal that can afford to miss a few calories here and there. They downside to the strategy is that they're super-specialized to thrive only in that environment; that is, their skillset degenerates into "how to stay employed at ABC Big Pharma". Consequently sometimes they have to transfer between mammals of the same species (i.e. subsidiaries) to survive. They day it was announced this particular subsidiary was being shut down by the parent, I saw groups of people openly weeping as if Princess Diana had died all over again.]


CONCLUSION

If you didn't get enough speculation already, read on. Plus this part also has colorful analogies that I think are nonetheless still useful.

- Though I haven't been able to find the papers, from my undergraduate classes in anthropology I learned that there was research done on Amazonian hunter-gatherers showing that there are village sizes beyond which there tend to be fission events. It's not that the village hits 150 and everyone draws straws to determine who moves, but there are dynamics that invariably take advantage of a trigger event to cause the split (the chief and his brother have a fight, there's a food shortage and some families move to find better hunting areas, etc.) This suggests that there are in general optimum sizes for human social organizations. This research may have a direct bearing on the productivity of small vs. large companies.

- The biotech industry in each part of the country where there is an active scene (the Bay Area, Seattle, San Diego, and Boston) is a notoriously small world. People often end up working together in different combinations at different companies, merely being re-sorted based on skillsets. In Edward Bellamy's 1888 utopian novel Looking Backward, he describes a system where workers have general industrial skills and are (centrally) resourced to new factories based on need. Of course Bellamy was arguing from a socialist standpoint but in biotech it seems that the free market has already generated exactly this arrangement.

- The pharmaceutical industry is not the only one that is dominated by deep-pocketed century-old behemoths that present barriers to entry and snap up competition. If biotechs are as everyone expects more productive than big pharma, this is bad for patients and bad for the economy, and yet there is no check on the growth of the largest companies. It's as if we're at the end of the Cretaceous (with animals so large they need second brains to coordinate their movements) or in the middle of the Second World War (where the incentive to build ever-bigger battleships yielded the monster Yamato.) In both cases, conditions changed (climate and aircraft, respectively), and selection no longer favored the most massive, but it's hard to see how this trend will ever reverse itself, since it's hard to see how capital accumulation can ever be economically selected against. That is, I don't know what would be capitalism's equivalent of Chicxulub or P-51 Mustangs that would obviate the uneven accumulations of capital, so for now we're stuck with biotech serving as free-range R&D for big pharma. (Unless tax burdens on the largest corporations goes up to make those accumulations into liabilities. Even so, this would be a dangerous game for small biotechs to want the government to start playing.)

An older version of this article is cross-posted at my science and philosophy blog, Cognition and Evolution.

How Do We Measure "Neighborhood" Chilling Effects?

Mohamed Naguib at M.D. Anderson Cancer Center has a paper in Anesthesia and Analgesia about a synthetic cannabinoid that has some of the benefits (relief of neuropathic pain) without the other psychoactive properties we associate with marijuana.

It's not clear that any recent changes in the body of law or law enforcement allowed this instance medical progress, it's very difficult to argue that it was not slowed by our current illegal drug classification system. The absurdity that marijuana is a Schedule I substance while methamphetamine and cocaine are Schedule II cannot be overstated. The irrationality of the classification system, as well as selective enforcement and public perception that stems from inconsistent policy, must have chilling effects on legitimate medical research, including for basic pain relief like Dr. Naguib's research. Even if physicians, medicinal chemists and the actual medical research labor force are willing to take these risks, their institutions and funding sources are understandably more nervous when they're dealing with any chemical entity even in the "neighborhood" of ones that are of particular interest as contraband.

The question is, how do we assess the damage done, both in economics as well as lost utility, by neighborhood chilling effects? Regardless whether a moral argument is made about the laws surrounding psychoactive substances, it seems obvious that in this case Naguib's research would be easier to do in the absence of substances in the same chemical family being illegal. Economists must have some way of modeling whether there would have been an overall difference to the economy or the growth of an industry in the absence of criminalization of related goods.

Sun Yat-Sen and the Enlightenment

I was confused to find universities in mainland China named after Sun, since I'd always associated him with the KMT and therefore the government now in Taiwan. Learning more about him he quickly stands out as a clear extension of the Enlightenment to the East. Scanning through Google Books you'll find some fascinating essays from Sun himself:

Monarchy has steadily shrunk as democracy has steadily expanded. Following the recent war in Europe, which witnessed the downfall of all its remaining autocracies, monarchy has been left with scarcely a foothold on the continent. This has been the tide of political progress throughout the world; it is beyond man's capacity to resist it, being precisely what the ancients meant by the "will of heaven." "Those who follow the way of heaven prosper, while those who defy it perish."

The Enlightenment in China didn't ignite independently of politics of the rest of the world - Sun attended the 'Iolani School in Hawaii and was especially inspired by Western principles through American political history, in particular by Lincoln. (Sun is considered the father of modern China both in Taiwan and on the mainland, hence the institutions named after him in both places; I wonder if this strong American influence on his philosophy is taught in schools in Beijing?) But it's exactly his ancestry to both China's capitalists and (at least nominal) communists that is key. Both Karl Marx and Adam Smith were arguing for liberties and an economic order based on reason and material improvement, rather than on authority invested in monarchs by a deity. Sun wasn't afraid to point out problems he perceived with either's theses or the constitutions of contemporary democracies, and as a result he still isn't easy to classify in any Enlightenment ideology dating after the free-market/central planning split. Go back up and read that quote again - this was a revolutionary speaking, but (ignoring the spiritual rhetorical fluorish) these could easily have been the words of Jefferson or Lenin. It has echoes of Marx's inevitable current of history, and every American President's evangelism about the expansion of democracy.

