E Coli o157:H7 kills people via tainted food. Where did it come from?
O157 and Hotrod Genes
©Richard Katz 1998. All rights reserved. If you're not reading this online on a computer screen, stop reading.
Updated 2001. Appended.
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The E. coli o157 bacteria is deadly because it makes Shigella toxin. Shig toxin is supposed to come from Shigella bacteria. That's how God figured it out. But somehow Shigella's cousin, Escherichia coli, acquired the ability to make the shig toxin, and kill people (or just make them deathly ill), starting sometime in 1982. Remember Jack-in-the-Box; think tainted meat. Remember Odwalla.
I've been wondering how that came to be.
Did a molecular biologist -- a gene hotrodder -- take the shig DNA from a batch of Shigella in one bottle, and move it to some E coli growing in a bottle next door? Did the scientist do this by mixing and matching parts, elegantly, the way a hotrodder does with cars and car parts? It's not that easy to get a Cadillac engine to express itself in a Studebaker pickup; and it's not easy to get "foreign" DNA to express itself in some other living cell. Everything is better about the hotrod: more torque; more horsepower, maybe even better looks, and a sense of accomplishment, perhaps even medals -- and the Studillac will still get you down to the corner store for a quart of milk. If some gene hotrodder custom made o157, they did a good job, because E coli o157 can make a person sicker from shig toxin than classic Shigella can.
I looked on the Internet to find out where o157 came from. The Internet didn't say.
Pondering the Literature
So one day I went to the University of California at Berkeley's Public Health Library to find out the origin ofE coli o157. The reference librarian on duty searched electronic databases for me for a minute or two. Somehow it felt anachronistic, epistemologically, to be looking up o157 in the time before it had a name. I saw the word "Infectious" randomly on her screen. I asked if there were a journal called "infectious" anything. There wasn't, but she consulted the screen and said the library had a journal called Infection and Immunity, from 1970 to 1989. I found the journal -- a shelf of brown books, some of them four inches thick, ponderous tomes indeed. I looked through the indices of volumes from the 1970's. Finally I found the words E coli and Shigella flexneri in the same entry.
The article I turned to put a new twist on the gene hotrodder scenario.
The article recounted a series of experiments (from the mid-70's) where the guy fed his lab mice some Shigella bacteria, and then fed the same mice some E coli. Normally, the mice would end up with no Shigella and a gut full of E coli. That's the way God did it. But the scientist was able, one way or the other, to subvert nature and produce some lab mice that had both Shigella flexneri and E coli coexisting in the guts of his mice.
The experiments these scientists did weren't quite like hotrodding some genes to make a custom bacteria. What they did was something more like what the Robert Proskey garage-owner character in the movie Christine did -- he operated a big garage, and rented out clean, secure space for guys to work on their cars. You were bound to get some cool cars out of that garage. God takes care of making that happen, providing the creativity. So these scientists provided the mice as garage space and then stocked them with bugs that were the biochemical equivalent of a junkyard of parts, a machine shop, and a box of tools. Christine was about a car who could auto-assemble herself. She just needed the right place to do it. Proskey's garage was perfect. She was an old heap; she got herself all cherried out. She got in a wreck; she straightened herself out again. Too bad she was homicidal.
Maybe that's what happened with the bacteria. They just threw the stuff together, and it auto-assembled. Into a viciously virulent infectious agent.
I decided to comb the literature with a finer tooth. But when I went to the computerized Medline database and started reading the abstracts of hundreds of journal articles about o157 published since 1982 (and the dozens of articles published about E coli enterotoxins just before that), the years I had spent as a biochemist and virologist came welling up from my stomach and made me feel sick. Those years of experience had given me a sixth sense for ancient journal articles standing so mute upon library shelves; and had thus let me find the one article I had; but like Alex in A Clockwork Orange after his Brodsky treatment, I just felt sick, and I couldn't read any more about it.
Accidents and Experiments
Penicillin was discovered by accident. A scientist put together two different bugs, entirely by accident. The second bug was actually a contaminant, introduced by sloppiness. The contaminant killed the first bug, and then, through a long series of incredibly serendipitous occurrences, penicillin became commercially available, about twenty-five years later. O157 might be the same in reverse -- a scientist combined two bugs on purpose, and they had some kind of sex with each other, and a serial killer/torturer was born, and got out to the general population of humans a few years later.
