Monday, August 30, 2010

Riding off into the twilight...



In "The Twilight of the Bombs", the last volume of his breathtaking account of nuclear history, Richard Rhodes describes the post Cold War problems and hopes associated with nuclear weapons. The book bears many of Rhodes's trademarks- it is extremely well-researched and contains sharp portraits of the major players as well as fast-paced accounts of key events that make you feel as if you were there. Rhodes's abilities as a storyteller are still remarkable. This book is relatively slim and does not command the high-octane prose of Rhodes's masterpiece "The Making of the Atomic Bomb" but as usual, Rhodes's authoritative knowledge of nuclear matters provides many revelations and he has a novelist's eye for detail which keeps the reader hooked.

The book can roughly be divided into four parts. The first part concerns the first Gulf War and the dismantling of Iraq's nuclear infrastructure, the second part describes the race to secure nuclear material in the former Soviet republics after the fall of the Soviet Union, the third part briefly talks about South Africa's nuclear ambitions and and then in more detail about attempts to contain nuclear efforts by North Korea and the last part concerns the run-up to the second Gulf War and some final thoughts on the future of nuclear weapons. One striking omission in the book is Iran, and I think readers would have appreciated Rhodes's insightful thoughts on the Iranian nuclear problem.

The first part examines the troubling evidence in the 1980s that Saddam Hussein was trying to build a nuclear capability. Rogue Pakistani scientist A Q Khan had even tried to unsuccessfully sell Iraq a bomb design based on a Chinese weapon. At the same time that the US was providing aid and goodwill to Iraq to support it against Iran in the Iran-Iraq war, it was also unearthing evidence in the form of dual-use equipment shipments and intelligence analysis that Iraq was pursuing enriched uranium. Interestingly, the technology that Iraq was using turned out to be electromagnetic separation, a primitive technology that the US did not initially believe would be used; for nations pursuing nuclear capability, separating uranium isotopes by using centrifuges is much more efficient. Yet electromagnetic separation is exactly the kind of technology that a relatively primitive and cash-strapped economy would pursue. This is a good example of how biases can lead to false conclusions in spite of supporting evidence. Later, Rhodes has pulse-racing accounts of searches for enrichment technology in Iraq conducted by the weapons inspectors of the IAEA and the UN. Even after the inspectors discovered evidence of enrichment in the form of equipment used for electromagnetic separation, this was not yet conclusive evidence of weapons building. Probably the most exciting moment was when, deep down in a small room in a basement, the inspectors discovered a report that did provide such evidence in the form of clear and detailed descriptions of materials and design for an implosion bomb.

The second part of the book deals with the fragmentation of the Soviet Union and the spirited and at times desperate race to acquire nuclear weapons from the former Soviet republics of Ukraine, Belarus and Kazakhstan. There are many heroes in this story which stands as a model of bipartisan cooperation against a serious threat. Among these are David Kay, Hans Blix and Bob Gallucci who were nuclear inspectors and disarmament specialists. Probably the most prominent ones are the Democratic and Republican senators Sam Nunn and Richard Lugar who worked day and night to acquire funds from Congress to secure nuclear material and weapons from the three countries and have them transferred back to Russia. Concomitantly, Secretary of State James Baker hopped from one capital to another, urging the presidents of the new nations to sign the NPT and START using a combination of carrots (in the form of monetary rewards) and sticks (in the form of possible sanctions and threats from Russia). All three nations agreed that they were better off without nuclear weapons, and the result was a transfer of thousands of strategic and tactical weapons back to Russia. A third important and massive effort involved blending down the enriched uranium from Soviet weapons to reactor grade and shipping it back to the US for use in US nuclear reactors; Americans may be amused to know that about 10 percent of their current electricity derived from nuclear energy comes from nuclear weapons that their former foe had targeted against their cities. Curiously, the biggest reformer in this drama was President George H W Bush who orchestrated the largest arms reductions in history (he abolished entire classes of weapons, including missiles with multiple warheads and all ground-based weapons), and he needs to get much more credit for doing this than what has been given to him.

