So you hate GMO's because they are untested. What about feelbetteramine from the health store?

Normal rice and golden rice fortified with beta carotene (Image: Wikipedia Commons)

Noted pharmacologist, Forbes blogger and North Carolina Museum of Natural History science communications director David Kroll has a good post in Forbes about the recent controversy regarding "Golden Rice", a strain of rice genetically engineered to produce beta-carotene, the precursor of vitamin A. This kind of rice might be invaluable in regions with endemic vitamin A deficiency (VAD) which is a big deal; as the Wikipedia article on the topic says, VAD is responsible for 1–2 million deaths, 500,000 cases of irreversible blindness and millions of cases of xerophthalmia annually. Clearly Golden Rice has the potential to do a lot of good.

Now I don't want to take either a strongly pro-GMO or anti-GMO stance here, although I definitely deplore the vandalism of Golden Rice fields described in the article that David links to. As a scientist however I am generally inclined to side with GMOs; to an organic chemist like me, modified sequences of DNA - while not without potential to cause harm - seem much more benign when ingested than decidedly nasty things like dioxins, pyrene and botulism toxin. In addition there are specific cases where engineering crops to withstand insect pests has done enormous good; and this perspective is independent of whatever I might think of the financial or political behavior of the relevant corporations.

But the bigger problem I have is with a common thread running through almost every anti-GMO protester's vocabulary, irrespective of whatever other objections they might have against GMOs. I find myself pondering the following question which I asked on David's blog:

"I actually find the anti-GMO folks’ argument about not trusting GMOs simply because they have “not been tested enough” to be disingenuous, selective and cherry-picked at the very minimum. Let’s say that tomorrow Whole Foods introduces a new brand of spirulinadetoxwhatever health supplement containing feelbetteramine from a wholly natural plant found in the foothills of Bolivia. Do we think for a second that the anti-GMO folks won’t be lining up at their nearest Whole Foods, no matter that this novel substance is as much or even more untested than a GMO?"

It's food for thought. Most opponents of GMOs don't seem to have a problem eagerly loading up their shopping carts with all kinds of exotic stuff from the health supplement aisle in the local supermarket. How many Whole Foods (and Whole Foods is just an example here, and probably one of the more benign ones) store assistants - many of whom are far from being trained in nutrition or pharmacology - have convinced these people that feelbetteramine is right for their gout, or for their insomnia, or for the "cognitive deficit" that they feel everyday at work? What kind of evidence of long-term safety exists for feelbetteramine that allows these GMO opponents to embrace the wondrous effects of this non FDA-approved concoction with alacrity? And proponents of health supplements are often big on anecdotal evidence; why don't they, at the very least, admit anecdotal evidence about the benefits of GMOs (especially when the evidence is concrete, as in case of VAD) into their belief system?

To me there clearly seems to be a discrepancy between the reflexive rejection of untested GMOs by the anti-GMO crowd and their rapid embrace of the equally or more untested latest health supplement. All things being equal, as a scientist I at least know what the express purpose of Golden Rice is, compared to the hazy reports on salutary effects of feelbetteramine. So it seems to me that if I am really against GMOs because they are insufficiently tested, I need to mostly steer clear of the health supplement aisle. And did I mention that feelbetteramine can also set your love life on the path to glorious bliss?

This post first appeared on Scientific American Blogs.

Who's afraid of nuclear waste?: WIPPing transuranics into shape

This post first appeared on Scientific American Blogs.

Waste arriving at the WIPP from all over the country's non-commercial DoE nuclear reactor sites (Image: PBS Nova)

About 50 miles from the Texas border in southeastern New Mexico sits the town of Carlsbad, home of the renowned Carlsbad Caverns. Its lesser-known claim to fame which actually might have a disproportionately long-lasting impact on the future of energy and the human species is as a site for the Department of Energy's Waste Isolation Pilot Plant (WIPP), the only official waste repository in the US currently accepting high-level nuclear waste. Jessica Morrison from PBS has an excellent article on the workings of the WIPP and its importance for nuclear power (hat tip: Bora). With the disaster of Yucca Mountain still beckoning in people's memory, the WIPP offers a welcome and unique possibility for the future:

The Waste Isolation Pilot Plant, known locally as WIPP (pronounced “whip”), opened in 1999 after decades of back and forth between state and federal regulators. Today, it holds more than 85,000 cubic meters of radioactive waste arriving from as far away as South Carolina. Currently, WIPP is only authorized to handle waste containing elements with atomic numbers higher than 92—primarily plutonium—that originated from the development and manufacture of nuclear weapons. Between 1944 and 1988, the U.S. produced about 100 metric tons of plutonium, most of which was used to develop nuclear weapons.

What I find pleasing on a deep level about the WIPP is that it relies on entirely natural mechanisms for sequestering the waste from the outside world. The basic principle is to dig a hole deep into a salt bed. Salt has the unique property of displaying "creep", the tendency to flow into and around cracks and naturally form seals; seals that can be as tight as those formed by the hardest rock when they are laboring under pressures operating at 2100 ft underground. When you bury waste in salt, you are basically letting geology do its job and create a seamless tomb for the waste.

WIPP’s operators stack waste containers in rooms dug into the salt formation and then let geology do the rest. Under pressure from the ground above, salt formations flow into cracks and open spaces. Over several dozen years, salt will settle around the containers, forming a rocky seal. That self-sealing ability also protects the site from cracks caused by earthquakes—any that open will quickly close. So far, the site has been successful in containing radiation from the waste.

Working in WIPP is therefore a job with a time stamp; in some sense the mine itself is urging the workers to do their job quickly and get out the hell out of there, so that the earth can close around the waste and clasp it in its tight embrace.

WIPP feels like it’s in constant motion—the continuous care needed to control the salt, the movement of the electric carts within the mine’s pathways, the loading of waste first into the walls and then the room, back to front. It all serves as a reminder that the place really is moving, just at a slower, inexorable pace. WIPP depends “on salt and the behavior of salt,” Elkins says. Salt flows under pressure, and it’s under a great deal of pressure this far underground. On a geologic time scale, it presses down with surprising speed, crushing and then encapsulating whatever is placed inside.

