The H-Bomb Fuchs?

And a very brief history of the US hydrogen bomb effort

How the Soviets got the H-bomb by 1955 has always been something of a mystery. Although they had top-notch scientists like Andrei Sakharov working for them, they still got almost exactly the same design as the Americans in just 4 years. Nobody denies Sakharov's tremendous contributions to the H-bomb effort. And yet the question lingers whether espionage helped H-bomb design just as it had helped Soviet A-bomb design, most famously through Klaus Fuchs's efforts.

Now a new book due to be released in January claims that the authors have uncovered a spy who gave details about the H-bomb design to the Soviets. 'The Nuclear Express' is co-authored by Thomas Reed, a former weapons designer who worked at Los Alamos for many years. The authors would not name the spy since he is now purportedly dead. Historians who have weighed in don't find the idea entirely implausible; after all it is hard to believe that security would have been so tight so as to completely preclude espionage. In addition even after Fuchs was apprehended, the Soviets still had a web of spies and sympathizers spread throughout the US that even as of now is not completely deciphered.

It is worthwhile at this point to recapitulate some of the US H-bomb history:

1942: Edward Teller, the 'father of the hydrogen bomb', builds upon a suggestion by Enrico Fermi and proposes the first design for a thermonuclear weapon. This is during a secret conference at Berkeley organized by Robert Oppenheimer that's supposed to explore the feasibility of a fission weapon, not a fusion device. Teller's basic idea is to use the extreme temperatures arising from an atomic bomb to ignite a cylinder of deuterium or tritium at one end, with the unproven assumption that the fusion fuel will ignite and continue to burn, thus producing a tremendous explosion equivalent to millions of tons of TNT. The H-bomb distracts the participants enough for them to speculate on its workings, but atomic bomb design (necessary for initiating a fusion reaction anyway) is wisely given priority. The as yet speculative thermonuclear weapon is christened "The Super". The Manhattan Project is kicked off. Throughout the war Teller goes off on his own H-bomb trajectory, often contributing to flared tempers and inadequate expertise at Los Alamos.

1946: After the war, Teller who is still obsessed with the weapon convenes a short, top secret conference. Klaus Fuchs is one of the participants. The conference concludes, mostly based on Teller's optimistic assessment, that The Super is feasible. At the end of the conference, Teller submits an overly optimistic report much to the chagrin of Robert Serber, an accomplished physicist who had been Oppenheimer's principal assistant at Los Alamos. Fuchs transmits the information from this conference to the Soviets.

August 1949: The Soviets detonate their first atomic bomb. Everyone is shocked, perhaps unnecessarily so. A high-level committee headed by Oppenheimer convenes in October on Halloween and debates H-bomb development. The almost unanimous opinion is that the H-bomb is not a tactical weapon of war but a weapon of genocide and therefore its development should not be undertaken. Priority should be given instead to the development of better, tactical fission weapons.

December 1949-January 1950: Edward Teller, spurred on by the Soviet A-bomb, starts recruiting scientists to join him at Los Alamos to work on the Super. Hans Bethe initially agrees, then after a chat with Oppenheimer and Victor Weiskopf, declines. Teller blames his change of mind on Oppenheimer. Later Bethe decides to work at Los Alamos only as a consultant, mainly because he wants to prove that The Super won't be feasible.

During this time, Stanislaw Ulam and Cornelius Everett at Los Alamos embark on a set of tedious calculations to investigate the feasibility of The Super. The result is decidedly pessimistic. The Super would need much more tritium, an extremely rare and expensive isotope, to initiate burning. Even if tritium is added the probability of successful propagation is extremely low. Teller's dream is dead in the water. Fermi, one of Teller's role models, confirms the bad news.

January-February 1950: Even as Ulam's calculations give a fit to Teller, Klaus Fuchs confesses his espionage. The country gradually starts descending into a state of paranoia. Against the advice of many experts, President Harry Truman initiates a crash program to build the H-bomb. Incidentally his announcement comes before that about Fuchs. And it comes absurdly even as Ulam and others have proven that Teller's Super would not work.