In the third part Rhodes first briefly talks about the dismantling of South Africa's nuclear program, which is a fine lesson for nations wanting to eschew nuclear weapons. In case of South Africa, the same reasons- internal strife, border conflicts and international alienation because of the government's apartheid policies- that provoked the country to acquire weapons also encouraged them to give them up. An uglier reason was their fear in the 80s that the weapons might fall into the hands of the black government.

Rhodes then describes in detail the difficult relationship between the US and North Korea in the context of North Korea's nuclear ambitions. Along the way, Rhodes also provides perspective by noting that the US had mercilessly bombed the North during the Korean War; since then the North Koreans have constantly been in a kind of perpetual state of war, surrounded by giant powers like Russia and China. It's also worth keeping in mind that the US had stationed hundreds of nuclear weapons in South Korea as a deterrent until about 1990. Although these actions by the US do not justify the North's nuclear efforts, they do explain the paranoia and deep sense of insecurity that has fueled North Korea's animosity towards the US. Again, there are heroes in this story, but one singled out by Rhodes is former President Jimmy Carter who went to North Korea of his own volition in 1994 and successfully mediated the Koreans' proposal to stop reprocessing in return for light water reactors; the consequence of this diplomacy was the so-called "Agreed Framework" to regulate North Korea's commercial nuclear program, which unfortunately broke down in 2003 in the face of North Korean non-compliance and disagreements. Since then, North Korea has always had to be kept on a tight leash and there have been several moments of tension between the two countries, but Rhodes's accounts make it clear how diplomacy has averted another Korean War. Rhodes also has succinct discussions of efforts to develop and implement a framework for the CTBT, which was signed by Clinton but unfortunately not ratified by the Senate.

The last part of the book concerns the run-up to the second Gulf War. This story has been told before but Rhodes tells it succinctly and well. Meticulous weapons inspections in Iraq between 1992 and 1998 had unearthed no evidence of a WMD capability, although Iraq had also not furnished clear documentation of the dismantling of its WMD capability. As Rhodes tells it, regime change had already been on the table, especially pushed by neoconservatives like Dick Cheney and Paul Wolfowitz but even contemplated by former Vice President Al Gore. But even after 9/11, it does not seem like Bush was thinking of attacking Iraq. However, as the record indicates, something changed in his thinking in the next two months, and invading Iraq became a concrete strategy in his mind. Rhodes thinks that a major reason for this shift in his thinking may have been the anthrax attacks which followed 9/11. It seems that these attacks really rammed the threat of terrorism home; at one point alarms even went off in the White House and Dick Cheney suspected that he himself may have been contaminated. Nonetheless, as is well-known now, Bush and his associates decided to invade Iraq fueled by the tried and tested strategy of threat-inflation and on evidence that was dubious at best. Rhodes clearly establishes the prevarications of the administration's claims about WMDs in Iraq, based on discredited reports about uranium shipments from Niger to Saddam (reports discredited even by the CIA) as well as Chinese imports of supposed aluminum tubes for centrifuges, which turned out to be parts for short-range rockets. At best Iraq was years behind the difficult goal of building a nuclear weapon, a goal which would have needed extensive operations of enrichment and processing which would most likely have been detected. No matter how you cut it, there was no concrete justification for invading Iraq except one based on ideology and belief. Bush also seriously damaged arms reduction efforts by withdrawing from the ABM treaty, by his belligerent rhetoric against North Korea (which withdrew from the NPT and tested a nuclear weapon in 2006) and Iran, by lifting sanctions on Pakistan (a particularly recalcitrant and prolific proliferator) and by agreeing to supply India (which had not signed the NPT) with nuclear-related equipment. And yet in the midst of this tragedy it is easy to miss Bush's one success in arms control in which he signed major arms reductions with Russia; these reductions brought down the number of warheads on US delivery vehicles from about 10,000 at the end of the Cold War to about 2600.

