Sunday, June 26, 2011

The Rational Optimist, Matt Ridley

Matt Ridley's The Rational Optimist is a very well written ode to the value of trade and how it contributes to a rational confidence that things will continue to improve for humanity as they have since we first appeared in the world.

Ridley's previous books have mostly been on evolution (though that includes the evolution of cooperation and virtue). Here he's focusing on how trade enriches us all, and how far back trading goes. He uncovers new evidence for the richness of trading in antiquity. One example is Oetzi, the mummified ice age hunter revealed by a receding glacier in the alps in 1991:

[He] was carrying as much equipment on him as the hikers who found him. He had tools made of copper, flint, bone and six kinds of wood: ash, viburnum, lime, dogwood, yew and birch. He wore clothes made of woven grass, tree bark, sinew and four kinds of leather: bearskin, deer hide, goat hide and calf skin. He carried two species of fungus, one as medicine, and other as part of a tinder kit that included a dozen plants and pyrite for making sparks.

Ridley's point is that Oetzi couldn't have collected, sewn, tanned, woven, smelted and sharpened everything he carried himself. The only way he could have accumulated so much useful equipment was through trade. I'm used to arguments for the early emergence of trade that show that quantities of obsidian or sea shells was found hundreds or thousands of miles from where it would have been regularly collected, but Ridley goes to great lengths to display evidence that trade was pervasive and that early people everywhere relied on it extensively for many items in their daily repertoire. It wasn't just an occasional trade for a high-value item, it was a part of routine life, and part of what people ate, wore, and used for healing, hunting, and food storage.

Ridley also carefully lays out the case for Ricardo's point that trade makes us all richer. Expanding the extent of trade increases the size of the market; with more people in your trading community, you can draw on the efforts of specialists who multiply the overall productivity you can take advantage of. Ridley argues that the increasing returns from trade taught our ancestors the value of trust and led to to more virtuous interactions, and better ethical instincts among our ancestors.

The underlying point of much of this is that increasing communication, increasing interaction leads to more and better ideas as we recombine the ideas in new ways, and this leads to the production of more wealth. Around the time of Malthus, it was still possible to argue that increasing production of wealth just made it possible for populations to increase, and didn't really make anyone better off. But sometime in the last two hundred years that started to change, and the recent demographic transition has made that position completely untenable. But pessimism is still more widely respected, and Ridley wants us to understand that a reasonable understanding of the sweep of history and of our evolutionary origins makes optimism a much better fit with our circumstances. Things have been getting better for hundreds of years, and while we can imaging things that might change that, none of them seems particularly likely.

More people are moving to cities where they are more productive and have fewer children. They live wealthier lives than before, and insist on and can afford a cleaner environment and healthier lifestyle. Government restrictions could prevent progress, or trap people outside the cities, or make it harder for them to buy the lifestyle and environmental values they will want, but the smart money goes with the trends. Ridley thinks that the pressure for progress will be sufficient to move governments out of the way, and that spontaneous order will enable people to get what they want. Technology will enhance our healthspan, and our ability to travel and communicate will continue to grow. We'll spend less time working and more on other things. China and Brazil will lead the way if politics in the West grows too stifling.

Sunday, June 12, 2011

The Long Tomorrow, Michael Rose

Michael Rose's book The Long Tomorrow discusses aging in the context of evolution. The book has something of the feel of a memoir— Rose writes about how he happened into this field, who helped and encouraged him, who was right and wrong, and what he was working on along the way.

Rose has spent most of his career single-mindedly breeding long-lived fruit flies (Drosophilia Melanogaster). This approach to achieving longevity has important implications for understanding the mechanisms of evolution and how they impact lifespan. Because the mechanism itself (selective culling and breeding) isn't applicable to humans, the implications for human longevity are indirect, even though they may turn out to be very important for us.

Rose begins his tale at a symposium he spoke at for the Templeton Fund, where eminent scientists and ethicists spoke against any attempt to pursue human longevity as respectively impossible and immoral. Christian theologians joined that chorus, but were opposed by a Jewish scholar, and by Rose himself, already pursuing longer-lived flies. This serves as a nice backdrop and introduction to the issues which allows him to refer back to the controversy and the parties later when he talks about his own views.

