RELIGION AND THE LAND OF THE RICH

A few years before Charles Darwin's birth, a theologian named Bishop William Paley advanced what was then seen as an ingenious argument for the existence of God, now familiar as the "argument from design". Just as an intricately designed watch that you may stumble upon signifies the existence of an 'intelligent designer', so does the magnificent diversity of life and the workings of the human body signify the existence of an intelligent and all-encompassing God. Darwin faced this argument squarely and demolished it by showing precisely how complex systems can arise spontaneously, guided by the laws of physics, chemistry, and natural competition. In one fell swoop Darwin did away with Paley's argument, and it lay buried in its grave when it was resurrected and dusted off a hundred and fifty years later essentially in just one country, suprisingly the most developed country in the world. No other developed country has so forcefully advocated this regressive argument known by the (oxy)moronic name of "intelligent design". Only in the United States have people sought to go back in time and so ardently embrace ignorant and outdated ideas about the existence of God. Why the United States? Why this glaring discrepancy involving the citizens of the most technologically advanced nation believing in the most backward-looking ideas?

New York Times columnist Charles Blow has a discussion on his blog where he wonders why the US is the only country where religion is so rampant in spite of great wealth and technological development. He points to a graph that denotes religious fundamentalism to be roughly inversely proportional to technological development, with one exception- the United States. Why is that so?

It's definitely a very interesting phenomenon to muse about, and three main reasons have always come to my mind:

1. The Argument from Great Resources:

One might argue that as much as fundamentalism seems to be widespread in today's America, it has been a strain endemic in American culture and belief ever since this country was founded. The reason why its effects were not felt so much earlier is because Americans largely managed to separate church and state partly because of great natural resources and access to technology that could keep the engine of scientific and economic progress running while keeping the engine of religious fundamentalism independently humming.

2. The Argument from Fear of Technology and Love of Money:

Ironically, the same technology that makes the US the most developed country in the world may be partly responsible for people's gravitating towards religion. These days much of technology seems incomprehensible and we must remember the well-known adage that "any sufficiently advanced technology is indistinguishable from magic".

For many common Americans, space exploration, the Internet, modern medicine and genetically engineered crops are black boxes whose fruits they enjoy while not completely understanding their inner workings. Religion tosses them some similar tidbits; to them creationism seems no more fantastic than evolution and so they don't have any problem believing in Biblical accounts of events. Since many technological advances seem like miracles to them anyway, they might as well believe in miracles in the Bible. The fault here lies not in technology of course but in the educational system and media of this country which frequently obfuscate the features of science and technology, either reducing them to oversimplified metaphors (comparing atoms to watermelons for example), or rooting them in a mass of complicated, confused jargon. Many surveys indicate that a disproportionate number of Americans don't understand evolution. If science education and the media do a better job of educating the public, they will start to see the difference between phenomena based on evidence and phenomena which were divined by prophets through personal faith.

The same kind of argument rings true with money. Money buys you comforts and technology whose origins- and limitations- you don't understand. The current morass on Wall Street is just another indication of Americans' love affair with green. Money also created a false sense of hubris and the belief that all this acquisition of wealth was somewhat related to the Christian ethic (or a perverted version thereof). Forgotten were the equally important Christian ethical notions of charity, moderation and stewardship of nature. Islamic fundamentalism brought a whole new aspect to such beliefs. The oil wars are also seen by some as the ultimate conflict between superior Christians who deserve only the best of wealth and technology, and backward populations, either godless or belonging to inferior make-believe religions, who deserve to be denied such technology and resources. The destruction of the environment that accompanies such an explosion of technology and wealth are seen by some fundamentalists as leading to the second coming of Christ. They would gleefully revel in excesses before they are catapulted to the wonders of the promised land. This is a good example of how technology, wealth, resources and religion feed off each other's products and ideas.

3. Argument from Clever Reaganite Proselytizing:

More than any other modern President, Ronald Reagan was responsible for bringing about the current inextricable meld of politics and religion, a paradigm taken to unprecedented heights by his less intelligent and more pernicious ideological descendent George W Bush. His appeasement of religious fundamentalists made even hardened Republicans like Barry Goldwater cower in revulsion. Reagan realized that he could shape the entire social and political structure of this country by making religion an essential part of political discourse and mobility. In doing this he violated a fundamental tenet of the constitution laid out by the Founding Fathers, who must have died a second time in their grave hearing him speak. Reagan's legacy is malignant and long-lasting, and it was furthered with conviction by his neo-conservative acolytes. Its effects are extremely far-reaching because it set in motion a vicious cycle; conservatives would woo religious fundamentalists and fundamentalists would vote for conservatives and infiltrate the While House and other public agencies. It is hard to see how this vicious cycle could be broken, especially after Bush honed its strong points to such a degree that religious fundamentalists could seriously swing elections. Unless conservatives and Republicans get out of appeasing religion, religion is marked to shape much of the political discourse and thus alter the fundamental legal and social landscape of this country. The end cannot be anything but disastrous.

The question at the end, one that is always the most difficult to answer, is what can be done? For one thing, moderate Republicans must take the lead and break this essential connection that has been formed between the Republican party and right-wing religion. John McCain with Sarah Palin is certainly not going to do that. As noted above, public education also has a very important role to play in convincing people that science and technology are not magic, and that religion undermines the basic process that brought them all those comforts that they enjoy so much and take for granted. And as for resources, we don't have to worry; they will run out by themselves and will force people to choose between a lifestyle of moderation and prudence and an eternity of desperation, civil strife, and longer lines at the gas station.

