On missives

Really great folks keep their correspondence, and then generations later it is still the fodder of insight and speculation. Now that we have the Internet, what will this mean to historians? Will it really matter how many Lolcatz I looked at in between figuring out how to make fluorinated organisms?

Anyway, I do maintain a reasonably robust correspondence with peers, and recently a captain of industry sent me the following unsettling piece about how farmers in the developing world are literally laying down to die because of the questionable biological and economic viability of genetically modified seeds:

http://www.nationofchange.org/monsanto-s-gmo-seeds-contributing-farmer-suicides-every-30-minutes-1333632229

To which I replied:

“That’s very unsettling … as are the comments that follow the piece. So, we know the benefits of science and technology. I guess I’m so used to thinking about the invisible hand as being ultimately beneficial (self-correcting towards upward progress) that I don’t really think about the possibility of rapacious companies (the Gilded Age, robber barons, and patent medicines aside).

The real folks who could do something about this … are in Monsanto. Why would they even get to this point? I’m sorry to be so naive, but if you had a product that was causing this much grief, wouldn’t you by God do something about it? For business reasons, even if it wasn’t the right thing to do?

Why does Monsanto get so much bad press? Why don’t they take steps to integrate their products with the consumers (farmers) that buy them? This would not seem that hard a thing to do.

I suppose they might say “High tech agriculture beats sustainable agriculture, and these folks would be laying down to die, anyway, once their incomes fell precipitously in a competitive global economy in which others used our products.” Maybe they’d be right. But they could also take steps to help make all boats rise by introducing products in a way that was most appropriate for local or regional agriculture.

Or maybe this is mis-reported? It’s easy to blame GMO for so many things, and one assumes that the suicide tsunami is real, and not a concocted fact. In the comments you can see the old canard about GMO being bad for you conflated with GMO destroying economies. I’m willing to buy into the latter, but I have never seen credible evidence for the former (which is also mechanistically implausible).

Anyway, having looked at it from many points of view, I think I’m just boggled that Monsanto apparently has no one dealing with PR, and would be very sad to find that we actually had a modern day Sinclairian Jungle in agribusiness.”

Now, you can all count me as naive as you want because of my child-like faith in business. But I am rather bullish on capitalism, as long as it’s practiced with social restraints. Those social restraints typically kick in via economic feedbacks, sometimes through political ones, but I am used to them kicking in. Smoking is harmful; smoking is restricted. That said, I think there may be a nascent sense that we have an economic Koyaanisqatsi, that the business world is decidedly out of balance. That capital has taken on a life of its own, separate from the people that use it. After all, companies are now people, as Romney likes to remind us. Such a transformation may be inevitable; capital is a very wondrous thing whose properties we continue to discover, many years after the death of Adam Smith.

If the economic world is indeed so far out of balance, that balance has to be recovered. That recovery will have to be guided by people, with the invisible hand chiming in to make things right on the money side. But it will be a conflict; it will quite possibly be a war. A war against our own money. What an odd thing to think or say. For me, at least. I only vaguely perceive the boundaries of this coming (continuing?) conflict. But the real-world attributes would presumably be a pushback against some of the perceived excesses. If agribusiness is indeed predatory and rapacious, then the seeds that bring hope to many and death to some can be further tampered with, and by those who are not in Monsanto. I do not currently know of engineered viruses that have been released in direct response to GMOs, but it really wouldn’t surprise me if they existed, or if they were on the drawing boards somewhere. As I’ve suggested elsewhere, I’m not particularly worried about the DIY Bio community writ large, but once social dislocation occurs, then the technological repsonse begins, likely first at the top (company on company warfare) and working its way down (people on company warfare) and possibly ultimately resulting in our old companion, people-on-people warfare. Bad times make for good wars.
 

- originally posted on Friday, April 6th, 2012 at 11:22

On good intentions

Ha, bet you thought I was gone. I sort of did, too.

I’ve been vastly disappointed with recent turns of events. Of course I am speaking of the actions of the appointed Guardians of the Universe, the National Science Advisory Board for Biosecurity (NSABB). This august group, at the behest of our own government, decided that certain knowledge, the mutations that make H5N1 more transmissible between ferrets, was too dangerous to be published in the open scientific literature.

This decision was, frankly, idiotic. Worse, though, I would argue that it has actually made the world a far more dangerous place, for a wide variety of reasons.

First, the knowledge of how one might make a more transmissible influenza virus is not equivalent to the knowledge of how to make a nuclear weapon (although I acknowledge that certain aspects of the outcomes of the two might be equivalent). In the latter instance, you can contain material. Nukes require nu-cu-lar stuff. Biology, on the other hand, as has been forcefully argued here and by many others, is just too damn easy. The reverse engineering of influenza virus is already possible. The tools are at hand, and could be spun up by virtually any government, non-state group, or even technologically competent individual. All that has happened is that some of the blue prints have been hidden for a short while.

Second, emphasis on that ’short while.’ The information is already out there; it has already been presented at scientific meetings. The moratorium is unlikely to stand for long, given the furor in the scientific community. And, honestly, ferrets are cheap. The evolution of a mobile virus is a dead easy process, apologies for the adjective. If someone really wants to do this, they’ll get ‘er done. And it can be hoped that the sequences will converge to what we (or at least some of us) already know and thus might be able to prepare for, as opposed to something new and even more deadly. Actually, one sort of suspects they will converge, given the press on the subject, which seems to imply that a relatively limited set of mutations are all that is necessary for transmission. If this is true, those mutations will arise again and again, in anyone’s hands who cares to look.

Third, the world now has a target for terror. We now have a US government-approved thing-that-is-too-bad-to-even-know-about, transmissible H5N1 influenza. Not exactly a secret, I know, folks have been talking about the H5N1 literally falling from the sky for awhile now. But there are really tons of bad things in the world of biology. Honestly, a terrorist could get all confused between targeted ricin attacks and bathtub ginned anthrax and arenavirus zoonoses. In honesty, I believe that’s one of the reasons nukes are so popular. You blow up. That’s it. Pretty simple to understand, on both the giving and receiving ends of things. With biology, there’s such a huge difference between diseases, transmission, weaponization … the message gets lost really fast. Think about the bogeys in your closet, and while there may be a Horseman of the Apocalypse labeled ‘Disease’ in their somewhere, I bet you can’t tell me what he or she is wearing. But now we can dress that Horseman to the explicit wishes of the US government and the NSABB. Certain mutations in H5N1 are officially bad. And thus officially a target for the types of folks who like to make big, symbolic gestures, like flying airplanes into buildings.