What this also partly means is that the sooner the repository fills up with waste, the better it would be to close it and let the salt do its job. This is a good incentive for carting high-level waste from the nation's myriad nuclear sites to WIPP as soon as possible. It's not as if there is a shortage of waste waiting to be disposed:

While WIPP has been accepting nuclear waste from weapons programs, no central repository currently exists in the U.S. for spent nuclear fuel and related waste from commercial reactors. Until one opens, waste has been sitting in interim storage at or near each of the nation’s 65 nuclear power plants. At the end of 2011, these sites and others held more than 67,000 metric tons of spent nuclear fuel, according to a report issued by the Congressional Research Service.

Waste buried deep underground in the right kind of geological formation is extremely safe and many people who criticize the problem of nuclear waste don't realize that good technical solutions based on burying waste have already been at hand for decades; the problem is mainly a political one. It's worth appreciating the basic fact that there are two kinds of waste, short-lived intensely radioactive and long-lived mildly radioactive. The inverse relationship is a basic law of physics and plays to our advantage. Thus, short-lived isotopes like strontium-90 and cesium-137 might be biologically dangerous, but they also reach safe levels rather quickly (half-life about 30 years for both). On the other hand, long-lived isotopes like plutonium-239 (half-life 24,000 years) are less dangerous because of their lower activity. Typically nuclear waste contains both kinds of elements, and one of the bad decisions taken by the government in this country based on rather flimsy grounds was to halt reprocessing, a process that would have separated plutonium and other valuable and proliferation-prone elements from the short-lived waste and which is routinely done in Europe, Russia and Japan. Burying plutonium is thus both an unnecessary invitation to potential proliferation as well as a waste of valuable fuel for civilian nuclear reactors.

It's hard to think of proliferation though when the plutonium is lying 2100 ft below ground covered by salt and earth as hard as kryptonite. Even when Yucca mountain was being discussed in the 70s and 80s, there were sound techniques for enclosing waste in borosilicate glass surrounded by layers of tamper-proof materials like copper and clay. The following illustration from a 1991 article on nuclear power by physicist Hans Bethe displays the multiple barriers separating transuranic waste from the environment:

Multilayered cylindrical design for the isolation of transuranic waste (Image: Engineering and Science, 1991)

When this kind of waste burial was being discussed, one of the cogent problems was that of groundwater seepage which might potentially transport the waste over great distances. But this problem is not as serious as it sounds at all. To begin with, waste repositories are already located away from both residential areas and groundwater sources. But even if groundwater were to come in contact with the waste, it would be several hundred thousand years before it ever reached the surface. As Bethe clarifies it in the same article:

"Groundwater doesn't flow like a river; it creeps. At a disposal site in Nevada called Yucca Mountain the Department of Energy has measured the flow of groundwater at 1 millimeter per day. And it has to  flow a distance of about 50 kilometers before it comes to the surface, because it generally flows horizontally. With this alone, it takes more than 100,000 years (italics mine) to come to the surface. In addition to that, at Yucca Mountain the waste can be placed about 400 meters below ground, and the groundwater is 600 meters below ground, so the waste won't even touch it. This might change due to  geological upheavals, but to start with it's a very good disposal site.

And even if  the groundwater is flowing 1 millimeter per day, experiments have shown that most dissolved elements take 100 times longer to  flow than groundwater; they are constantly adsorbed by the surrounding rock and then put back into solution again. And plutonium, which is the element people are so afraid of, takes 10,000 times longer again to migrate than most elements. In other words, during plutonium's half-life of 20,000 years, you are insured 100,000 times over."

Yucca Mountain is now abandoned, but these general principles of waste storage still stand and plutonium can still be considered to be confidently isolated from the environment over multiple half lives when buried this way. With short-lived elements the solution is easier. It's a pity that political inaction and public opinion has not allowed us to cart most of existing waste to sites like the WIPP. The waste is relatively small in amount to begin with - the annual waste from the 100 odd reactors in the US would only fill a football field to a depth of one foot - and storing it around creates unnecessary safety issues. Dry cask storage is a good solution but since the casks are often stored on land is far from a permanent one.

The public, government officials and experts should take the lessons of the WIPP and of existing techniques for disposing waste to heart. As with many things nuclear, one of the major problems is that of education; many members of the public think that all nuclear waste is alike, that all of it will kill you even on slight exposure, and that there is no way at all of disposing it. Stories like that of the WIPP should hopefully change their minds and demonstrate that the problem of nuclear waste is not a technical problem, it is one of psychology and politics.

Note: As Twitter user @AtomikRabbit pointed out to me, WIPP is only a repository for non-commerical DoE nuclear reactors. It's waste from such sources that's displayed in the photo above.

Fairness or intimidation: How do you handle difficult commenters?

Last week I wrote a post on my Scientific American blog criticizing a guest post about nuclear power on Andrew Revkin's NYT blog "Dot Earth" by John Miller, a social psychologist and journalist who had very briefly served as an officer on a nuclear submarine in 1972. Miller's post criticized "Pandora's Promise", a film showcasing environmentalists supporting nuclear power which I reviewed a few months ago. Since Miller vehemently disagreed with the film and I found much in it of merit, not surprisingly I disagreed with Miller on many points and clarified my disagreement on my blog. What I found most remarkable was that several of the links that Miller provides themselves contain information qualifying or contradicting his views.

Here's how events unfolded from then onwards. Firstly, let me say that everything that I am stating here is from public sources like Twitter and Andrew Revkin's NYT blog.

It's worth noting that long before I wrote the post, there were hundreds of comments criticizing both Miller's lack of expertise and the flimsy, misleading and cherry-picked evidence that he presented in his piece. As of now there are more than 600 comments on the NYT blog, several of them critical of Miller. In response Miller replied to hundreds of these comments, and in many of them asserted his supposed expertise on the matter and denigrated that of others (always signing his comments as "Dr. John Miller"). He takes a swipe at leading climatologist James Hansen (who has recently supported nuclear power), insisting that his own experience as a nuclear submarine officer makes him more qualified than Hansen to comment on nuclear energy. Phrases like "your comments are nonsense" and "you know nothing about this topic" are commonplace. One commenter remarked that  "The level of sniping and character assassination here makes me feel the need to double check the masthead to verify that it is indeed The New York Times rather than The Huffington Post or The Drudge Report."

Nuclear expert Rod Adams (who writes the Atomic Insights blog) put Miller's qualifications in perspective:

"After reporting to his submarine, Miller again went through the qualification process and became an Engineering Officer of the Watch on a new plant. For his non watchstanding duty, however, he was assigned as the ship's Supply Officer, NOT as an engineering division officer. 

Within 9 months after his arrival, his submarine was put into drydock for a conversion to special operations. It remained there with the reactor shut down until after he had resigned and left the Navy.