Dear Laura and Bob
Hope you had a great time in China and I really hope that the harsh Party rules forbade you from accessing the internet for a month. You are going to be coming back to the land of the spree and the home of the grave. I don't know how much news about your country has trickled through to you beyond the great wall, but even if it has I am sure you are going to be shocked when you come back. You go away for a month and this is what happens! This is one of those few times when you find yourself constantly running out of words. On one hand, they are having the biggest financial crisis since the Great Depression and on the other hand they have a vice presidential candidate a heartbeat away from the presidency who is utterly incompetent, ignorant and incoherent (those adjectives admittedly apply to the presidential candidate as well). One is a current disaster, the other one is a disaster waiting to happen. I hope you come back soon and get ready to vote. It's going to be necessary than ever. Have a safe trip back and hope you had a lot of fun. Your stories are going to be the only thing enlivening an otherwise gloomy time so I am looking forward to meeting you.
Take care
Ashutosh

P.S. Although I have to admit that this event may mire Republicans in deep muck for good and make Obama's victory almost certain. I think there have been few circumstances where members of a political party in the US have so blatantly voted against their own leaders' wishes.

WHAT WE WILL DO

I was discussing the candidates, politics and the future intensely with a friend of mine yesterday and we asked each other what we would do if either McCain or Obama wins.

If McCain wins, I will buy a big bottle of premium scotch, amble over to my friend's place and then both of us will drink ourselves to sleep without saying a word. After that I have pledged that I will lose all interest in politics, cease talking about it and get along with the parts of my life over which I exercise at least a little control.

If Obama wins, we won't really celebrate, because it's going to be premature. I think if he wins, we should simply breathe a sigh of relief and sit back, then watch.

The point is that the country is so messed up right now that even Obama may not be able to do much. That's why celebration after he wins would be to too soon. We can all hope then that we will get a great chance to celebrate in four years, or hopefully eight.

PLEASE, DON'T STAND IN THE WAY OF THIS MAN

This is as sensible and assertive a statement about evolution that we can expect from a Presidential candidate

Do you believe that evolution by means of natural selection is a sufficient explanation for the variety and complexity of life on Earth? Should intelligent design, or some derivative thereof, be taught in science class in public schools?

Obama: I believe in evolution, and I support the strong consensus of the scientific community that evolution is scientifically validated. I do not believe it is helpful to our students to cloud discussions of science with non-scientific theories like intelligent design that are not subject to experimental scrutiny.

This is from the latest issue of Nature whose cover story is about the candidates' views on scientific issues, views that are going to be of paramount importance to the future well-being of this country. Nature asked the candidates 18 questions about science and technology, including questions about increasing funding for basic research, speeding up the track to permanent residency for talented foreign students, and pumping more funds into biomedical innovations.

Not suprisingly, McCain's camp declined to answer with specifics and Nature dug up relevant statements from his old speeches that mainly included boilerplate sound-bytes. Obama's camp on the other hand provided rather eloquent and clear answers that actually talk about facts. It's pretty amazing to hear answers that actually are filled with details about science. McCain's cast of "science" advisors looks like a Gilligan's Island outfit and includes HP chief Carly Fiorina (who thinks Sarah Palin is quite competent to be President), James Woolsey, a former CIA director and Meg Whitman, former CEO of EBay. This group seems as miscast for science as Sarah Palin is miscast for being Vice President. Obama's advisors on the other hand include some real scientists, including Dan Kammen from Berkeley and Harold Varmus from Sloan Kettering Cancer Center.

Obama would speed up the residency process for foreign students, minimize barriers between private and public R & D (this is going to be very important). And Obama is as clear about nuclear energy as anything else

What role does nuclear power have in your vision for the US energy supply, and how would you address the problem of nuclear waste?

Obama: Nuclear power represents an important part of our current energy mix. Nuclear also represents 70% of our non-carbon generated electricity. It is unlikely that we can meet our aggressive climate goals if we eliminate nuclear power as an option. However, before an expansion of nuclear power is considered, key issues must be addressed, including security of nuclear fuel and waste, waste storage and proliferation. The nuclear waste disposal efforts at Yucca Mountain [in Nevada] have been an expensive failure and should be abandoned. I will work with the industry and governors to develop a way to store nuclear waste safely while we pursue long-term solutions.

Most importantly, Obama promises to reform the political environment for scientific opinion; this would include appointing a Chief Technology Officer for the government and strengthening the President's Scientific Advisory Committee, a key source of scientific advice for the President that was abolished by the odious Richard Nixon

Many scientists are bitter about what they see as years of political interference in scientific decisions at federal agencies. What would you do to help restore impartial scientific advice in government?

Obama: Scientific and technological information is of growing importance to a range of issues. I believe such information must
be expert and uncoloured by ideology. I will restore the basic principle that government decisions should be based on the best-available, scientifically valid evidence and not on the ideological predispositions of agency officials or political appointees. More broadly, I am committed to creating a transparent and connected democracy, using cutting edge technologies to provide a new level of transparency, accountability and participation for America’s citizens. Policies must be determined using a process that builds on the long tradition of open debate that has characterized progress in science, including review by individuals who might bring new information or contrasting views. I have already established an impressive team of science advisers, including several Nobel laureates, who are helping me to shape a robust science agenda for my
administration.

This point is the most encouraging policy vision, after a 8 year tradition of bullying, manipulating, cherry picking, ignoring and roughing up science and objective facts. The cost of scientific ignorance will be progress in all its forms.

Reading this is like being immersed inside a gutter for all your life and suddenly coming up for fresh air in the bright sunlight with a gasp. This man deserves to lead this country. This country deserves to be led by this man.

