Field of Science

Corn on the sob

There's an interesting debate in the December issue of C&EN, which pits two professors and well-known energy experts- David Pimentel of Cornell and Bruce Dale of MSU- on opposite sides of the biofuel debate, specifically the ethanol from corn debate.

The debate is quite instructive and you can read about it yourself (access should be free). I have been an opponent of ethanol from corn ever since I first heard one of David Pimentel's viewpoints. The main issue concerns the "energy balance" of corn production. It turns out that by many estimates, more energy from fossil fuels (in terms of corn fertilizer, transportation etc.) is put into producing ethanol from corn than is obtained from using the ethanol. Pimentel believes that this balance is negative; you put in much more energy than what you get. Dale makes some arguments which I find strange, arguing that one must consider the exact character of the fossil fuel sources that are being used (gas, coal or oil) otherwise one is comparing apples to oranges. As far as I am concerned, all are fossil fuels, so it's not going to matter which one is used. All are going to be expensive in the future, in one way or the other. Ethanol from grass provides a better alternative to that from corn, but even there Pimentel contends that that sheer volume of carbon source that one gets from grass is less than that from corn.

In any kind of energy source evaluation, it is always important to consider the ancillary sources involved that may contribute unfavorably. For example, in considering solar and wind-power, one must consider the cost of materials for construction, the land used and the fate of those materials in the future to name a few significant factors.

Many Americans don't realise that diverting corn away from food production can have an immense impact on the American way of life. Michael Pollan's truly excellent The Omnivore's Dilemma makes it clear how much dependent Americans are on corn, which pervades almost everything they buy in the supermarket. We should shudder to think of an "American Corn Famine" akin to the Irish Potato one. If corn is diverted to produce ethanol, Americans will wake up to an unpleasant shock, where almost everything they buy for their daily consumption has become expensive. More than 60% of all corn goes not in human food products directly, but into animal feed. Cattle, hens, and even salmon are fed corn these days. (Maybe that's why grandmothers don't like meat that much anymore). Cheap corn-fed beef is a luxury we may not enjoy if corn supply starts getting diverted into producing ethanol. And even with much corn being used for fuel, as Pimentel demonstrates, it won't fulfill more than a small amount of this energy-hungry nation's energy needs.

In any case, I have always thought that the reason ethanol from corn has received so much attention is because of the gratuitous lobbying in Washington from corn companies, and the resulting shameless pandering that Bush and other officials have demonstrated in terms of the obscene subsidies that corn gets. Seriously, is the United States truly a free market economy, with such ridiculous subsidies offered to corn and oil?

Clearly there has to be a better solution. As with so many other things, ethanol and corn seem to have been oversold by George W. Bush, along with the accompanying corny lines.

Invasion

You remember how all those mean, giant alien ships were slowly grouping and getting into their positions in preparation for a massive coordinated attack on earth's denizens in "Independence Day"?

That's how I kind of feel about little Myco right now

A relatively rare example of docking-based virtual screening

ResearchBlogging.orgMany studies published in the last few years have demonstrated that in general, ligand-based methods are better for virtual screening compared to structure-based docking methods. For example, a 2007 Merck study showed that 2-D similarity searching methods are quite good for finding similar leads, while 3-D methods can do some scaffold hopping and find new families of structures. Both methods are generally superior to docking. One of the reasons for this is that docking is not really designed for virtual screening; docking is much more valuable for prediction of crystallographic conformations and most importantly, predicting binding affinity, which is the holy grail of the industry. The latter task is still extremely challenging, although dents have been made in tackling it.

In any case, so this group from Vertex tackled a kinase inhibitor search problem for Pim-1 kinase using docking, and this seems to be one of those cases where docking with Schrodinger's Glide program helped complement and indeed improve upon HTS. The group screened a large database enriched in kinase inhibtors by HTS and got only a 0.3% hit rate. They decided to find out if VS could do better. They used Glide to screen a corporate collection that was less enriched in kinase inhibitors, to avoid bias. They used Glide not in the VS mode but the regular docking mode which takes more time but is more accurate. They used some astute filters to avoid getting false hits from large molecules that fit better in the site. They also used an C-H aromatic hydrogen bond constrain in the docking.

