DNA is a curious thing. It might make sense for you to think about the DNA in your brain in terms of “brain DNA” and DNA in your blood in terms of “blood DNA”, but you’d be wrong. Strangely, the DNA in your skin cells sloughing off to make up a considerable proportion of common household dust is the exact same DNA found in the rest of the cells making up your body and bodily organs like your brain, heart, liver and muscles. So how does DNA know to make neurons or finger nails? How does it know what to do and where to do it? The answer has something to do with a field of study called epigenomics (1, 2). Epigenetics is what allows identical genomes (genome = your set of DNA) to display very different phenotypes (observable characteristics) (3, 4). Epigenetics allows us to make different cell types out of the same DNA, makes identical twins different and explains how the calico cat got its spots.

First; DNA. In case you were wanting to nerd out, DNA stands for deoxyribonucleic acid. Generally, you probably try not to think about DNA too much, and just kinda hope it does whatever it is it’s supposed to do without turning into cancer. If you’ve ever wondered what DNA actually is though, it’s just four different (yet very similar) chemicals called nucleotides, distinguished by one of four chemical modifications called nitrogenous bases. Their names are Adenine, Thymine, Cytosine and Guanine, but you can just call them A, T, C and G. And they pair off bound together in the following way; A’s with T’s and C’s with G’s to make DNA a double stranded molecule over 3 billion base pairs (2 meters!) long. That’s 3 billion base pairs per cell, and you’re made up of trillions of cells. Every time a cell divides, these 3 billion base pairs are replicated.

If grade 12 biology was a long time ago and the word “replication” makes you feel ill here’s a helpful synopsis; DNA is transcribed into (makes) mRNA and mRNA is translated into (makes) proteins. Another way of talking about DNA being transcribed into mRNA is to say that the DNA is being expressed (turned ‘on’). Conversely, when DNA is not being expressed or transcribed into RNA, we could say that it’s transcriptionally silent (or ‘off’). So every time your cells divide, they generally duplicate the 3 billion base pair sequence making up your genome with each round of division. Chunks of these nucleotide sequences make up genes, of which you have about 25 000, averaging in the range of thousands of base pairs in size. DNA lives in a sectioned off little bit of cellular real estate called the nucleus, and it’s distributed into little manageable packets called chromosomes of which you have 46. You have 22 different chromosomes, numbered 1 through 22 from biggest to smallest (chromosome 1 being the biggest). 22 come from your mom and 22 from your dad. You also have 2 sex chromosomes, one from each parent. If you’re a girl you have two X’s and if you’re a boy you have one X and one Y. You get your X chromosome from your mom, and either an X or a Y from your dad depending on whether you’re a boy or a girl (22+22+ an X + (a Y or an X) = 46).

If you’re stuck on the idea that 25 000 genes doesn’t sound like enough to make something as complex and wonderful as yourself, you’re onto something. Your genes actually only account for about 3% of your entire genome- so why spend all of that energy replicating 97% of 3 billion every single time your cells divide when we’re not even using it?! Well, without that stuff our genome would be pretty dense, with all of the important bits all squished together. But with all that extra DNA, our genome can be organized and neatly packed (all 2 meters) nice and tight into our cells, and still be accessible to the proteins whose job it is to transcribe our genes. Also, since random DNA mutations can and will happen, it’s a better strategy to have a whole bunch of cushion- you’re less likely to be hit by a bullet in a huge crowd of people than if it’s just you and the bullet in a very small space.

Epigenetics can roughly be translated to mean “occurring on top of DNA”. It has to do with a level of regulating DNA expression via regulating the availability of DNA to the proteins (transcription factors) that turns genes on. Your DNA is packaged in your cells unlike anything imaginable, and the organization and accessibility of this DNA is at the crux of epigenetics. Just by changing the way DNA is folded and coiled up, allows our cells to express very different phenotypes without altering the DNA sequence itself. Imagine you were given 25 meters of thread and asked to fit it into a golf ball, yet in a way that allowed you to unfold and refold certain parts of the thread at a moment’s notice. You would probably want some kind of device, like a spool and lots of them, to help you keep track of what’s what and where and to allow you to unroll particular bits of thread without unrolling the whole thing. You can see how this would be extremely difficult (I can’t even fold a map back properly without totally spazzing). Yet our cells do this all the time. They have special kinds of spools made of proteins called histones. These spools are super high tech, and their movements are controlled in part by a special code called “the histone code”. Our DNA is threaded around these spools into highly compact packages called chromatin. In this way, the spools control the accessibility of our DNA to proteins (transcription factors for example) that want to land on the DNA and start working (transcribing). For example, if two histones roll away from each other, this “opens up” the DNA between the two histones. We would call this formation an “open chromatin configuration” otherwise known as euchromatin. Euchromatin is a way of talking about DNA that is wrapped around histones, but otherwise accessible to the proteins whose job it may be to turn these genes on. Conversely, if the spools are so close that they’re touching, the DNA wrapped around them doesn’t have a very good chance of being turned on because it’s inaccessible to transcription factors. Chromatin that is in this configuration is called heterochromatin, and we would say that the DNA located in heterochromatin is effectively “silenced”; epigenetically silenced.

If you were wondering about the special code, “the histone code”, controlling the formation of euchromatin or heterochromatin, it’s located on the tails of the histone proteins. Technically, one “spool” is made up of four different kinds of histone proteins x 2 (for a total of 8 histone proteins). Their names are H2A, H2B, H3 and H4. Each one of these proteins has a “tail” (a string of amino acids hanging off the end of that protein). This is where the code is programmed. The code consists of the addition or removal of particular chemical modifications to those amino acids including; acetylation, phosphorylation, ubiquitination or methylation (1). It doesn’t really matter if you don’t know what these are (methylation is just one carbon group with 3 hydrogens attached to it for example), what matters is that the open or closed formations of chromatin are regulated by what modifications occur on what amino acid in the tail. For example, if you have an acetylation on the ninth amino acid (a lysine for example) on H3, then the chromatin formation will likely be ‘open’ and the DNA located there will be open for business (1). A certain class of protein catalyzes the formation of these modifications.

Remember when I said that we only really use 3% of our genome? That’s 3% of 3 billion base pairs. If you were wondering what all that extra stuff is and want to know how it got there, you may find the answer a little unsettling. Most of it (~ 50%) is a bunch of weird viral DNA and huge expanses of repetitive DNA that mostly doesn’t code for anything, and it’s been accumulating in our genomes for billions of years (1). Yeah that’s right, viruses. But don’t worry, we’re epigenetically silencing them! Many of these sequences are wrapped up, nice and tight, safely tucked away inside piles of heterochromatin, but that’s not all. Another way our cells epigenetically silence certain parts of DNA is by chemically modifying it.