Fourth, and really this is the most important one, you just lost us again, US government. Remember when you arrested and prosecuted Thomas Butler at Texas Tech? That was meant to send a message to the scientific community, and boy did it. It sent the message that we should never, ever trust law enforcement, that we should view you as adversaries. That we should cease work on biodefense, just leave it to the professionals outside academia. That when in doubt about something the last thing we should do is contact you. That incident left a very bad taste in our mouths, and the furor was only beginning to abate … and now this. By labeling research ‘bad,’ by saying that the fruit of the tree of Knowledge really isn’t for us, you’ve just alienated an entire constituency that could have been your front line of defense. Because in the end, there is only one defense against biology, and that is human intelligence. Sensors are useless. Vaccines are useless. Remediation is useless. It is as though plutonium could assume a million forms, each one with its own unique and deadly specifications. In the end, you need to know about biology before it hits you, not after. And the people that need to tell you about what’s out there … are the biologists. We could have been your eyes and ears, if you hadn’t managed to spank the monkey that Speaks No Evil.

Fifth, the extension of this is not only that you’ve lost us, but you’ve created a constituency that has no reason to seek your exalted permission in the future. There are other ways to disseminate information than Science and Nature. And you don’t know what we know. You only know it if we tell you. And if we tell you in ways that don’t go through editorial boards … what exactly are you going to do about it? This Blog, for example, has always been a mild form of civil disobedience: telling the world the bad things that many scientists know and internalize and largely keep mum about. Because knowing is almost always better than not knowing, unless you are very, very sure about what you’re containing (see: nukes versus flu, above). Having human intelligence ready to hand is almost always better than trying to second guess an army of smart, innovative, and mostly contrarian folks. Don’t be surprised if scientists now think twice about clearly presenting the implications of their work, and if the new recipes for disaster are buried in Supplemental Methods (how exactly did you recombine HIV, Pim?) or just posted online.

Sixth, the security apparatus is a good thing (I truly believe this, despite being pissed as hell at the current turn of events), but it is not an efficient thing by any measure. If you apply security concerns to biology, if you begin to mark knowledge as Sensitive and FOUO and NOFORN and (God forbid) Secret and TS and SCI … then research will grind to a screeching halt, at least in certain areas. Whew, that’s what you want, right? Those bad scientists, they should just … slow down. Good thing our Chinese pals are going to slow down. And our Slovakian pals. And so forth. It’s like trying to regulate the Internet from within the confines of Fortress America: it can’t be done. It’s just stupid.

Well, I think that’s sort of out of my system. Two months of opening this page, and then being unable to write anything because I was just so annoyed with the whole thing. Maybe I’ll get back to my own brand of weird observations soon. Or maybe the site will be shut down or pilloried. Who knows? It’s a Brave New World, courtesy of the NSABB.

 

- originally posted on Tuesday, February 21st, 2012

On Man’s Best Frenemy

Wug, it’s been awhile. Lots to write about, but I’ve been a laggard.

To the topic at hand. We’ve previously discussed how zoonoses, viruses that spread from animals to man, can be a real biodefense threat (or at least have the appearance of being a biodefense threat, dpending on whether they appear to be natural or man-made). Being a biochemist / evolutionary engineer, I’m not as informed about the possibilities for zoonoses as many others. With that, I recently enjoyed a visit to campus by Colin Parrish, one of the great virologists of our time. I’ve previously learned a great deal from Colin, and this time was no exception.

While the rest of the world runs around and worries about H5N1, the bird flu, Colin thinks there is a threat much closer at hand. He and co-authors such as Eddie Holmes at Penn State authored a paper on “Microevolution of Canine Influenza Virus in Shelters and Its Molecular Epidemiology in the United States” (J. Virol, 84:12636). As you might have guessed, this paper focuses on our pals, the dogs, and the influenza they carry. It’s a particular serotype known as H3N8, and its transmission to dogs is relatively recent. Indeed, it has been shown that “… it was initially recognized in greyhounds in a Florida training facility in 2004 and was then spread around the United States by infected greyhounds in 2004 and 2005 ….” (although it may have been circulating in dogs as early as 1999; at least according to Anderson et al. in the most recent edition of Vet J., hitting your newstand December 16 … or not). Since then it has begun to spread much more widely, and can now be found in dog shelters in the Northeastern United States. If this was a Sherlock Holmes novel, it would be called “The Strange Case of the Parimutuel Betting Disease.”

Why should we be worried about dog flu? Well, we should be worried about the flu in general, but the scary influenza epidemics are the ones where we have very little extant protection, where the viruses have mutated and recombined in an animal host, or more than one animal host, with birds and swine being pervasive reservoirs and providing opportunities for many contacts with man. As the virus changes in one or both species, and as those species come in contact with man, there is always the opportunity that a new variant, an animal experiment from the flu virus’ point of view, will also be transmissible to humans. This has of course happened several times with the H5N1 bird flu, but the second part of the scary equation, the ability to jump not only from animals but between humans has not happened … yet.

It’s hard to predict what changes may be necessary to yield human-ready variants of influenza. It’s just clear that mutations are needed, otherwise we’d already be infected. It’s like the virus is spinning a combination lock with its mutations, searching for the right set of mutations that will allow it to cross over and spread like wildfire in the human population. This is what disturbs me, that spinning of the lock. It happens when a strain is not yet well-accommodated in a given species, when it is first learning how to effectively infect its host.

In this regard, the dog flu didn’t just leap out of nowhere, it “resulted from the transfer of an H3N8 equine influenza virus,” and contains several new mutations that were clearly necessary for or occurred as a result of the crossover to dogs, including 8 amino acid changes in the hemagglutinin protein, the protein that helps influenza interact with cells, whether they be horse, dog, or human. Interestingly, these changes do not seem to have accumulated during the virus’ short tenure in dogs; they may have been present at the time of transmission. That’s comforting; the virus doesn’t seem to be spinning the lock the last few years.

Still, the virus is going to keep on coming. There was a second, independent transfer to dogs in 2007, in Korea. This time it was the H3N2 variant (Gibbs and Anderson, Animal Health Research Reviews, 1:43, 2010). And this time it was out of birds, rather than horses.