A GOOD CASE FOR GOVERNMENT INTERVENTION IN ENERGY

The energy crisis is not going to solve itself without government intervention in the form of taxes and incentives. That's because while the free market can potentially tackle the problem, many experts on climate change have said that it cannot do that soon enough before we are already in a devastating free fall. While many libertarians (or "religious libertarians"- those who stick to extreme libertarianism) opposed climate change precisely because its solution would entail government intervention, now even libertarians realize that the government will have to step in if big change has to be affected soon enough. In an informative and engaging interview with Charlie Rose, Thomas Friedman gives a good example of why the government needs to shape the free market to move to a cleaner future.



He gives the example of someone inventing the first cell phone and bringing it to you. You would be willing to pay 1000$ a piece and buy 10 pieces because it's going to be enormously useful to you. But naturally as many people invest in this product the way you did, prices will go down and cell phones will become widespread and cheap. Why can't the same happen for, say, solar power (I am not really a fan of solar power but this is an example)? Why can't someone bring an expensive solar panel to your house, expect you to buy it and watch as the cost curve goes down? Simply because right now you don't recognise a real need or advantage for solar power. You don't really care where you get your electricity from because it's cheap.

But the reason it's cheap is because oil has been subsidised. So the oil and gas market has never even been a free market. Friedman asks what would happen if you were asked to pay the full cost of the oil and coal that power your house. This cost would ideally also include the cost of deploying troops to the Middle East to secure oil deposits as well as the cost of maintaining friendly relations with the big oil producers there.

If you really had to pay this cost and if there were no subsidies for oil, then powering your home with oil would become about as expensive as initially powering it with solar power. Then you would be willing to give solar power a shot, after which economics would slowly work its way down the cost curve.

Clearly we will have to get rid of subsidies and perhaps tax oil if alternative energy has to become cheaper. The other thing we can do is wait until desperation, global energy conflict and disastrous climate change make us painfully aware of switching to other sources of energy. By then it would have been too late. That's why the best option is to start right now and have government shape the energy market that was previously designed for dirty oil. Then market forces will work their magic and we can soon see a landscape of clean alternative energy.

A WRECK

An interesting and witty talk by Thomas Frank which I attended yesterday showed how profoundly undemocratic conservatism in America has become. His recent book "The Wrecking Crew" How Conservatives Rule" shows how conservatives have essentially turned the country into a totalitarian stronghold that deeply despises democracy and freedom under the guise of promoting "morality" and free markets. Concomitant reading of J. Peter Scoblic's "U.S. vs Them" shows how this breed of conservatism, far from being restricted to the Bush administration, has been nurtured and furthered since the end of World War 2 when rabidly anticommunist conservatives honed threat inflation, pseudomoral philosophizing and downright bullying to a fine art. Their principles were clear; anyone who advocated any form of government intervention was automatically a godless communist, anyone who advocated negotiation with the enemy was a coward. In fact Scoblic's book makes it clear how dogmatic and totalitarian today's conservatives are by deftly narrating how their forebearers had a deep disdain even for Eisenhower and Nixon!

I hope that just as communists gave those who would argue for government intervention a bad name, so would these modern American conservatives give a necessarily and well-deserved bad name to those who keep on advocating rampant and totalitarian capitalism. Interestingly as Frank quipped yesterday, the same conservatives who keep on opposing government intervention now have the government working around the clock to save the country. Irony would find this ironic. But that should not be surprising; the stated goal of today's conservatives is to be in bed (literally) with big business. If government intervention is necessary to appease big business, so be it. And yes, did Bush tell you that your taxpayer money is going to be on the line now? So much for the "read my lips- no taxes" motto that trickled down from his father. People's hard-earned money be damned if appropriating it is going to help Uncle Care Bear. If this does not convince anyone of the hypocrisy of Republicans, it's hard to see what will. They care about lowering taxes only as far as that can keep big business fat and happy.

Let's just hope that the recent market failure and many similar incidents expose the evils of dogmatic thinking of any kind- whether socialist or laissez faire capitalist- and teach people to take a more nuanced and moderate stand that advocates different policies and actions based on the situation and times. The point is that it is not possible to sustain one stock, extreme philosophy for too long, a fact that naturally does not go down the prickly gullets of idealogues in administrations such as this one. They want to see the world in black and white. No matter that it's not just shades of gray but gray that often changes into other colours.

Politics should be flexible and should be able to choose and draw from a wide variety of options in different proportions based on requirements for that age. There is no such thing as a completely socialist or completely libertarian or completely anarchist or completely nihilist philosophy that would work for all times and all people. A full century of extremism- from Stalin's totalitarianism to the Chicago Boys' laissez faire support for totalitarian regimes in Central America- should more than warn us about constantly dealing in absolutes and monolithic economic models. Brendon Barber put it very well for the BBC:

This is not the final crisis of capitalism, but it ought to be the end of the road for a particular version of it.

The truth is that there is no single economic model of capitalism.

There has always been a considerable difference between Europe's social market and the Anglo-Saxon version in the US - not to mention the wild-west excesses of post-communist Russia or the strange hybrid that now operates in China.

What we have seen in the last few days should rather be the last gasp of the belief that the way to secure prosperity is to let free markets rip and tear up any regulation that gets in the way of short-term profit.

Already the view that the state has no role to play has gone with the nationalisation of Freddie, Fannie and AIG in the US and Northern Rock in the UK.

The lessons that we need to draw are that we have given far too much importance to the City and neglected other sectors - not just traditional manufacturing, but new environmental jobs and the creative sector, to give just a few examples. This should be neo-liberalism RIP.

But the paradox that has yet to work its way through is what this means for politics.