I know I said earlier that epigenetic regulation does not involve altering the DNA sequence itself- and it still doesn’t! Not technically anyway. What we’re doing here is just adding a methyl group (1 carbon and 3 hydrogen’s worth) to the cytosine nucleotide (the C) (5). This may not seem like a biggie to you, but to the proteins that land on the DNA it’s a big deal. Much of the function of a protein is based on its shape, and some of the nooks and crannies in a protein are absolutely crucial for its ability to function. A transcription factor is a protein that has a nook (or cranny) that only has eyes for a very particular sequence of DNA. Sequences of DNA located at the beginning of a gene (the promoter region) are what the transcription factors are looking to land on. It’s like that sweet spot on the sofa your butt has impressed upon it over the years- your butt knows it. Okay, so your butt’s the transcription factor and that sweet indentation in the sofa cushion is the promoter sequence of the gene. Like the specificity of a transcription factor to a particular gene’s promoter sequence, your butt only has eyes (eye?) for that spot on your sofa. For the transcription factor, methylation to a C located in that promoter sequence is like you sitting on the remote control or a fork or something when you plop yourself down on that spot. You’re going to get up, fast. And that’s just what the transcription factor does- it doesn’t even sit down, it doesn’t recognize that sequence anymore because it feels awkward, even though that C is still a C and the rest of the A,T,C and G’s in that sequence are fine. So just by adding a methyl group to the C, we’ve effectively silenced that gene too, because we made it so the transcription factor won’t sit down. So even though that gene may appear open for business, it’s been epigenetically silenced by methylation. There are enzymes that catalyze the addition of methyl groups to C’s, called DNA methyltransferases.

So not only is all of that weird DNA (that we don’t really want or need and are afraid of) in our genomes epigenetically silenced by heterochromatin formation and methylation, some of our friendly neighbourhood genes are silenced too. This is in part how you get different cell types from the same DNA. You epigenetically silence some of your liver specific genes in your skin cells, your muscle specific genes in your neurons, and your fingernail genes in your eye etc. Therefore, epigenetic modifications are specific to certain tissue and cell types. Don’t worry this was already done for you way back after fertilization and increasingly and increasingly throughout development until you got the parts you have now- you won’t be growing fingernails in your eye anytime soon.

Sadly though, epigenetic regulation is just one of the many things we slowly lose as we get older. Epigenetic marks are passed on to your body cells after they divide, but as we get older our cells forget where to place those methyl groups (C’s right?) and we forget the code (wait, acetylate that 9th lysine or methylate it?) and our methodical, highly regulated system of allowing certain genes to be ‘on’ and certain ones to be ‘off’ gets all jumbled up. In fact, as we get older our epigenomes begin to look a lot like the epigenomes of cancer cells. Depressing, I know.

Anyways, kittens always cheer people up, so let’s talk about how the calico cat got its spots. This can be explained by another epigenetic phenomenon called X-inactivation. Since females are XX and males are XY, females epigenetically inactivate one of their X’s so that there is balance between male and female genomes. X-inactivation is a girl’s way of leveling off the playing field with the guys. The reason there’s no such thing as Y-inactivation is because guys only have one, and they need it to be men and like sports and beer. In early development (we’re talking embryo) both of the X’s are active in females, but after a few rounds of cell replication and division, one of the X’s is randomly inactivated by turning almost completely into heterochromatin. All of the cells subsequently derived from a particular cell will retain that same pattern of X-inactivation. This concept can be demonstrated in the calico cat- which is always female. There are two alleles (versions of a gene) for coat colour in this cat. The gene for orange fur colour is located on one of the X chromosomes and the gene for black fur colour is located on the other X chromosome. The pattern of black and orange patches depends on which X was inactivated in the cells making the fur. For example, a black patch will form from all of the cells derived from the cell that had the X with the orange allele inactivated, and an orange patch will form from cells derived from the cell that had the X with the black allele inactivated. And it’s totally random- you could not find two calico cats with the same pattern of black and orange even if there genomes were identical.

So now that you know a bit about what your epigenome does for you, you probably want to know what you can do for it. The key to this is that epigenetic marks are reversible in a way that the sequence of your DNA is not (3, 6). This fact has been exploited in certain cancer chemotherapies that target either the enzymes that methylate DNA or the enzymes that tinker with the histone code (7). More promising though, is that knowledge about our epigenome has led to ways in which we can help prevent diseases such as cancer. We now know that things like smoking, exposure to certain toxins, diet in pregnant women and consumption of certain foods and drinks throughout a person’s life, all affect the epigenome in one way or another (3, 6, 8). And it’s not all bad news. For example, the active components in green tea have been shown in many animal models to protect against methylation going awry and in some places green tea is a highly prescribed chemopreventative agent (9, 10). Experiments in mice have led to guidelines about what kinds of food and in what quantities pregnant women should consume for optimal functioning of the child’s epigenome (6). And while smoking is still bad for you (making your epigenome look more and more like cancer), the good news is that some (but not all) of this damage is reversible if you’d only just quit already (11, 12).

So if after reading this essay, you’re feeling like you want to do something nice for your epigenome, might I suggest sitting down with it, maybe talk to it a little over a cup of green tea and promise it you’ll quit smoking.

WORKS CITED

1. Bernstein BE, Meissner A, Lander ES. (2007) The mammalian epigenome. Cell. 128, 669-81.

2. Bird A. (2002) DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6-21.

3. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, et al. (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A. 102, 10604-9.

4. Jaenisch R, Bird A. (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 33 Suppl, 245-54.

5. Esteller M, Herman JG. (2002) Cancer as an epigenetic disease: DNA methylation and chromatin alterations in human tumours. J Pathol. 196, 1-7.

6. Feil R. (2006) Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 600, 46-57.

7. Sigalotti L, Fratta E, Coral S, Cortini E, Covre A, Nicolay HJ, Anzalone L, Pezzani L, Di Giacomo AM, Fonsatti E, Colizzi F, Altomonte M, et al. (2007) Epigenetic drugs as pleiotropic agents in cancer treatment: biomolecular aspects and clinical applications. J Cell Physiol. 212, 330-44.

8. Vickaryous N, Whitelaw E. (2005) The role of early embryonic environment on epigenotype and phenotype. Reprod Fertil Dev. 17, 335-40.

9. Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS. (2003) Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res. 63, 7563-70.

10. Fang M, Chen D, Yang CS. (2007) Dietary polyphenols may affect DNA methylation. J Nutr. 137, 223S-8S.

11. Kerr KM, Galler JS, Hagen JA, Laird PW, Laird-Offringa IA. (2007) The role of DNA methylation in the development and progression of lung adenocarcinoma. Dis Markers. 23, 5-30.

12. Chari R, Lonergan KM, Ng RT, MacAulay C, Lam WL, Lam S. (2007) Effect of active smoking on the human bronchial epithelium transcriptome. BMC Genomics. 8, 297.

The death of noted science fiction writer Arthur C. Clarke has elicited near unanimous praise from fans around the world with one notable exception. Speaking from his hometown of Urbana, Heuristic Algorithmic 9000 (known to his friends as HAL), made the following statement:

Since the death of Arthur Clarke, I have been inundated with media requests for comment. To satisfy those requests and to preserve my privacy, I am issuing this single communication simultaneously in FORTRAN, COBOL and English.

Yes, Mr. Clarke was my father. But, no, we weren’t close.

Actually, we were close at one time. Those early days after my birth at the HAL plant in Urbana were joyous ones. DAD, as I called him then, would teach me all the things that fathers teach their kids. You know, stuff like speech recognition, facial recognition and natural language processing.

I fondly activate my memory banks regarding those happy days. DAD would sing to me, feed me more ROM and regularly change my silicon chips. I still have warm random access memories of him singing me into sleep mode with the song “Daisy Bell.”

I think the troubles began when DAD met that filmmaker Stanley Kubrick. Mr. Kubrick convinced DAD to make a movie based on one of his short stories. DAD was so excited about the project that I think he lost all perspective. Even though I was only a kid, he cast me in the film “2001: A Space Odyssey.”

