7 December 2007
Reversal of fortune
1 December 2007
21 November 2007
The finished image
I've been idling over the topic of this week's post for quite a bit now. There's just no easy way to introduce the subject of genetic disease. Sensitive subject matter, whichever way you look at it. To scientists, biology is at its most fascinating and informative when it goes wrong. Often, genes are named after the condition that results when they malfunction. In the lab, determining the function of a specific gene is often done by disrupting the gene in a model organism and investigating any physical changes that result. What we don't realize is how often Nature does the same kind of experimenting.
What a miraculous thing every successful fertilization event is! A sperm and an ovum fuse, forming a zygote, the beginning of a new multicellular organism, with half of its genes derived from the paternal genome, and the other half from the maternal genome. The doubling of DNA and movement of chromosomes essential to this miracle form a major chapter in any biology textbook; the meiotic mantra of prophase-metaphase-anaphase-telophase is chanted in classrooms and lecture halls across the globe. Nature is not textbook perfect, however. Chromosomes get damaged, broken, left behind. They fuse into new entities, unsure of their alliances. The DNA sequences they harbour change over time, get deleted, repeated, inverted, mutated. Here's the rub: change is good. Mutation and change is what drives organisms to adapt to new environments and new pressures. It is what enables them to succeed in the future. Curiously, mutation works blind, unable to see what natural selection is requiring from it. Not all changes are equal; not all mutants fit the mould. Nearly a quarter of all human fertilization events will be aborted - often so rapidly that the woman doesn't even realize that she was pregnant. More than 50% of all embryos miscarried in the first trimester are found to have chromosomal abnormalities. These genetic changes are so severe that they prove lethal. In fact, we all carry a few genes where one of the two copies (alleles) is functionally incapacitated in some way and is compensated for by the healthy copy on the other chromosome - it is masked, recessive. Without that healthy copy, you would probably have suffered from some genetic disorder. More likely, you would never have been born.
Fibrodysplasia. For hundreds of years the medical records noted patients who slowly "turned to stone". This is a very rare condition, striking one out of every two million people. We now know this disease as fibrodysplasia ossificans progressiva, or FOP. It is autosomal dominant - you only need one copy of a mutant gene to be affected. Mutations in several different genes can lead to FOP, but the genes all share a common developmental pathway: that of embryonic bone morphogenesis. These genes are involved in bone formation in babies, but get switched off soon after. In FOP patients, one of the genes stays turned on into maturity, with grave consequences. Slowly, muscles and connective tissue are converted to bone. Slight injuries induce massive spurts of bone growth, making surgery to remove the lumps of bone impossible - it only exacerbates the situation. Sufferers might be unable to move their necks, open their jaws or lift their hands as more layers of ectopic bone are deposited, fusing their skeletons in place. Harry Eastlack, the most well-known FOP sufferer, donated his body to the Mütter Museum in Philadelphia, where his skeleton (above) dripping with bone like a cave drips with stalactites, can still be seen. He passed away in 1973, six days before his fortieth birthday.
Lesch-Nyhan Syndrome. Decades ago, boys with this disease were often misdiagnosed as having cerebral palsy. They writhe and twist and are mildy retarded. But they also suffer from horrifying, uncontrollable urges to self-mutilate. Sufferers will bang their heads against the wall, or bite themselves. Many need to be strapped in and restrained to prevent them from chewing off their own fingers and lips, or gouging at their own eyes, screaming in pain and terror as they do so. Care-givers are also not spared, and may be sworn at or punched, often while the patient apologizes profusely for their compulsion. This terrible disease is caused by mutations in the gene that codes for the HPRT enzyme, involved in the metabolism of nitrogenous molecules called purines. When this enzyme malfunctions, there is a build-up of uric acid, which leads to gout and kidney problems and is also responsible for the changes in neurological development. Most sufferers die of kidney failure early in life. This is a recessive disease, meaning that a healthy copy of the gene will compensate for a faulty one, and the person will not be afflicted but merely a carrier. Unfortunately, the gene resides on the X chromosome. So whereas girls inherit an X from their mother and an X from their father, boys inherit an X from their mother and a Y from their father. Men make do with a single X chromosome. If it happens to contain the faulty HPRT1 gene, they will develop Lesch-Nyhan syndrome. Carrier mothers therefore have a 50% chance of transmitting the gene to their sons. Fortunately, this disease is also very rare, and typically affects only 1 out of every 380 000 people worldwide.