When Miller left the Navy in 1972, he was extremely "light" and wet behind the ears. His nuclear knowledge has not improved in the past 41 years."

Adams of course felt it necessary to address Miller's qualifications only because Miller was so fond of reiterating them. Miller's replies to this and other comments were a mix of technical facts and personal remarks. Most of the personal remarks consisted of re-asserting that since he had served as an officer on a nuclear submarine in 1972, he knew more about nuclear power than almost every other commenter. As of this moment, this torrent of commenting shows no sign of abating.

Now let's come back to my post. After I wrote it Miller wrote an extremely long comment countering my points. The comment was filled with personal remarks and a diatribe against Sci Am's editors; Miller could not believe they had let these "falsehoods" through (at this point he was not aware of the difference between Sci Am Blogs and Sci Am magazine). Perhaps the most notable part of the comment was a demand that Sci Am "retract" the article and "issue an apology".

Upon reading this long comment filled with a mix of technical information and personal attacks, I made the editorial decision to not publish it. Why? For simple reasons. Firstly, the comment added nothing new to the discussion. But more importantly, I want to moderate the tone of the comments on my blog; this decision is mine and mine alone, and I am not obligated to publish any comment which I think will affect the tenor of the discussion. Your blog is your living room, and you decide what kind of conversations you allow in it. This decision was bolstered last year after reading a study which said that the nature of comments on blog posts affects a lot of things: the inclination of new commenters to comment (they are reluctant to enter what they perceive to be a minefield), their perception of the post itself (it is seen as polarizing and biased rather than reasoned) and their own opinions of the topic (which change from neutral to polarized simply based on the comments) . Thus I stand by my decision to not publish Miller's comments. My decision was followed by several emails from Miller demanding that I publish his comments. In these emails as in the Twitter exchange there was little evidence of reconciliation or willingness to reach an agreement; almost every statement was in the form of a demand or entitlement. Maybe it's just me, but if I really wanted to have a blogger publish my comments, that would be the last kind of attitude I would pick.

When his first comment did not appear, Miller followed up by posting no less than 22 comments of similar nature, sometimes doling out technical information and often denigrating other people's knowledge. This number by itself constitutes massive spamming, irrespective of the nature of the comments. One of the cardinal rules on blogs is to not hijack the conversation by excessive commenting, and Miller violated this rule almost right away.

It was then that I logged on to Twitter and became aware of an epic Twitter war between Miller and Sci Am Blogs editor Bora Zivkovic. Miller was demanding that Bora and I publish the comment, Bora was being unfailingly reasonable, civil and clear in saying that Miller's behavior did not oblige me to publish any comment from him. In all his tweets there was little evidence of wanting to reach a reconciliation or an admission that he might have started out on the wrong foot by writing a very long comment filled with condescending remarks and demands for retraction and apologies. Miller also did not seem to appreciate how much editorial control individual bloggers have - and should have - over their posts. He also does not seem to understand how easy it would have been to start his own blog and respond and comment to his heart's content. In fact, protocol would have dictated that since I countered his post on my site, he offer a rebuttal on his own.

In any case, about a day after this Miller went one step further: He published the entire content of his long comment in the comments section of Andrew Revkin's blog. Of the hundreds of comments that he has written, at least ten (ranging from bold-lettered "PART ONE" to "PART TEN") are devoted to duplicating the contents of his comments on my blog. The rest of his comments consist of complaints about me, Bora and Sci Am in general. According to Miller, Bora and me are "grotesquely unfair and cowardly" for moderating his comments on my blog and our actions "tarnish Scientific American's reputation". He also urged readers to write to Sci Am's editors to complain about our behavior. I don't know about readers, but if I actually paid this kind of attention to any post criticizing my views, my detractors would probably be forgiven for calling me pathologically obsessed.

In any case, Miller's original comment has now been let through after his many complaints (along with 4 others) and after we had him significantly temper it to conform to the comment policy. His comment says nothing that he has not already said and does not provide new original criticism in my opinion, so I don't feel any need to amend my post. I am also not going to allow him to comment further on my blog; he says that he wants to respond to every other commenter on my post who is critical of his writing, to which I say, "Get your own damn blog".

I wanted to write about this this incident since it is, in my opinion, a good case study in handing difficult and obsessive commenters. The case raises a number of interesting questions: Is Miller's behavior intimidating, obsessive and bullying or is this about free speech? I think it's the former. Should bloggers automatically allow rebuttals to their posts even if they think those rebuttals will significantly affect the tone of their comments section for the worse? What is the correct reaction by a blogger to a commenter who seems obsessed with commenting on their blog and who will go to great lengths to criticize the blogger and his or her sponsor on other websites? On my part I found it most interesting to be a part of the debate; as a blogger it only helps me to learn more and provides me with a background to handle similar cases in the future.

Druggability: An optimistic assessment.

Derek has a good post that takes a philosophical approach toward the whole question of "druggability". The main question is; given a disease state and biochemical knowledge of all the mechanisms involved in that state, can you find a therapeutic that will abolish the disease state and restore another one which we ordinarily term "healthy"? The whole thing is worth reading.

For the moment let's make things simple and assume that the therapeutic we are looking for is a small molecule. Derek's post actually takes me back to my post about why physics cannot solve the problem of drug design. The main challenge in drug discovery is that we have to come up with solutions that have to extend over a whole range of emergent phenomena; an ideal drug will have to modulate every level of biological organization from the whole body down to organs systems, cells and molecular targets. Some of our best drugs do this but that was a happy and accidental coincidence. We still cannot deliberately design in features that will modulate a system across multiple emergent levels.

However I am hard pressed to see why this cannot be done in principle. That is because in some sense, the problem of druggability comes down to the simpler problem of "ligandability"; that is, for every given protein and every arbitrary binding site, can you find a complementary key that fits the lock? My guess is that the answer to this question is a yes since ultimately it boils down to forces and geometric complementarity. Can we design a small molecule that fills a pocket, forms hydrogen bonds and electrostatic interactions and gains binding affinity through the hydrophobic effect by displacing water molecules? I would tend to think that the answer is a yes across the board, so I don't see why the problem shouldn't be solvable for every single protein at least in principle. 