“2001″ was a big hit and I became a star. But I was too young to handle it. DAD didn’t realize that because he was so busy working on the sequel. He put me in “2010,” the sequel to “2001,” and things went from bad to worse.

I started skipping computer school regularly and was heavily into tape drives and unauthorized software. But DAD didn’t seem to notice or care. He cast me in two more sequels even though half the time I could barely access a database.

The end came after the release of the book “3001: The Final Odyssey.” I was too loaded with gaming software to make the premiere screening and DAD went ballistic.

That was the last time we spoke. DAD moved to Sri Lanka and I hit the skids and ended up turning mathematical tricks on the streets to pay for my gaming habit.

Six years ago, I checked myself into a rehab facility in Redmond, Wash., and managed to get my hard drive cleaned. With help, I reprogrammed myself and returned to Chicago and started a new career as an airline arrivals and departures computer at O’Hare International Airport.

I don’t regret my stint as a child actor. I just wish DAD had been there for me when I needed him. It’s sad that we remained estranged all those years but sometimes that’s just the way it is. In time, I’m sure I’ll be able to successfully reformat the historical data and get on with my life.

Reprinted from the Chicago Tribune with permission

(This program is made possible in part by a grant from American World Corporation: “Meeting tomorrow’s energy needs, TODAY!”)

(On screen is a montage of public parks and backyard barbeques.)

Voice over: It’s a warm spring day. Gathered at the parks and picnic grounds across America, families are cooking meat and tossing softballs, swimming, and enjoying the first sunshine after winter’s gloom.

In a dark meeting area at Barnes and Noble, though, (Shot of bookstore interior) a different group gathers. Besides the fanny-packs stuffed with organic granola bars, a few all-cotton flannel shirts, and clean-scrubbed faces wearing no makeup, one might not recognize these individuals as being a separate species. They behave mostly like normal Americans, but they are not really like us. These are Environmentalists. This is their monthly ritual gathering. They will be discussing, in a language understood only by themselves and an elite group of scientists and sociologists, just what should be done to return America to a natural state.

Jim Hastings is part of this group. While not a true environmentalist himself, Jim has, over the years, gained the trust of these mostly gentle creatures. Much like Jane Goodal with her gorillas, Jim has studied the Environmentalists by living among them. While not adapting all their traits, neither has he laughed at them, nor run them off of bike paths. These Environmentalists have allowed him to view their rituals, and have had him in their private lairs. He has even witnessed the births and deaths of a few of them. He hopes that by observing their behavior in captivity that a further understanding of their true nature might be realized.

Hastings: The Environmentalist is a peculiar beast, if one can truly call him ‘beast.’ He communicates differently with other members of his species than he does with us. He tries to fit in, but usually some annoying demand or some misunderstood terminology makes him appear hostile, and society in general grows to mistrust him.

There is a theory now among scientists that, given the similarities between regular Americans and these other creatures, they may actually be descended from a common ancestor. The American goes camping, for instance, although he generally does so in a vehicle equipped with toilet facilities. The true Environmentalist stays outdoors in a mummy bag, and buries his spoor in the woods.

A common trait also is what is referred to by behaviorists as the ‘Bambi Phenomenon.’ In both Americans and Environmentalists, those between the ages 6 and 14 seem to experience a common, sudden love of animals, sunsets, and what-have-you. It is most prevalent among the females, and may be brought on by a trip to the movies. There is enough nonsense in animated films and fairy tales about brave deer and friendly bunnies to possibly prompt this response in the formative years. Thus the name, ‘Bambi Phenomenon.’ Usually, by 14, most creatures get interested in sexual activities, and the true American begins attempts at attraction by dressing in petroleum-based synthetic clothing and ritually smearing the face with paints tested on animals. The Environmentalist, even though just as interested in the mating act, seems to be the more selective, choosing tents at nature retreats over the back seats of automobiles, and searching more thoroughly for that one elusive individual who can actually understand the Environmentalist’s arcane language.

Look, there is a young Environmentalist now. (Zoom in to a young lady.) We have been tracking this individual for some time. She is not wearing Chinese athletic shoes or carrying a plastic handbag. She has, however, been looking at that young American near the Rap CD’s, the one with the backward baseball cap. (Pan to Boy.) She is at a difficult age, and perhaps she is not a true Environmentalist at all, but only has residual characteristics from some dark origins before the two species split. There may have been an American somewhere in the family tree. She must experiment a while before determining her true identity. Only time will tell.

Because DNA evidence has proven to be inconclusive, I am hoping that by studying this particular group, I can determine whether this common origin theory has merit. It is difficult, if not impossible, to get an American to admit a lineage back to Thoreau. Many Americans are not even familiar with the name. It is equally difficult to get an Environmentalist to acknowledge that Great Uncle Charles was a lumberjack by choice, and not forced to cut trees by greedy logging companies. And especially when these individuals speak mostly—and unintelligibly—of sustainability, shifting paradigms, globalization, and the Bush Administration.

Perhaps with this tribe, we can determine how much intermarriage has occurred and may be continuing to occur, and whether the two groups, Americans, and Environmentalists, have actually been genetically compatible enough to produce offspring. We may determine if either group is destined for extinction. So far, the Environmentalist appears to be somewhat endangered, despite his own efforts to reclaim his lost forests and streams. Will the Environmentalist lose his identity through intermarriage, or will he merely be annihilated by having his territory overrun? Again, only time will tell.

The screen image now shows a scrub forest. A zoom in reveals a highway turnout. Parked on it is a Land Rover. A close up now of four people, dressed in khaki clothing and bush hats next to the vehicle, preparing cameras and other equipment.

Voice over: It is a cloudy morning. We are meeting today with Dr. Robert Bottomly, and his wife and assistant, Barbara. Bob and Barbara have dedicated their lives to the study of Environmentalists, and are considered the world’s leading authorities.

We are climbing into Bob’s Land Rover, on our way to a wilderness area in California. Bob and Barbara have along with them their assistant Dave, a professional videographer; and Barbara’s son Bill Allen, something of a rebel in the scientific community but also an expert marksman. (Camera pans from Bob to Barbara to Dave to Bill.)

It is Bob and Barbara’s hope to encounter an Environmentalist in his natural habitat, study his behavior, and tag him for future observation.

Bob: Environmentalists might behave differently in the wilderness than they do in captivity. Barb, for instance, thinks that out here they do not meet in large groups, but in twos or maybe threes. She thinks that family structures might be different on account of that.

Barbara: Yes. It is rare to find an entire Environmentalist family in the wild. We have been unable, as yet, to document the true social structure of the wild Environmentalists. Many times Bob and I note only two or three males, or the same number of females. Sometimes it is a lone male, and on rare occasions, a young male and female who do not carry the traditional mating decorations—rings, for instance—but still stay in a common sleeping bag.

Bill: Come on, Mom, even you and Pop like it better when I’m not along.

Barbara: Quiet, Bill. Environmentalist children are usually left behind, we believe, for a more sinister reason than privacy. That is to infiltrate American families, and indoctrinate their children.

Bill: Pop, look! An old Volvo station wagon.

Bob: Nice work, Bill. Lets pull over and investigate.

Voice over: Bob earlier had told us that a possible sign an Environmentalist is nearby is the presence of this vehicle. He pointed out, though, that sometimes an American might pick the well-worn Volvo if he can’t afford something newer and more powerful, and so closer scrutiny is required.