I can't prove that o157 was an accident. Someone could disprove it: If someone could find a scientist, a gene hotrodder, who 'fessed up to making that bug up custom in his shop, on purpose, then you'd have proof -- especially if he had kept all the old parts in his freezer. Because that hotrodder -- and only that hotrodder -- knows what functions he was after.
Maybe the function he was after was to make a wolf in sheep's clothing -- E coli with a mean streak. Maybe this was part of the war effort; E coli laced with shig gene is an ice cream cone compared to some of the treats that have been concocted by the US Department of Defense and discussed at some length in the pages of The New Yorker. Smallpox, anthrax, botulism -- terrible plagues for scientists to work on as weapons, right up there with physicists working on A-bombs. This project was obviously a big success, although I could never imagine what anybody was thinking when they were sitting around the lab concocting this creature. Shig gene in Shigella only causes dysentery; shig gene in E coli has been described as "like having a sheet of hot metal placed on your stomach." It's possible that somebody purposely hotrodded a Shigella part into the E coli chassis. Along with enough linkage to get it to function, smooth as silk, and better'n stock.
If o157 arose spontaneously, most scientists would have no problem with the statement that "God made it". Scientists refer to God like the guy in the lab next door, or maybe a kind of Institute Director, or maybe just a real good scientist, like Frances Crick.
If a gene hotrodder put o157 together, then he was, as scientists like to say it, "Playing God". In actual practice, physics, biology, and chemistry are like a religion, where you don't think, or even believe, you just act. A religious experience: Just do what comes next. Incremental science.
If o157 arose not quite spontaneously (not an act of God, to be met with a shrug) but through the incremental misguided mindlessness of some Igor in a lab somewhere, like the guys I read about in the literature, that would be a damn shame. Can we start to evaluate what these guys were doing when they (like scientists generally do ) mixed up cells that God would never put together so intimately? These scientists put together a flock of mice with Shigella and E coli cohabiting in their guts. Just like in Christine; they provided the "space" for God to work in. Does God carefully construct things, or does God let things self-assemble? Could we possibly have any idea at all about a question like that?
It's got to be okay to experiment. Otherwise, you're paralyzed. You won't get your grant renewed, or you won't get your degree, or you won't attract any more venture capital or shareholders, or you won't get any fame or glory, and you won't make any progress. Nobody ever foregoes an experiment because of reservations about the outcome being gruesome or apocalyptic. You just keep putting one foot in front of the other; if it leads to the destruction of humankind, so be it.
Update Part One:
The Modern Biology of o157, where DNA is just a place to start.
Since I wrote that essay about how E coli o157 and its seeming origination by gene hotrodders -- "slicker'n stock" is what I said then -- the complete sequence of E coli K12 and the complete sequence of E coli o157:H7 have been elucidated and published.
(for example, http://www.dna-res.kazusa.or.jp/6/6/01/HTMLA/ .) *
I read through a few articles about the genome sequence (the complete DNA sequence) of the chromosome of o157. It appears to me (who's practically a layman in these matters) that o157 DNA bears an uncanny resemblance to E coli K12 DNA. My understanding is that K12 -- the canonical "wild type" --- was just an arbitrary isolate of fecal bacteria, decades (way over half a century) ago, that became famous because it was used for research. It's the microbiology / molecular biology lab rat. Am I wrong in saying that o157's resemblance to K12 is no accident? This o157 is first cousin to a lab rat E coli. This pathogenic curse appears to be a child of the lab, no? What else could these data be telling us? (Note the same sort of thing with the lysogenic lambdoid phages that seem to be involved.)
The Japanese author/experimenters who sequenced the Sakai-city strain of o157 said that their particular scourge had all kinds of goodies grafted into its genome that made it hell on wheels for virulence (o157's evil "islands of pathogenicity" that have been revealed by the sequencing.) I said something like that a few years ago, with absolutely no data to back it up. (Actually, at the time, in 1998, I was more than willing to give the research community the benefit of the doubt, and ascribe the lab origins of o157 to more accident than design.) The Japanese illustrated their work with a DNA map that compares E coli o157 DNA to E coli K12 DNA. Most of the genome of o157 superimposes on the genome of K12. It's a match. The interspersed sections that don't match, though, are the ones that code for the disease. It really does look like stuff has been grafted on, or spliced in. The Japanese researchers colored those sections red.