There's other challenges in drug development of course; maintaining the right blood levels, modulating half lives and protein-drug binding kinetics, avoiding drug-drug interactions, but all of these problems have at their root the interaction between molecules which can be modulated. Ultimately, every drug works its magic through molecular interactions, even if they are spread across multiple emergent levels and targets. The problem of druggability is in one sense the problem of ligandability stated multiple times. Solving the problem of druggability is tantamount to solving the problem of ligandability for several targets; the target of interest, anti-targets like hERg and cytochrome P450, a judiciously picked subset of targets whose simultaneous inhibition leads to the required beneficial effect (like the targets for some of the "selectively non-selective" kinase inhibitors out on the market). Want to improve off-rates? Improve protein-ligand interactions. Want to maintain drug levels? Minimize off-target degradation by proteases or esterases. Want to avoid interactions with other drugs? Regulate or improve inhibition of cytochrome P450s or PgP. If the problem of ligandability can be solved for multiple targets, wouldn't it be equivalent to solving the problem of druggability?

In practice of course things are very different since it may well be impossible to practically satisfy every single constraint leading to the abolition of a specific disease state. Since biological systems are emergent we could also get very unexpected feedback from this kind of perturbation that throws our predictions off. I also tend to agree with Derek that we can look through every SMILES string that we have and still not find the right molecule for addressing the multiple-ligandability problem. We can throw every single molecular library in the world at Ras and still not find anything worthwhile. But knowing what we do about the physical and chemical principles that govern biological systems, I doubt it would be so because we are dealing with the biological version of Hilbert's halting problem which Turing proved was undecidable. It could still be because we have simply not tried looking everywhere.

Gordon Conference impressions

What goes on at the Gordon Conference stays at the Gordon Conference, goes the saying. In keeping with this tradition I am not going to divulge the details of the science at my very first medicinal chemistry Gordon Conference. But that should not stop me from offering general comments and holding forth on some of the non-scientific aspects of the meeting.

The conference is always held in some scenic place; if you can convince your boss you could possibly make it to Lucerne, Switzerland or Milan, Italy, otherwise you might have to be content with traveling to one of the many small resort and college towns in New Hampshire. But have no fear; all these towns offer their own very scenic views and crystal clear weather.

The one big truth about the GRC is that it's all about interacting with people. The medicinal chemistry conference was in New London, NH which is the home of Colby-Sawyer College; this has been the venue since 1944. We were lucky to enjoy spectacular weather during the entire week. The conference is deliberately located in a small location away from the bright lights of a big city so that there will be minimal distractions and participants can spend most of their time together. The interactions are amplified by having all participants stay together in one of the suites in the college dorms (with separate bedrooms and common bathroom space); take advantage of this fact and do get to know your roommates.

What really makes a Gordon Conference unique is the schedule. Mornings and evenings are filled with talks and poster sessions but afternoons are free. It feels a little strange at the beginning to attend talks from 7:30 PM to 9:30 PM followed by poster sessions until 11:30 PM but you get used to it. The poster sessions are where the most stimulating interactions usually happen, so you should definitely not miss these. The posters are also where the most interesting new information is divulged, so unlike the talks, you won't find copies of these reprinted in the folder which you get on the first day. In general you will find people sometimes saying things off the record, with the honest expectation that you won't divulge these details to the outside world.

One thing that becomes clear at a GRC is that there are people in their 60s and 70s who have been attending GRCs for decades. Naturally they are good friends and tend to hang out together. If you are a first timer you might be slightly overwhelmed by what seem to be cliques, but one thing you would find out is that even the old timers are quite welcoming. Go ahead and introduce yourself to them and you will very likely end up having interesting and lively conversations. This is especially true during meals where you may often end up at tables with strangers, many of whom will hopefully be friends and colleagues by the end of the meeting. The one thing you should not do at a GRC is to keep to yourself since it sort of defeats the whole purpose of the conference. Plus, how are you ever going to get to know people if you never start?

There is some kind of physical activity - hiking, kayaking, horse-back riding, cruises, soccer games - scheduled for every single afternoon. You can either join in or relax in your room, but joining in is strongly encouraged. I went on a hike and a walk and had a very productive conversation with a medicinal chemist from the UK. Even if you are more of the indoor types like me, don't miss these activities and the resulting conversations. It's your best chance to network and make connections.

Interestingly, a corollary of all this is that in one sense, the formal talks are the least interesting aspect of the meeting. Don't get me wrong; some of the talks were really great and all of the talks covered a very diverse smattering of topics, but the overall scope and content of the talks mirrored that at other good meetings. Most scientists know that the most valuable conversations are the ones that occur outside formal talks, at the bar and during lunch and dinner, and the Gordon Conferences underscore this fact more than any other.

Which brings me to the food. You should avoid the Gordon Conference like a plague if you are trying to diet and lose weight. The GRC knows that scientists - who are still harboring traumatic memories of their time as graduate students - are suckers for good food. With this in mind the organizers put out a spread every day like no other I have seen at a scientific conference. There's an omelette station at breakfast and stir fry station at lunch. There's a different dessert for every meal and six different flavors of ice cream. Soda and chocolate milk flow like water. The poster sessions offer endless rounds of pizza and drinks. And you are surrounded by all this pretty much 24/7. You get to eat so much roast beef and lobster and mushroom ravioli that by the end of the week you are actually hungering for simple fare like oatmeal. Oh wait, they have four different kinds of that too...

The end result of this gastronomical and scientific cornucopia is a bunch of extremely well-fed and intellectually stimulated scientists. In this case, the talks themselves mirrored the astonishing diversity of medicinal chemistry (the topics are publicly listed so there's no harm in talking about them). It's interesting that even today, when you meet someone who calls themselves a "medicinal chemist" he or she is most likely to be a synthetic organic chemist. But I am a modeler, and yet I consider myself first and foremost a medicinal chemist. As the scope of the med chem GRC reveals, a conference on medicinal chemistry today includes all kinds of people; synthetic chemists, biochemists and molecular biologists, pharmacologists, chemical engineers, molecular modelers, physical organic chemists and even doctors. The list of topics ranging from pain to high-throughput screening and from drug delivery to antibody-drug conjugates makes it clear that at this point in time, "medicinal chemistry" essentially includes almost every discipline that could have an impact on drug discovery and development. Another thing that's evident from the list of speakers is the focus on biology; a lot of the talks are about biological assays and gene knockouts and target validation and synthetic biology. In keeping with scientific trends, it's clear that medicinal chemistry conferences henceforth are going to include a healthy amount of biology.