The 4-1-1 (as the kids say) can be summarized by an abstract from Vet Clin North Am Small Anim Pract (39:251, 2009) (I have no idea what this stands for; oftentimes even scientists are limited as to what journals are available electronically; them budget cuts, they do eat up our libraries something fierce), by one E. Beeler: “Influenza has long been absent from the list of infectious diseases considered as possibilities in dogs and cats. With the discovery that avian influenza H5N1 can infect cats and dogs, and the appearance of canine influenza H3N8, small animal veterinarians have an important role to pay in detection of influenza virus strains that may become zoonotic.” I couldn’t agree more. I also think that the same wonderful vet that we take our dogs to is utterly unlikely to be cognizant of his role in taking down one of the Horsemen of the Apocalypse (I could be wrong; I’ll ask the next time we need heartworm pills).

So, to summarize: virus jumping into cats and dogs circa 2000, mutations abound, many opportunities for companion animals to get back at you for not giving them that extra treat.

But, well, why? I mean, sure, it may be that the virus is just now getting around to beating on cats and dogs, but that seems weird. They’ve been our companion animals for quite sometime, and both we and our livestock have been overrun multiple times over the last few millenia by influenza variants. Is there something else going on? Eddie Holmes thinks there is: “… there is some evidence for adaptive evolution. Most notably, an analysis of viral population dynamics provided evidence for a major population bottleneck of EIV H3N8 during the 1980s, which we suggest resulted from changes in herd immunity due to an increase in vaccination coverage.” (Murcia et al., J Virol, 85:5312, 2011).

Yes, that’s right, we may have done it to ourselves, again. Horse flu was perfectly content to just beat on horses, and to achieve some sort of rolling genetic optimum that placed it far away from beating on other animals, such as dogs and cats. But along we come with our fancy schmancy vaccines, and in making horses all better, we give the virus little option … but to find new genotypes. And those new genotypes just happen to be far enough afield that they can search for new victims, like dogs and cats. To round out our best intentions gone astray, as the flu spreads in cats and dogs some kindly multinational company will come up with an awesome vaccine for our companion animals, driving the flu into a new hunt for a likely victim. Someone close. Someone who doesn’t go on walks nearly often enough. Someone who hogs the covers at night.

PS: none of the above should be taken as an indictment of vaccine technology. Rather, the evolutionary consequences of vaccination is and should remain an active area of study, as we continue to attempt to predict viral evolution, thus finally getting ahead of these scourges for good.

 

- originally posted on Monday, December 26th, 2011

On ricin

Well, I have often thought that the threat of domestic terrorism is much greater than the threat from abroad. That’s not because I have some sort of fuzzy-minded notion that no one outside of our borders hate us. Hey, I’ve traveled on Eurail, where everyone is a Canadian. No, it’s more that the opportunities and abilities inside our borders greatly exceed what is present outside. We have very capable proto-terrorists on our own soil.

Or at least that’s what I used to think. Now enter Mssrs Frederick Thomas, 73; Dan Roberts, 67; Ray Adams, 65; and Samuel Crump, 68, our new grey terrorism band, who apparently wanted to bring freedom to our shores by killing people. Yes, it doesn’t make sense to me, either.

They were apparently inspired by Faux News and its minions, which should also come as no surprise to anyone who has watched that network degenerate into a slugfest of stupidity. From Media Matters (http://mediamatters.org/blog/201111020009):

“Fox News is now actively concealing a link between an Alabama-based blogger repeatedly featured on the network as an expert and allegations of a domestic terrorist plot. This morning on America’s Newsroom, Fox News ran an extensive report on yesterday’s arrest of four Georgia men accused of plotting an attack on federal employees and U.S. citizens using explosives, guns, and the biological toxin ricin. At the end of the segment, correspondent Jonathan Serrie pointed out that one of the defendants “allegedly cited the online novel Absolved, which discusses small groups of citizens attacking U.S. officials,” with the defendant allegedly “saying that the attacks would be based on events in that novel …. But Fox’s report neglected to mention the allegedly inspirational novel’s author, who is no stranger to Fox viewers. Indeed, the author, Mike Vanderboegh, has been mainstreamed by the network, which has repeatedly featured him as an expert on the ATF’s failed Operation Fast and Furious. Fox has identified Vanderboegh as an “online journalist” and an “authority on the Fast and Furious investigation,” and has consistently failed to acknowledge his extremist views, actions, and affiliations.”

But beyond the warped insanity of modern American ‘journalism,’ you have to ask yourself: why ricin? What was the point? Despite their apparent descent into some sort of Teabagger Alzheimer’s, these guys really should have known better. Various of them previously had jobs with the Navy, the USDA, and the CDC (although this latter was as “maintenance work” (http://www.ajc.com/news/atlanta/georgia-militia-plot-affidavit-1214918.html).

But cutting to the chase, here is the lesson of the day for proto-terrorists everywhere: ricin sucks. Ricin is a crap bioweapon. Yes, it’s easy to make, and if you’re a Bulgarian with an umbrella it’s Hell on wheels. But, seriously, dissemination? Production (I mean, you want to make some serious ricin, you need bacterial overexpression constructs like ours)? Communicability? You can take out your local salad bar, but not much more. And before someone jumps all over me for supposedly enabling the enemy, there is much more enabling information in the Washington Post Blog that I’ll cite below.

In the end, the point of terrorism … is terror. As the New York Times so very helpfully tells us:

“”It makes of the most mundane object, death: a doorknob, a handshake, a breath can become poison. Like a nuclear bomb, the biological weapon threatens such a spectacle of horror — skin boiling with smallpox pustules, eyes blackened with anthrax lesions, the rotting bodies of bubonic plagues — that it can seem the province of fantasy or nightmare or, worse, political manipulation.

Brett Giroir, a former director at the Defense Advanced Research Projects Agency, told the magazine that advancements in laboratory technology had made that fantasy much closer to real possibility than ever before.

“What took me three weeks in a sophisticated laboratory in a top-tier medical school 20 years ago, with millions of dollars in equipment, can essentially be done by a relatively unsophisticated technician,” Giroir said.” (from: http://www.washingtonpost.com/blogs/blogpost/post/ricin-plot-charges-four-ga-men-accused-of-planning-bioterrorism-attack/2011/11/02/gIQA0YuZfM_blog.html). Yay, Brett! Scary stuff.