But the Japanese experimenters have said not a word about the origin of this DNA, of how it came to be.
All molecular biologists repeat the mantra of "evolution". All the guys and gals in white lab coats say that E coli o157, and all other critters, arrive at what they are by some well measured process that is basically "Darwinian"; like, things change, at some certain rate, and so if you measure how much they changed, you know when they started to change. Mutations, changing a genome at a certain "mutation rate", according to a "molecular clock". ** But hey, guys: E coli o157 just arrived twenty years ago! Those graphs and charts and figures with "molecular clock" somewhere in the text or the caption are always "millions of years" on the abscissa or the ordinate. Twenty years / millions of years -- somebody explain this to me. Please. Twenty years is way less than the twinkling of an eye. Twenty years, to a genome, is not yesterday, or even this morning. It's more like, now.*** It's happening. Just watch.
Update Part Two: About those Hotrodders
The friend of mine who came up with the concept of gene hotrodders is named Phil Brumder. He's a machinist and lives in Park City, Utah. I explained about how o157 seemed to be made mostly on the frame of one bug with parts from other bugs, and he came up with, "Gene hotrodders." I don't think he knows much molecular biology at all, but he nailed that one.
I got to thinking about it a bit more, several months or a year later, and I wondered if the analogy broke down at the intersection of good and evil. Were there, I asked Phil, any evil hotrodders? Could there be? Whoever made this o157 up custom in his shop is an evil bastard, no doubt about it. How does that analogize to mechanical hotrodders?
By the doctrine of Fair Use, I'm going to quote from Sonny Barger's book Hell's Angel. (I have shortened it for length only; I hope I didn't leave anything out that President Barger would object to being left out. You can find the full text on pp 62 and forward of his book.)
"It's funny when you think about it now, but in order to look cool and have our own look, we cannibalized Harleys to the point where Harley dealers didn't even want us near their shops. We'd destroyed the original Harley design and image by taking stuff off "their" bikes and replacing them with our very own parts
"I think the Hell's Angels are responsible for a lot of the current designs and workmanship on modern motorcycles. When you look at current custom Softail motorcycles you see a lot of our design innovations "
President Barger makes a good statement of hotrodding here, communicating both the philosophy, the necessity and the rewards of building and then driving your own custom vehicle. No knowledgeable person would ever actually say that a chopper is a hotrod &endash; a chopper is the ultimate hotrod. Let it go at that; a chopper is the ultimate hotrod, and President Barger is a longstanding expert on choppers.
So what about evil hotrodders?
President Barger discusses this in his book, obliquely but pretty openly.
President Barger discusses the bikers he's hung out with and tells us that a few of them engaged at times in criminal activity related to bikebuilding. In particular, he relates the story of a time in 1967 when three clubmembers stole twenty-seven motorcycles in one day:
"I told them they'd fucked up," he says to the clubmembers on page 63. "I told them they'd crossed a thin line between right and wrong, so I made them return every bike. Actually, since they had already been stripped down, we had to have each guy come over to Fu's house and pick up his stolen motorcycle in a box."
The 27 bikes belonged to a club from up North that had come down to Richmond, California, to party. The Club had a rule that you couldn't steal a bike from in front of a clubhouse, so the three clubmembers had moved the 27 bikes down the street a ways, whilst the owners were in jail temporarily after the party was raided.
What President Barger does for us here is to illustrate a really good point about evil. In fact, he even tells us what that point is:
That thin line between right and wrong he refers to, becomes a yawning chasm when it turns into the difference between good and evil. Nobody is going to confuse stealing parts for fun and profit with something evil. President Barger's reminiscences illustrate this perfectly, showing just how close a hotrodder can go, and it's still a long, long way from anything remotely resembling the construction of any mechanism of mass annihilation.
These few Rules that his club adheres to are what's lacking, perhaps, in the club of science; the scientists need a few Rules. Maybe they should consult with the President.