But Sun was primarily concerned with the legitimate basis of governance and liberty - which Jefferson and Lenin largely shared - not with economics. In contrast, today's religious terrorists have more in common with yesterday's deity-justified hereditary autocracies. Even without debating the moral definition of legitimacy, we can look at the practical impact. Countries with strong, predictable, transparent institutions, along with freedom of speech and the press and assembly and open elections, are the ones with the most sustainable growth. Certainly at the two extremes of economic policy, having either zero safety net or absolute redistributivism would hamper development, but the imposed tax burden or lack of social supports turn out to be secondary influences on the fates of nations, after resilient institutions and liberties. When these conditions obtain, it is assured that the political system in question will have mechanisms to correct itself by allowing innovations (which sometimes shine through despite a bad system's best efforts.) It seems that Sun had deduced this early on, since he was willing to align with the communists even though he was not one. Little did he know in 1911 how seriously and literally communist revolutionaries in Russia and later in his own country would take the points of Marx's program for a dictatorship of the proletariat. And how curiously disinterested they would be in its eventual dissolution, as Marx also wrote.

It's also worth observing that although China's communist government appeared later than the Soviet Union's, China's anti-monarchist revolution occurred 6 years earlier. This might lead us to ask why China had a 38 year interregnum between its revolution and the establishment of its lasting government, when Russia's was less than 1 year. More generally it's also worth asking why the U.S. was so fortunate in terms of instability. The U.S. had a 6-year interregnum (the Articles of Confederation) from the official end of hostilities with Britain to our Constitution, but very little fighting, even including my own pugnacious home state of Pennsylvania. Compare these light casualties to the post-revolutionary histories of Mexico and even France. Why was the transition in America so relatively tranquil? But these are separate questions.

In the end, Sun was at heart a patriot who wanted to see a stronger China, and patriotism is a relatively recent phenomenon. When your master and de facto owner is Louis XIV or the Tokugawas, why bother being proud of being part of a French or Japanese nation? Why did it matter if any subject liked or approved of their government? The idea probably would have seemed a little precious and naive to le roi or the shoguns, and puzzling and pointless to peasants. As such, Sun initially approached the Qing court with suggestions for a stronger China. These were either rejected or ignored. In the Qing Dynasty, if you weren't Manchu, your chances of having any influence were slim, although you still had some chance of access to the inner circle of you were willing to jump through the hoops: learn the classics and pass the civil service examinations, all relatively costly signaling that you would devote all your attention and time to the pointless exercises set by the Qing, rather than doing something useful and merit-based. Sun wasn't willing to do this, and many sources connect his turning from a would-be reformer to a revolutionary to these experiences in the mid-1890s. (Modern corporations and governments take note! Do you want talent, or do you want people willing to submit to mindless ritual?) But the Qing were not long for the world, and the resources they forced their best-and-brightest to waste on hoop-jumping was doubltess one factor in their demise.

Finally: the Western world would benefit from a new, well-researched account of the colonization of the New World, as well as of the classical era from the Battle of Marathon through the fall of the Western Roman Empire, by East Asian authors. Doubtless there are artificial distinctions we make and myths that have been promulgated for centuries that Westerners no longer notice or question, and that Asian writers would quickly identify and explode.

The EAC: East African Community

Burundi, Rwanda, Tanzania, Kenya, and Uganda are turning into a single-visa zone for foreigners. They're already in the process of eliminating work visa requirements for each others' citizens, and ultimately they're aiming for a common currency. This will hopefully stabilize these countries economically and politically (less ethnic violence when all five governments have an interest in each other, and much less probable bad unilateral economic policy decisions.) We'll also have data on another experiment in political and economic cooperation. There is already a West and Central African Franc, although I'm not aware of any studies showing whether this has been good or bad for that currency zone.

Nationalization could be seen as the opposite of this process, in that it makes economics and the security of assets in the country less predictable. It would be interesting to compare the fortunes of eager-to-nationalize states like Zimbabwe, Bolivia, and Venezuela, based on Peruvian economist Hernando de Soto's argument that economic take-off of developing economies is based on transparent property-ownership conventions that encourage value creation. Are there studies correlating nationalization with foreign capital inflows and growth rates? Granted, Zimbabwe's ruination was also caused by a monetary approach that should have gone out with the Weimar government, but looking across all nations, we could still see an effect. You could even make the argument that internal nationalization would have the same effect on private capital within the country. Late-in-the-game price controls on new pharmaceuticals are the classic game theory example of sunk-cost gotcha's.

No doubt these governments and many progressives in the developed world would argue that they have the right to nationalize assets in their country, but unfortunately, in the world of trade and investment this is beside the point. If your assets aren't safe in a certain country, you're not going to put money there. Maybe these governments (or more accurately, their insulated leaders) are willing to endure the pain of international investment pull-back in order to achieve independence from foreign influence, but there is a large trade-off between absolute independence and growth rate requiring foreign capital. How much is absolute economic independence worth?