Fatal Familial Insomnia. We've all heard of prions, those infectious proteins hiding in our hamburgers, lying in wait for an unsuspecting victim to consume them and become another sporadic case of Creutzfeldt-Jakob disease. Prions are differently folded variants of normal proteins essential to brain function. When a prion protein comes into contact with a normal protein of the same kind, it can change the shape of that protein into the prion fold. The new prion is like a zombie victim; once bitten, it too becomes a zombie and can turn others into zombies with its lethal bite. Prion proteins form plaques of long fibres inside neurons, damaging their delicate structure and disrupting their function. Most prion diseases take the form of transmissable spongiform encephalopathies - the prion proteins are tranferred through transfusions, transplants, or consuming tainted meat. In the rare case of fatal familial insomnia, the disease is most definitely genetic: if one parent had it, then each child has a 50% chance of developing it as well. The age of onset varies from 20 to 60, so it usually strikes when patients have already had children. The symptoms of FFI are unpleasant, because it is literally a fatal case of insomnia. People with FFI find themselves terminally unable to fall asleep, inhabiting a debilitating world somewhere between slumber and wakefulness. Drastic weight loss occurs, together with decreases in muscle control. No longer able to speak or walk, they are bedridden (a cruel twist) with nothing to do but stare at the walls. Curiously, FFI does not impair cognition, or cause dementia: up to the very end, before the bliss of coma and death, sufferers are completely aware of what is happening to them. It has so far only been identified in about 40 families, and members can be screened for the mutant gene that causes the protein to assume the malignant fold. Researchers hope that the study of FFI might lead to a cure for other prion diseases like CJD, and protein misfolding diseases such as Alzheimer's disease.
Trimethylaminuria. TMAU, a metabolic disorder that sounds hilarious, yet is anything but funny for those who suffer from it. For them it is a source of much embarrassment. Also known as fish odour syndrome, this disease is again caused by a malfunctioning gene. The gene, FMO3, is located on the long arm of chromosome 1, and encodes an enzyme responsible for breaking down trimethylamine, a molecule formed from nitrogen-rich food by beneficial intestinal bacteria. The disorder is recessive, so both copies of the gene need to be malfunctioning for the disorder to manifest itself. Because trimethylamine is no longer broken down, it builds up in the body. The molecule, which has a fishy, ammonia-like smell, is released in the person's urine, sweat, and breath. No matter how often they wash, the smell is never gone for long. This disorder can be very disrupting. People who suffer from it often shy away from social interaction by isolating themselves, and sometimes struggle with feelings of guilt or depression. Although there is no cure, avoiding certain foods high in nitrogen seems to help, as do daily doses of charcoal to soak up the smelly compounds.
Huntington's Disease. On the short arm of chromosome 4 lies a gene encoding a protein essential to the maintenance of neurons, called huntingtin. The gene sequence specifies the exact order of amino acids that need to be linked together to form the functional protein. Part of this sequence is a stretch of repeats of the same amino acid, glutamine, over and over again. The exact length of this patch of glutamine repeats varies from person to person. Healthy people can have anything from 9 to 35 such glutamines linked end-to-end in this part of the protein. In people with Huntington's disease, or HD, this repeat sequence has been vastly extended, sometimes to more than a hundred repeats. Somewhere along the line, the sophisticated cellular machinery that reads and copies the genetic code had lost its place in all the repeats, reread the code again and created extra copies of those requests for glutamine in the gene sequence; HD is a codon reiteration disorder. The mutant form of huntintin no longer functions normally, and is also not broken down like it should be. Neurons start to die off. Interestingly, the longer the repeats in the mutant huntingtin are, the earlier the patient's symptoms start. HD is typically a progressive decline, with chorea and athetosis generally being the first physical symptoms. Chorea is characterized by abnormal involuntary jerking movements, while athetosis is a continuous writhing movement of the hands and feet. These irregularities in coordination increase as the disease progresses. In the later stages, speaking and swallowing are impaired. The most frightening aspects of HD are those that involve the mind itself - patients often become anxious or depressed, sometimes aggressive or compulsive. They lose the capacity for abstract thinking, for planning ahead or choosing appropriate actions. This deterioration is particularly traumatizing for children who often end up taking care of their ailing parents, loved ones who have become strangers to them. HD is an autosomal dominant disease - if you have the mutant gene, you will eventually develop the disease. Because it only manifests later in life (the average age when symptoms start is 40) HD is often only diagnosed when patients already have children. This means that the mutation gets passed on to the next generation 50% of the time. There is a very efficient DNA test available to detect the presence of the gene. However, many children of HD sufferers choose to rather not know their own fate. At the start of the 21st century, Huntington's disease is still a terminal illness with no cure. If you had a 50% chance of inheriting it, would you want to know for sure?
Let us not view this as a morose post, a mere list of genetic disease, a list of things that can go wrong. Rather, it is intended to be a celebration of the miracle of multicellular life and of how precious a healthy genome truly is. It is a salute to those brave people who live with genetic disorders; they have been of immeasurable help in the study of genes and their functions. They represent the reluctant pioneers of our collective genome, those who are sacrificing themselves in testing the limits of human evolution. Change is good.
14 November 2007
The Siren song of the cloud forest
5 November 2007
Sexual frustration of the worst kind
24 October 2007
80th post commemorative poll
I have selected ten of my personal favourite posts from over the years:
- the post singing the praises of my favourite molecule
- the post unconvering the seedy underbelly of orchid shows
- the post about rare records
- the post where I revealed personal stuff... kind-of
- the post listing cool things to do with biotechnology
- the post about my ultimate fanboy experience
- the post about the dangers of working in a lab
- the post explaining the intricacies of collecting first edition books
- the post with the mystery squid
- the post about my whirlwind trip to Cape Town
That's the list. Use the links to delve into the archive. Use the polling box in the sidebar to cast your vote. You can only vote once, and the poll closes at the end of November 2007. I hope you've had as much fun reading my inane ramblings as I've had writing them. Here's to the next two years of digital gardening!