Voters are shifting to the right in their voting intention, but shifting to the left in many policy preferences as they expect government to tax the rich more, regulate the energy sector and restore sensible regulatory structures in the City.

As Frank said yesterday, one good thing should undoubtedly come out of the recent sham- Hoover should not get his second term.

THINKING ABOUT ALZHEIMER'S DISEASE AS HISTORIANS

Head slumped forward, eyes closed, she could be dozing — or knocked out by the pharmacological cocktails that dull her physical and psychic pains.

I approach, singing “Let Me Call You Sweetheart,” off key. Not a move or a flutter. Up close, I caress one freckled cheek, plant a kiss on the other. Still flutterless.

More kisses. I press my forehead to hers. “Pretty nice, huh?” Eyelids do not flicker, no soft smile, nothing.

She inhales. Her lips part. Then one word: “Beautiful.”

My skin prickles, my breath catches.

It is a clear, finely formed “beautiful,” the “t” a taut “tuh,” the first multisyllable word in months, a word that falls perfectly on the moment.

Then it is gone. The flash of synaptic lightning passes. That night, awake, I wonder, Did Pat choose “beautiful?” Or did “beautiful” choose Pat? Does she know?

This heartbreaking and sad account by a husband of his wife's early slide into Alzheimer's Disease (AD) reminds us of how much we need to do to fight this. I personally think that of the myriad diseases afflicting humankind, AD is probably the cruelest of all. Pancreatic cancer might kill you in three months and cause a lot of pain but at least you are in touch with your loved ones till the end. But this is human suffering on a totally different level.

The search for the causes of Alzheimer's disease continues, and I have recently been thinking in a wild and woolly way about it from an evolutionary standpoint. While my thoughts have not been well-formed, I want to present a cursory outline here.

The thinking was inspired by two books- one book which has been discounted by many, and another which has been praised by many. The lauded book is Paul Ewald's "Plague Time" which puts forth the revolutionary hypothesis that the cause of most chronic diseases is ultimately pathogenic. The other book "Survival of the Sickest" by Sharon Moalem puts forth the potentially equally revolutionary hypothesis that most diseases arose as favourable adaptations to pathogenic onslaughts. Unfortunately the author goes off on a tangent making too many speculative and unfounded suggestions, leading some to consider his writings rather unscientific. As far as I am concerned, the one thing that the book does offer is provocative questions.

On the face of it both these hypotheses make sense. The really interesting question about any chronic disease is; why have the genes responsible for that disease endured even after so many millennia if the disease kills you? Why hasn't evolution weeded out such a harmful genotype? There are two potential answers. One is that evolution simply has not had the time to do this. The other hypothesis, more provocative, is that these diseases have actually been beneficial adaptations against something in our history. That adaptation was so beneficial that its benefits outweighed the obvious harm that it caused. While that something probably does not presently prevail, it was significant in the past. What factor could possibly have existed that needed such a radical adaptation to fight it?

Well, if we think about what it has been that we humans have been fighting the most desperately and constantly ever since we first stepped foot on the planet, it's got to be a foe that was much older than us and more exquisitely adapted than we ever were- bacteria. The history of disease is largely a history of a fierce competition that humans and bacteria have engaged in. This competition plays by the rules of natural selection, and is relentless and ruthless. For most of our history we have been fighting all kinds of astonishingly adaptable bacteria and there have been millions of martyrs in this fight, both bacterial and human. Only recently have we somewhat eroded their malign influence with antibiotics, but hardly so. They still keep evolving and developing resistance (MRSA killed 18,000 in the US in 2005), and some think that it's only a matter of time before we enter a new and terrifying age of infectious diseases.

So from an evolutionary standpoint, it's not unreasonable to assume that at least a few genetic adaptations would have developed in us to fight bacteria, since that fight more than anything else has been keeping our immune system busy and our mortality high since the very beginning. But instead of thinking about genes, why don't we think about phenotypes, about the actual effects manifested? Hence arose the hypotheses that many of the age-old chronic diseases that are currently the scourge of humanity may sometime have been genetic adaptations against bacterial infection. While the harm that is done by these diseases is obvious, maybe their benefits outweighed that harm sometime in the past.

When we think of chronic diseases, a few immediately come to mind, most notably heart disease, diabetes, Alzheimer's and cancer. But one of the best cases in point that illustrates this adaptive tendency is hemochromatosis which is an excess of iron absorption and storage, and it was this disease that made me think about AD. A rather fascinating evolutionary explanation has been provided for hemochromatosis. Apparently when certain types of bacteria attack our system, one of the first nutrients they need for survival is iron. By locking down stores of iron the body can protect itself from these bacteria. It turns out that one of the species of bacteria that especially needs iron is Yersinia pestis, the causative agent of the black plague. Now when Yersinia attacks the human body, macrophages rally to the body's defense to swallow it. Yersinia exploits iron resources in macrophages. If the body keeps iron stores from macrophages, it will keep iron from Yersinia, which however will lead to a buildup of iron in the body; hence hemochromatosis. The evidence for this hypothesis is supposed to come from the Black Plague which swept Europe in the Middle Ages and killed almost half the population. Support for the idea comes from the fact that the gene for hemochromatosis has a surprisingly higher frequency among Europeans compared to others. Could it have been passed on because it protected the citizens of that continent from the plague epidemic? It's a tantalizing hypothesis and there is some good correlation. Whether it's true or not in this case, I believe the general hypothesis about looking for past pathogenic causes that may have triggered chronic disease symptoms as adaptations is basically a sound one, and in theory testable. Such hypothesis have been formed for other diseases and are documented in the books.