This brings us to the final, eloquent part of Rhodes's book where he talks about the possible abolishment of nuclear weapons. He describes the very serious problem of nuclear terrorism; in his view, while it may be very difficult for terrorists to use a sophisticated nuclear weapon, it may be much easier for them to acquire enough material for a crude explosive. Even state-owned nuclear weapons are susceptible to accident, miscalculation and misunderstanding. The bottom line is that as long as nuclear weapons are around, there is always a possibility that they may be used. The only, truly final solution for reducing the threat of nuclear weapons is to get rid of them. How do we achieve this? I would have appreciated more detail from Rhodes in this regard, but he describes promising developments. For one thing, simple laws of physics dictate that without nuclear material one cannot make nuclear weapons. So securing nuclear material is key and the Nunn-Lugar initiative has set a worthy bipartisan example for achieving this goal. Many recent initiatives to reduce the threat of nuclear weapons have also been refreshingly bipartisan. Efforts to ban nuclear testing have already been fine-honed for decades, and getting all nations on board the CTBT would mean a lot; in this context Rhodes singles out Australian diplomat Richard Butler and his Canberra Commission for special praise. The fact is that, in spite of nuclear proliferation, there have been hundreds of nations which have found it prudent not to develop nuclear weapons for various reasons (not the least of which is their expense; according to Rhodes it costs the US 50 billion dollars just to maintain its current stockpile of weapons), so there is hope.

In the end though, only political will, strong leadership and international cooperation can rid the world of these terrible weapons. At some point, owning a nuclear weapon needs to become a crime. It is absolutely necessary to stop regarding these weapons as partisan, parochial concerns which can be leveraged to score political points in elections. To underscore this point, Rhodes recounts a fascinating idea put forth by the Scottish writer Gil Elliot in his book "Twentieth Century Book of the Dead". Elliot talks about the international efforts to prevent and cure infectious disease and believes that war should similarly be treated as an international anathema that is to be abolished. Efforts to eradicate disease through public health campaigns crossed boundaries and saw even countries who were otherwise very hostile towards each other mutually cooperating. This was because disease was not seen as some other country's problem but as a common threat. Because of their sheer destructive power, nuclear weapons similarly pose a common threat to all of humanity. Rhodes says that only when nuclear weapons are similarly and completely depoliticized to the extent that infectious diseases are, only when the world sees them not as instruments of aggression and patriotism owned by specific nations but as a common scourge that threatens all of humanity irrespective of our political leanings and differences, only then will we all work together to abolish them.

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Saturday, August 28, 2010

Miles to go before...

A New York Times article describes a study conducted by the NIH that basically asked scientists to simply sift through the massive evidence of the past twenty years to answer one question; what factors can cause or prevent Alzheimer's disease? The answer is unsurprisingly depressing- there is basically no proven therapy, personal habit, dietary supplement or mental task that correlates with the prevention of AD. AD is still as much a disease without a cure or preventative remedy as it ever was. We have almost as much work to do as Alois Alzheimer would have in 1908.

The bad news about AD has just kept on coming in over the last few years. Part of the reason is the very disappointing verdict on the role of beta-amyloid, reached after dozens of clinical trials which targeted the clump of protein in AD brains and failed to reverse the debilitating effects of the disease. Along with these studies, there has been a panoply of articles suggesting everything from crossword puzzle solving to Gingko biloba extracts that could possibly prevent the disease.

But as the NYT article reports, most of these recommendations are based on faulty 'studies' which are typically called "observational" studies. These studies are essentially accounts of observations made after someone has started on a measure that's assumed to be preventative. In addition, most of these observations are self-reported. Thus, evidence from such observations is spotty at best and is a far cry from the double-blind controlled clinical trials required to establish efficacy. After sifting through the evidence, the NIH study group concluded that they were sure only about one measure- Gingko biloba. And here the verdict was that Gingko biloba does not prevent AD. Apart from this, most other factors touted as preventive measures- including cognitive stimulation, vitamin E and antioxidants- could not be correlated with decreased incidence of AD with any degree of certainty. There's just no good evidence.

Part of the problem is simply the amount of time patients enrolled in trials would have to be observed in order to draw any conclusion about prevention. AD typically emerges around age 50, but its effects become apparent only in the late 60s and early 70s. A true clinical trial to study prevention would probably have to start during the young years and subjects would have to be followed for at least two to three decades, an expensive and complicated endeavor.