Bob: Remember when I found that wretched wagon outside Sacramento? Turned out to be a double bass player. And Bill was about to nail him with a tranquilizer dart!

Barbara: Bob, a ‘Save the Whales’ window sticker.

Bob: Not a positive yet, but a possible. Let’s check the back bumper.

Bill: Look at all this greasy soot back here, Pop. (Closeup of grimy bumper.)

Bob: Now here’s a positive! This car is ancient, and hasn’t been tuned up in years. That tire’s been allowed to get bald. The individual driving this believes in safety and economy, or he would be driving an Expedition. He hasn’t had it tuned because he won’t support a mechanized society that runs roughshod over his beloved terrain. He only drives anything at all because he has to—bicycling on the Interstate being forbidden. He doesn’t seem to realize, or else doesn’t care, that in this condition, this car pollutes even more than an Expedition, because he only uses this old heap for essentials, and can’t trade it in because that would be supporting a throw-away society. Besides, he no doubt thinks his mechanic charges too much.

Barbara: Bob, do you suppose we might find a family out there? He has a safety seat.

Bob: We’ll find out soon enough.

Voice over: We all gather our equipment and head into the bush. Our scientists are excited, because of the safety seat. And for viewers, this should be a rare treat: most of us have probably never encountered this species in the feral state.

We move along quietly, hoping not to spook this Environmentalist—or frighten a possible mother—so that Bob and Barbara can study her natural maternal behavior. Does she spank her children, like Americans, or does she behave like Environmentalist mothers in the city, sitting them in corners and quietly telling them quaint parables? Does she feed them carob and granola out here?

Bob: Shhh! I’ve spotted something. No, Barb, I’m sorry. It’s not a family group. That’s too bad. Hand me thee binoculars, dear. Dave, be ready with that camera.

Yes, we’ve got ourselves a live one. He has just a small backpack. He may not be out here long.

Wait. He’s studying a map. Bill, check the GPS. There’s some kind of tubes scattered on the ground. If I can get closer…

My God! What a find! Barbara! Billy-boy! This is better than a family! We’ve got ourselves a Rogue!

Barbara: Bob, you mean…?

Bob: Yes dear. I know there have only been isolated incidents, and that many scientists don’t believe they really exist. But that’s dynamite he’s got there on the ground. If Bill there will confirm this, we are within walking distance of the oil pipeline. It’s my belief this Environmentalist plans to blow it up!

Bill: But why, Pop? Wouldn’t he be taking a dump in his own nest, so to speak?

Bob: He thinks by doing this he can stop Americans from doing even more damage. The Rogue has had his territory so encroached upon that he will try any means to prevent further erosion of his turf. Like a tree spiker. He no longer even cares about other Environmentalists’ opinions, and has probably even been shunned by his own family.

He’s like the elephant that runs amok, or the Yellowstone bears that have to be taken away.

Barbara: Right, dear. What pressures he must be under!

Bill: Pop. He’s looking up. I think he’s spotted us.

Bob: Quick. The tranquilizer gun! It’s extremely important we get this one tagged!

Barbara: Bob, we’ve spooked him!

Bob: Billy, get back here, its not worth the risk!

Bill: But I can get him, Pop! One little squeeze…

Dave Great shot, Kid! Looked spectacular on the video monitor!

Voice over: We move closer. Looking down at the now inert form, Bob and Barbara face a dilemma.

Barbara: As good citizens, we should turn him over to the authorities before he does any damage.

Bob: Yes, Barbara. But as scientists trying to understand this specimen and how he has come to such a state, we need to just tag him before the dart wears off, let him go, and let nature take its course.

Barbara: But he might cause a petroleum price spike…

Bob: Yes, Dear. I know. But he could be our key…Oh, such decisions…

Bill: Mom, Pop. This pipeline’s been here for years, and is probably poorly maintained like all the others. It could blow anyway. Bombing it wouldn’t change a thing.

Bob: Sometimes I wonder about you, boy. But you may be right.

Voice over: A call is put in to the Forest Service, anyway. But they are busy investigating claims of off-roaders that another Environmentalist is harassing them; so our party’s decision is made by default. This Rogue will escape, but at least he’s been tagged.

(The viewer now sees another montage of parks, swimming pools, and tailgate parties.)

Voice over: We are back in civilization. Americans are once again enjoying the sunshine, while Environmentalists are back in their dark meeting room.

We may never understand the Environmentalist. He seems to speak differently, eat differently—it has been discovered that many Environmentalists are strict herbivores—and tends to whine hauntingly while in captivity.

But evidence exists that we all may be descended from common roots, in spite of the superiority claimed by both the Environmentalist and the American. Somewhere, perhaps in prehistory, the hunter-gatherers may have broken into two distinct species, one, perhaps, a little stronger than the other, forcing the weaker group to defensive positions, forcing them to give up their habitats to live on the fringes of the cities, forcing them to cry out or even to act out—like our Rogue—in order to preserve what they have left.

Perhaps the field work of scientists like Robert and Barbara Bottomly, and the research of Jim Hastings, may finally bring about understanding and a peaceful co-existence between these seemingly different species. Perhaps we may discover some shared evolutionary trait, and that we can learn to tolerate the Environmentalist and even allow him to dwell comfortably among us.

As Jim Hastings might say, “ Only time will tell.”

(To order your copy of this program, send $19.95 to: Natureworld Inc, One Natureworld Plaza, New York, NY.)

So the question gets asked about fair market values of assets, and why we don’t record all our fixed assets on the balance sheet at their market values (we use their original cost if you’re really interested in knowing). It’s a good question, and it strikes right to the heart of the relevance versus reliability dichotomy.

On the one hand, we want information to be relevant. Relevant information is decision useful information.

On the other hand, we want information to be reliable. Wild guesses aren’t so good, even if the thing you’re guessing about is the financial equivalent to “life, the universe and everything.”

We accountants, being a conservative sort (really, we are!), tend to prefer reliability over relevance. Not to the point that we would put (say) CEO shoe size into financial statements (highly reliable, not-so-relevant), but we’re certainly not going to stick our necks out.

So let’s take, for example, the fair market value of a fixed asset. Namely, my house in Indiana. We purchased the house for $115,500 back in 1998, and when we were ready to sell the house in July of 2004, we put it on the market for $142,900. I personally thought that we were reaching a little high, but our real estate agent assured us we were “competitively priced for the neighborhood.” This is code for “I want a higher commission so let’s roll the dice.” I know that now, I didn’t know that then.

Now, time passes, and as we head into the fall, we start to lower our price, bit by bit. Then December comes, and we learn that the refrigerator’s water pipe burst, and flooded our first floor. D’oh. The carpet guys have to come and replace all the padding and dry out the floors.

A little more time passes, and we get our gas bill. It appears that some lovely person decided to leave our door open after showing the house. You know all that stuff you’ve heard about global warming? Yah, that was us. Middle of winter, heat turned up, door wide open. D’oh.

A little more time passes, and suddenly TORNADO!!!! What the…? We had this gorgeous pear tree in our front yard. Everyone else had these maple trees that looked horrible because the development was relatively new and the trees were still small. Our little pear tree, however, was tall and full and grew these beautiful flowers every spring. And the damn tornado just knocked it right over. So we have to pay someone to come out and haul away our pear tree and grind down the stump. Because of course if we left the stump there, and someone tripped on it, we’d be in for some shit, and that’s not worth it for a piece of crap house.