Here’s another point, not for the terrorists, and one I’ve made many times before. QUIT SCARING THE HELL OUT OF EVERYONE. Seriously, what good does this do? We all go to sleep looking for umbrellas under our beds? We wonder if the sneeze guard will fully protect us from aerosol bottles of a ricin concentrate? Now, that is not to say we shouldn’t defend against the very real threats posed by bioterrorism. But I do wish the press and its enablers would quit giving the terrorists an easy win by making ricin into smallpox, which is in essence what the damn NYT article cited above did. Terrorism is at root psychological warfare, and the amplifier of the press is really what it feeds on.

And one final point, sort of a Mobius strip of logic: OK, the government is dedicated to keeping us safe. Go, government (I mean that sincerely, amongst all the snark)! And here we have former government employees wanting to kill us. That is not out of the norm, there are whackjobs everywhere. Just look at Lehman’s crash if you want to revisit something truly delusional. But sneaking-up-on-the-point-here-it-is … why are the government whackjobs, who should presumably know better, ’cause they’re working with or are the folks that are trying to protect us … using ricin? If everyone from me to the Washington Post blogging staff knows that ricin is a crap bioweapon … WTF?

There are two explanations for this discrepancy, mine and Alex Jones’: mine is that the government is still sadly incompetent in many ways. Alex Jones’ would be: the government is purposefully seeding the minds of its own disgruntled employees with low-level, incoherent, and incompetent terrorist plots, so as to incur multiple, random false flag events that will further enable the command-and-control structures that the brave Truther-Birther-Teaparty movement combats by frothing on the radio every day. Like much with Alex, the thought starts off in a sort of interesting way and then … winds down. Much like this post.

 

- originally posted on Thursday, November 3rd, 2011

On the gripping hand

I just got through going to DNA17, which is one of the two big conferences put on every year under the auspices of the ISNSCE … the International Society for Nanoscale Sicence, Computation, and Engineering (isnsce.org). Ha, I remembered … which really shouldn’t be such a travail, since I’m currently President of this Society. What, you may ask? Why is a non-nano-ite such as myself on point for these folks? Long story, but suffice it to say that they are all very fun, as you’ll see in a moment.

And I should take this opportunity to mention / plug the third conference that will appear under ISNSCE auspices, BIOMOD (biomod.net), the International Bio-molecular Design Competition. This is the dreamchild of Shawn Douglas, currently of the Wyss Institute, but I do hope the ISNSCE maintains its association with this burst of youthful energy in some way into the future. BIOMOD will be to DNA nanotechnology what iGEM was to synthetic biology: a definition, a source of future leaders, and kickass fun as long as it remains relatively freeform (unlike the more recent iGEMs).

What I like about the DNA nanotechnology field is that it’s a technology in search of an application. This was nowhere more apparent than at the first panel discussion, which featured Ned Seeman, Erik Winfree, Eric Klavins, and Luca Cardelli. Each panelist had their own take on “Visions for DNA Computing and Molecular Programming.” Ned stressed control and precision, as he always does. We need to be able to place atoms with greater surety. Erik emphasized complexity, as he always does. We need to be able to build circuits that are ever more complex, and that will eventually scale as does electronic circuitry. Eric Klavins suggested that we needed to crossover to biology, using the remarkable toolsets that we have developed to better program metabolism and organisms.

I think each of these is a laudable vision, and is likely a vision shared by many in the community. I also think that each of these visions is … incomplete. Even though by this point it may seem like I disagree with thought leaders just for the sake of disagreeing, that’s really not true. Like lots of scientists, I just tend to have my own vision, and a lack of humility to go with it.

In the science fiction classic The Mote in God’s Eye, we are introduced to the Moties, a species that is trapped near a star without interstellar travel, but that has evolved extraordinary abilities. Anatomically, the Moties have two normal hands … and a third one, which gives them the ability to make and manipulate tools with great dexterity. This leads to the idiom of “on the gripping hand,” following “on the one hand or the other,” and suggesting another way, a better alternative.

This phrase was one I’ve kept with me throughout my life (and is suggestive of the power of good science fiction to hopefully foment good science). I find that many fields devolve into orthodoxy rather quickly. Indeed, new fields tend to have greater orthodoxy than most, because the pioneers have had to plow some hard rows in order to have their science be more broadly accepted. So, from my own vantage, I am President of the ISNSCE because I am obviously a heretic. I often wage pitched battles against orthodoxies of all sorts.

So, with that in mind, I arrogantly review the panelists’ points. Ned is right, greater control is necessary. But greater control is far from the only way to pursue DNA nanotechnology. DNA origami (ala Paul Rothemund) is a heresy on the controlled DNA structures Ned has spent a wondrous lifetime building. We need to keep in mind that self-assembly can and probably should at some level be a messy, error-prone, robust process. Erik is right, we need greater complexity. But DNA is decidedly not electronics, and never will be. Earlier in the field, there was the notion that DNA could compete with computers, via massive parallelization. This quickly proved false, and led to a retrenchment that Erik’s circuits are just now beginning to move beyond. Still, I think the same danger remains, of looking at computers and trying to … be them … but with grossly inadequate maceomolecular tools. Eric Kalvins is also right, that DNA nanotechnology has much to teach biology. This is especially true given the recent glorious demonstration from Pam Silver’s lab that organized, functional RNA structures could be generated inside of cells. There may indeed be input/output devices based on DNA nanostructures and circuits, and these input/output devices may operate on nanostructured platforms built inside of cells. But in the end, the cellular operating system is as foreign to many of the concepts of DNA nanotechnology as the latter is to electronics. Cells are evolutionary machines that have crafted operating systems that work without design. To now impose design is akin to what the Tea Party seeks to do with the US Constitution in ignoring hundreds of years of court interpretations. It can be done, but it would be pretty primitive compared to where we are now.

Which brings us to the gripping hand. I believe the same two core principles that virtually everyone at DNA17 accepted as a given: (a) that in order to manipulate matter at the nanoscale, you have to have an information-rich, programmable structure such as DNA, and (b) that there is something very special about matter computation, molecules executing their own instruction sets, and again this requires an information-rich, programmable structure such as DNA. But I also believe that these two core principles strongly argue against DNA nanotechnology being either electronics or biology. I believe it will be the gripping hand, a new operating system better than either of its predecessors. And it will run on a platform yet to be conceived, a matter computer made for the execution of DNA circuitry.

And since I am so obviously a non-nano-ite, I can without fear of conflict of interest add the following: program managers take note. These folks may not know exactly what they want to build, but what they will build will change the world in a very profound way.