Yet the reports cited in the NYT should not be as depressing as they appear. For one thing, many people now think that the real reason none of the therapies for AD are working is simply because they are administered too late. Two new promising studies based on PET scans and spinal taps could make it easier to detect AD earlier and start treatment immediately. Plus, it's precisely the fragmented nature of the reported observations that provides opportunity for studying them further. Also, as depressing as the amyloid-targeting trials were, at least they provide good evidence of something that does not seem to be working. In science, the misses are almost as important as the hits. Finally, it's not like long-term studies cannot be attempted; the famous Framingham study followed the inhabitants of a small Massachusetts town not just over years but over generations to establish the connection between high cholesterol and heart disease. Perhaps a Framingham-style study for Alzheimer's is due.

Until these deep questions are resolved though, AD patients and their families will keep on living their private version of hell and will keep on trying to stave off the terrible malady by trying anything that remotely seems to work. The least we can all do is keep on searching.

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Friday, August 27, 2010

From bull horns to under the lens of Anton


In 1988, a young computer scientist named David Shaw was working at Morgan Stanley, one of the first Wall Street firms interested in using computer algorithms for trading. Shaw was an expert in parallel processing, speeding up calculations by executing them in a parallel process over multiple processors. Previously he had been a computer science professor at Columbia University had tried to sell his computer skills to a number of companies, but only Morgan Stanley was genuinely interested. As Shaw started working at the company, he began to think not just of programming strategies but of creative ways in which they could be applied to trading. In a meeting where he was supposed to talk only about his algorithms, he went one step beyond and described better methods for trading using these algorithms. Eyebrows went up in the room. Shaw was essentially seen as overstepping his bounds as a programmer. The higher-ups told him clearly that his job was simply building the computer architecture. He could leave the trading to them. Shaw quit and started his own company. Ten years later, it was one of the most successful hedge funds in the world and Shaw was a billionaire. One can only speculative how much the Morgan Stanley executives cried over the loss they had suffered when Shaw left.

But now D E Shaw is a totally different animal.

One of the most anticipated talks at the American Chemical Society meeting in Boston which I just came back from was by this Wall Street mover turned pure scientist. He is a remarkable and brilliant man. What other Wall Street hedge fund manager who made billions using mathematical algorithms for trading (and was known as “King Quant” at one point) basically retires from the dizzying world of finance to fully engage himself with computer simulations of proteins and drug discovery research? Well, Shaw has done this, and is blazing his way toward some potentially revolutionary research. In a nutshell, molecular dynamics (MD) is a technique that simulates the motions of systems at the molecular and atomic levels. It is especially useful for proteins since it can accurately capture their real-life motion in living organisms. MD is based on Newton's laws of motions and essentially involves solving the equations of motions to calculate the forces and velocities of all the atoms in the system. In practice, due to the very large number of atoms in a typical protein (usually thousands, surrounded by tens of thousands of water molecules) MD is quite computationally intensive and challenging to implement; until now, most simulations have been restricted to nanosecond time frames (which can easily correspond to days of actual computer time).

Shaw heads D E Shaw Research, a company totally separate from the financial powerhouse that has as its long-term goal, a fundamental transformation in the process of drug discovery. As the story goes, Shaw got somewhat bored of making millions and wanted to attack scientific problems that could benefit from the application of advanced computer algorithms. He got his old job as computer science professor at Columbia University and started looking around for the right problem. Fortunately for the field of biochemistry, Shaw started having discussions with a friend of his, the well-known physical chemist Richard Friesner at Columbia who is also the chief scientific advisor for the computational chemistry company Schrodinger. Friesner piqued Shaw’s interest and started giving him little problems in computational chemistry and biology which Shaw solved during his spare time. Finally he realized that MD simulations of proteins which had previously been typically restricted to the nanosecond time range stood a chance of being truly and very significantly useful if they could be expanded to the 10 microsecond-millisecond range, since this is the time scale on which most interesting biological motions occur.