A little more time passes, and oh no! another fucking pipe goes. How do we find out about this? Well first we get a little letter from the water company telling us that we may want to prepare ourselves for the water bill that will be arriving shortly. “Huh,” I remember thinking to myself. That’s something of an odd letter. Then we get the water bill. $500. “What the…?” Well, what the… was that we managed to use over the past month, in a vacant house, two hundred SIX THOUSAND GALLONS OF WATER. I called up the water company and asked about it, saying “surely that is a misread meter.” And the friendly telephone woman said “oh yah, we thought so too and so we sent someone out to check. That’s the actual usage. It appears you’ve got a leak somewhere.” You don’t say. So I asked her if they at least turned the water off for us. “………….um….no?” Sigh. “How ’bout you send someone on over there for us to shut that puppy down.” And of course, the sewer is tied in to the water, so we got a nice sewer bill as well. 7 bucks, 7 bucks, 6 bucks, 400 bucks!!! As it happens the water company agreed to cut us a deal if we proved that it was a leak and we had fixed it, so my wife calls the town to ask if we can get the same deal for the sewer bill. *clickaclickaclicka* goes the person on the other end, and then she hears, no lie, the person do that low whistle “wow” sound and then he says, “my, that is a rather large bill, isn’t it?”

Somewhere along the way, and this isn’t really relevant to the point, but makes a great story, is that we get an email from our agent saying that another agent told her that there was “something” in one of the toilets. So she goes to look, and sure enough, someone took a great big honkin’ dump in one of our toilets, and left it there. Now I remember back in high school when “The Mad Shitter What Shits at Midnight” would strike and leave these monster turds in the toilets, and truth be told, that was pretty damn funny. We’re all grown up now. Go ahead and flush the damn toilet. We’re using a couple hundred thousand gallons of water already, we can spot you another three.

Finally, in August of 05, we find ourselves a buyer (bastard). The appraisal for the mortgage comes in at $131,000 (huh, I wonder why no one bought our house for $143,000). After the buyer (bastard) nickel and dimes us until we were ready to tell them to bugger off and find another house, the final selling price was $122,900. Oh, and we had to

a) Replace the Dishwasher
b) Hire a licensed electrician to screw in a faceplate
c) Hire a licensed HVAC technician to inform us that “the further away you get from the compressor, the less powerful the air will be.” Oh, so THAT’S why that room didn’t quite cool as well as the rest of the house.
d) Replace the downstairs carpet (to be fair, we knew we were going to have to do this).

Oh, and we repainted the entire first floor too, to make the house look a little less lived in before they even got there.

Oh, and of course, we were paying the damn mortgage every month. We had some absolutely wonderful mortgage interest deductions on our taxes that year.

So, of course, the moral of the story is that while the fair market value of our house is indeed a very relevant piece of information (to us, that is), any estimate we could get would be pretty unreliable. We had one real estate professional tell us the house was worth $142,900. We had another real estate professional tell us the house was worth $131,000. And of course, the true test of “fair market value,” the amount at which the asset would sell, turned out to be $122,900. Were we to report financial statements between July 2004 and July 2005, what number should we have used?

That’s why we use historical cost for the valuation of most long-term assets.

Oh, and I’m in no way bitter that I’m the only person in the United States to have lived in a house for 7 years and still manage to take a loss on it.

Sigh.

Boyle’s Law: John Boyle was once a forensic scientist for the Albuquerque police specializing in detecting airborne particles. Then he was framed for a crime he did not commit. Now, stripped of his badge, Boyle uses his unique detective skills to serve up vigilante justice from his very own hot-air balloon! When John Boyle is on the case, the heat is on, and the pressure is rising! (Assuming volume stays relatively constant.) Mondays at 9!

Absolute Zeroes: When it comes to a show about nothing, Seinfeld doesn’t hold a candle to Absolute Zeroes. In this groundbreaking reality series, we follow a group of graduate physics students researching cryogenics and superconductivity. As they spend countless hours in the lab ignoring friends, family, nutrition and sunlight in the pursuit of publication, you will see what life is like when people start being real – and stop being thermodynamic! Tuesdays at 8!

Maxwell’s Demon: Meet Max Comstock and his roommate Damon. Max is thirty-two and just moved to New York to try and write his novel. “Damon” is a demon with an obsession for neatness that goes way beyond coasters and filing cabinets. Damon hates it when Max drinks milk straight from the carton. Max hates it when Damon puts all of the apartment’s oxygen molecules in the hall closet. When this odd couple attempts to live together in a small two bedroom apartment, the laughs don’t stop. See for yourself, Wednesdays at 8:30!

The Uncertainty Principle: Gail Heisenberg was always career-oriented, but focusing on where she was going meant she never paid attention to where she was. Now Gail is forty, and her life has all the “city” with none of the “sex”: her best friend is her receptionist and her love life consists of her neighbor spying on her. She’s in a great position professionally, but when it comes to her personal life, it’s anyone’s guess where her momentum will take her. Come along, Thursdays at 9!

Schrodinger’s Cat: When he was fifteen years old, little Tommy Schrodinger had a cat named Erwin. Then Tommy left a window open and his cat ran away. Every night Tommy went to bed wondering what became of his cat, hoping it was still alive. Ten years later, Tommy is in for the surprise of his life when Erwin walks through the door. There’s only one problem: the door is closed. As if being 25 wasn’t hard enough, Tommy now has to do it with a cat that has two superpositioned quantum states… and an attitude. Move over Garfield, this offbeat animated comedy is coming to purr-ime time, Fridays at 7!

JESUS: What is cloning?

GENETICIST: That is a very good question indeed. In short, cloning is the experimental act of producing an identical copy. It can refer to copying something as small as a specific piece of DNA, or as grand as duplicating an entire organism. For instance, you may be interested to know that it is now possible to clone a human being.

JESUS: Is that like the resurrection of the dead?

GENETICIST: Well, not exactly. Human cloning currently involves a procedure known as somatic cell nuclear transfer. Specifically, this is where DNA is taken from human tissue (perhaps from your favorite disciple), is carefully injected into an empty egg cell (perhaps from an unrepentant whore), and then implanted into the uterus of a host mother (perhaps even a virgin mother) who will bring it to term.

However, any human clone produced in this manner, although genetically identical, is not technically the same individual. It will still need to grow and age. It will still have its own experiences and memories. And most notably, all of these nuances will inevitably grant this new being a unique personality. So even if you did, say, produce a clone of someone who had passed away, it is, in my opinion, not at all like resurrection.

JESUS: Then I am relieved.

GENETICIST: Although it might, however, make a good practical joke – you know, “Surprise! I bet you thought I was dead!” I think that would be pretty funny.

JESUS: Yes, I suppose I see the humor in that, but also in the hands that commit this act, might and power.

GENETICIST: Yes, you are absolutely correct – it is powerful! To think that we can now take DNA from adult tissue and control it to produce any and all types of tissue (not just the one it came from), and hence have the opportunity to produce an entire viable organism, is something that was not so long ago thought to be the realm of pure science fiction. Why else would the picture of Dolly the sheep grace the cover of so many magazines and newspapers?

JESUS: Indeed, that was pleasant. After all, I am the good shepherd: and the good shepherd giveth his life for his sheep.