 

- originally posted on Sunday, September 25th, 2011

On Fukushima

Before beginning my usual irreverence, let me just say that one of the great stories of modern bravery were the workers who stayed on at Fukushima, isolated, surrounded by death, and did their jobs. That said, I have thought alot about this crippled reactor, ever since the tsunami tore it asunder. The reason is, it’s such an anomaly. There’s almost nothing like it on this Earth.

But first a digression. Being an official old person, I was actually a graduate student at the time of the last major nuclear disaster, Chernobyl. In fact, I was in Switzerland at the time, with my then-advisor Professor Steven Benner, at the ETH. The plume that was created by Chernobyl was a very real thing. Since we were graduate students in a molecular biology lab, of course we had Geiger counters (dosimeters), and it was not a problem to find the short-lived isotopes that were spewed across borders. They were on our balconies, the street, our shoes … everywhere. It was sort of neat, you could run the probe along a railing, and just pick out the little dribs and drabs of radioactive debris that had fallen from the skies; hot-not hot-hot-not hot-screaming hot. In a few days, it was gone, mostly, since the really hot stuff dissipated pretty quickly.

And this must be what it’s like to live downwind of Fukushima these days. Except it is nominally a more urban area than Chernobyl, and it hasn’t yet been sealed in a protective caul.

But the uniqueness of Fukushima, like the uniqueness of Cherobyl, stems from its chemistry, that heady brew of elements that aren’t found many places outside of nuclear power plants or stars. Fukushima is essentially a point source for weird chemistry. And the radioisotopes it spews forth are relatively easy to identify, especially if you use detectors that are much more sensitive than our puny handheld dosimeters. Moreover, those elements have a variety of decay rates, and as they fission downward can create reasonably long-lived isotopes, in an abundance that should reflect the time of their generation. Isotopes of plutonium, iodine, cesium, tellurium barium niobium, ruthenium, molybdenum, technetium, lanthanum, beryllium, and silver, all found in the soil outisde of Fukushima. And, if we are to believe the reports of monitoring stations, the plume wafted almost worldwide. “Nine days after the accident, the radioactive cloud had crossed North America. Three days later when a station in Iceland picked up radioactive materials, it was clear that the cloud had reached Europe. By day 15, traces from the accident in Fukushima was detectable all across the northern hemisphere. The radioactive materials remains confined to the northern hemisphere as dividing line between the northern and southern air masses.” (http://www.ctbto.org/press-centre/highlights/2011/fukushima-related-measurements-by-the-ctbto/fukushima-related-measurements-by-the-ctbto-page-1/)

Except for the local areas, I’m not particularly worried about the long-term health effects. No, it isn’t good to have additional radioactive isotopes in the environment. But, again, the critical effects are relatively short-lived, outside of the area immediately affected. I haven’t been to Chernobyl, but I’ve heard it’s a lovely nature preserve at this point. I have been to Puerto Rico, where our government set out a whopping Cobalt 60 source in the rain forest, to see what would happen. It initially burned away the surrounding flora, but it all came roaring back within years, apparently unmutated enough to look pretty much like the rest of the rain forest.

What interests me, as I said, is Fukushima as a chemistry point source. We know the time and the place of release of isotopes with few other cognates in the environment. We know something about the plume of release, and presumably something about the continuing release. Some of those isotopes are taken up by green things and beasties in the food chain and ultimately by, well, us.

When I was a kid, I’d hear parents ask each other “Do you remember where you were when JFK was shot?” Now we may not even need our parents to ask “Where were you when Fukushima went down?” Could someone with a sufficiently sensitive detector figure out where on the Earth you were based on the proportions of radioactive clocks in your blood or other tissue sample? Does Fukushima nail all of our positions, like a giant chemical GPS? And even better, does Fukushima continue to tag us, day-by-day, so that algorithms could be developed to track our movements as we move in and out of the worst of the plume? Hey, don’t laugh: your hair contains an excellent chemical record of what you’ve come in contact with over time (and can even pinpoint your assassin, if you happen to have been Napoleon). Why shouldn’t that chemical record extend beyond arsenic and lead to radioisotopes, and beyond mere composition to a detailed, cumulative analysis of the half-lives of the little clocks, ticking away, from plutonium in the millions of years to xenon in a few days.

Normally I like to think I rise above paranoia, that I know my own oddities well enough to disavow them. But remember how the Germans absolutely knew the Americans were working on nuclear weapons prior to the onset of World War II? There were so few publications on fission! Obviously the government was restricting the work (as opposed to the reality that no one had made sufficient progress to publish much). Well, giving a nod to past and current paranoia: why hasn’t anyone else written about this?

 

- originally posted on Tuesday, August 23rd, 2011

On nanotechnology

The public’s view of science always seems weird to me. On the one hand, despite the incredible impact that science has on everyone’s lives, all the time, most of the time we are ignored. This is probably a good thing, because the few times we’re noticed, what we’re said to do seems to be so far removed from either reality or context as to be unrecognizable. The recent dust-up with Creationism, Inc. was a good example of this. So, too, was Ted Kaczynski’s manifest and worldview, which posited that modern technology was driving the world (not just Ted himself) mad.

Most recently we find the same strain of anti-intellectual terrorism in the bombing of Mexican scientists who were loosely associated with the catch-all term ‘nanotechnology’ (http://www.washingtonpost.com/world/americas/package-bomb-explodes-injures-2-professors-at-university-campus-in-suburb-of-mexico-city/2011/08/08/gIQAldeM3I_story.html). The accompnaying manifesto (there’s always a need to explain why you’re a homicidal maniac, isn’t there? It’s not just enough that you’re a homicidal maniac) says that:

“The manifesto expressed fears that that nanoparticles could reproduce uncontrollably and form a “gray goo” that would snuff out life on Earth.

“When these modified viruses affect the way we live through a nano-bacteriological war, unleashed by some laboratory error or by the explosion of nano-pollution that affects the air, food, water, transport, in short the entire world, then all of those who defend nanotechnology and don’t think it is a threat will realize that it was a grave error to let it grow out of control,” according to statement.”

Now, I’m used to the notion that the scion of England is inbred enough to believe that gray goo is going to begin to drip out of his faucet and invade his orifices (and incidentally: way to go, Prince Charles; I hope you’re so proud). But I expect better from anarchists. Heck, my friend Antonio Lazcano recently examined this topic on his radio show in Mexico City, and he expects better from anarchists, too.