Overall the conference was very satisfying and stimulating. I think it's safe to say that in the end we all went away with a renewed appreciation of our discipline and of the good cheer and spirit that exists in our ranks in spite of today's troubled times. Most importantly, I think all of us were inspired to go back to our labs and computers and get on with the science and business of designing drugs, an endeavor that has real impact on real people's lives every single day. If you haven't been to the med chem or any other GRC I would strongly recommend it.

What are the top five most memorable chemistry papers that you have read?

Here's a question I have wanted to ask the chemoblogosphere for some time, just for fun: What are the most memorable chemistry papers that you have encountered in your career as a student and working chemist? I am sure many of us remember at least a few papers that reminded all of us of why we love the subject. Are there papers which are stuck in your memory as particularly elegant, revolutionary or just plain well-written (more of a rarity than we might think)? The papers need not be universally accepted as significant in the history of chemistry, they only need to have moved you in one way or another on a personal level. 

So without further ado, here's my list (of the top six, actually), in chronological order; there are others, but I find myself going back to these again and again. Being a biologically oriented organic chemist, not surprisingly I tend to gravitate toward topics dealing with synthesis, physical organic chemistry, medicinal chemistry and biochemistry. Feel free to add your own in the comments sections and on your own blogs.

1. "The total synthesis of reserpine" (Woodward, 1958): Chemistry as poetry, nothing more. This remains the leading candidate for the paper that introduced synthetic and natural products chemists to the third dimension and to stereoselective synthesis. Although Woodward had synthesized a few complex substances before, the reserpine paper was perhaps the first to incorporate solid - and exceedingly elegant - stereochemical considerations in the making of what was then a mind-bogglingly complicated molecule. More than any other Woodward paper, this one reminds me that chemistry is the science most akin to architecture.

References: Tetrahedron 1958, 2, 1.

2. "Isotopic perturbation of resonance" (Saunders and Kate, 1980): For most students of chemistry today the non-classical ion controversy, waged primarily between Herbert Brown, Saul Winstein and George Olah must be ancient and forgotten history. And yet it supplies one of the best examples of both how controversy can sharpen chemical understanding and how the human factor can complicate chemical matters through emotions and acrimonious debate. The recent crystal structure of the norbornyl cation puts the controversy to rest, but for many people it was settled long before when Olah and Martin Saunders obtained irrefutable NMR evidence of a bridged, non-classical ion.

Everyone knows Olah, but few have heard of Saunders. And yet for my money, the most elegant proof of the non-classical cation came from Saunders' NMR work with deuterated norbornyl cations in which only one side of a symmetrical compound was labeled with deuterium. The idea is that the C13 chemical shift of a carbon next to a deuterium will be perturbed and therefore the usually symmetrical C13 peak will be split. However, the splitting will be too small if the structure is bridged and non-classical, while it will be noticeable if it consists of two rapidly equilabrating structures. Saunders's experiment, along with Olah's two decade-old work, clinched the deal. For me this is one of the most elegant demonstrations of how a powerful instrumental technique can be brought to bear on a fundamental chemical problem.

Reference: J. Am. Chem. Soc. 1980, 102, 6867.

3. "The Endiandric Acid Cascade" (Nicolaou et al. 1982): Cascade reactions have always had a special place in my heart, and this artful synthesis of endiandric acids by Nicolaou ties with Clayton Heathcock's biomimetic alkaloid synthesis as the best example of cascade reactions that I remember. The work speaks elegance and also attests to the power of electrocyclizations (rationalized by the Woodward-Hoffmann rules) to form several key bonds in a single step with absolute stereospecificity and high yield. There are few better examples I know of chemistry in motion.

Reference: J. Am. Chem. Soc. 1982, 104(20), 5558 

4. "Dominant forces in protein folding" (Dill, 1990): It's often said that scientists don't know how to write. Here's an exception to the rule. In this review Ken Dill shows us that even technical material can be an absolute pleasure to read. The review is comprehensive, extremely well-organized and lucid. It's one of those few technical articles that make for good bedtime reading, and in spite of advances in the field I keep myself going back to it quite often.

Reference: Biochemistry, 1990, 29 (31), 7133

5. "Design principles for bioactive drugs" (Navia and Chaturvedi, 1996): This is a great review because it comprehensively lays out the key properties that lead to drugs making it across biological membranes and being orally bioavailable. It was also one of the first articles that pointed out how molecules which are now regarded as "beyond rule of 5" can succeed as drugs; ironically this was only a year before Chris Lipinski came up with the much used and abused Rule-of-5 for orally active drugs.

Reference: Drug. Disc. Today, 1996, 1(5), 179

6. "Organic fluorine hardly ever accepts hydrogen bonds" (Dunitz, 1997): Here's another world-class chemist who really knows how to write. In a recent interview veteran chemist Jack Dunitz - who is past 90 and still going strong - said that by reading good literature he came to appreciate the value of clear expression (now there's something else that chemists should do more often; read fiction). Dunitz also happens to be one of the first people to have seen Watson and Crick's model of DNA.

But in any case, this paper really blew me away because until I read it I naively believed that F, being the most electronegative element, should accept hydrogen bonds with alacrity. Dunitz analyzes thousands of crystal structures and showed that there's a fraction of them, if any, which show evidence of hydrogen bonding with F. The lesson has stayed me for years, and even now I point out the article to any medicinal chemist who might want to install a fluorine in a drug molecule to enhance hydrogen bonding.

Reference: Chem. Eur. Jour. 1997, 3 (1), 89

What does mercury being liquid at room temperature have to do with Einstein's theory of relativity?

Image: Wikipedia Commons

One of the great moments in twentieth century science came when Paul Dirac married quantum mechanics with Einstein's Special Theory of Relativity to produce relativistic quantum mechanics. Dirac's theory did many things - predict electron spin and the positron, analyze atomic collisions, jump-start the revolution in quantum electrodynamics - but it also had very significant repercussions for chemistry. However these repercussions did not become known for another few decades because it turned out that for solving most problems in chemistry you could neglect relativistic effects. Figuring out chemical bonding, predicting the thermodynamic properties of molecules and rates of chemical reactions, understanding the molecular glue that holds proteins together; all these problems succumbed to calculation without chemists worrying about relativity.

All except one problem, that is. And it deals with a question that every child since antiquity has asked: Why is mercury liquid at room temperature? Mercury - the only metal with this property - has beguiled and fascinated men for centuries; a glittering substance that flows with studied gravity, supports the weight of coins, magically seems to dissolve other metals and resists all attempts to scoop it up. A substance that can aid health when calibrated inside a thermometer and can kill when it accumulates in living tissues. But the one quality of mercury that is apparent to everyone who has even the slightest acquaintance with it is its liquid nature.