1950: Throughout 1950 the options for the Super keep on looking bleaker. In June the Korean War begins, fueling more feeling of paranoia. Teller's mood blackens. At one point after Ulam reports his latest set of calculations, Teller is said to be "pale with fury"

December 1950-January 1951: Ulam makes a breakthrough. He realizes that separating the fission weapon and fusion fuel and using the extreme pressures generated by the fission weapon will cause compression of the fusion fuel, thus dramatically increasing the odds of thermonuclear burning. Ulam floats the idea to Teller who enthusiastically espouses it and also crucially realizes that radiation from the fission "primary" would do an efficient job of compressing and sparking off fusion in the fusion "secondary". The idea is so elegant that Oppenheimer calls it 'technically sweet' and now supports the program. Bethe agrees to work on the device because suddenly everyone thinks that the Soviets will now not be long in discovering it. Later, Teller makes significant efforts to discredit Ulam's role in the invention. But the Teller-Ulam design becomes the basis for almost every hydrogen bomb in the arsenals of the world's nuclear powers.

1951-1952: Work proceeds on a thermonuclear weapon. In November 1952 the world's first hydrogen bomb, Ivy Mike, explodes with a force equivalent to 650 Hiroshima type bombs. Mankind has finally invented a device that comes closest to being a weapon for complete annihilation of nations.

So that is where matters stood in 1952. That gives the spy a window of two years or so to transmit the information. It's instructive to note that after Fuchs was outed, Oppenheimer actually hoped that he had told the Soviets about the H-bomb design from the 1946 conference, since that design had been shown to fail and would have led the Soviets on a wild goose chase. However the initial thoughts that Bethe, Oppenheimer and others had about the Soviets discovering the Teller-Ulam mechanism soon don't look unfounded to me. There were experts who thought that the idea of using compression and radiation to ignite and burn the thermonuclear fuel would occur to anyone who had thought hard and long about these matters. Niels Bohr thought that a bright high-school student would have thought about it, but that's probably going a little too far. The truth could well be in between, with both original thought and espionage playing a role. In any case the new book promises fresh fodder for atomic aficionados and I have pre-ordered it.

Deconstructing Little Boy and Fat Man

A high-school educated truck driver uncovers the classified details of the first atomic bombs with unlimited verve and imagination

The details and specifications of the first two atomic bombs developed by humanity- Little Boy and Fat Man- are still secret. While a lot of material about nuclear weapons has been declassified, the specs for the first bombs dropped on Hiroshima are still considered out of reach, and probably absurdly so. Even after other countries have built countless nuclear weapons like Little Boy and Fat Man and vastly improved ones, the original bomb design details remain under a shroud of secrecy.

Now, a truck driver with a high school diploma has uncovered these details in excruciating detail. His work has been lauded by prominent historians including Richard Rhodes. His fascinating story is recounted in the December 15 New Yorker. John Coster-Mullen, with the "Coster" in his name curiously being the last name of his wife, has gone to simple but extraordinary lengths to get detailed information on the design of the first two nuclear weapons. He has succeeded to a degree that no professional scientist or historian has before, and which no national laboratory scientist will admit.

Coster-Mullen's story proves that to make significant headway in a problem you don't have to be a professional historian or a professor with a PhD. All you need is the patience to stick with a topic and keep on drilling deep into it. Coster-Mullen has worked with this single purpose for the last fifteen years or so, and has exploited almost every publicly available source to put together the details of Little Boy and Fat Man. These include museum exhibits around the world, scores of books written about nuclear weapons, thousands of documents declassified in the last fifty years, and testimonies and interviews with everyone from top scientists to machinists who worked on the bombs. The most important asset that Coster-Mullen brings to bear on the problem is unremitting determination and pure old common sense.

Consider the instance where he looked at an old and commonly seen photograph of two scientists carting the core explosive 'physics package' for the device exploded in the first atomic bomb test- Trinity- into a sedan. Coster-Mullen simply looked at the height of the sedan doors, figured out which model it was (a 1942 Plymouth) went into a car museum to measure the height and width, and then by simple proportionality deduced the size of the box the men were carrying. In another instance, he deduced the length of a crucial plug used for Little Boy from the account of the number of turns needed to screw it in. His general approach is to patch together material from a variety of sources and then connect the dots using simple deductive logic. While there are still unresolved questions about the designs, he has put together an extraordinary amount of detail. This is classic detective work at its best. The culmination of this work is Atom Bombs, a book about the detailed designs of the first atomic weapons that Mullen is selling on Amazon for 50$.