Here’s my beef with the manifesto (the beef with homicidal maniacs being obvious). What does it even mean? What is a “nano-bacteriological war?” All bacteria live at the nanoscale, so we’ve been under nano-bacteriological attack since the dawn of human history. And the engineering of biology began well in advance of any appreciation of physics at the nanoscale. Is using yeast to make beer an example of a nano-bacteriological attack on human consciousness? Or can we just down one in the local pub without fear of reprisal?

But I’m coming from the biological side of the fence, and Dexter Johnson got at this underlying confusion way before I did (http://spectrum.ieee.org/nanoclast/semiconductors/nanotechnology/nanotech-terrorists-apparently-dont-know-what-nanotechnology-is):

“It seems to me there might be much to be radical about in this day and age, but focusing your frustration and outrage at a bunch of material scientists who ride their bikes to work and spend their days focusing atomic force microscopes hardly seems like it’s well directed or helpful.

It’s even worse when you clearly have no idea of what you’re talking about. You need to know what nanotechnology is before you can be outraged by it.”

So, between Dr. Johnson and I maybe we can bat the exploding packages back-and-forth between the nanotechnology and synthetic biology communities. Or maybe we can just agree that making the Andromeda Strain is not really within the realm of possibility, and move on? These folks could perhaps save their ire for, I dunno, some sort of Che-versus-Trotsky cage match?

The real issue is that while the gap between the rich and the poor grows increasingly wider (Middle class? What’s that?), the gap between the technosavvy and the ignorant also gapes. Here’s a clue for our anarchist pals: if you don’t understand what you’re talking about, then don’t bomb it. There was a time, not so long ago, when scientists helped determine the outcome of a Very Big War. In that Very Big War some Very Smart Scientists who truly understood the impact of their work said “Hell no, we ain’t workin’ for the Nazis, where’s the door” (seriously, this is a direct quote from Einstein, look it up). The technosavvy voted with their feet, voted for an alternative social and political system. You anarchists got anyone like that? Anyone at all who actually, say, has a Nobel prize or even an advanced degree? No? Then kindly realize that you have no idea what you’re talking about and go back to visiting your homicidal tendencies on your internecine political squabbles. You’re making yourself look worse than ethically deranged; you’re making yourself look ethically deranged *and* stupid.

And for the rest of the populace who may have a similar level of technological knowledge: we scientists do appreciate being left alone, for the most part, but if it’s going to lead to a general backsliding into a new Dark Ages, then perhaps we (scientists and the public) should all take our games up several notches. As the classics say:

“When I use a word,” Humpty Dumpty said in rather a scornful tone, “it means just what I choose it to mean — neither more nor less.”
“The question is,” said Alice, “whether you can make words mean so many different things.”
“The question is,” said Humpty Dumpty, “which is to be master – - that’s all.”

We scientists indeed know what we mean, and the mechanistic underpinning, as well. Just screaming “Nanotechnology!” and lighting a fuse does not make the notion that some materials scientist is making a chemical replicator any more likely than it does that a synthetic biologist can make a crystal with a metabolism. We really are more than happy to explain these things to you, as the incredibly free distribution of scientific knowledge attests. You just have to be willing to listen, and not so inclined to blow us up.

 

- originally posted on Sunday, August 14th, 2011

On Venter envy

At one point, I think I spawned the phrase “Venter envy” to describe the feeling that many of us who are not corporate titans that can make entire chromosomes at will must feel. Surely this applies to you, yes? Well, anyway, what are the little people supposed to do? The answer to this vexing question has come, at some level, from that champion of the oppressed, George Church at Harvard. George recently published the follow-up to his most excellent MAGE paper, that showed how one can use small oligonucleotides to site-specifically alter mutiple sites in a bacterial chromosome in parallel (Wang et al. (2009), Nature 460:894). As they say in that great film, Treasure of the Silicon Valley, “Assembly? We don’ need no stinkin’ Gibson assembly.” I think MAGE is very cool, almost as cool as PACE (what is it with these Harvard folks and their acronyms? Can’t they at least invent science-y faux words, like ‘aptamer?’). I also think that it will likely be utilized in industry (certainly any industry that George starts up) and perhaps by more than a few academics.

Unfortunately, though, the efficiency of MAGE is extremely low, and while it does not require automation for success (in Texas, automation = undergraduates), it surely helps. Said automation is not beyond the reach of most academics, but it is something that requires the substantive investment of a scientific superstar like Church. This is another something I’ve been musing about for a bit, the development of upper level ’syncytia’ that freely exchange ideas, materials, personnel, and of course money between academia, industry, and government. If you can get your DNA synthesized on chips at low cost for demonstration purposes, and then hand off the products to a pendant company, it surely does help do genomic engineering projects. Sadly, I think such a model is actually a good idea for American science, but not all of us can operate that way. This really does raise the question of: what are many Universities doing in the research game? Go big, or go home (and if many of the recent “efficiency” critics of Texas Universities have their way, it will be “go home;” yeah, Massachusetts, cry me a river).

But I (typically) digress. MAGE is cool, MAGE is the nads. And CAGE, the horizontal shuffling between MAGE’d strains that the Church lab invented more recently (Isaacs et al. (2011), Science 333:348) further allows genomes to be built to spec, just like Craig Venter did, but again with many fewer oligos. To that end, Church and company are making us the Amberless Coli, where an entire stop codon is replaced with other stop codons, and thus is ‘recaptured’ into the genetic code, for other uses.

However, this all again involves very low efficiencies (“On average, 59 clones (10^-6 frequency) were observed per recombination.”). Wow. So, starting from a process where we already have typically 10^-6 frequencies of transformation / oligo, and where we’re trying to put together multiple such oligos in a single strain, we also have to pray for the outcome of the recombination event? I think a rough estimate of the probability of the Amberless Coli coming to be is therefore on the order of [10^-6]^10 (efficiency of an individual hunk o’ chromosome by MAGE) x 32 (number of segments that were MAGE’d) x [16 + 8 + 4 + 2 + 1] x 10^-6 (number of CAGE breeding events) = very, very, very small number. Obviously, this proves Intelligent Design, as do all really small numbers.

Which finally brings me to my point: we still don’t have the goddamn Amberless Coli!!! The most disappointing line in the modern scientific literature is not “Paylines have fallen to 8%” but “Thus far, 28 of 31 conjugations have been completed ….” Arrgghh! I know, I know, it’s coming. And why not get two Science papers out of it? Venter got, what, three, by teasing us through that great miracle of modern biology, the synthetic chromosome. So, I sympathize, I really do, but we all want the Amberless Coli!