*There's a funny thing about this that ought to be noted here. It's just not that easy to find this genomic information on the web. Several thousand practicing molecular biologists have also noted that it's not so easy, and they're wondering out loud why all of their hard work is sequestered by a few for-profit publishing houses who have a seeming monopoly on glossy paper. I'd give you their URL but it's pretty hard to find too; maybe the final version of their idea is http://genomebiology.com. It's hard to say. Genome Biology is a publication, actually, but it's not free. Well, it's sort of free. This is an endless discussion, this "free" concept. After you read what Richard Stallman has to say about "free" we can discuss it further. Generally, though, I'll weigh in with this version of what "free" means: Free doesn't mean "free, but ..." So for example, Genome Biology will give away web pages that have research articles, but you have to subscribe to get review articles and other materials. I guess that's to bring in some revenue. They have a lot of online ads. You'd think that would pay the rent.
**Another funny thing: You can tell you're hearing this mantra when you hear someone intone the phrase "molecular clock". I don't want to go into the liturgy of this "molecular evolution" thing. I think the molecular clock thing is all bullshit. But don't listen to me about it; find somebody who will be more equivocal, and bore you to death, and make you feel better about it. One of the men who pretty much originated this "molecular clock" thing was Vince Sarich. Turned out he was a racist par excellence and was hooted out of his teaching position at Berkeley. True story. I'm pretty sure he was a tenured faculty member at the time. The racism and the "molecular clock" stuff are related. Take the students' word for it; the faculty did. That's mostly just my remembrances; I looked on the 'Net, and I could find no reference to Vince and the students.
***Yet another funny thing: Try looking up "bioterror" and "o157" together on the internet, with, say, Google. Nothing. Gornisht. Anthrax, botulinum, plague, the usual suspects are all there. Not a word about o157. I think that's odd. However, you can find sentiments similar to mine on the net. Have a look at
whose last paragraph reads
Another factor that would give an overestimate of divergence time is artificial genetic engineering. Artificial genetic engineering involves rampant recombination and transfer of genes across divergent species barriers. Now that sequence data are becoming widely available, one ought to be asking the serious question as to whether genetic engineering might have contributed towards the emergence of E. coliO157 some twenty years ago .
Richard Katz , email@example.com 2001
2002 Update on E coli o157
If you read what's new at www.meatingplace.com,
or if you read the Wall Street Journal,
you'll see reports of some humongous recalls of E coli o157 - contaminated meat.
In September of 2002, one of these recalls merited a whole article in the WSJ.
Here's what I wrote about it:
To: Scott Kilman WSJ
Dear Reporter Kilman:
Good article about E coli o157 (Friday's WSJ "Cargill Expands Beef Recall, Shuts Plant Amid E. Coli Fears" .) You touched on at least one complexity of the situation, how by the time you recall the stuff it's already been eaten, slightly-behind-the-headlines in true WSJ fashion. I don't recall anybody ever revealing that disturbing aspect before. And I am somewhat of a student of the subject.
o157 is a fascinating story that I have never seen written up in depth, the way your paper does sometimes (usually on the first column front page). You know, this bug was first reported (seen; serotyped) way back in 1972, in pigs. Already, that's more of a chronology than has been in the newspapers. Then it was seen in humans in 75. Then it became a disease in 82. As I recall, Jack in the Box disease dates from 93. (Getting an authentic-enough chronology of that story is just the sort of thing I would ordinarily rely on the WSJ for; the 72 data must be in Washington somewhere.) That's strange enough. But what's truly strange is, What happened just before 72? And most interesting to me is, Why did whoever created this bug create it? Molecular biologists refer jokingly to "Playing God" experiments. This work apparently was something just like playing God.
I'm pretty sure nobody has written up this story because nobody realizes it's a story. Everybody figures that God did it. I don't think so; or rather, No Way.
Here's a caveat: It's easy to sound like an idiot talking about microbiology, if you've never worked as a microbiologist (I have, BTW). And of course, if you are the Newspaper-of-Record, you sure as hell don't want to sound like an idiot. I think you or your editors would find it difficult to sift through the skepticism and conservatism of microbiologists in general who will dismiss your initial questions about whether there is a story there. "No, of course not," will be the answer. "o157 evolved naturally. Didn't you read your Darwin?" I've never been a newspaperman (although I am a published author), but I suspect that your boss and your boss's boss have kept intact a healthy skepticism for all the people who comfortably maintain that there is no story here or there; whilst not running off chasing down every dumbass conspiracy theory story.