In the mid-70s, when Rose was trying to get started in biology, Crick & Watson's theories had been accepted, but the implications weren't yet clear. Scientists were starting to investigate the molecular mechanisms for all kinds of biological effects, both to see how they interacted with evolution and to find the cellular mechanisms that made life function. Hayflick's proposal on the impact of cell division problems on lifespan was getting publicity, but there were few posited mechanisms based on evolutionary reasoning. The Hayflick limit was an observed and accepted fact, but so far without much theoretical context. Thirty years earlier, J. B. S. Haldane had suggested that Huntington's disease (which waits until carriers of the causative genetic defect are in their 30's or 40's to attack) was a consequence of selection's pressure: genes that debilitate before the carriers reproduce will be weeded out, but diseases that crop up later can survive more easily in the population. Peter Medowar expanded on these ideas, but got the evolutionary causality wrong. George C. Williams straightened out a few clues and pointed out that processes that are helpful in the young, and therefore reinforced by evolutionary pressures, might be costly for mature animals but they wouldn't necessarily be corrected because reaching maturity is so much more important evolutionarily than surviving it. Finally, in 1966, William Hamilton put the pieces together and provided an argument based on evolutionary principles that explained why aging would arise. Once Rose studied the history, it was clear that there was some evolution-based theory, but no significant experimental results validating the evolutionary basis of aging. He thought he'd be able to make a mark on this new field fairly quickly.

Brian Charlesworth was Rose's mentor and supervisor when he started the research. Charlesworth had worked out the math for how much selective pressures should fall as a creature aged. Since selection pressures are strongest on the young, you'd expect to see less weeding out of deleterious mutations that affect the mature and the aged than of those that affect the young. Charlesworth proposed that Rose look for an experimental demonstration of that difference in drosophilia, by showing that the fall in fecundity of female flies followed his formulas. Rose spent more than a year in the laboratory, and counted more than a million eggs before analyzing his results. The results showed that Charlesworth's predictions were wrong.

But Rose had started a parallel experiment about half-way through the first one, based on a paper by J. M. Wattiaux (published in 1968) which showed that offspring of older parents lived longer than those born to younger parents. Wattiaux had been unable to demonstrate what he expected to be environmental causes of the difference, but when Rose read the paper, he realized that age of reproduction was the crucial variable that evolution could select on. If only eggs produced from older parents were allowed to reproduce, then the selective pressure (acting on potential parents) would be towards flies that stayed healthy long enough to meet the delayed date. A year after sharing the results of the first experiment, Rose showed that the new procedure (delaying breeding) produced flies that were already living about 10% longer than under standard fly care.

From that point, Rose (and later his students) studied the interactions between longevity, stress resistance (starvation and desiccation), diet and diet restriction, and body fat and other energy storage. They established a positive correlation between long life and all kinds of stress resistance, and showed that body fat and other energy stored in the flies' bodies increased stress resistance. Diet restriction seems to work because it encourages retention of more energy reserves. But all of these mechanisms (except diet restriction) work over evolutionary time scales. Rose wanted to find treatments that can lengthen the lives of those already alive. So he started to investigate molecular mechanisms to see if we can tell what's different within the cells of those predisposed to longer life when compared to their counterparts.

A later series of experiments demonstrated that the death rate, which increases with age, only actually increases from the start of reproduction to its cessation. What this means is that the death rate is strongly controlled by evolutionary pressures. For any species, evolution acts to reduce the death rate as much as possible before the onset of sexual maturity. After that point, it allows the death rate (from natural causes, primarily) to increase relatively smoothly. Once sexual reproduction ends (or possibly a bit later if individuals are still contributing significantly to the life success of their offspring) evolution stops being able to apply selective pressure. This means that the rate at which individuals die (in deaths per capita per annum) stops increasing. For most populations the rate is pretty high by this mature age, and the number of individuals reaching each later age is small, so it's hard to see that the rate isn't changing. But separate experiments done by Rose, Charlesworth, and Larry Mueller show that manipulating the age of last reproduction in populations of drosophilia directly effects the death rates of the resulting populations in only a few generations.

In humans, Rose says that 95 is the age at which mortality rates stop increasing. From 15 to 90, there is exponentially increasing mortality, but after 95, the rates stop increasing. This has two interesting implications for humans. First, many more people are going to make it to their 90s in coming decades, just because we're living so much more healthily and robustly than we used to. That means that there will be much larger cohorts which will see their mortality rates stop increasing, so we should see gradually rising maximum ages, even if nothing else changes.