Again, Coster-Mullen has nothing more than a high school diploma and works as a truck driver and part-time photographer. His example eminently indicates that what is needed for success is an iron will to uncover something, and knowing where to look for the data. Read the entire article- it's fascinating.

Buying Used Books on Amazon

As a book-hungry graduate student whose money is a precious commodity, it's not surprising that I am loathe to walk into Borders and buy a brand new book. If the book is older I would rather haunt used book stores, comb through the hundreds of sometimes boring titles, and pick the one gem ensconced among them which others' eyes have not noticed. Needless to say, this gnaws away at another one of a graduate student's precious commodity- time.

However, another option is Amazon's used books service. I was hesitant to use this but was finally egged on to try out a few titles. My conditions were simple: spines should be intact, and there should be absolutely no underlining or highlighting inside. The rules are pretty simple too: go for sellers offering books whose condition is marked "very good" or better, who have at least a 97% rating and who have been selling at least for a year or so. Most importantly, buy ex-library books if they are available; the seller will usually indicate this explicitly. These books get you the biggest bang for your buck. They are usually wrapped in plastic with the tender loving care characteristic of many public libraries, their dust jackets are usually firm and intact, and they may have some library stamps on the first page or on the sides.

But if these simple rules are satisfied, then ex-lib books can be better than even brand new books. Consider that hardbacks usually cost no less than 18-20$. So if I do end up buying new books, I buy paperbacks whenever they are available. Paperbacks cost between 10-15$. Now consider ex-lib books which I have gotten for about 3$ on average. Even with the shipping it comes to 7-8$. A well-protected hardcover ex-lib book warmly clasped with a plastic-covered dust jacket beats a brand new paperback even if the hardcover is a few years older.

Until now I have had a great experience ordering these ex-lib hardcovers from Amazon. Starting about six months ago, I have already ordered about 30 of these and have been satisfied 99% of the time. There may have been one or two which looked none the worse for wear, but in their defence, they were selling for 20 cents apiece. There's a limit to what you can expect.

∆G, ∆G†† and All That: Implications for NMR

Since we were on the subject of NMR and determining conformations, I think it would be pertinent to briefly discuss one of the more slippery basic concepts that I have seen a lot of chemistry students (naturally including myself) get plagued with; the difference between thermodynamics and kinetics. I find myself often besieged by a distinction between these two important ideas that encompass all of chemistry. Simply saying that thermodynamics is "where you go" and kinetics is "how you get there" is not enough of a light to always assuredly guide students through the sometimes dark corridors of structure and conformation.

Going beyond the fact that thermodynamics is defined by the equilibrium free energy difference (∆G) between reactants and products and that kinetics relates to the activation barrier (∆G^††) for getting from one to the other, I want to particularly discuss the importance of both these concepts for determining conformation by NMR spectroscopy.

There are two reasons why determining conformations in solution can become a particularly challenging endeavor. The first reason is thermodynamics. Again consider the all-important relation ∆G = -RTlnK which makes the equilibrium constant exquisitely sensitive to small changes in free energy (∆G). As mentioned before, an energy difference of only 1.8 kcal/mol between two conformations means that the more stable one exists to the extent of 96% while the minor one exists to the extent of only 4%. In practice such energy differences between conformers are seen all the time. A typical scenario for a flexible molecule in solution will posit a complex distribution of conformers being separated from each other by tiny energy differences ranging from say 0.5-3 kcal/mol. Again, the above exponential dependence of equilibrium constant K on ∆G means that the concentration of minor conformers which are higher in energy than the more stable ones by only 3 kcal/mol will be so tiny (~0.04%) as to be virtually non-existent. NMR typically cannot detect conformers which are less than 2-3% percent in solution (and it's too much to ask of NMR to do this), but such populations exist all the time.