After screening out compounds that were too large and hydrophobic, they got 4 compounds (a 4% hit rate) with activities ranging from 90 nM to 550nM. Two of these could be crystallised and it was confirmed that the experimental conformation was very close to the predicted binding conformation. Glide also picked up the "weak" C-H aromatic hydrogen bond. The authors conjecture that the reason why Glide chose this H-bond is because the traditional hinge region of Pim-1 kinase is more hydrophobic than that in other kinases because of a proline residue. The study demonstrates how VS can serve as a valuable complement to HTS.

Pierce, A.C., Jacobs, M., Stuver-Moody, C. (2008). Docking Study Yields Four Novel Inhibitors of the Protooncogene Pim-1 Kinase. Journal of Medicinal Chemistry DOI: 10.1021/jm701248t

70% of Americans may find nano "morally unacceptable"

More inspired ignorance among people according to the WSJ, this time manifested in fear of the small
"Our first reaction was that 70% of people must not know what nanotechnology is – President Bush, who has openly relied on moral views to shape his scientific agenda, has made nanotechnology one of his scientific priorities, after all. And Dietram Scheufele, the University of Wisconsin professor who led the survey, agrees to a point. People’s understanding of what nanotechnology is hasn’t advanced much over the last few years, he tells the Business Technology Blog. “So people rely on mental shortcuts,” lumping nanotechnology in with other new technologies like stem cell research and genetically modified foods, he tells us. The same people who object to those fields – often on religious reasons – object to nanotechnology. (Incidentally, the heathen Europeans are just fine with nanotechnology.)"
Mental shortcuts are naturally the best way to reach the greatest number of conclusions in the least amount of time. And finding GM foods or stem cells morally unacceptable is also equally ditzy. Of course, the WSJ should know that President Bush himself has made nano one of his scientific priorities without understanding what it is. But that's ok, one needs time to understand such things. After all, it takes time for one to collect one's thought.

A fair effort

My advisor does not trust QSAR. And for good reason. Every week hundreds of papers are published, with someone trying to predict molecule activities by building QSAR models; few if any are actually predictive, but many explain the known data fairly well.

But I was curious to know what pitfalls lie in the way of QSAR, so I convinced him to let me do a small QSAR project. To make it more interesting, me and two friends started with the same data for about 50 molecules with activites ranging from 10s of micromolars to 10s of nanomolars. We all used a program by a well-known company, and all started with the same molecules in the training and test sets. From then on we were on our own, and in the end we would compare results.

In the end, we each got a decent model. Since we may possibly publish the work later, I cannot say which molecules we were working on. But I actually ended up learning more about statistics than QSAR itself. The main point is that the usual statistical predictor, the correlation coefficient r*2, can be made as high as you want by including more factors in the partial least squares (PLS) regression, and yet you may end up with a model that's nonsense. A high r*2 can mean you have simply fit the existing data fairly well, or it can mean you have overfit the data.

On the other hand, another predictor, q*2 is the correlation coefficient for the test set. That really tells you how well your model can predict new activities. The interesting thing is that a q*2 above 0.50 or is considered publishable, that's how inefficient and relatively primitive QSAR is. Then there's also the third common statistical parameter, the standard deviation. The standard deviation should be as small as possible, but logically it cannot be smaller than that in the experimental data.

The most interesting observation was that all three of us felt that we should lay emphasis on totally different parameters in the model building. Yet with our own unique approaches, we managed to get models with similar statistics.

I learnt that QSAR is indeed not very helpful, but like some other methods, it works if you don't have anything else to go on. A lot of times computational results are simply idea generating devices that save time spent by mere educated guesswork. In fact sometimes the hit rate for educated guesswork might be higher, but the time taken may be longer. In such cases, computational methods can be deemed useful even with a lower hit rate.

In the end, there's one thing we always have to remember about statistics, the rather ribald statement about it which I am still going to quote because I think it's apt (and apologies to women!): Statistics are like women's skirts. What they show us can be useful, but what they hide is much more interesting.

Who should be the next President's Science Advisor?

With hope and clear skies possibly on the horizon, it is going to be very important for the next president to choose a capable chief science advisor. Sound science is going to dictate many of the directions this country takes in the next few decades. The former president has virtually trampled science and the science advisory system underfoot. Who could be an apt candidate for this key post? Here is a list of a few that I like...and one that I don't...