Shaw started D E Shaw research and collected a team of highly talented chemists, biologists and computer scientists to tackle the problem. After a decade or so, these efforts have manifested themselves as Desmond, a protein MD program that has vastly accelerated computer simulations of proteins. Desmond essentially relies on many ingenious methods to simplify the calculation of forces and velocities involved in a typical MD computation. What is even more remarkable is that Shaw’s group has designed ‘Anton’, a 512 node state-of-the-art machine, a special purpose machine explicitly designed for protein MD and named after Anton van Leeuwenhoek, the legendary 17th century Dutch scientist who trained the microscope on the microbial world and unearthed a wondrous universe teeming with life. Just like the 17th century Anton probed the events of the bacterial world, the 21st century Anton seeks to probe the molecular-level events of the protein world, The machine does only MD, and it does this using a razor sharp scalpel.

To give an idea of the kind of quantum leap Anton provides for MD simulations, Shaw gave some numbers, and I can swear I saw some people who were almost nodding off suddenly become wide awake. According to Shaw, the fastest supercomputer which does parallel processing today can crunch about 200 nanoseconds per day for a typical sized protein. Anton surpasses this number by two orders of magnitudes and spews out 17,400 ns or 17 microseconds per day. Such numbers would have been unthinkable a decade ago; until Desmond appeared on the scene, the world record for long protein MD simulations had been held by a group from the University of Illinois, with a total time of 10 microseconds.

So what’s the significance of being able to simulate in this time scale? Tremendous. It’s like the difference between nuclear weapons and the biggest conventional bombs previously available. When nukes arrived on the scene, some politicians like Winston Churchill shrugged them off by thinking that they were “just bigger bombs”. But as the old saying goes, quantity can have a quality all of its own. Nuclear weapons heralded a completely new era of warfare because of the ability of a single weapon to raze a whole city. The basic unit of destruction changed from a human being to entire cities. Desmond and Anton promise such conceptual transformations. As mentioned before, breaking the 10 microsecond barrier is a real turning point since most interesting physiological events happen on time scales of microseconds-milliseconds.

Entering the world of millisecond simulations is like unlocking the door to a rainforest with millions of exotic species that you suspected existed, but which you had no way of viewing and studying. In the last few years, Desmond has been used to study highly significant conduction events in ion channels proteins which conduct sodium and potassium, has been used to reconcile experimental and conceptual contradictions in the structure of proteins called G-Protein Coupled Receptors which are absolutely crucial in both basic physiological processes and in the action of drugs, and has been used to study proteins called kinases whose misregulation in involved in cancer. All these events are very slow with respect to conventional MD and were until now mostly inaccessible. Shaw showed some spectacular examples of proteins actually folding and unfolding multiple times. In some cases his group has obtained quantitative agreement with experiments.

I think it was the end of the talk which made a few jaws drop. When you have a protein structure and want to find out a small drug molecule which can modulate its activity, one of the key goals is to first find out where the drug binds. Almost all drugs regulate the activity of proteins- and therefore treat diseases in which these proteins are misregulated- by binding into very specific pockets on the proteins. With the kinds of time scales available, Shaw can achieve this with a devastatingly straightforward simulation. In a video that appeared a little surreal, he simply let the drug roam all around the protein surface and find the binding pocket. Like a curious dog sniffing around for the buried bone, the little guy went in and out of crevices and gullies, lingered for some time outside the binding site, and then, with a little hesitation, finally ensconced himself firmly in his cozy home.

Molecular dynamics by itself is not going to revolutionize drug discovery. But it can provide unprecedented insight into the behavior of biological systems at the molecular level. What we witnessed in that room on Thursday was a different ball game. One in which the ball had been hit out of the park. More surprises should follow.

