Andy Ellington's Blog

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?

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.

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.