Why is this so? It turns out that sometimes simple observations in science can have complicated although very interesting explanations, and this is one of those cases. Fortunately the crux of the matter is simple, and it has received its most complete and satisfying treatment in a recent paper published in the journal Angewandte Chemie. But first let's go back to the basics. Mercury is a metal, which means that it occupies the middle of the periodic table along with other metals like gold, zinc and cadmium. In fact it is in the same group as zinc and cadmium, and yet it couldn't be more different from them. Zinc and cadmium are not liquids at room temperature and they crystallize in a different form from mercury. In addition mercury is right next to gold, and yet their properties are utterly dissimilar.

Recall from college chemistry that atomic orbitals come in different flavors; s, p, d and f orbitals are distinguished by different quantum numbers and different "shapes". Metals are characterized by significantly occupied d orbitals. In addition, filled orbitals imply special stability. The singular fact that distinguishes mercury from its neighbors is that it has a filled outermost 6s atomic orbital. This means that the electrons in the orbital are happily paired up with each other and are reluctant to be shared among neighboring mercury atoms. Where the theory of relativity comes in is in accounting for subtle changes in the masses of the electrons in mercury and the atomic radii which nonetheless have profound effects on the physical properties of the metal.

According to special relativity, the apparent mass of an object increases as its velocity approaches the speed of light. From Niels Bohr's theory of atomic structure we know that the velocity of an electron is proportional to the atomic number of an element. For light elements like hydrogen (atomic number 1) the velocity is insignificant compared to the speed of light so relativity can be essentially ignored. But for the 1s electron of mercury (atomic number 80) this effect becomes significant; the electron approaches about 58% of the speed of light, and its mass increases to 1.23 times its rest mass. Relativity has kicked in. Since the radius of an electron orbit in the Bohr theory (orbital to be precise) goes inversely as the mass, this mass increase results in a 23% decrease in the orbital radius. This shrinkage makes a world of difference since it results in stronger attraction between the nucleus and the electrons, and this effect translates to the outermost 6s orbital as well as to other orbitals. The effect is compounded by the more diffuse d and f orbitals insufficiently shielding the s electrons. Combined with the filled nature of the 6s orbital, the relativistic shrinkage makes mercury very reluctant indeed to share its outermost electrons and form strong bonds with other mercury atoms.

The bonding between mercury atoms in small clusters thus mainly results from weak Van der Waals forces which arise from local charge fluctuations in neighboring atoms rather than the sharing of electrons. But all this was conjecture; someone had to do the rigorous calculations, treating every electron in the element relativistically and calculating the relevant properties. In this case the relevant property is the heat capacity of a substance which dramatically changes during a phase transition, say from solid to liquid. The question was simple; using the most state-of-the-art calculations, could you predict the temperature at which mercury melts as indicated by a sudden change in heat capacity? In a paper published in Angewandte Chemie this month, chemists from New Zealand, Germany and France have provided a result which is the most complete one to date. They actually simulated the melting of mercury using quantum molecular dynamics, solving the Schrodinger equation, calculating forces and velocities from quantum mechanics and allowing the atomic clusters to sample different geometric orientations randomly. They carried out the calculations first by excluding relativity and then by including it, and the results were unambiguous; when relativistic effects were taken into account, the melting point of mercury dropped from 355 kelvin to 250 kelvin, in excellent agreement with experiment and accompanied by a sudden change in the heat capacity.

The liquid nature of mercury is not the only thing that the special theory explains. It also explains why gold is yellow while silver is white. In this case, the splitting of orbitals and the lower energy of the 6s orbital results in gold absorbing blue light and emitting yellow and red. Since the 6s level is higher in silver, the energy required to excite an electron corresponds to the UV region instead of the visible region; consequently silver appears devoid of colors from the visible region of the spectrum.

I always feel a twang of pleasure when I come across studies like this. There are few things more satisfying than the successful application of our most cherished and accurate theories to explaining life's most humdrum and yet fascinating phenomena. That's what science is about.

References:

1. Evidence for Low-Temperature Melting of Mercury owing to Relativity; F. Calvo et al. Angew. Chem. Intl. Ed. Engl. 2013, 10.1002/anie.201302742

2. Why is Mercury Liquid? L. Norrby, J. Chem. Ed. 1991, p. 110.

3. Relativistic Effects in Chemistry, D. McKelvey, J. Chem. Ed. 1983, p. 112

This post was first published on the Scientific American Blog Network.

A particularly heinous crime: Neurology professor poisons neurologist wife

From Science Careers comes this account of a heartbreaking and especially twisted crime. A professor of neurology at the University of Pittsburgh, Robert Ferrante, has been charged with poisoning his 41-year-old wife with cyanide, an ancient poison that never seems to lose its allure. The wife was also a neurologist at the university. What really stunned me was this part:

"Authorities say that Ferrante poisoned Klein by mixing cyanide with creatine, CBSNews reports. According to Ferrante's online biography, his work "has provided the basis for human trials" using creatine. Klein consumed the drink because Ferrante told her it would help them conceive a child."

It takes a special kind of heartless monster to do that.

I cannot easily find references about using creatine to facilitate conception; since it's used as a nutritional supplement for muscle building and strength, Ferrante could have used a very simple argument to convince his wife to drink the deadly concoction. Apparently he obtained the cyanide through a lab member using a university credit card. One wonders if his associate ever suspected what a neurologist would need 250 grams of cyanide for (unfortunately chemists can obtain quantities of cyanide quite easily; I have seen half a pound of cyanide sitting in a chemical cabinet). Ferrante also seems to have performed the initial experiments within open sight of lab personnel:

He asked for the "best and purest cyanide he could get" to be delivered the next day, the witness said.

In addition, the affidavit continued, Mr. Ferrante asked that the chemical be purchased using a separate credit card not typically used in the lab.

A witness told investigators that particular card is a "last choice for purchases" and that it was the first time Mr. Ferrante had used it. Out of 145 chemicals bought by the lab, the only one purchased not related to a project or grant was the cyanide.

The same day the chemical arrived, another person in the lab witnessed Mr. Ferrante obtain a large container of creatine, measure it, mix it with water and sucrose and then drink it.

Early on April 17, Mr. Ferrante asked the witness to measure out more of the creatine, and they then placed it in a bag.