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Friday, August 13, 2010

Open-sourcing Alzheimer's disease diagnosis

In the middle of all that disappointing news about failed treatments targeting the beta-amyloid peptide involved in AD, here's some silver lining. A lot of people think that the real reason all these drugs are not fighting AD is not because they are ineffective per se but because they are administered too late, long after the disease has manifested itself. Thus the logical step toward making these therapies more effective would be in detecting AD earlier. In the last few months, a slew of articles has detailed several techniques for diagnosing AD early which look promising, from better brain imaging to spinal taps. An article in today's New York Times looks at the integrated effort that has spawned these developments. It turns out that the effort has come about from several government agencies, universities, non-profit organizations and imaging and pharmaceutical companies collaborating to find early biomarkers for AD. Biomarkers are unique chemical or biological signatures that signal the onset or presence of a particular disease. They can range from specific proteins to small organic molecules that are uniquely associated with that disease. One of the biggest endeavors in medicine today is to find biomarkers that are produced very early during a disease's development, when the disease has not yet become full blown and when the chances of targeting it with drugs is the highest. The joint initiative cited in the article has pooled together several million dollars from each contributor. As everyone wisely realized, AD is much too complex to be tackled by single research entities (what disease isn't?). As one participant said:
"We all realized that we would never get biomarkers unless all of us parked our egos and intellectual-property noses outside the door and agreed that all of our data would be public immediately.”
"Parking their egos" outside would be necessary for the diverse and large studies required to gain insight into true AD biomarkers.
“The problem in the field was that you had many different scientists in many different universities doing their own research with their own patients and with their own methods,” said Dr. Michael W. Weiner of the San Francisco Department of Veterans Affairs, who directs ADNI. “Different people using different methods on different subjects in different places were getting different results, which is not surprising. What was needed was to get everyone together and to get a common data set.”
But that would require a huge effort. No company could do it alone, and neither could individual researchers. The project would require 800 subjects, some with normal memories, some with memory impairment, some with Alzheimer’s, who would be tested for possible biomarkers and followed for years to see whether these markers signaled the disease’s progression.
The problem is of course is that it can be tricky as hell to distinguish true biomarkers from spurious ones (the old problem of distinguishing correlation from causation). It would take some time to zero in on those biomarkers that truly signal the onset of the disease. But this bit of news is gladdening for two reasons; firstly because it indicates that people are perhaps moving away from the obsession with targeting amyloid (which nonetheless continues to be a fascinating entity), and more importantly because it indicates that there are still people willing to park their egos outside the door and publicly collaborate to address a very complex medical challenge. Hopefully this endeavor should provide inspiration for tackling other diseases.

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Friday, August 06, 2010

Remember

From Nobel Laureate Kenzaburo Oe:
Moments before the atomic bomb was dropped, my mother’s friend happened to seek shelter from the bright summer sunlight in the shadow of a sturdy brick wall, and she watched from there as two children who had been playing out in the open were vaporized in the blink of an eye. “I just felt outraged,” she told my mother, weeping.

Even though I didn’t fully grasp its import at the time, I feel that hearing that horrifying story (along with the word outrage, which put down deep, abiding roots in my heart) is what impelled me to become a writer. But I’m haunted by the thought that, ultimately, I was never able to write a “big novel” about the people who experienced the bombings and the subsequent 50-plus years of the nuclear age that I’ve lived through — and I think now that writing that novel is the only thing I ever really wanted to do.

In Edward W. Said’s last book, “On Late Style,” he gives many examples of artists (composers, musicians, poets, writers) whose work as they grew older contained a peculiar sort of concentrated tension, hovering on the brink of catastrophe, and who, in their later years, used that tension to express their epochs, their worlds, their societies, themselves.

As for me, on the day last week when I learned about the revival of the nuclear-umbrella ideology, I looked at myself sitting alone in my study in the dead of night . . . . . . and what I saw was an aged, powerless human being, motionless under the weight of this great outrage, just feeling the peculiarly concentrated tension, as if doing so (while doing nothing) were an art form in itself. And for that old Japanese man, perhaps sitting there alone in silent protest will be his own “late work.”

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Remember

From Nobel Laureate Kenzaburo Oe:
Moments before the atomic bomb was dropped, my mother’s friend happened to seek shelter from the bright summer sunlight in the shadow of a sturdy brick wall, and she watched from there as two children who had been playing out in the open were vaporized in the blink of an eye. “I just felt outraged,” she told my mother, weeping.

Even though I didn’t fully grasp its import at the time, I feel that hearing that horrifying story (along with the word outrage, which put down deep, abiding roots in my heart) is what impelled me to become a writer. But I’m haunted by the thought that, ultimately, I was never able to write a “big novel” about the people who experienced the bombings and the subsequent 50-plus years of the nuclear age that I’ve lived through — and I think now that writing that novel is the only thing I ever really wanted to do.