Of course, we want more than the Amberless Coli. We want the Coli with the collected works of Shakespeare written in the intergenic regions, and the Coli that can set itself on fire, and whatever other weirdnesses synthetic biology comes up with. We still want to be Craig Venter. We still want to create bacterial genomes at will.

And that brings me to my sad conclusion: I am still not Craig Venter. I’m not even George Church. I’m not even sure that George Church is George Church, in the sense that … really? You’re going to do this all again? Again, back of the envelope: 15 authors (minus George) x (let’s say) 3 years of their lives = 45 FTE years / new genome? While the future is probably more rosy (as Dan Savage likes to say, “It gets better”), still! No, as much as I admire MAGE and CAGE, I think Craig and his army still win. The surety of DNA synthesis at the outset trumps the tiny numbers for MAGE / CAGE. If we are to make new bacteria it will likely be by full synthesis followed by tricks for manipulation and integration or recombination of large (100s o’ kb?) DNA pieces. We do need Gibson assembly, because it works and it’s way more likely to give you what you want in the end.

Given that I have a gift for being an anti-prophet, this almost certainly means that MAGE or its offshoots will work way better than full synthesis. Ha.

 

- originally posted on Friday, August 5th, 2011

On idiocy

The Discovery Institute, largely a spent force both intellectually and politically since Dover, has chosen to take issue with my comments at the State Board of Education. This is especially amusing as the original disputation of their idiocy came many years ago, and has been published via a NSCE publication for quite some time. Indeed, I refer to this publication in my previous testimony, which was and is available to the Discovery Institute. From this, we can conclude that the Discovery Institute is woefully behind the times not only in terms of science, but even in terms of their own shallow attempts to provide a revisionary context to science. Guys, this just can’t be good for your funding posture. Try to keep up.

But let’s get down to the science, eh? Here’s what’s going on (see previous Blog entry for at least some details):

(1) The Miller-Urey experiment brilliantly showed that it was possible to make organic matter (amino acids) from inorganic matter under relatively simple conditions. That was the point of the Miller-Urey experiment. That is still the point of the Miller-Urey experiment, including in textbooks.

(2) The DI, in attempting to revise all of science to fit its faith-based models, calls the Miller-Urey experiment an “Icon of Evolution” that is somehow false, because the early atmosphere was likely less reducing than Stanley Miller knew at the time he carried out the experiment. Forget for the moment that the experiment was not meant to be a time machine, but rather just a demonstration of mechanism. That evil ol’ Stanley, since he didn’t have a time machine, has somehow foisted off lies on subsequent generations.

(3) The fact is that no one, not even the DI, can say with any assurance just how much amino acid was necessary to kick start life. It is an unknown, because the mechanisms for life’s origins are still being investigated. This is why science is an inquiry-based endeavor, rather than the hot air-based endeavor that the DI has been attempting to sell, with increasingly smaller returns (you lost again yesterday, guys, in case you didn’t notice). It is also why we in the scientific community approach such open questions with the attitude “We don’t know” rather than with the DI attitude of “How can we twist this to a preconceived point of view?”

(4) Since no one knows whether one milligram or one kiloton of amino acids were necessary, nor whether they were necessary for minutes, months, or millenia, really the only point of the Miller-Urey experiment is point the first, above: you can make amino acids from simple conditions, whether reducing or neutral.

(5) The previous piece that I referred to (“Gas, Discharge, and the Discovery Institute”) again points this out. It also points out that the DI’s “Icons of Evolution” piece that said this was impossible, is wrong. Factually wrong. You guys at the DI may recall this, because several years ago it was one of the many things that kept Texas from adopting “Icons” on its approved textbook list. The fact that it was factually wrong. Did I say that enough yet? You were factually wrong.

(6) That said, it sure would be nice if the simple conditions corresponded to the early Earth, as best we can figure those out. So, yes, it would be nice if the production of amino acids was robust (whatever that may mean relative to milligrams or kilotons) in a neutral atmosphere.

(7) Oh, wait, it is possible to get more robust production in an overall neutral atmosphere! You just have to have pockets that are more reducing. This has been pointed out many times, although again when you’re a faith-based, hot air outfit, facts are an inconvenient thing. For the DI to object to the notion that there were reducing pockets on the early Earth is akin to the DI saying “We don’t think there were ever volcanoes, deep sea hydrothermal vents, or really any other anomaly on the smooth, smooth, unbroken surface of our planet.” I leave the refutation to anyone with eyes.

(8) So, when the DI has a vague, anonymous scientist (apparently the only kind that the DI employs) point out, as they do in their current idiot posting (please note the use of the word ‘idiot,’ as it absolutely applies to the DI for their complete lack of understanding of the extant scientific literature) that “This experiment did not ‘revisit’ the Miller-Urey experiments but rather was carefully intelligently designed to convert a neutral environment into a reducing one that is favorable to producing amino acids” (http://www.evolutionnews.org/2011/07/andy_ellingtons_citation_bluff048651.html), the only comment that can be made is: well freaking duh. Yes, whether volcano or hydrothermal vent or “Organic synthesis from neutral atmospheres [that] depended on the oceanic availability of oxidation inhibitors [such as ferrous iron] ….” the scientific community has been saying the same thing all along. Point (1), above, is still valid, and has never been invalidated. It’s just now even more validated by expanding the range of possible reducing pockets on the Earth’s surface to potentially include the whole ocean.

The DI claims this all as a teachable moment, saying that “What we see evidence of here is a scientific debate over the origin of life ….” No, actually, the problem with that claim is that science for the most part requires experimentation. You guys don’t do experiments. We do. You guys just carp about our experiments, and you don’t even do that very well.

Nonetheless, I agree that this is a teachable moment. So, students and educators around the nation, you have here a supposed scientific debate, although really since this is the blogosphere this is more of the typical sort of vain shouting match that characterizes much of what you’ll see on the Internet (again, there’s a pretty good reason why you don’t see the DI in actual scientific publications, but only on the Internet, ranting). With that in mind, let’s have some discussion questions for our classes:

(A) Which would you rather see helping to set policies relating to teaching biology, literally millions of scientists who spend their entire careers doing experiments, or a handful of folks at a faith-based think tank whose jobs largely depend on trying to make inconvenient facts go away?