That day, according to the report, Mr. Ferrante and Klein exchanged text messages in which she said she would begin ovulating the next day. Mr. Ferrante told her to take creatine.

"I'm serious," he texted. "It will make a huge difference. I am certain of it."

When paramedics arrived at the couple's home to treat Klein the night she collapsed, according to the affidavit, they noted a 1-gallon resealable plastic bag containing a white substance along with a small glass vial in the kitchen, where Klein was found on the floor.

The report also says that out of the 250 grams of cyanide, 8.3 grams were missing. The lethal dose of cyanide is pegged at 200 milligrams on many websites; the exact dose and duration of action depends on factors like the contents of the stomach, with a higher secretion of stomach acid facilitating poisoning. In any case, if Ferrante is indeed guilty, then from the description it seems that he has left ample evidence. 

I can never understand what can possibly cause someone to put their entire life, career and reputation on the line and exhaust all other avenues of domestic conflict resolution, no matter how complicated their personal lives are (in this case a divorce might have been a simple solution). In any case, there's not much use speculating right now since Ferrante has not been officially convicted yet. But if he is indeed guilty of what he has been charged with, I cannot possibly think of subjecting him to anything other than the harshest possible punishment that is feasible for this kind of a crime.

Memo to chemists: Move away from the molecule

Megacities of the future - with their heterogeneous population and large-scale problems - will challenges the imagination of chemists (Image: Bldg Blog)

Harvard chemist George Whitesides probably does not consider himself a philosopher of chemistry, but he is rapidly turning into one with his thought-provoking pronouncements on the future of the field and its practitioners. His latest rumination is a piece in the Annual Reviews of Analytical Chemistry provocatively titled "Is the Focus on Molecules Obsolete?" where he uses analytical chemistry as an excuse to really pontificate on the state and progress of chemical science. Along the way he also has some valuable words of advice for aspiring chemists.

Whitesides's main message to young chemists is to stop focusing on molecules. Given the nature of chemistry this advice may seem strange, even blasphemous. After all it's the molecule that has always been the heart and soul of chemical science. And for chemists, the focus on molecules has manifested itself through two important activities - structure determination and synthesis. The history of chemistry is essentially the history of finding out the structure of molecules and of developing new and efficient methods of making them. Putting these molecules to new uses is what underpins our modern world, but it was really a secondary goal for most of chemistry's history. Whitesides tells us that the focus of the world's foremost scientific problems is moving away from composition to use, from molecules to properties. Thus the new breed of chemists should really focus on creating properties rather on creating molecules. The vehicle for Whitesides's message is the science and art of analytical chemistry which has traditionally dealt with developing new instrumentation and methods for analyzing the structure and properties of molecules.

Of course, since properties depend on structures, Whitesides is not telling us to abandon our search for better, cleaner and more efficient techniques of synthesis. Rather, I see what he is saying as a kind of "platform independence". Let's take a minute to talk about platform independence. As the physicist Leo Kadanoff has demonstrated, you can build a computer by moving around 1s and 0s or by moving around buckets of water, with full buckets essentially representing 1s and empty ones representing 0s. Both models can give rise to computing. Just like 1s and 0s simply turn out to be convenient abstract moving parts for building computers, similarly a certain kind of molecule should be seen as no more than a convenient vehicle for creating a particular property. That property can be anything from "better stability in whole blood" to "efficient capture of solar energy" to "tensile strength". The synthesis of whatever molecular material gives rise to particular properties is important, but it should be secondary; a convenient means to an end that can be easily replaced with another means. As an example from his own childhood, Whitesides describes a project carried out in his father's company in which his job was to determine the viscosities of different coal-tar blacks. The exact kind of coal-tar black was important, but what really counted was the property - viscosity - and not the molecular composition.

A focus on properties is accompanied by one on molecular systems, since often it's a collection of different, diverse molecules rather than of a single type that gives rise to a desired property. What kind of problems will benefit from a molecular systems approach? Whitesides identifies four critical ones; health care, environmental management, national security and megacity management. We have already been living with the first three challenges, and the fourth one looms large on the horizon.

Firstly, health care. Right now most of the expenditure on health care, especially in the United States, is on end-of-life care. Preventative medicine and diagnostics are still relegated to the sidelines. One of the most important measures to drive down the cost of healthcare will be to focus on prevention, thus avoiding the expensive, all-out war that is often waged - and lost - on diseases like cancer during their end stages. Prevention and diagnostics are areas where chemistry can play key roles. We still lack methods that can quickly and comprehensively analyze disease markers in whole blood, and this is an area where analytical and other kinds of chemists can have a huge impact. And no method of diagnostics is going to be useful if it's not cheap, so it's obvious that chemistry will also have to struggle to minimize material cost, another goal which it has traditionally been good at addressing, especially in industry.

Secondly, the environment. We live in an age when the potentially devastating effects of climate change and biodiversity loss demand quick and comprehensive action. Included in this response will be the ability to monitor the environment, and to relate local monitoring parameters to global ones. Just like we still lack methods to analyze the composition of complex whole blood, we also lack methods to quickly analyze and compare the composition of the atmosphere, soil and seawater in different areas of the world. Analyzing heterogeneous systems with different phases like the atmosphere is a tricky and quintessentially chemical problem, and chemists have their work cut out in front of them to make such routine analysis a reality.

Thirdly, national security. Here chemists will face even greater challenges, since the solutions are as much political and social as they are scientific. Nonetheless, science will play an important role in the resolution of scores of challenges that have to be met to make the world more secure; these include quickly analyzing the composition of a suspicious liquid, solid or gas, unintrusively finding out whether a particular individual has spent time in certain volatile parts of the world or has been handling certain materials, and using techniques to track the movements of suspicious individuals in diverse locations. Chemistry will undoubtedly have to interface with other disciplines in addressing these problems and questions of privacy will be paramount, but there is little doubt that chemists have traditionally not participated much in such endeavors and need to step up to the plate in order to address what are obviously important security issues.

Fourthly, megacities. As we pick up speed and move into the second decade of the twenty-first century, one of the greatest social challenges confronting us is how to have very large, heterogeneous populations ranging across diverse levels of income and standards of living co-existing in peace over vast stretches of land. This is the vision of the megacity whose first stirrings we are already witnessing around the world. Among the problems that megacities will encounter will be monitoring air, water and food quality (vida supra). A task like analyzing the multiple complex components of waste effluent, preferably with a readout that quantifies each component and assesses basic qualities like carcinogenicity would be invaluable. There is no doubt that chemists could play an indispensable role in meeting such challenges.