But I want to hazard such a guess for the causes of AD. I started thinking along the same lines as for hemochromatosis. Apart from the two books, my thinking was also inspired by recent research that suggests that amyloid Aß peptide- a nasty aggregated protein that is a ubiquitous signature in AD brains- binds to copper, zinc, and possibly iron to generate free radicals that cause damage to neurons. Damage they may cause, but we have to note that such damage is also extremely harmful to bacteria. Could amyloid have evolved to generate free radicals that would kill pathogens? Consider that in this case it's also serving a further valuable function akin to that in hemochromatosis- keeping essential metals from the bacteria by binding to them. This would serve a 'double whammy'; denying bacteria their essential nutrients, and bombarding them with deadly free radicals. The damage that neurons suffer would possibly be a small price to pay if the benefit was the death of lethal microorganisms.

For testing this hypothesis, I need to know a couple of things:

1. Are there in fact bacteria which are extremely sensitive to copper or iron deficiency? Well, Yersinia is certainly one and in fact most bacteria are to varying extents. But since AD affects the brain, I am thinking about bacterial infections that affect the brain. How about meningitis caused by Neisseria, one of the deadliest bacterial diseases even now which is almost certainly a death sentence if not treated? Apart from this, many other diseases affect the brain if left untreated; the horrible dementia seen in the last stages of syphilis comes to mind. Potentially the brain would benefit against any of these deadly species by locking its stores of metal nutrients and generating free radicals to kill them, a dual function that amyloid could serve. I have not been able to say which one of these bacteria amyloid and AD might have evolved against. Maybe it could have been against a single species, maybe it could have been a general response to many. I am still exploring this aspect of the idea.

2. More importantly, I need epidemiology information about various epidemics that swept the world in the last thousand years or so. In the case of hemochromatosis, the causative stimulus was pinned down to Yersinia because both the disease mechanism and the pandemic are documented in detail. I cannot easily find such detailed information about meningitis or syphilis or other outbreaks.

3. In addition, while risk factors have been suggested for AD (for instance the ApoE epsilon4 gene variant), no specific genes have been suggested as causal factors for the disease. There is a clear problem with correlation and causation in this case. Also, the important role played by environmental factors such as stress and diet is becoming clear now; it's certainly not an exclusively hereditary disease, and probably not even predominantly so.

4. Most importantly, I think it is impossible to find instances of AD occurences in history for a simple reason-the disease was simply unknown before 1906 when Alöis Alzheimer first described it. Even today it is not easy to make an assessment of it. All cases of Alzheimer's before a hundred years back would have been dismissed as cases of dementia causes by old age and senility. Thus, while the causative hypothesis is testable, the effects are hard to historically investigate.

The fact that AD is a disease of age might provide some credence to this hypothesis. Two things happen in old age. Firstly, the body's immune defenses start faltering, and this might need the body to marshall extra help to fight pathogens. Amyloid might do this. Secondly, as age progresses evolution is less worried about the tradeoff between beneficial and harmful effects because the reproductive age has already passed. So the devastating effect of AD would be less worrisome for evolution. Thus, the same AD that today is thought to reduce longevity would have ironically increased it in an age where infection would have reduced it even further.

However, if AD is an adaptation especially for old age, then it begs a crucial question; why would it exist in the first place? Evolution is geared toward increasing reproductive success, not toward increasing longevity. There is no use as such for a rather meticulously developed evolutionary adaptation that kicks in after reproductive age has passed. I think the answer may lie in the fact that while AD and amyloid do affect old people, they don't suddenly materialize in old age. What we do know now is that amyloid Aß is a natural component of our body's biochemistry and is regularly synthesized and cleared from the brain. Apparently in AD something goes wrong and it starts to suddenly agglomerate and cause harm. But if AD was truly an adaptation in the past, then it should have possibly manifested itself in younger age, perhaps not a much younger age but an age where reproduction was still possible. Consider that for evolution some dementia is much preferred to not being able to bear offspring, and so AD at a younger reproductive age would make evolutionary sense even with its vile symptoms. If this were true, then it means that the average age at which AD manifests itself has simply been increasing for the past thousand years. It would mean that AD is not per se a disease of the old; it's just become a disease of the old in recent times.

So after all the convoluted rambling and long-winded thought, here's the hypothesis:
Alzheimer's disease and especially Aß amyloid is an evolutionary adaptation that has evolved to kill pathogens by binding to key metals and generating free radicals

There are several details to unravel here. The precise relationship between metals, amyloid and neuronal damage is yet to be established although support is emerging. Which of the metals really matter? What do they exactly do? The exact role that amyloid plays in AD is of course under much scrutiny these days. And what, if anything, is the relationship between bacterial infection and amyloid Aß protein 'load' and function in the body? Which bacteria really matter?

In the end, I suggest a simple test that could validate at least part of the hypothesis; take a test-tube filled with fresh amyloid Aß protein, throw in metal ions (copper, iron, zinc, etc.), and then throw in bacteria that were thought to be responsible for major epidemics throughout history. What do you see? It may not even work in vitro- I wonder if it could be tried in vivo- but it would be worth a shot.

Now I will wait for people to shoot this idea down because we all know that science progresses through mistakes. At least I do.

WHERE ARE THE LIBERTARIANS?

To be honest, I am disappointed by libertarians' lack of reaction against this recent profligate spending from the public coffer. I strongly feel that the libertarians need to come out and condemn the government's 200 billion dollar bailout of Fannie Mae and Freddie Mac. It's money straight out of our pockets, and out of our butler's and tailor's.