Thus, thermodynamics is often the bane of NMR; in this case the technique is plagued by its low sensitivity

If thermodynamics is the bane, kinetics may be the nemesis. Rotational barriers between conformations (∆G^††) can be even tinier compared to thermal energy available to jostle molecules around at room temperature. For example, the classic rotational barrier for interconversion in ethane (whose origins are still debated by the way) is only 3 kcal/mol. Energy available at room temperature is about 20 kcal/mol which will make the ethane conformations interconvert like crazy. So even for energy barriers that are several kcal/mol, conformational interconversion is usually more than adequate to observe averaging of conformations and consequently all associated parameters- most importantly chemicals shifts and coupling constants- in NMR. The resolution time of NMR is on the order of tens of milliseconds, while conformational interconversion is on the order of tens of microseconds or less. Now in theory one can go to lower temperatures and 'freeze out' such motions. In many such experiments, line broadening at lower temperatures is observed, followed by separation of peaks at the relevant temperature. But consider that even for a barrier as high as 8-10 kcal/mol, NMR usually gives distinct, separate signals for the different conformers only at -100 degrees celsius. For barriers like those in ethane, the situation would be hopelessly challenging. As an aside, that means that sharp, well-defined resonances at room temperature do not indicate lack of conformational interconversion but can simply mean that conformational interconversion is fast compared to the NMR time scale.

Thus, kinetics is also often the bane of NMR; in this case the technique is plagued by low resolution time

Now there may be situations in which either thermodynamics or kinetics is favourable for carrying out an NMR conformational study. But for the typical flexible organic molecule, both these factors are usually pitted against the technique; rapid interconversion because of low rotational barriers, and low thermodynamic energy differences between conformers. Given this fact, it probably should not sound surprising to say that NMR is not that great a technique. However, as is well known to every chemist, its advantages far outweigh its drawbacks. Conformational studies comprise but one important aspect of countless NMR applications.

Nonetheless, when conformational studies are attempted, it should always be kept in mind that thermodynamics and kinetics have both conspired to make NMR an unattractive method for our purposes. Thermodynamics leads to low populations. Kinetics leads to averaging of populations. And yet the average information gained from NMR is invaluable and can shed light on individual solution conformations when combined with a deconvolution technique like NAMFIS or molecular dynamics. On the other hand, fitting the average data to a single conformation for a flexible molecule is inherently flawed and unrealistic. No one who has tried to take pictures of a horse race with a low-shutter speed camera should believe that NMR by itself is capable of teasing apart individual conformations in solution.

For determining conformations then, NMR alone does provide a wealth of data locked inside a safe. Peepholes in the door may illuminate some aspects of the system. But you need a key, best obtained from other sources, that will allow you to open the door and savor the treasures unearthed by NMR in their full glory.

Does a protein-bound ligand exist in only one conformation?

I have been thinking a lot recently about studies in which people have determined the bound conformation of a ligand by transfer-NOESY experiments, essentially by transferring magnetization off another ligand to the protein and then back to the ligand of interest. With the known bound conformation of the first ligand, one can apparently locate the conformation of the second one. Many such unknown protein-bound conformations have been worked out. In my field of research, the ones which are relevant are of agents that bind to tubulin, especially discodermolide. In this case, the conformation of discodermolide was deduced via competition transfer-NOESY experiments with epothilone. These experiments are non-trivial to carry out and, as is the case for other biomolecular NMR studies, should be interpreted carefully. But in the end they look like nifty techniques that can shed light on unknown bioactive conformations, something that's very valuable for drug design.

Essentially it's again a problem of fitting the bound conformation NMR data to a single conformation. In solution we know for sure that this is a fallacious step. The (not so) obvious assumption in doing this for bound conformations is that there's got to be only one conformation in the active site too. But I have always wondered if a ligand in a protein active site could also have multiple conformations. MJ's comments on a past post and the discussion there makes me think that even in a protein active site, there could possibly be multiple conformations of a ligand, something that runs counter to what we conventionally think. How diverse those conformations might be is a different question; one would probably not expect large conformational changes. But even 'small' conformational changes could be significant enough to distinguish between different conformations in the active site. It's a problem worth thinking about.

Sleep well through chemistry...forever

Molecules of Murder: Criminal Molecules and Classic Cases
By John Emsley
Royal Society of Chemistry, 2008

In this highly engaging, detailed and morbidly fascinating slim volume, chemist John Emsley narrates the stories of those who made use of science for killing their fellow beings through deadly means. Emsley recounts the use of famous chemicals used as poisons in famous and some not-so-famous murder cases.He tells us ten stories in ten chapters, each devoted to a specific poison and specific murder case in which it was used. The cases are fascinating for science buffs because of the scientific background about the poisons, and for others for the ingenious thinking that went both into the murders and the detective work involved in solving them.