The other implication is that mortality rates don't increase to 100%. There is always a chance of surviving another year if you aren't hit by a bus. And if Aubrey de Grey is right, our first step is just to clean up our constitutions so that we keep the mortality profile of a 40-something, and we'll vastly improve life-spans. As Rose says:

Aging is not an infinitely high wall of mortality, rising faster and faster as we get older, until everybody is dead. It is a ramp that takes us from a phase of low childhood mortality to a much later phase of high, but relatively stable, mortality. Postponing, retarding, or otherwise mitigating aging does not require pushing back a wall of death of infinite height. It requires smoothing out a ramp of mortality, and possibly lowering the height of the top of the ramp.

At this point, Rose seems to get serious about the implications of his research for human longevity. At the prodding of New Scientist, in 1984, he wrote a lead article proposing that a major, government-backed program to produce long-lived "methuselah" mice would be valuable. He pushed the idea with potential funders from government and the private sector, but never found anyone willing to actually underwrite the proposal. Rose never mentions Aubrey de Grey's Methuselah Mouse project, which I've talked about before. de Grey found private funders to endow a prize, rather than attempting to organize a single Manhattan project-style (Rose's own description) effort.

Having failed at his own efforts to start a project to find ways to apply his research to humans, Rose continues to be upbeat at the prospects that someone will succeed. He finishes the book by offering lots of advice and suggestions on which scientific paths are likely and unlikely to bear fruit, and what modes of organization are worth trying, particularly by people with different skills than his.

My own postscript involves pointing out that Rose didn't talk about what happened to his fruit flies in the end. He was a co-founder of the company Genescient, which uses modern gene assay techniques to look for nutraceuticals that can reproduce the cellular effects present in the Methuselah flies. Rose's name doesn't appear on Genescient's site, so there appears to have been some sort of split. Genescient has spun out Life Code, which markets Stem Cell 100, a nutraceutical based on this research. I haven't started taking it yet, but I do continue to investigate.

Wednesday, June 08, 2011

Darkship Thieves, Sarah A. Hoyt

Sarah Hoyt's Darkship Thieves is a fun read, with a reasonably freedom-oriented bent. I think it's the strongest of this year's finalists for the Prometheus award. Athena Sinistra is the daughter of a wealthy tycoon who is kidnapped from her father's space yacht, and rescued by Christopher "Kit" Klaavil, an apparent ne'er-do-well from Eden, a colony founded by genetically enhanced humans in hiding from Earth. Eden seems to survive by siphoning off energy from Earth's orbiting power collectors.

Athena's and Kit's adventures together provide an opportunity for a look behind the scenes at how the society on Eden works. Athena can't be returned to Earth without revealing Eden's location, so she has to figure out how to earn a living on her own. The people are receptive and friendly, but insist that everyone find a way to support themselves. Athena has some skills, and finds a way to apply them, even though she's more used to people expecting her to take advantage of her father's wealth and position. It's a peaceful and progressive society and she earns people's respect, but wants to return home to Earth.

When they get back to Earth, Athena learns that the circumstances of her kidnapping weren't what she thought. Kit and Athena end up rescuing one another a few times, and they end up puzzling out some interesting mysteries about both their ancestries.

Hoyt throws in some plot twists involving cloning, brain transplants, and genetic enhancement.

Wednesday, June 01, 2011

Gawande on Cowboys and Doctors

Atul Gawande gave a commencement address at Harvard last week, and focused on the subjects he covered so well in his book The Checklist Manifesto. Given the setting, he adds a charge to the graduating class to enact the reforms he argued for. The line in his speech that caught my attention and makes me hopeful that the health care system may be moving in the direction he promotes was this:

Two years ago, the Institute for Healthcare Improvement started its Open School, offering free online courses in systems skills such as outcome measurement, quality improvement, implementation, and leadership. They hoped a few hundred medical students would enroll. Forty-five thousand did. You’ve recognized faster than any of us that the way we train, practice, and innovate has to change.

If the next generation of doctors understands and is buying into the idea that we need more systemic approaches to managing health care, there may be a chance that the system will gradually (or we can at least hope, rapidly) reform into something more sustainable, and directed at effective care.