...Read the rest of the entry on Desipundit

Fraud galore: another plagiarisophilic chemist

Boy, do people have a good time doing research or what:
A CHEMIST IN INDIA has been found guilty of plagiarizing and/or falsifying more than 70 research papers published in a wide variety of Western scientific journals between 2004 and 2007, according to documents from his university, copies of which were obtained by C&EN. Some journal editors left reeling by the incident say it is one of the most spectacular and outrageous cases of scientific fraud they have ever seen.

The culprit, sources say, is chemistry professor Pattium Chiranjeevi of Sri Venkateswara University in Tirupati, India. SVU conducted an investigation into Chiranjeevi's work after a journal editor presented evidence to university officials that the professor had plagiarized and possibly falsified several manuscript submissions. Chiranjeevi, who communicates through a wide variety of e-mail addresses, has not responded to multiple requests for comment by C&EN.

Chiranjeevi retains his teaching position at SVU, according to a university source who has requested anonymity. "He is a permanent employee of the university, and the administration cannot fire him easily," the source says. Instead, Chiranjeevi has been barred from research and research supervision and from holding any administrative post at the university.

"Chiranjeevi claimed to be using advanced instrumentation not available at the university," the source says. "The chemistry in most of his papers is illogical—the chemistry itself is wrong. How did this get past reviewers?"

"I hated seeing papers from this guy," says Gary D. Christian, who is editor-in-chief of the Elsevier analytical chemistry journal Talanta, one of the journals that published Chiranjeevi's research. Christian, who is professor emeritus of chemistry at the University of Washington, Seattle, says Chiranjeevi's tactic was to flood journals with manuscript submissions in the hopes of wearing down editors who would eventually publish some of his work. "He published 70-plus papers in 25 journals in three years," Christian says. "The case is unprecedented."

Chiranjeevi's papers have appeared in Talanta and four other Elsevier journals: Food Chemistry, Journal of Hazardous Materials, Analytica Chimica Acta, and Chemosphere.
No wonder he did not get caught. Who reads these journals anyway? ;) But on a more serious note, this really points again to the massive information overload everyone has to deal with.

C & EN news story
Link via Abi

Top 5 reasons why intelligent liberals don’t like nuclear energy

This is based on my own experiences. I am sure there are several reasons and some of those reasons are commonly known. But I have still always been surprised and intrigued by why members of the liberal intelligentsia display a consistent aversion to nuclear energy. Here is my own list based on my personal interactions with reasonable and intelligent people who argue against nuclear power.

1. Ignorance: This simple reason remains pervasive. I am not trying to sound preachy or elitist here but reading two or three books would greatly benefit people who have a gut reaction against nuclear energy. The whole set of misconceptions about any kind of radiation being harmful, about nuclear plants releasing large amounts of radiation (when in reality they release fractions of what everyone naturally gets from the environment), about nuclear waste being a hideously convoluted and insoluble problem (the problem is largely political, not technical) can be dispelled by reading some basic books on radiation and nuclear energy. The most important revelation in this context is how, in our daily lives, we face risks that are hundreds of times greater than those from nuclear energy (transportation, air pollution etc.) without getting nonplussed.

There are of course many books for understanding such concepts, but for a general overview, I would recommend Richard Rhodes's article in Foreign Affairs and his book Nuclear Renewal, Samuel Glasstone's timeless classic Sourcebook on Atomic Energy for basics, and Gwyneth Cravens's very informative book which I am currently reading. Another informal, breezy and excellent treatment is Scott Heaberlin's A Case for Nuclear-Generated Electricity: (Or Why I Think Nuclear Power Is Cool and Why It Is Important That You Think So Too). For those who are ok with a little heavier dose of science, I would strongly recommend David Bodansky's Nuclear Energy.

2. Bad connections: There are two bad connections which many liberals automatically make, both of which are unjustified and contribute to their dislike of nuclear power. One is the connection between nuclear power and nuclear weapons. Again, knowing the basics about how different weapons are from reactors can contribute to mitigating this misunderstanding. Somewhere, I think there is also this connection between nuclear power and nuclear proliferation. While there is some truth to this, the fundamental thing to be understood is that every power source carries some risks, and the danger from nuclear proliferation mainly exists because of human stupidity and its manifestations, not because of some inherent problem with nuclear energy. The thrust should be at maintaining an international system that safeguards nuclear material from being used for weapons, not to ban the material itself. And even with the proliferation risks, the benefits of nuclear power far outweigh the risks.