Maybe you recall (but probably it was before your time) that in 1972 or so, many biologists including many heavy hitter molecular biologists declared a moratorium on E coli genetics experiments, i.e. on "certain kinds" of experiments. I was a grad student at the time; I found that puzzling, and I have always found it puzzling. I can see, now, that if some of my seniors had access to knowledge of "certain kinds of experiments" that they knew were being done, they would want to stop the whole subway train, and they did, for a few years, as I recall. I recall that the whole thing was forgotten about in a few years; it was the sort of thing that is revisited now in the controversy about "stem cell research" (that is not an analogy about the "danger"; that's an analogy about how controversial it was/is for whatever reason.)
So, Who created this bug? and did they create it for germ warfare? We do care about germ warfare, I believe. That's in the papers.
It's like where did AIDS come from, where the heavy duty AIDS scientists say, "Doesn't matter. What we need to do is Fight the Disease!" And other folks, not in the headlines, say "Well, maybe we should spend a little time on that." Of course, that particular issue (Where Did AIDS Come From?) was litigated, and the journalist lost pretty badly , so maybe it's a bad example. His magazine (Rolling Stone) really didn't care one way or the other, so they caved.
Here's why I am writing to you now:
I just recently came up with that 72 date for first sighting of 0157:H7 serotype of E coli. I found it on the internet, at the website of a law firm which sues food poisoning defendants. I came up with it, just by coincidence, whilstI was sending a letter touting a play I wrote, to a theater company in NYC.
I re-read the play partially, and discovered (literally, discovered: I hadn't seen this passage in many years) that apparently way back in 1969 or 1970, I had found a DoD grant number for money to do research on "Shigellosis in E Coli". That's the recipe for E coli 0157. (o157 is a variant of lab rat E coli that has acquired shigellosis genes presumably from Shigella bacteria; but the genes are now codenamed SLT for "ShigLikeToxin" = SLT. They stand out like a red thumb in the recently sequenced genome of o157; like, where the hell did THOSE come from, so neat and tidy? )
But you see, that was NOT E coli o157, back in 1969 or 1970, because "E coli o157" had not been evolved/invented yet. Keep your head on straight here: This is both a forward and backward anachronism. You've got stuff in the present that is out of place in both the past and the present, and I was revisiting my own past (as a writer) and coming up with things that were out of place. At first, I assumed that I had made this up, with the benefit of hindsight, in 1986-7 when I wrote the play. But a closer examination of my notes seems to indicate that I saw the reference in 1969, in Philadelphia, at the headquarters of the American Friends Service Committee -- the Quakers. Doing research, I presume. I am not certain that I actually visited the place; I recall that it was on Spring Garden Street in Philly, and that I went there when I was a student at Penn. I don't recall why I went to visit there; perhaps I was looking for something else, something about the Vietnam War, and I just happened to look at some books that had DoD grant numbers in numerical order. Those books, or printouts, whatever they were, may very well still be there.
Going forward in time, this would indicate that my original rantings about o157 , about Gene Hotrodders, written in 2000,
are not correct, because genetic engineering had not been invented yet, in 1972. The first specific endonucleases had not been isolated yet, or had perhaps just been. I'm theorizing here, a little bit. But it will always be theorizing, because we just have no way to know what the germ warfare folks were up to, in this country, or in the USSR -- or other countries. Your Newspaper's recent article about Ken Alibek ("To Fight Bioterror, Doctors Seek Ways to Spur Immunity" Tuesday Sept 24, 2002) getting a grant from the US Govt to do more of his "research" shows that we just don't know who's working on what, in this field, even now; and in the past, Alibekov was waaay ahead of our game.
The only reference I could find to expressing Shig(ellosis) genes in E coli were from an ag laboratory in France! And that was decades AFTER 1972. But, apparently, the original research was before the time, when anything from that time, would appear as a reference on the internet. And, to complicate matters, one could never know how long ago such research might have been commenced.
And just why is this so interesting, or important, or newsworthy? Because, if the story were investigated, your Friday October 4, 2002 story about Cargill/emmpak "Cargill Expands Beef Recall, Shuts Plant Amid E. Coli Fears" would have been written differently. Simple as that. That's why it's news. Not trivial.
On the other hand, maybe it's just another conspiracy theory that isn't news at all.
You tell me; because if it's not news to the editors of the WSJ, then I'll just forget about it.