JUST LIKE US

I personally feel that the scariest thing about the upcoming election is that the people want to vote for someone "just like them". In spite of the fact that this is a path straight to disaster, as should have been obvious from the 2004 election. It's really hard to see why people don't understand the simple fact that the President of the United States should understand their problems but he or she simply cannot be just like them; he or she has got to be smarter, more capable and tougher. Otherwise why would that person be fit to hold the highest office in the land? Isn't the difference between understanding the problems of the common man and being a common man yourself clear? Apparently not to the people of this great land.

What gets my goat even more is that in speaking thus, people also allude to Lyndon Johnson, Truman, JKF and FDR who were apparently "just like them". This is just ganz falsch. FDR and LBJ may have understood the problems of the common man but they were far from being like the common man. Both FDR and JFK were born in privilege and lived as elites, a fact seldom remembered. LBJ and Truman might have been the closest to the common man, but LBJ was a man who was one of the toughest and most savvy politicians of the century; one just has to read Master of the Senate to understand what kind of a political heavyweight he was. Truman may have been underappreciated before he became President, but again, David McCullough's magisterial biography clearly denotes the immense capability and potential he had already demonstrated. LBJ, Truman, JFK and FDR; they were far from being "common men". Or let's just say they were common men of uncommon ability.

Previously Americans seem to have appreciated such leaders, exceptional men who were more than fit to lead. Now though, they want common men of common or even subcommon ability to rule over them. This is one of the most fatalistic and downward-looking streaks in the current American voter. They demonstrated this streak in 2004 when they elected Bush because they thought he would be fantastic as a beer-drinking partner. Now they are demonstrating it again by embracing Sarah Palin as someone who espouses "small town values"; this is a woman they hadn't even heard about a month ago, and who is almost completely clueless about the past 8-year history of her country. She doesn't have any idea what the Bush Doctrine is, and she is sending her son to Iraq because she still seems to think it's Saddam who attacked her country on 9/11. One would be extremely hard-pressed to find a Vice Presidential contestant who was this frighteningly ignorant in such a crucial time; her selection seems to almost border on the surreal at times.

But in an ominous development, Thomas Friedman accurately notes that since Americans vote with their gut feelings they are actually warming up to Palin. On the other hand, Friedman notes that Obama who had that gut connection with especially young Americans a couple of months ago, no longer seems to radiate that tough and highly inspired attitude that rouses the irrational among us. I tend to agree. In fact in some of his recent interviews Obama frighteningly has a demeanor similar to John Kerry's; congenial and forthcoming, yet not connecting to voters' deeper centres.

And William Kristol of the NYT comparing Palin to Truman and LBJ simply indicates that the delusion is complete. The future of this country really seems to be in jeopardy, not because of its politicians but because of its people. Democracy never had a more glamorous display of its inherent problems.

THANKS FOR ALL THE FISH

The LHC begins crashing protons tomorrow. The following from Stephen Hawking captures it the most accurately:

"It is a tribute to how far we have come in theoretical physics that it now takes enormous machines and a great deal of money to perform an experiment whose results we cannot predict"

Since one of those unpredictable results is the end of the world, we might as well depart with song and dance:



But as imbibed with levity as this matter is, it reminds me a very similar matter brought up during the making of the atomic bomb; the suspicion by Edward Teller that the atmosphere might go up in flames. Teller first brought up the topic during a secret 1942 Berkeley summer study headed by Oppenheimer. Oppenheimer was concerned enough to go to Michigan and discuss it with Arthur Compton, one of the administrative heads of the project. The two actually decided to stop work on the project if this scenario posed a non-trivial risk. But the resourceful Hans Bethe by then had worked out the energy balances of the reactions involved and concluded that there was a "vanishingly small" possibility that this might happen...

Fast forward to 16 July 1945 at the site of the world's first atomic bomb detonation. Enrico Fermi was cheerfully taking bets on whether the bomb would ignite the entire planet or just the state of New Mexico...

DON BOUDREAUX IS OUR SAVIOR

In a flippant, hand-waving and one-sided piece full of childish metaphors that neglects a whole slew of facts, Don Boudreaux assures us that oil will never run out. His contention is that oil exploration is a matter of economics, not physics. He tells us the rather well-known fact that getting more oil out of the ground is just going to become more expensive, not impossible. Surprise!

There is absolutely no mention of the effects of oil consumption on climate change, or even the geopolitical implications of continuing to probe around in politically unstable regions where oil is difficult to extract. Nor does he think that there's something inherently wrong and problematic in a resource becoming super-expensive and unaffordable to the majority. We are simply supposed to feel good about the fact that we can always get oil, even if we have to slit throats and plunge a majority of the world's citizens into abject poverty.

And based on that last statement, lest someone think I am a bleeding heart liberal, let me also say that Don Boudreaux is also not a good economist; a good economist tries to say which resource it will be most profitable and efficient to utilize, not which resource we will kill ourselves over.

Oil indeed will never run out, not if we disconnect one half of our brain and keep on constructing half-baked and biased arguments.

VYTORIN: NEW PROBLEMS FOR A NEW ERA

The NYT has a piece today in which it describes the problems riddling Vytorin, a combination of ezetimibe and simvastatin, which is taken by 3 million around the world and makes 5 billion for its owners, Schering-Plough and Merck. The piece says that in spite of such widespread usage, there is apparently no clinical trial data that demonstrates that the second piece of the cocktail- ezetimibe- is efficacious. Much more concerning is the fact that there may be a link between ezetimibe and cancer, although the link looks fragile at best right now.