Another bad connection is between environmentalism and boycott of nuclear power. Environmentalists are mainly responsible for reinforcing this connection, with their decades-long opposition to nuclear energy, which started with some reasonable premises, but then mainly descended into irrational, uninformed and exaggerated polemic. Helen Caldicott, whose opposition to nuclear weapons is commendable, is a prime example of peacemongers gone awry. Her latest book warps and misrepresents facts grossly in some cases and demonstrates simple ignorance of matters, not to mention cherry picking. One expected better from such people whose original intentions were honorable. Liberals need to know that nuclear power is completely compatible, if not especially so, with environmentalism. It releases very little greenhouse gases and is a model for power efficiency.

3. Waste: A point again related to 1. Many people think that this is the single greatest threat from nuclear power, that we will all be inhabiting vast atomic wastelands if we allow nuclear power to flourish. Again, read some books! It's not a trivial issue, but mostly a political issue that's also related to inefficiency and increased proliferation threats from burying valuable plutonium-containing nuclear waste.

4. Damn dem Republicans: There is actually a third connection- that between nuclear weapons and right wing belligerent political leaders, mostly Republican. If the erroneous connection between power and weapons is made, then it is not too difficult to perceive a connection between power and right wing fanaticism. It does not help that some leaders such as Republican Senator James Inhofe who is vehemently and stupidly against global warming, are also pro-nuclear power. The only way to stop oneself from treading this false path is to be reminded that this is not a political issue. Just because some environmentalists oppose nuclear power does not make it flawed, nor does Inhofe's support make it promising. The merit of nuclear power lies in science, and thus bows to no political or partisan mongering, and especially not to hacks like Inhofe.

5. Fear of the unknown: Again related to 1. above. I was at a climate change dinner and happened to have an amiable journalist covering the event sitting at my table. We got into discussing the merits and problems with nuclear power and what she said still simply captures the sentiments of many reasonable and intelligent but anti-nuclear people. She said "I am just afraid of something I cannot see". Well, if there's one thing that distinguishes man from other species, it is his ability to uncover nature's secrets and appraise and harness them, especially the ones that cannot be seen. Man's great capacity to face unknown challenges, understand them and use them to his benefits underpins much of our technological prowess. We cannot see x-rays, yet have no problem having x-ray scans (ironically something that delivers a greater dose of radiation than nuclear power plants). Only increased and better dissemination of knowledge about nuclear energy can dispel such doubts of the unknown, something which we should be proud of doing in the past.

The simple fact that a piece of uranium the tip of your finger can deliver as much energy as almost 2000 pounds of coal should be evidence of man's astounding achievement in wresting nature's essential source of energy from her. In the discovery of nuclear power we have done the unimaginable. We have brought the sun and the stars to our world. Extinguishing their flames will be conduct unbecoming of our vast and unique place in the universe, and a very great tragedy.

Score for the British

"Using a small nuclear reactor at Pavia, in northern Italy, the researchers subjected hairs said to have been taken from Napoleon at different stages in his life to eight hours of irradiation. They found arsenic levels even higher than previously suggested; "a hundred times the average found in hair today," said Adalberto Piazzoli, who led the study.

But by testing other samples, including locks of hair taken from Napoleon's wife, Joséphine, the team discovered that such levels were normal. "The environment in which people were immersed at the start of the 19th century evidently led to the ingestion of quantities of arsenic that we would consider dangerous today," Piazzoli said. Possible sources included "dyes, glues and the smoke from wood fires," Angela Santagostino, a toxicologist, told the daily La Stampa."
Ok, one French blow to British character retracted. But what about Napoleon's own trusted friend Marquis De Montholon who was also a prime suspect? The story of Napoleon's possible assassination by arsenic was one of the tales that got me interested in science. Sten Forshufvud, the Swedish dentist who investigated this did some classic and absolutely fascinating detective work that was described in The Murder of Napoleon. I need to go back to his book; it seems unlikely that he didn't think of running others' hair through a mass spec as a control.

The negative IQ people at the State Department

This is really ridiculous. We are writing a paper with a friend and collaborator of mine who is a NMR specialist at a prominent university in the US. He just came back from India after a stay of more than two months. He said that his original trip was planned for only a month. So why did it take so long?