I'm simply baffled that it's never been explicated in the papers. I'm testing out the theory that the only reason it hasn't been looked into in the WSJ (which in my thirty years of reading it has never ceased to surprise me in what they WILL look into; the WSJ is not afraid to look into ANYTHING) is simply that the editors are completely unaware of the baffling and POSSIBLY nefarious origins of this poisonous bug.
A playwright can afford to speculate on whether the scientist is a tragic figure who creates such a bug in a Faustian manner: He takes the Government's DoD money, but has to sell his soul and make germ warfare materiel. The Scientist's solution to this Faustian dilemma is the opposite of Faust's: Faust was damned proud of his bargain that he drove with the Devil's Disciple (I'm going with the Marlowe version here, featuring Mephistopheles); your basic molecular biologist has his blinders on, denying that he's workin' for the war at all. At least I think that's the case; I've never had authentic enough journalistic credentials to go out and ask these guys. BTW, as a former biochemist, I'd be the wrong guy to go out and do the asking anyway; when a guy says "I don't know" I let it go at that. That's good science. That's terrible journalism.
Hey, one last thing, if you're still listening:
Tell your Editors (All of Them) that while the WSJ does a better job than anybody else of spelling out E. coli o157:H7 , it's not quite good enough. There are other strains of E. coli that are normal intestinal flora. I can't seem to find out whether they are good for us, or just not bad for us, but they seem to be "natural" enough. So in the headline (and I am aware that headlines need to be terse) it just won't do to keep saying just "E. Coli" . At least say "E. Coli o157". You'd be doing better to start saying, perhaps, just "o157". See, after you publish an article about how o157 was a germ warfare project that got outta hand, you'll have a problem if the public goes overboard, the way the public tends to do, and starts a witch hunt for E. coli. So you want to be real "scientific", or at least taxonomic. As my favorite professor at Berkeley used to say, Nomenclature is important. (He also used to say, whilst peering into the microscope, "Living things tend to have pleasing shapes." That was Prof Horace Barker.)
And that lower case o for o157 is just a little crutchwork for the reading public; quite a few people out there think that's a zero. That sort of thing gums up the works over at the Google factory.
Sincerely, Richard Katz, Berkeley CA 510 236 1865 OR
E coli o157 2006
Popeye and The Semiotics of Spinach
(C) 2006 Richard Katz
One thing I totally missed in my whole E coli o157 rant www.frogojt.com/o157.html was the symbolism of the purported mad scientist's infectious process: This sick person engineered a bug that infects humans through their food; and then instilled his virulent bug at a Jack-in-the-Box restaurant.
Surprise!!! Pop Goes the Weasel!! Yer Dead!
Later on, Mr Mad Scientist struck at Odwalla Juice, the Holier-than-Thous Juice Company from California, where they were so fresh, so wholesome, they didn't even have to pasteurize their products. The Boss at Odwalla believed that the acidity of orange juice was insurance enough. Such hubris, compounded by such ignorance! (He was simply wrong about the acidity thing, of course.)
And then there was o157 infection traced to a petting zoo. Not even a petting zoo, really; it was a petting booth, or petting amusement, at a county fair in the Midwest. The cute abused animals, in cages for kids to pet, took the blame.
Now, in Fall 2006, there's E coli o157 in the fancy pre-cut pre-washed spinach-in-a-plastic-bag. Take that, nouveau riche motherfucker! Organic --- I'll show you organic, suck on this; that's the attitude.
I can't entirely fathom the Sakai City, Japan, outbreak of E coli o157. It was the most bizarre of them all, but only if you were actually there. I wasn't actually there, but I saw it on NHK (Japanese) television, which is as close to being there as I or most anybody else has been to Odwalla or Jack-in-the-Box or Earthbound Farms. The televised image of Japanese school cafeteria cooks and chefs boiling lettuce, and looking sorrowful (for the lettuce) and contrite (for having killed the children they were feeding) was overwhelming, especially if you've ever been to Japan or experienced enough Japanese culture to grok how spiritually significant this all was. Semiotically, this was deadly.
Spinach, though: Now THAT is the last straw. Popeye ate CANNED spinach and got supernaturally strong and crafty. Ponder that; feel the deadly sarcasm implicit in fresh, contaminated spinach.. Whoever is doing this is not only an ace biotech engineer, he's a world class semiotician to boot.