Statins have been the wonder drugs of our time, with Atorvastatin (Lipitor) being the best-selling drug in the world. Their efficacy in reducing heart attacks has been demonstrated in large-scale trials. Ezetimibe which blocks cholesterol absorption in the intestine and reduces LDL has much more tenuous effects. Recent large-scale studies found that while ezetimibe does reduce LDL, it's effect on the variables that actually matter are far less certain; there was no evidence that it actually reduces heart attacks. Yet it continues to be prescribed by thousands of doctors around the country, with patients shelling out considerable amounts for it.

However, the article raises the much bigger issue of knowing exactly when a drug is efficacious. According to the article, utility of a drug is usually gauged by "surrogate endpoints", that is, endpoints which indicate reductionist type effects rather than an actual increase in life-span or quality of lives. Take cancer for example. For most cancer drugs, tumor shrinkage is a convincing endpoint, not an actual increase in life-span. Or take cholesterol medications. The causal link between LDL cholesterol lowering and reduced heart attacks is apparently well-proven. Yet the body is complex enough for this causal link to be questioned; such questions arise most often in truly large sample studies, when the drug is on the market. Clearly the only true indication of side-effects or efficacy will come from such large-scale studies.

But there's a dilemma here as far as I can see it. The reason why surrogate endpoints are used seems clear to me; it's simply much more easy to look for such effects and ascribe them to drug action than effects like "increase in life-span" which can be controlled by multiple factors. Let's say two men who are the same age have been prescribed the same cancer medication. Both show shrinkage in tumors. Apparently the medicine works. But can this be translated into an observation about the difference in their life-spans, which can be attributed to so many different factors. Especially if the general health of one of the patients is worse than the other, then the cancer medicine can basically be an adjuvant and not the primary cause for his prolonged survival. How do we know that it's the cancer medicine and not his general health condition that actually increased his life-span? Naturally a reduced incidence of heart attacks is much easier to analyze than an increase in life-span. But even there it seems that so many factors can be responsible for a heart attack that it would be a problem trying to attribute specific effects to the medication, or especially the lack thereof of its effects.

The article also says that the FDA has become stringent about medications that address chronic problems like heart disease. The stringent bar set for a true study of efficacy seems to be about 10,000 patients over about four or five years. If every pharmaceutical company needs to do such a study to get approval, they might as well start digging their grave right away. Drug development is already so risky and expensive that putting a drug through 10,000 patients over five years and having the FDA almost certainly reject it after that would spell doom for all drug makers. Yet it is clearly unethical for doctors to keep on prescribing medication whose efficacy has not been demonstrated.

There does not seem to be an easy way out of this problem. To me right now it seems that, with all the compromises and problems it entails, the best bet might be to set such a stringent bar for medications for which good alternatives exist (and medications for chronic heart disease seem to fall into that category now) but relax the need for such large-scale trials for unmet and critical needs for which no good drugs exist. I am pretty sure the FDA is not going to set the bar for cancer so high.

So what's the way out for companies? To me the soundest scheme for now seems to be for doctors to provide information on the label saying that the drug did not show efficacy in a fair number of patients, and let the patient decide for himself or herself. It would be ridiculous in my opinion for the FDA to demand that the company withdraw the drug. Also, as a general thought, I think that both the FDA and public opinion need to get over their obsession of approving drugs only if they show efficacy in 100% or even 90% patients. What if a drug shows efficacy in 50% of patients? The rational thing would be for doctors and companies to explicitly say this on their label and let the consumer decide. That's the kind of thing that should happen in a liberal society.

Note: Over at The Pipeline, Derek has quite a few posts on this

TIPPING POINT




The Revenge of Gaia: Earth's Climate Crisis and the Fate of Humanity
By James Lovelock
Basic Books (2007)

In this clarion call to arms, eminent scientist James Lovelock warns us cogently and eloquently of the impending doom that we have forced upon our planet by global warming. Lovelock is well-qualified to offer such gloomy predictions; it was this extremely versatile scientist who in the 1960s and 70s proposed the idea of Gaia, the notion that the earth is a self-regulating organism whose regulatory mechanisms are intimately coupled to the activities of species in its biosphere. One species- man- has tilted the balance of these mechanisms and thrown them into disarray. The species that will pay the biggest price for this deed is also man himself. Through careful speculation and excellent scientific arguments about details, he rationalized this notion until it has now become widely accepted.

Lovelock's premier argument is that global warming (which he amusingly always refers to as "global heating") has already rendered our planet incapable of the self-regulation that it has admirably demonstrated for millennia. The temperature rises which global warming are going to bring about are beyond those which the earth can endure in a homeostatic manner, and its catastrophic effects are likely going to manifest within decades. There is a horrific precedent for believing this; the same kinds of temperature rises fifty five million years ago led to catastrophic mass extinctions and sea-level rises, inducing an ice age that lasted 200,000 years. We are in danger of inducing such a global pandemic by our efforts right now. The most serious manifestation of man-made global warming is in positive feedback. Two examples suffice; the well-known melting of ice which leads to less reflection of sunlight which leads to more melting, and the heating of the upper layers of the ocean that kills algae. These algae are crucial players in maintaining cooling by the emission of sulfur compounds that serve to reflect sunlight from clouds. Lovelock documents both these effects well as well as others that are resulting from the 'double whammy' that we are serving our planet; simultaneously emitting CO2 and depriving the earth of biomass that normally absorbs it.

While the first part of the book describes Gaia and how it's been affected irreversibly by global warming, the second part basically deals with the muddle headed perceptions of energy, food sources and environmentalism that affect many in the political establishment and media, most prominently environmentalists themselves.