Apparently, his visa was delayed. The fine folks at the US State Department saw the dreaded word "nuclear" in his job description. Alarm bells went off in their experienced minds. Nuclear Magnetic Resonance? Surely this is suspicious. Off they went doing s background check for more than a month. In the end of course they found nothing. But my friend had to stay for an extra month, delaying his work here, not to mention our own work.

This is outrageous. NMR is one of the most important techniques ever in chemistry, biology, materials science and drug discovery. For crying out loud, life-saving MRI is based on it. Every single day, hundreds, if not thousands of papers are published in journals worldwide that involve the use of NMR in one way or the other. Four Nobel Prizes have been awarded to NMR scientists. My own PhD. thesis is mostly based on the interpretation of results obtained using NMR (I have mentioned about it here) NMR has nothing remotely to do with atomic bombs.

But the bull-headed rocks at the State Department cannot even distinguish between the "nuclear" in NMR and that in "nuclear weapons". Why can't they hire specialists who actually know something basic about science (and common sense) instead of randomly spouting gut reactions and going ballistic every time they see the word "nuclear"? In some ways, it would give people like me sadistic pleasure to think of all those floor scrubbers in the department running around trying to find out if I have a Jihadist background. But as everyone knows, unfortunately in the end the person who will lose the most will be me.

Despicable, and it reminds me of Goverdhan Mehta's shoddy treatment at the American consulate. But considering the ultimate authority they answer to, we can trust them not to look at trivial things like facts and details.

At least now I know what word to not include in my job description when I file for a Visa. "Magnetic Resonance" will have to do. Sigh.

Richard Rhodes@Google

As part of the Authors@Google talk series that Google has organised, everyone's favourite nuclear historian Richard Rhodes gave a talk at the company, partly on general nuclear history and policy and partly about his new book (which I reviewed here). In the end, he asked the bright folks at Google for advice about how best one could possibly implement an international system of tracking nuclear material.



There were several interesting points about both history and current policy that he made that I think are worth noting as summaries (for those who may not have the time to watch the entire one hour talk)

1. Paul Nitze was a highly influential official in the State Department who served through six administrations, advising presidents on nuclear policy. After surveying the damage caused by atomic bombs in Japan and comparing it with the damage caused by strategic bombing, he erroneously concluded that atomic weapons are not much different in their effects from conventional incendiary bombing. He set the tone for policy partly grounded in this belief in 1950 when he drafted a key document named NSC 68 which outlined George Kennan's containment doctrine and advocated increasing nuclear weapons building as the best way to counter the Soviets. Although the report was opposed for its exaggerated tone by some, the Korean War that began that year sealed the deal, and the report more or less set the tone for US nuclear policy for the next six decades. Nitze could well be called the "father of threat inflation"

2. Most of the estimates about nuclear weapon targeting made during the Cold War or at least during the early years were underestimates because they neglected the effects of fire. Fire effects and the resulting strong winds cause a firestorm in a nuclear attack, and they can contribute up to 60% of all the effects. Most initial calculations only included blast effects. In a somewhat dramatic illustration, Rhodes showed the possible blast and fire radius of an attack on Google with a 300 kT weapons. The fire radius is much larger than the blast radius, and in addition fires can spread far and wide depending on vegetation.

3. In another telling illustration, Rhodes showed the nuclear winter that would result from a "limited" exchange of about a megaton between India and Pakistan. Within a few months, the simulation shows that the average temperature of the world could drop by 5 degrees, a catastrophic result. One can scarcely comprehend the nuclear winter that would have resulted from an estimated exchange of 10,000 megatons between the two Cold War superpowers. The illustration showed that even a small regional war waged with nuclear weapons could have extremely serious global consequences.

4. The real problem with nuclear proliferation is that like any complex machine, the system can go haywire and is subject to "normal accidents". More accounts than would make us comfortable exist of nuclear weapons accidentally armed or delivered somewhere instead of conventional weapons. Rhodes also noted that both the Indian and Pakistani nuclear arsenals don't have Permissive Action Locks (PALs). This makes the situation uncomfortable. I am interested in knowing his sources for this information.