In Edward W. Said’s last book, “On Late Style,” he gives many examples of artists (composers, musicians, poets, writers) whose work as they grew older contained a peculiar sort of concentrated tension, hovering on the brink of catastrophe, and who, in their later years, used that tension to express their epochs, their worlds, their societies, themselves.

As for me, on the day last week when I learned about the revival of the nuclear-umbrella ideology, I looked at myself sitting alone in my study in the dead of night . . . . . . and what I saw was an aged, powerless human being, motionless under the weight of this great outrage, just feeling the peculiarly concentrated tension, as if doing so (while doing nothing) were an art form in itself. And for that old Japanese man, perhaps sitting there alone in silent protest will be his own “late work.”

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Wednesday, August 04, 2010

Shattering the nuclear sword



"Every man, woman and child lives under a nuclear sword of Damocles, hanging by the slenderest of threads, capable of being cut at any moment by accident, or miscalculation, or by madness. The weapons of war must be abolished before they abolish us.”- John F. Kennedy, speech to the UN, September 1961.

"Countdown to Zero" is one of the best accounts of the dangers of nuclear weapons for the layman that I have recently seen. The film which opened last week takes a comprehensive yet succinct look at the risks posed by nuclear weapons, and is set against the backdrop of John F. Kennedy's speech to the United Nations in which he quoted the words cited above. JFK talked about a "Sword of Damocles" hanging on our head that is secured by a flimsy thread. As the film emphasizes, the most important operative words in Kennedy's speech are "accident, miscalculation or madness" which can all cut the thread holding the sword. To illustrate how this could happen, the film showcases interviews with leading arms control experts and policy personnel, including former CIA agent Valerie Plame, Harvard professor Matthew Bunn, nuclear terrorism expert Graham Allison, WMD expert Joseph Cirincione and world leaders like Mikhail Gorbachev and Tony Blair.

The fact is that no matter how responsible the leaders of countries with nuclear weapons may be and how well-protected the weapons may seem, the extremely complex nature of the system always increases the chances of miscalculation, accident or madness. The film gives concerning examples. For instance, a few years ago, nuclear weapons instead of regular ones were loaded on a plane in North Dakota and flown almost halfway around the country without anyone noticing it. The Cuban Missile Crisis is of course well-known, lesser known are the Palomares incident and half a dozen others when nuclear weapons were accidentally dropped from mid air. Fortunately none detonated. But the danger is pervasive and the film also recounts some chilling events. The most heart-stopping is an incident in 1995 recounted by Cirincione, when the Russians mistook the flight of an experimental rocket from Norway for a nuclear launch. The codes were ready, everyone in the Russian hierarchy was convinced, and all that remained to launch a nuclear strike against the US was President Yeltsin's approval. Thankfully for the world, Yeltsin was "not drunk" and he did not trust the officials' judgment enough, leading to a narrow brush with catastrophe. The problem is that the complex protocols embedded in the use of nuclear weapons allow much opportunity for misunderstandings and accidents and very little time for response and corrective action. Even a President would have typically no more than a few minutes to make a decision, thus increasing the possibility of triggering armageddon. The simplest and most ludicrous of causes can set off false alarms; in one case, the setting off of a nuclear alert was the result of a malfunction in a single computer chip costing less than a dollar.

One of the most jaw-dropping instances I remember was from Richard Rhodes's book. Zbigniew Brzezinski, Jimmy Carter's National Security Advisor, was woken up in the middle of the night and told that there were 1500 Soviet nuclear missiles headed for the US. As Brzezinski was contemplating what to do next, the caller called back and said that the number of missiles had been upgraded to 15000. Hearing this, Brzezinski just sat on his bed; there would be no point in alerting anyone. Of course, it turned out to be "computer malfunction".