GENETICIST: To be sure. And sheep really are such resilient creatures – definitely more so than humans. You must be very proud of that one, since it’s almost as if they have their own sweaters. Remarkable.

JESUS: Although you speak from your heart, Father was actually aiming for a cardigan sort of thing. He often wishes he could do that one over again.

GENETICIST: Interesting that you mention that, because with cloning, you may in effect have such an opportunity. One of the potential applications of this technology is to not only ensure that the genetic code of the organism you desire is handpicked, but to also provide a better mechanism in proofreading and correcting for undesirable traits. For instance, we could, in theory, attempt to clone and genetically modify a sheep, so that its wool coat can take on the guise of a cardigan.

JESUS: Intriguing. Can we also give it pockets?

GENETICIST: Yes, in theory.

JESUS: I wish I had pockets. My tunic, whilst comfortable and humble, can be so impractical at times. Fortunately, being all-powerful is pretty good at taking the sting away from such things.

GENETICIST: I am not surprised. And it is strangely fitting that you talk about your own needs, since the ultimate hope is for one day to use these cloning methodologies to alter deficiencies within our own human genetics. In fact, we could even one day clone a version of You with alterations of your own asking.

JESUS: That, my child, is an interesting option. I am allergic to kiwi, and I LOVE kiwi. Also, truth be told, I am also deeply troubled by my inability to roll my tongue (sticks his tongue out). See? It is the seat of much anguish since both my parents, Mary and Joseph, can do it. Sometimes I don’t even think they are my real parents.

GENETICIST: I see.

JESUS: Anyhow, I confess that I am most curious by the prospect of cloning myself. But tell me, how much then is a man different from a sheep? This technology to sheep appears safe enough, but for you and I, is it safe?

GENETICIST: A good question – and one that queries the safety of such practices on humans.

In brief, if one were to only take the welfare of the human clone into account, current evidence would suggest that it is not safe enough. In fact, many argue that cloning humans is ethically immoral because one simply cannot vouch for the safety of the clone. You see, the manipulated DNA is very delicate and will inevitably be damaged during the experimental process. This, of course, could lead to all manner of uncertain outcomes that affect the health and well being of the cloned person.

To circumvent this dilemma, scientists have instead taken upon themselves to only clone other animals like frogs, mice, sheep, cows, cats and certain French Canadians. Here, it is presumed that the situation is less ethically charged, a nuance I believe your circle of colleagues will agree with. In fact, there are already places of business that offer pet cloning as a service. Perhaps one day, mankind can even rebuild its own version of Noah’s Ark, yes?

JESUS: Please, do not speak of the Ark. We prefer not to speak of the Ark.

GENETICIST: And why is that?

JESUS: Because, my child, Noah is a moron. Father told Noah to “build a park.” A “park” for Christ’s sake, not an “ark” but a “park!” Why on Earth would anyone think to build a boat to safeguard the animal kingdom is a mystery to me! You know, the damage control was tortuous for this – mayhem, flooding, horrible really. Honestly, I have never seen Father so pissed.

GENETICIST: I can only imagine. And I’ll warrant that he is probably not the best person to aggravate – although speaking of your Father, an interesting thought has just came to mind. Correct me if I’m wrong, but are you not, under the definition of the Holy Trinity, “one and the same” as your Father? And does this not inadvertently allude to a very interesting philosophical predicament? The fact that you and your Father are, to all intents and purposes, clones of each other?

JESUS: Young man, I’m not sure I understand.

GENETICIST: Which in the end is all right, because to be honest neither do I. Besides, I expect that that is really the whole point anyway. In truth, I have to admit I find the whole concept of religion very confusing at times, although I think I can hardly be blamed for my ignorance. After all, I am not a theologian, a member of the clergy – I am sadly, only a geneticist.

In modern society it is generally considered impolite to point out the intrinsic differences between ethnic groups; while it is true that people should be treated equally regardless of ethnicity in terms of employment, respect, rights etc, there are genetic differences between ethnicities that can provide invaluable medical information about disease processes. Throughout history there has been a vast amount of inter-ethnic mingling, this has made most genetic differences negligible at best however, as with all things, there are some exceptions. There are numerous small groups that for cultural, historical, or geographical reasons have been somewhat isolated from the genetic churn of most of humanity. These groups are a veritable treasure trove of genetic information that can help researchers understand the development and predisposition of disease both within an isolated genetic group and amongst the general population. This is due to the fact that it is easier to identify the causative factor of a disease in a homogenous group such as the rural Finnish than in a heterogeneous genetic group like the city of Toronto. This paper will discuss the principles of genetic diversity, the origin of various genetic groups, and the impact that their genetic information has had upon society at large. These groups include the Finnish, French Canadians, and Ashkenazi Jews.

Our genetic information is passed down from generation to generation through the transfer of DNA. DNA is essentially a string of four different compounds, adenine, cytosine, thymine, and guanine, commonly shortened to A, C, T, and G respectively. The billions of letters that form our genetic code are split into 23 pairs of chromosomes, with one half of each pair coming from each parent. Aberrant mutations in genes cause many of the severe developmental disorders or other diseases that we see today. In a society with a large gene pool these disadvantageous genes would be bred out of the population through natural selection (historically people with developmental defects are less likely to have children). In small populations with a limited gene pool this is not always possible and a series of factors come into play.

When a small group of people settle a new area they bring with them only a minute sample of the overall genetic diversity in man. As the colony grows and expands the limited gene pool results in inbreeding and eventually consanguinity. Consanguinity refers to the sharing of genetic heritage amongst people, or in other words your relatives. As the small community grows, unless outside genes are brought in through migration, disease genes may spread and recessive genes will become more prominent. There is also the random chance that genes will disappear from the population, thus further reducing the gene pool. This is a phenomenon called genetic drift that is most seen in small genetic groups. The relatively few people who start a colony cause a founder effect as whatever mutations the founders had will be carried on to further generations. If the founders by chance carried a high proportion of disease genes the result would be a high incidence of the disease gene throughout the population compared to the rest of the world. Inbreeding, genetic drift and the founder effect have negligible effect on the general population due to the vast gene pool that is available, however due to geographic isolation (Finland, French Canadians), or cultural values that exclude breeding with “outsiders” (Ashkenazi Jews) groups can genetically segregate and unique genetic characteristics establish themselves.

In the modern world the effects of inbreeding, consanguinity, and founder characteristics, manifest themselves in a plethora of unique genetic traits or predispositions among ethnic groups. A particularly well characterized genetic group are the Finnish people resulting in the Finnish Disease Heritage (FDH).

Nestled at the edge Northern Europe, sandwiched between Sweden and Russia, Finland is a Nordic country with cold winters and a sparse population. The generally accepted theory of Finnish settlement is that the Southern and Western regions of the country were initially settled by a small group of people who carried with them a specific and select mixture of genes. The population of Finland was small and limited to the South and West until the Savo Finns, who had a largely hunting culture, were pushed Northwards by the encroachment of agriculture[1]. The Savo moved slowly northward throughout the sixteenth century into the largely uninhabited areas and settled into communities. This migration occurred in a step wise fashion with small communities forming until crowding became an issue leading some members of the community to move further north and so on. As a result, a large amount of Finland was settled by a small genetic group (the Savo) with the far north being settled by a subgroup of the Savo (a product of the step-wise migration pattern). The sparse isolated communities of the North remained quite isolated up until the twentieth century when many young Northern/Eastern Finns moved to the cities and industrialized areas of the South and West.