5. Rhodes again outlined an ambitious plan by many former US experts including Henry Kissinger, George Schultz and Sam Nunn for universal disarmament. These gentlemen were early advocates of security through minimal deterrents. But after 9/11, they realised that nuclear terrorism makes only universal disarmament an ideal goal to be pursued for securing peace. Rhodes makes the accurate observation that nuclear proliferation can be stopped only by satisfying nations' security needs. However, I disagree with his projection for Pakistan's nuclear disarmament. Senior Pakistani officials have ostensibly said that they would disarm if India would disarm. But I doubt it because the Pakistani arsenal (about 40 weapons) is as much a deterrent against India's conventional forces superiority as it is against India's nuclear arsenal (about 60 weapons), and India inherently has the conventional advantage because of its size and resources. I don't see how this could stop being seen as a threat by the Pakistanis.

Woodward, rest in peace

Readers may remember the fascinating story of the synthesis of quinine and questions about Woodward's synthesis of the molecule in 1945 that were discussed insightfully by Jeff Seeman in a review in Angewandte Chemie last year. I had an opportunity to take Dr. Seeman out to lunch and we had a great time discussing his article among other things. Clearly, the single most important question was; did Woodward actually synthesize quinine, considering that he had only synthesized quinotoxine, which was one step away from quinine? Woodward assumed that since Paul Rabe had already synthesized quinine from quinotoxine in 1918, the total synthesis of quinine had been achieved (strictly by today's standards, it should have been called a formal synthesis). This question was really amplified by Gilbert Stork, when in his elegant 2001 synthesis of quinine, he questioned the Woodward (and the Rabe) synthesis.

The whole story is exceedingly fascinating and classic detective story-like. When we were discussing this stuff with Dr. Seeman, there was even talk of people trying to unearth 80 year old samples of quinine (?) and then analysing them. Paramount to the resolution of the problem was one central question; can one convert quinotoxine to quinine using the conditions that Rabe used? If so, both Rabe and Woodward would be saved from history and vindicated.

At that time, Dr. Seeman said that a as-yet-undisclosed chemist was trying to reproduce the conversion. Now we know that that chemist is Robert Williams from Colorado State. And he has saved Rabe and Woodward by converting quinotoxine to quinine using primitive conditions that Rabe must have used, without any modern, sophisticated methodology. Interestingly in their conversion, impure Al powder worked better than pure Al powder, in one of those classic quirks of chemistry! But finally, they cinch the deal.
"Finally, the conclusions reached by Seeman on the validity of the Rabe–Kindler work now have firm experimental support which vanquishes any resilient doubts initially raised by Stork in a letter to Woodward in 1944 (apparently unanswered), in which he queried whether the Rabe–Kindler procedure had been repeated at Harvard; these concerns were then made more visible in his series of publications in 2000 and 2001 questioning the 1918 Rabe– Kindler publication[2] and the ensuing Woodward–Doering (formal) total synthesis. The Woodward and Doering paper concludes unambiguously: “In view of the established conversion of quinotoxine to quinine, with the synthesis of quinotoxine (emphasis ours) the total synthesis of quinine was complete.” The experimental facts reported herein reaffirm that assertion. Our validation of the formal total synthesis of quinine as originally reported by Woodward and Doering in 1944 should serve to remove the blemish asserted on the reputations of Rabe and Kindler as well as those of Woodward and Doering. The Supporting Information to the present work provides the complete experimental details to the chemical literature of the Rabe– Kindler d-quinotoxine into quinine conversion in both a modern experimental setting as well as a pre-1944 setting; may Paul Rabe and Karl Kindler requiescant in pacis.
Requiescant in pacis indeed! One lingering question that I have that remains unanswered is; why didn't the intrepid and meticulous Woodward not carry out this last step just to clinch the final product and convince himself that he indeed had quinine with Rabe's conditions? I guess the price we may pay for answering a major question of history is perhaps to let this relatively minor but intriguing question to go unanswered.

Life's Matrix

Philip Ball's excellent new Chem. Rev. review on water and its importance in the chemistry of life.

Judah Folkman

Judah Folkman is no more. He was the man who pioneered the idea of angiogenesis as an essential condition for tumour cells to survive and proliferate, and hinted at possible cancer cures that would result from targeting tumour angiogenesis. In my opinion, especially considering the current proliferation of therapies that are doing just this, he deserved the Nobel Prize. He was at my university a couple of months ago as part of a symposium. Because of some prior commitments, I could not attend his talk. Now I wish I had. Cancer Cell has an informative obituary.

Also cross-posted on Excursions