There is clearly a rift between environmentalists that threatens to slow down action against climate change. One section, unfortunately the bigger one, is the more vocal one consisting of organizations like Greenpeace, who have a wrong-headed and irrational perception of environmentalism. They tout phrases like "sustainable development" and "renewables" without really understanding their limitations. They participate in emotion-laden protests and demonstrations just to prove their point. Their environmentalism mainly deals with trying to save cuddly creatures and colorful birds in remote parts of the world, while there are organisms much more in need of saving, including the microorganisms and algae which play extremely crucial roles in maintaining the homeostasis of Gaia.

The second group of environmentalists is a minority, and Lovelock is one of them. They understand that global warming has already done its damage and our goal now should not be mainly "sustainable development" but "sustainable retreat". They understand that much more important than saving a few endangered species in New Guinea is to prevent deforestation and use of more landmass even in developing countries. They know that debate about saving the environment cannot be dictated by emotion. Most importantly they understand that nuclear energy is the best short-term and perhaps long-term solution for our energy needs.

When it comes to energy sources that we should pursue, Lovelock's thesis is clear and rational. Renewables (solar, wind, biofuels) may sometime make a dent in the energy equation, but renewables are not going to save us soon enough. The phrase soon enough is important here. Lovelock is a reasonable man and does not discard renewables entirely. The problem is in trying to find good energy sources as fast as we can. But each one of the renewables is currently fraught with problems of inefficiency, environmental unfriendliness and lack of scale-up plans. Solar panels are expensive and inefficient. Wind farms consume huge tracts of land, land on which forestation usually soaks up carbon dioxide, and in addition need back up from fossil fuel generators when the wind is not blowing. Biofuels struggle with maintaining energy balances and pose similar land-use problems. It will be at least 50 years before renewables make a significant contribution to our energy needs and their use becomes cheap and widespread. But by that time it will be too late. The single-most important factor here is time.

The answer is clear and rational; especially for the short term future, nuclear power is the most efficient, readily available, widely-implementable, environment-friendly and safe source of power. Even if the problem of waste disposal is not trivial, it pales in comparison with the benefits we will incur, and especially the catastrophe that we will find ourselves in if we don't do it.

While Lovelock hopes fusion will become important soon, fission is currently our best bet. We already have the technology unlike that for renewables. Its efficiency is marvelous- a good numerical argument to keep in mind is this; global CO2 emissions for a year make up a mountain that is a mile in diameter and sixteen miles in height, a behemoth. In contrast all the nuclear fuel providing power for a year will constitute a cube that is sixteen meters on a side. It was Lovelock's espousal for nuclear power that represented a break from the 'green' party line. But now, nuclear is going to be as green as we can think of. To stave off fears of nuclear waste, Lovelock has even offered to bury the waste from a nuclear reactor in his backyard and use its energy for heating his house. In addition to these facts, Lovelock also clearly describes the paranoia that the public has for nuclear power, while all the time they face risks and dangers much more damaging and insidious.

One very cogent point that Lovelock makes is about how religious faith has caused problems in enabling our stewardship of the planet. He correctly points out that all religious texts were written at a time when man and his life were the focus. At very few places in the Bible or the Koran or even the Eastern texts is there an emphasis on the planet. None of the major world religions put nature before man. Now however, emphasizing man is going to be meaningless unless we emphasize Gaia, because without Gaia we won't be around. There need to be new "religious" principles, infusing the care and stewardship of the planet into children's minds, instead of the narrow self-serving interests of man that will become irrelevant once the sea-levels rise or the North Atlantic current slows down.

The same factor- time- that makes a good argument against renewables, also makes the strongest argument against libertarian "solutions" to climate change. Libertarians argue that the free market will eventually find solutions to the climate change problem without government intervention. But even if this solution might work in principle, 'eventually' is not going to be soon enough, good enough for us. We may have a little more than 20 years to beat a respectable retreat. For that we need legislation against carbon emissions, against use of oil for transportation, against land use right now. The libertarian approach may have worked 50 years ago when we had time. Thinking about renewable sources could have saved us if we had begun 200 years ago. But now even if these solutions work, they almost certainly will come too late to save us. As they say, "operation successful, but the patient is dead". To save the patient in time, we are going to inevitably have to make compromises, sacrifice at least some of our freedom to large scale government actions. We have to operate now in a manner reminiscent of how we operate in wartime. In times of legitimate (and in these times I stress the word 'legitimate') war, citizens don't complain about sacrificing freedom because they know their lives depend on it. Now Lovelock says we face a similar scenario.

On the downside. Lovelock makes some statements which I think should be better referenced. For example, I would not completely trust his contention that most of the cancers that we are going to die from are caused by our breathing oxygen. While oxygen certainly can produce free radicals and cause damage, such a significant role should be more firmly supported by evidence.

It is very difficult to find wholesome solutions to climate change. We seem to have now done a good job of recognizing the problem in the first place. But unfortunately it's too late to implement quick fixes that will wake us up from this nightmare when we will find that everything is all right. In an age where politicians are pushing for more oil drilling, rapid action and awareness is essential. We have to beat a retreat and live to fight another day, unlike Napoleon in Russia in 1812. For that we need coherent and rational thinking and global fixes, with all the compromises that they might entail. Going nuclear, and perhaps even indulging in grandiose fixes like "space reflectors" which reflect sunlight from miles-wide arrays, may be possibilities. Lovelock sounds an alarm in his book that is backed up by evidence and grim prognostication. Gaia will do whatever it takes to establish her equilibrium, equilibrium that's inherent in the laws of her physics and chemistry, equilibrium that will be established even if it means the loss of humanity. As a pithy line in an X-Files episode once put it, "You can't turn your back on nature, or nature will turn her back on you". It's simple.