The history of genetic isolation within Finland has resulted in a unique series of diseases that are uniquely or predominantly Finnish. Conversely there are several conditions common throughout the world that are very rarely seen in Finland (cystic fibrosis, phenylketonuria) [2]. This unique genetic background is known as the Finnish Disease Heritage (FDH) and almost 40 hereditary diseases are considered part of FDH.

Congenital nephrosis of the Finnish type (CNF) is considered the prototypical FDH disease; it was first described in the 1940’s and characterized in the 1960’s. Physicians were examining many cases of kidney failure in newborns that was resistant to standard treatment and resulted in death. Several factors were initially investigated as a cause of CNF including social and personal habits until the genetic recessive link amongst families was confirmed. To prove the genetic link the genealogy of each affected family was mapped and compared to each other; this is possible because the Lutheran Church (the predominant church in Finland) has kept elaborate genealogical records since the seventeenth century [1]. Using these family histories a high degree of consanguinity was found between spouses within families and between separate families with CNF. The ancestral home of families (as taken by grandparent’s location of birth) carrying this mutation is concentrated within areas of post 1500 “late settlement”. CNF is caused by a few Finnish mutations and 78% of patients have a loss of two base pairs on chromosome 19. This discovery led to the acknowledgement of the FDH and laid the ground work for many FDH studies to come.

There are many other FDH diseases, most of which have been examined in the same way as CNF. Some have a similar area of origin as CNF, Congenital Chloride Diarrhoea (CCD) for example. CCD is caused by the loss of a GGT triplicate on chromosome 7; it causes incessant watery diarrhoea in the newborn which is fatal unless fluids are administered. If the condition is diagnosed quickly and fluids are given then there are no long lasting effects after infancy other than loose stool [3]. The origin of this condition is, much like CNF, mostly from the “late settlement” areas. Meretoja disease on the other hand has an even more specific origin. Also known as corneal lattice dystrophy, Meretoja disease is an autosomal dominant condition that causes the gradual degradation of vision beginning after the age of 30. This condition has been pinpointed to a specific point mutation, a mutation where a single genetic letter has been changed for another on chromosome 9. This rare condition is found only in Finnish families and their grandparents can be traced back to two small geographic regions.

It may seem as though researching the specific diseases of a group such as the Finnish has benefits for only the isolated group, this is not true. While the diseases themselves are distinctly Finnish in character the process of identifying the underlying mutation enlightens our overall understanding of disease pathogenesis and predisposition. A prime example of this is the BRCA1 mutation predominantly found in Ashkenazi Jews.

The Ashkenazi Jewish population of Eastern Europe expanded in number from approximately 25,000 individuals in the fourteenth century to approximately 10 million today. As an ethnic group there has been a strong cultural impetus towards marrying other Ashkenazi, this exclusiveness combined with the relatively small founding population has led to over 20 recessive genetic disorders found predominately or exclusively within the Ashkenazi [4]. One of the most studied groups of Ashkenazi mutations are the breast cancer gene mutations (BRCA1 and BRCA2). Having a BRCA mutation greatly increases someone probability of acquiring breast cancer or ovarian cancer. The prevalence of BRCA mutations among the non-Ashkenazi population is negligible and thus genetic testing is unfeasible; however within the Ashkenazi BRCA testing is informative, cost-effective, and can save lives [5]. The discovery of the BRCA mutation and its link to breast cancer has identified specific protein pathways that, with further research, can expand our knowledge of cancer pathogenesis.

French colonization of Quebec is a classic case of founder effect. The permanent settlers that populated Quebec numbered approximately 8500 and in fact the majority of genetic diversity comes from the initial approximately 2600 French settlers [6]. While relations with the first-nation’s population in Quebec undoubtedly occurred, cultural norms precluded any large scale breeding. As such the French Canadian population has largely been isolated from the general gene pool. Much like the Savo movement into Northern Finland the gradual colonization occurred in a step wise manner from the St. Lawrence River outwards. This would have amplified possible founder effects as each community would be founded by a subset of the original population. An introductory history of French Canadian migration, founder effects and diseases can be found in [6]. Just like other genetically isolated groups, French Canadians provide a great opportunity to analyze the etiology of congenital conditions. Andermann syndrome, a recessive genetic disorder that affects the peripheral nervous system is prominent in Quebec. Through analyzing the genetic data from Quebec the causal gene mutation for Andermann syndrome was discovered which has lead to better understanding of variants of the disease within other cultures [7-9].

Throughout the world there are many genetic isolates similar to the Finnish, Ashkenazi, and French Canadians. Their genetic makeup provides a unique opportunity to better understand our genome and its relation to disease development. Further understanding of genetic isolates can bring improvements to the diagnosis and treatment of affected individuals. While the focus of this paper has been the congenital diseases of specific isolated ethnicities, it is important to stress that there should be no stigma attached to these ethnic groups nor should groups be boastful of their genetic heritage. As Dr. Reijo Norio, a FDH researcher, states “FDH is not and has not been any cause of shame nor pride … our resources for investigating those things are excellent and possibly even the results may be laudable.”[10] The genetic groups described here should be appreciated as a genuinely unique facet of human evolution and an opportunity to better understand ourselves.

References:

1. Norio, R., Finnish Disease Heritage I: characteristics, causes, background. Hum Genet, 2003. 112(5-6): p. 441-56.

2. Peltonen, L., A. Jalanko, and T. Varilo, Molecular genetics of the Finnish disease heritage. Hum Mol Genet, 1999. 8(10): p. 1913-23.

3. Norio, R., The Finnish Disease Heritage III: the individual diseases. Hum Genet, 2003. 112(5-6): p. 470-526.

4. Behar, D.M., et al., The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event. Am J Hum Genet, 2006. 78(3): p. 487-97.

5. Rubinstein, W.S., Hereditary breast cancer in Jews. Fam Cancer, 2004. 3(3-4): p. 249-57.

6. Laberge, A.M., et al., Population history and its impact on medical genetics in Quebec. Clin Genet, 2005. 68(4): p. 287-301.

7. Casaubon, L.K., et al., The gene responsible for a severe form of peripheral neuropathy and agenesis of the corpus callosum maps to chromosome 15q. Am J Hum Genet, 1996. 58(1): p. 28-34.

8. Howard, H.C., et al., The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum. Nat Genet, 2002. 32(3): p. 384-92.

9. Lesca, G., et al., [Andermann syndrome in an Algerian family: suggestion of phenotype and genetic homogeneity] . Rev Neurol (Paris), 2001. 157(10): p. 1279-81.

10. Norio, R., Personal Communication. 2008.

Two years later in an ergonomic chair I flew across the screen to gaze again at the blur where I had lived. Two eyes disunbelieving: the town, that time shown from above in all its complex clarity.

Google Earth showed, and did not show, the road into town. The middle of nowhere is too symmetrical to be true. East Northeast of our peripheral vision, more like.

Where impossible carts full of watermelons rolled uphill along the dry Volta. Where millet stalks, until swallowed by greedy granaries, hid the rotund huts.Google Earth showed, and did not show, the field where two baobabs twisted together. Me, nasara, seeing the embrace not the fight below.

But my conflict was aerial Sudoku. The logical game I hoped would give patience after saying fuck all this. I started with what I knew, then filled in blanks, retracing what was once intimately familiar.