(B) Discussion and debate are valuable things in science. How long should we debate notions such as “Do things fall down because of gravity?” or “Does the Earth go around the sun?” or “Is the fact and theory of evolution proved to the same degree as the first two questons?” Do such debates enhance our understanding of science? Or do they make it ever more likely that you are going to have a future biotechnology or health care industry job outsourced because you can’t do it as well as your counterparts in other countries?

(C) When the Discovery Institute talks about science, what do they really mean? Observation, experimentation, and hypothesis testing? Weak and isolated misinterpretations of a huge body of knowledge? Or just whining for the sake of whining?

Well, Casey, I hope this gets your page hit count up somehow. God knows you need it. But really I don’t think that picking a fight about the facts is going to help you guys much in your further, currently grossly unsuccessful attempts to show your relevance. You didn’t even have boots on the ground at the Texas SBOE hearings this time, you just sent a 80 page screed that in the end didn’t change one word in one textbook up for consideration. Sad, really. But, there ya go. Happy trails.

 

- originally posted on Friday, July 22nd, 2011

On the circus

Today I’m at the State Board of Education hearings on textbook adoption. Or, in other words, the once every-so-often meeting that helps to determine whether or not Texas makes itself a laughingstock with respect to the teaching of evolution. I guess this is sort of my first “live blog,” which is just weird.

I continue my love / hate relationship with Texas. On the one hand, this board meeting is democracy in action (not necessarily a good thing in a Republic): every idiot gets their say. On the other, their say means very little. The larger forces at work will drive both curriculum and the impact of that curriculum. Governor Perry has touted Texas for job creation while at the same time undercutting education both in spending and in direction. I live in an interesting microcosm where Texas is outsourcing its education to other states, letting others carry our burden for education, and then saying that they should come here to start businesses and take tech jobs. This same scenario is of course playing out between nations, as the United States outsources not just call centers, but essential aspects of education, research, and development, all in the name of an efficiency that often does not trickle down to the local level. There is an argument to be made for local inefficiency.

From another vantage, though, these forces favor advance. Texas is no longer the juggernaut driving textbook adoption that it once was, because the entire publishing industry has undergone such change. “Textbooks” themselves are almost things of the past, and the approval of electronic resources is moving away from national or even state control towards local control (ala recent law from our other circus, the Lege). Of course, this gives any school district the opportunity to undercut the education of its children by serving up Creationist and Intelligent Design prattle. But it also provides an opportunity for scholars, scientists, and educators to point this out. In an era where ‘publishing’ is both more of a niche market and more of a distributive endeavor, the opinions of content providers may matter as much (or more) than the opinions of consumers. And make no mistake, scientists are watching very, very carefully what publishing companies do here today. Watering down the fact and theory of evolution in your textbook will be viewed as capitulation to an anti-competitive, know-nothing attitude that does not serve our nation well. There is an argument to be made for local innovation, counterbalanced by global scrutiny.

OK, soapbox off. Here’s my testimony, for what it’s worth:

“It has been only a few short years since my previous testimony before the State Board on the need to teach evolutionary biology to Texas students. Much has happened in the scientific world since that time; can the same be said for those who promote teaching the supposed weaknesses of evolution, but who in fact are arguing for teaching intelligent design or Creationism? Let’s take a look at what factual errors the board would have made or has made based on what happened before, and compare the track records of the scientific and political communities.
“Previously, I testified on the validity of the experiments carried out by Stanley Miller, the so-called Miller-Urey experiments that show that biological materials can be created by gas discharge experiments. The Discovery Institute had chosen to highlight these experiments as a false “Icon of Evolution,” something that the scientists supposedly got wrong. Once this was brought to my attention, I wrote and published a refutation, “Gas, Discharge, and the Discovery Institute,” available via the NCSE. To my knowledge, the facts in this article have not been countered by the Discovery Institute.
“Imagine, now, that we had decided several years ago to utilize the materials backed by the Discovery Institute or others, that we had accepted that there were supposed ‘weaknesses’ or ‘flaws’ in the theory. While science moves on, advances, corrects and expands itself, the opponents of science teaching never seem to update their stories or ideas or facts. Indeed, recent work completely overturns the fly-by-night interpretations of “Icons.” An article in 2008, authored by Dr. Jeffrey Bada of the Scripps Institute, showed that “… contrary to previous reports, significant amounts of amino acids are produced from neutral gas mixtures.1″
“If we had allowed teachers to utilize materials that clearly have a philosophical, anti-scientific axe to grind, several generations of Texas students would have used factually incorrect material, and would quite literally have been lied to by the Discovery Institute, amongst others.
“The best source of science is scientists. If you choose to use facts, interpretations, or materials that are not validated by the scientific community, you will almost certainly find yourself in a position of trying to explain to Texas students, Texas parents, and Texas businesses why your actions have led to the willful propagation of falsehood. We cannot afford the loss of trust nor the loss of competitiveness.
“Please vote to adopt the recommendations of the Commissioner. Please do not on a whim attempt to change the contents of textbooks that have been labored over for months. I commend both the reviewers and the publishers for standing up for scientific integrity. In this era where the very nature of publishing is changing so quickly, good relations between content providers (in short, scientists) and the industry are essential, and watering down the fact and theory of evolution will almost certainly disrupt that relationship on a scale that reaches far beyond Texas.

1 Cleaves, H. J., Chalmers, J. H., Lazcano, A., Miller, S. L. & Bada, J. L. A reassessment of prebiotic organic synthesis in neutral planetary atmospheres. Orig Life Evol Biosph 38, 105-115, doi:10.1007/s11084-007-9120-3 (2008).”

And, at least in my own view, this absolutely impacts defense issues. Imagine a country trying to maintain a nuclear stance when many of its leaders or political entities refused to believe there was such a thing as fission. That’s sort of where we are with respect to biodefense and evolution. When we decide that diseases are just happenstance, acts of God, rather than evolving and evolvable entities (and this, at some level, was the Millenialist stance of at least some former administrations, including one where The Band Played On), then we automatically build our defenses on a contradiction. Not a Shining City on a Hill, but a house of straw.

Postscript: I would like to thank the Discovery Institute for accurately reporting my remarks (http://www.evolutionnews.org/2011/07/idiots_and_laughingstock_unive048641.html), since they seem to get virtually nothing else right.

 

- originally posted on Thursday, July 21st, 2011 at 4:21