The stories span a range of countries, periods and motives for murder. They feature famous victims such as former FSB agent Alexander Litvinenko as well as lesser-known victims whose killing was also equally deadly and well-planned. Each story has comprehensive details on the personal or political background of the victims and murderers and their times, as well as detailed background on the poisons themselves, including their history, chemical and biological characteristics, use and availability and actual administration to the victims. During this process, Emsley uncovers a range of diabolical and murderous characters who each had their own motives, personal or political, for causing the death of one or several persons.

While the famous murders like Litvinenko's from polonium and Bulgarian dissident Georgi Markov's from ricin are told in fascinating detail, so are the murders involving relatively low-profile and yet deadly poisons like adrenaline, diamorphine and atropine. Emsley also covers murders that used the standard and deadly poisons carbon monoxide and cyanide. Many of these chemicals are relatively easily accessible and that makes their use more difficult to control. Particular chilling is the case of Kristen Gilbert, a nurse who used adrenaline to kill her patients essentially by giving them fatal heart attacks. The story is made more grim by the fact that Gilbert was a nurse who was supposed to be a giver of life, and that adrenaline which is a substance produced naturally by the body is a very clever choice for a poison since its levels rapidly fade and it's hard to detect it as a foreign poison.

The first and last chapters dealing with the Litvinenko and Markov murders from polonium and ricin merit special attention because of their high-profile political nature and the rather exotic identity of the poisons used. Markov was murdered by an agent aided by the KGB while standing on a bridge on the Thames River in London. The murder weapon used was most unlikely; an umbrella with a tip containing a pellet with an extremely tiny amount of ricin which was injected into Markov's thigh by an 'accidental' jab which he hardly felt. Ricin is one of the most toxic substances known to man, and within three days Markov had died a painful and inexplicable death. The murder was well-planned and ingenious. Emsley who himself was involved in this case as a scientific expert gives a fascinating description of the rather simple but ingenious forensic work that went into ascertaining the amount of poison used, which made it possible to eliminate many well-known poisons.

The Litvinenko case is still fresh in everyone's mind. Litvinenko was a former agent of the FSB (the successor of the KGB) who accused prominent Russian politicians and businessmen of nefariously bringing Vladimir Putin to power. His murder also took place in London in a cafe with another unlikely poison- tea laced with radioactive polonium 210. The fact that he could not be saved in spite of 50 years of knowledge about radioactive substances and their effects on biological systems indicates how we can still miss the 'obvious'. It took a long time before polonium 210 emerged as a suspected poison, and this apparently is the first case when this rather well-known substance was used for assassinating a political target. The source was almost certainly a nuclear reactor or some other facility in Russia. While the attempt was successful, the choice of poison was less than perfect since the polonium left a trail of radioactive hot spots literally leading from one location to another. While this combined with Litvinenko's extensive testimony before his death made it possible to finally uncover the suspect, as of now the man is enjoying political immunity in Russia, a fact that may give some credence to the suspicion that Putin may somehow have known about Litvinenko's murder.

These and other morbid cases Emsley narrates with details about the science, chemical history and detective work as well as the politics, personal and social history of the victims and murderers that should keep anyone engaged. For science fans, it is important reading about how science can be used to do harm, and for others, at the very least it is a fascinating set of detective stories that should keep them glued to their chairs. The one problem I had with the book was its format; the font could have been more attractive and the illustrations should have been interspersed within the text instead of curiously being stitched together at the end. But these are minor shortcomings of an otherwise fascinating and lucid book.

I can only end by saying that in this period of paranoia about terrorist acts, it may not be a good idea to read this book in the airport security line.

Article on NAMFIS in IIT-D magazine

A short holiday break and a rather protracted bout of the flu have kept me from blogging. So I will link to an article of mine that just got published in the magazine of the Chemical Society of the Indian Institute of Technology (IIT), Delhi. The article is written for the layman and talks about the importance of realizing that flexible molecules have multiple conformations in solution. Such conformations cannot be determined by NMR alone due to their rapid interconversion.

In the article, I describe NAMFIS (NMR Analysis of Molecular Flexibility In Solution), a joint computational-NMR approach which can derive a Boltzmann population for flexible molecules in solution. This information can be very useful for deducing, for example, the protein-bound conformation of a drug. But it can also be useful under other circumstances where determining conformation is important, such as for organic molecules assembling on a surface. Comments, criticism and questions are of course always welcome.