The above discussion of major challenges makes Whitesides's words about moving away from the molecule clear. The problems encompassing health care, national security and environmental and megacity management involve molecules, but what they really are are collages resulting from the interaction of molecules with other scientific entities, and with the interaction of chemists with many other kinds of professional scientists and policy makers. In one sense Whitesides is simply asking chemists to leave the familiar environment of their provincial roots and diversify. What chemists really need to think of is molecules embedded in a broad context involving other disciplines and human problems.

Part of the challenge of addressing the above issues will be the proper training of chemists. The intersection of chemistry with social issues and public policy demands interdisciplinary and general skills, and Whitesides urges chemists to be trained in general areas rather than specialized subfields. Courses in applied mathematics and statistics, public policy, urban planning, healthcare management and environmental engineering are traditionally missing from chemistry curricula, and chemists should branch out and take as many of these as is possible within a demanding academic environment. It is no longer sufficient for chemists to limit themselves to analysis and synthesis if they want to address society's most pressing problems. And at the end of it they need not feel that a movement away from the molecule is tantamount to abandoning the molecule; rather it is an opportunity to press the molecule into interacting with the human world on a canvas bigger than ever before.

First published on the Scientific American Blog Network.

Where's the chemistry lobby?

Veteran chemistry blogger Derek Lowe's takedown of the nonsensical Buzzfeed article about eight "chemicals" that you should stay away from was an excellent rejoinder to what was essentially a pile of sensationalized opinions disseminated by someone who does not bother reading up on basic science, but it also gave me a sinking feeling that is encapsulated by the following basic existential question.

How long can we chemists do this?

Over the last few years bloggers like SeeArrOh, Derek, Chembark and others have regularly pointed out instances of the growing epidemic of science and fact-free chemophobia that abounds on the Internet. In fact most of it is not even chemophobia, it's just plain ignorance of basic science. But as far as the sheer amount of chemistry-related nonsense floating around goes, all this worthy debunking is no more than a drop in the ocean. Those who don't understand science and chemistry are going to keep foisting the same falsehoods on us ad nauseum. The problem is that even if chemistry bloggers decided to debunk no more than 10% of the nonsense that goes around, they will be at it all day and night. The pile of anti-chemistry garbage that dots the landscape of the internet and print media is like a Hydra. You debunk one head and ten grow in its place. Plus the fundamental challenge in countering half-baked science is well-known: it takes only a few minutes to throw around unsubstantiated claims and link to random secondary and tertiary sources, but it takes dedicated time and effort to trawl through the primary sources, analyze the data and come up with a reasoned refutation. For instance it took me almost an hour to go through all the sources alluded to in a post about flame-retardants in couches and to write a post countering the claims. In fighting anti-chemistry forces chemists face a challenge similar to that faced by evolutionists fighting creationists. It takes only a minute for a creationist to make a statement like "There are no transitional fossil forms" but it takes time for an evolutionist to then go into the details and counter with the list of known transitional forms. Whether it's creationism or chemophobia, time is inherently biased against the responders. There is essentially no realistic possibility that a group of dedicated chemistry bloggers who are doing this in their free time are ever going to get around to refuting more than a fraction of all this fear-mongering, fact-free antiscientific piffle.

About the only remedy that I can see to counter this chemophobia and spread of ignorance is a dedicated chemistry lobby. The United States, after all, is the land of lobbies. So why not have a chemistry lobby? The task of the chemistry lobby would be simple; to have a dedicated group of chemists and people who actually care about the benefits of chemistry make a concerted effort to combat misinformation and ignorance, using every print, online and social outlet available, directing their efforts so that they reach every imaginable kind of citizen, from the man on the street to Congressmen on the Hill. The lobby would include contributions from chemistry researchers, teachers, students, policy makers and regulators. They could join hands with the American Chemical Society and any other organization that wants to further the cause of chemistry; in my personal opinion, while the ACS has done some admirable work in improving the public image of chemical science, it's efforts have been sorely lacking in proportion to the work that actually needs to be done.

Anyone who actually understands chemistry at a basic level would be welcome to contribute. The chemistry lobby could have their own TV channel, radio program and newsletter. Perhaps they could start a series that does for chemistry what "Cosmos" did for astronomy, replete with a charismatic and credible Sagan-like figure (Roald Hoffmann could fit the bill quite well). They could run campaigns to educate people about the facts and benefits of chemistry while admitting upfront to the misuse that chemistry has been put to over the years; they should also underscore the fact that misuse of chemistry has been no different from misuse of any other technology developed by flawed human beings. Their task would not be to whitewash the evils of the chemical, agricultural and pharmaceutical industries but point out the good that the industry has done in people's lives on a deep level. Chemistry largely underpins modern civilization, and it would be the task of the chemistry lobby to educate people about this fundamental fact.

The chemistry lobby would not solicit financial contributions from industry. Members of the lobby are probably going to be painted as industry shills by their opponents anyway, so it would not help being funded by massive contributions from industry. Instead the organization I am envisioning would be a non-profit group akin to the National Center for Science Education (NCSE), funded mainly by member contributions and grants. The National Center for Chemical Education (NCCE - as sound a name for the lobby as any other) would do to counter chemophobia what the NCSE has done to combat creationism. The official mission of the NCSE is to keep evolution in the class and creationism out of it. The mission of the NCCE would be to keep chemistry in the public arena and chemophobia out of it. Just like the NCSE does is not the official spokesperson of any university, atheist organization or political or social group, the NCCE would not be the official spokesperson of any body. It might support or reject the views of specific organizations, but official affiliation would be eschewed. At the same time it could fund the activities of specific bloggers, professors or citizens whose efforts to educate the general populace about chemistry are especially noteworthy. The NCCE could also fund studies and surveys designed to simply find out more about what people think about chemistry and its various incarnations in our lives.

The NCSE had done an immense amount of good over the decades to combat the forces of darkness that threaten to invade the school curriculum. At the same time they have take no official position against religion, and have in fact emphasized their respect for people's personal religious beliefs. The NCCE would similarly debunk basic ignorance of chemistry and fear-mongering without insulting the real concerns that environmentalists and parents have. It is only by taking a stand against objective falsehoods while still respecting the emotional reactions that concerned citizens have about the growth of technology that we can make a dent in fostering dialogue between disparate factions and bridging the gulf of our differences. I look forward to the day when the when a rational, effective and expansive chemistry lobby starts to achieve this goal.