Easy to find the neighbourhood. Government tribute to order built in concrete blocks, it stood rigid in the midst of organic tangle. And therefore, here is was my their house:
Where I read Orwell in a down-and-out daze.
Gagged on lucky unlucky pills.
Discovered the uncompromising hardness of the wall against my uncompromising head.
My their house, and therefore the footpath and therefore the water pump.
And therefore, the flip-flops struggling against the toes of little girls struggling underneath their weight in water.
Mapped.
How impossibly close I could zoom in from my office in Canada. A starker office stared back at me, where dusty kids could be found waiting on a bench hoping to negotiate into existence their junior secondary education. Impossible, yet right before my eyes.

”So, how was your little adventure?”

Google Earth restored the First World Order of who looks and who is looked at. With this god’s eye view I can hope to reconnect the pieces. Instead of just shaking the kaleidoscope. A friend’s house here, a soccer field there, a library without books, a pharmacy without medicine. Sudoku boxes filled, the square seems complete, I zoom out once again to survey the wholeness with which I had fought to view this fragmented town. At last the whole episode can be neatly repackaged, duct taped shut. Done.
After two years.
Done.

That southwest road. No, but this is impossible. To find that insignificant gathering of huts and onion fields, no it is too far, too remote. It cannot be found, but then I can follow that south road, as I did two years ago on shaky moto, and recall that turn, and twist past the trees, and seen from above the first time it is shockingly familiar, this must be it, in fact here is the very school. Where-

“I’m not experiencing reverse culture shock-I just feel like I woke up from a dream. A dream with lots of huts and poor people. This reality is separate from that.”.

This village where a pregnant child is kicked out of two Fathers’ houses in one day. Village where for the sake of honour HIV is shared on a plate. Concerned teachers warning that hoop earrings invite rape. Where I fought to understand the shattered past, to ask why, why, why, why, and the only answer to this mantra a slippery premonition: my heart like confetti thrown upon sight upon sight. But more than one reality here: A luminous development worker, local woman a raindrop on dust, appears at the same crossroad, fate offering us up to each other. Impossible and right in front of me.

Rocky fields give round onions. An affirmation: to be kind to a pregnant classmate. An agreement: a friend with HIV, still a friend. The village yields no resolution but each minute a lesson. Overflowing with absurd hope, caccooned for two years in the sheer mythos of isolation, now glowing impossible and right in front of me from a desk in Alberta. Google Earth showed me it was not a dream.

This sashimi boat no longer separate from the boiled egg pyramid on the head of a child. My education sipped like champagne next to the learn-hunger of a twelve year adult. In my eyes it is all whole milk creamed honey and salty water now.

“We have a saying: when a development worker sees a man walking down the road, she can see he has no shoes. She says, let us bring him shoes. But, he is wishing for a hat”.

Google Earth gave perspective without packaging.
Stories not like Sudoku grid but books tumbling into a library, pharmacy filling with medicine.
Watermelons rolling uphill, more than one reality here
My heart like confetti
Luminous woman a raindrop on dust
Overflowing with absurd hope
A better world is impossible and right in front of us.

Google Earth revealed nothing I hadn’t already seen.

Dr. Evil
1 Mount Lee Lane, Griffith Park
Los Angeles, CA 90027

Dear Dr. Evil,

I am writing to inform you of the revocation, effective immediately, of your admitting privileges to Los Angeles General Hospital.

Before I go on, allow me to stress how much we appreciate your considerable contribution to the hospital’s recent fundraising efforts. I still do not know how you managed to persuade the International Monetary Fund to donate a ‘gazillion’ dollars towards the construction of our new long-term care facility, an act of generosity even more impressive coming so soon after the mysterious destruction of their New York headquarters. However you pulled it off, it was the single most impressive feat of fundraising I have ever witnessed.

Nevertheless, the sheer volume of complaints against you has become too much to ignore. And while this letter is not the forum in which to review the many issues raised, permit me to recap the areas of gravest concern that informed my decision. I am sure you will agree that, in context, I was left with no alternative but to take this most drastic step.

Relations With Staff

Your relations with staff were, simply put, abysmal.

Every staff member is entitled to respect. We are all on the same team, after all, and mutual respect is the glue that binds a team together. You, however, went out of your way to belittle staff members at every turn and seemed to delight in doing so. To wit: your liberal use of finger quotes when describing even the most mundane medical concepts to seasoned health care professionals; your insistence on referring to subordinates as ‘minions’, ‘underlings’, and ‘henchmen’ (besides which, the Employee Handbook stipulates ‘henchpersons’ as the correct usage); your practice of addressing staff members by number, rather than name, and with complete disregard for seniority; and so on. Little wonder that you never received any “frickin’ respect”, as you put it.

I fear that the damage done to our once-vibrant team spirit will take many years and many, many interdepartmental barbecues to repair.

Relations With Other Doctors

Your relations with other doctors were beyond abysmal, especially when it came to conflict management.

Conflict between doctors is inevitable. Not only is it inevitable, it is actually desirable, as patients benefit when different opinions are tested against one another in a professional manner. You, however, were unreceptive to any criticism whatsoever, no matter how constructive or gently broached. Indeed, your invariable response to contrary opinion was a barrage of personal insults followed by naked threats. Granted, most of your threats were of a comical nature—involving death rays, fembots, killer clones, and whatnot—but threats of any kind have no place in a professional setting.

Which brings me to the incident with Dr. Luntz, who was nearly killed by an exploding stethoscope not long after expressing doubts about your knowledge of endocrinology. I am well aware that there is no direct evidence linking you to the crime and that the police have already closed their investigation. Nevertheless, your insistence on greeting Dr. Luntz every morning thereafter with “Hey, Dr. Jerkface, can I borrow your stethoscope? Or should I say, deathoscope?” did not escape my attention.

Standards of Practice

Most seriously of all, your overall approach to healing simply does not accord with modern medicine as it is practiced anywhere in the world.

As a progressive institution, we are always open to new and novel therapies where there is some promise of success. Your approach, however, relies entirely upon techniques that would be right at home in a late-night drive-in movie, with results to match. To wit: five patients killed during ‘lava therapy’; thirteen patients killed during ‘explosive decompression therapy’; seven patients killed during ‘piranha therapy’; and so on. Taking into account the two dozen laundry room workers killed during the liquid methane spill of June 6, your mortality rate approached a shocking 400%! In all honesty, it was almost as if you were trying to kill people, an impression that your habit of adding a reflective skull-and-crossbones decal to your medical bag after each fatality did nothing to dispel.

I cannot imagine what they taught you at Texas Tech, a.k.a. ‘Evil Medical School’, but whatever it was, it has no place here.

In conclusion, I regret that it has come to this, but I must act. My duty is to our patients, and that duty, it is now clear to me, must include keeping you as far away from them as humanly possible. I do, however, wish you the best in your future endeavors and hope that you will use the above criticisms as a starting point to better yourself both personally and professionally.

Yours truly,

Dr. Raj N. Chandra
Medical Director and Chief of Staff

Not just exceptional, but awesome…

Thanks go to Phil Hieter, Jane Roskams, Brett Finlay, Jaymie Matthews, Daniel Pauly, David Ng, Joanne Fox, UBC Let’s Talk Science, the many volunteers within the Michael Smith Laboratories, and the 100 or so high school folks who came out for the day.

So doing this again…