Apart from such misunderstandings, the other reason why nuclear weapons pose such a great danger is of course because they may fall into the hands of terrorists, and deterrence does not apply to such stateless actors. Al Qaeda has been trying to get their hands on nukes for years. What makes the situation worse is the relatively easy accessibility of enriched uranium in the former Soviet Union. After the Cold War ended, many nuclear facilities in the former Soviet republics found themselves orphaned, severed from central control, with their workers out of a job. While many of the facilities were later secured with US cooperation, many others were ludicrously insecure, with barely a padlock preventing access to nuclear material; in the words of a former Soviet official, "potatoes were guarded better". Selling a few grams of uranium to potential buyers would allow impecunious laid-off workers from these facilities to make a lucrative buck. The film documents that there have been literally dozens of instances when former nuclear workers have been caught trying to smuggle a few grams of nuclear material across borders in Russia and Central Asia. In addition, countries like Iran, North Korea and Pakistan are happy to trade nuclear-related technology to wannabe buyers.

This nuclear material is notoriously hard to detect. As the film says, smuggling a few kilograms of enriched uranium by shielding it in a lead pipe is child's play. This is mainly because the relatively weak radiation from uranium can be almost completely shielded by lead, but also because this uranium could be hidden in any one of a whopping 100,000 shipping containers entering the US every single day. Finding a few kilos of U-235 in a heavily shielded lead casing in one of these countless containers is an unimaginably difficult problem to solve. Set the detectors on high and one would not detect the low-intensity radiation. Set it on low and one would detect almost everything else (including fruits, papers and wood) which emit comparable ambient levels of radiation.

If terrorists manage to get past the most difficult step of acquiring nuclear material, they can easily build a crude nuclear bomb. Plus, paraphrasing Churchill, terrorists don't have to do their best, they just have to do enough. Exploding a crude bomb in the port itself would not be what they have in mind, but it would still be enough to bring about chaos and panic, possibly collapsing the financial and economic system of a country.

So what can be done to address this life-threatening problem? One of the biggest truisms about nuclear weapons which separates them from other WMDs is that if you don't have uranium or plutonium, you cannot build these weapons, period. Thus in theory, you completely solve the problem if you secure the material. Programs for securing material from the former Soviet republics have been instituted for years, but funding has embarrassingly been a problem. Plus there is no accurate estimate of how much material may have been stolen after the Soviet Union collapses. Securing this material would be the first thing to do. Secondly, countries who want to peacefully pursue atomic energy must be provided nuclear material by an international body under the strictest of safeguards.

But most importantly, there is one almost perfect solution which there is no getting around: reduce the nuclear arsenals of the world to zero. Nada. Zilch. There is no doubt that the US and Russia which still stock the lion's share of nukes should take the lead, a point which has been belabored often to scant effect. This should especially be ludicrously easy for the US which still has thousands of nukes on hair-trigger alert and which has conventional forces that could easily overwhelm any other country's defenses and offenses. If there is one country that does not need any nuclear weapons, it's the US, followed by Russia. The psychological impact of the US renouncing every single nuclear weapon would be hard to overestimate (Nixon did it with chemical and biological weapons in the 70s). It would be tremendous and would offer the US an unprecedented moral authority to ask others to do the same. While it may not be easy for countries like India and Israel which share extensive boundaries with unstable and dangerous regimes, such an act will signify huge potential. This was a dream that President Reagan often talked about. As idealistic as it sounds, it should be feasible at least for the US. Most refreshingly, amid all the partisan bickering that we keep hearing about, such an initiative has gained traction with a wide swathe of influential statesmen from both parties. In a compelling document last year, several former highly influential bipartisan officials like Henry Kissinger, George Schultz, William Perry and Sam Nunn called for the abolishment of nuclear weapons. President Obama has latched on to this dream. It remains to be seen what he actually does about it.

As JFK said in his speech, "the weapons of war must be abolished before they abolish us". In 1986, during the very promising Reykjavik meeting when Reagan and Gorbachev came within a hairsbreadth of getting rid of all nuclear weapons, Reagan told Gorbachev about a dream that seems straight out of a movie. He said that once the world has decided to get rid of all nuclear weapons, he and Gorbachev would meet again in Reykjavik, each holding the last nuclear missile in their hands. They would both be so old that they would hardly recognize each other. Gorbachev would squint at Reagan and say "Ron, is that you"?. And Reagan would say, "Mikhail?". And then they would both destroy the last two nuclear bombs on the planet, and the whole world would have a giant party.

We will have the champagne ready.

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