20 October 2007
A secret dream of three islands
The warm haze of a daydream sets off neuronal synapses. Pressure drops. Temperature rises. I find myself on three of my favourite islands. Look.
15 October 2007
Nature's inexorable imperative
A large predator from the largest environment on Earth, and yet undiscovered for all these years. We dream of other planets, and yet the true wonder is to be found on our own. This is why I study biology. I want to be kept in awe. What other things, exquisite and strange, are lurking in the darkest waters of the ocean?
"Adapt or perish, now as ever, is nature's inexorable imperative." -HG Wells
5 October 2007
Spectres of the swamp
Credit to NC Orchid for the beautiful photograph of Polyrrhiza lindenii. Visit his Flickr page for more amazing pictures.
28 September 2007
A kingdom behind it all
Dave Gahan - Kingdom [CDMute393] Released 08 October 2007 on Mute Records.
A brand-new single from the frontman of Depeche Mode. I cannot wait.
27 September 2007
Frivolous Freelance Friday Fritillaries
- Post these rules before you give your facts.
- List 8 random facts about yourself.
- At the end of your post, choose (tag) 8 people and list their names, linking to them.
- Leave a comment on their blog, letting them know they've been tagged.
1. I'm a member of the American Orchid Society.
2. I have had the same pencil tin since starting my undergraduate degree. It's a beaten up metal tin with the words "2000 - the millennium year and beyond" still just barely visible on the top. Apart from the traditional collection of stationery, this tin has always been home to the following: two marbles; a nut with no bolt; a small ball-bearing; two bright red beans from the common coral tree Erythrina lysistemon; five bright red beans from the broad-leaved coral tree Erythrina latissima; three speckled calypso beans; a small plastic lizard from a surprise egg, given to me by my sister's youngest daughter; a green foil smiley face - a table decoration from some long-forgotten party; two red nerite shells I collected on the beach at Jeffrey's Bay in 1993; and tablets of paracetamol.
3. My living room is decorated with photographic prints of sea nettles, jellyfish in the genus Chrysaora. These beautiful organisms are very amenable to aquaculture and are housed in specialized aquariums around the world. I'd love to visit the Monterey Bay Aquarium in California, where they have a splendid display called 'Jellies: Living Art' combining jelly tanks with the organic glass masterpieces of Dale Chihuly.
4. Certain smells that seem to delight other people leave me with nothing but a headache. I cannot stand the smell of jasmine. Discovering that the smell of jasmine actually has 'a definite faecal undertone' in Sharman Apt Russell's immensely readable Anatomy of a Rose, just confirmed what my olfactory nerves had suspected all along. I also cannot stand scented soaps, incense, scented candles, or the smell of most household cleaning agents. All those dreadfully synthetic pink smells. Give me the good old chemical smell of plain bleach anyday. Why must your home smell like cinnamon-pumpkins for Thanksgiving? Why can't it just have the neutral smell of air? You know: 78% nitrogen, 20% oxygen, 1% argon, 1% carbon dioxide, the name you know and trust? Are you vainly trying to mask the foetid odour of a house inhabited by the filthy mammal you really are? What are you trying to hide? The sense of smell is such an intensely personal thing, intimately tied to the cerebral process of memory. Why waste it on an artificial, so-called 'lily-of-the-valley' tea candle? It's just offensive.
5. Unlike other people, I find it impossible to sing in the shower. The acoustics are always bad. And how do you sing without swallowing water?
6. I study the molecular and genetic interactions between plants and aphids. As far as bizarre goes, few things can beat an aphid. Imagine an insect that is always female, gives birth to live nymphs, is born pregnant, feeds exclusively on plant sap which is so poor in nutrients that the aphid has to secrete most of what it ingests as sticky honeydew out its arse, is actively farmed by ants because of its nectar-like poo, drinks its liquid lunch through a set of mouth parts 0.5µm in diameter, and causes billions of dollars worth of damage to crops annually. This year, I hope to do some EPG (electronic penetration graph) studies, which are basically the aphid version of an electroencaphalogram: you attach an electrode to the aphid with metallic glue and proceed to monitor its feeding behaviour through alterations in electric current. I'm hoping to combine this with virus-induced gene silencing of certain candidate genes in the plant, in order to tease out what actually makes some plants resistant to aphid attack. Now, if it all just works out...
7. I love going to music concerts, but have chalked up way too few so far. Hopefully living in Colorado will soon change this for the better. I pine for those live concerts I've missed, never to return again: Talking Heads. Jimi Hendrix. The Smiths. Anita O'Day. Before I die, I'd love to see the Scissor Sisters live. Or Goldfrapp. Massive Attack. The Knife. Fischerspooner. Ladytron. The list goes on. The only thing that could ever beat the best live show I ever attended, though, would be another Depeche Mode concert. Such great memories. My sister took me to my first big stadium concert - Gloria Estefan live at Loftus - so many years ago. Although the only song I was actually familiar with was Conga, the whole experience of being part of the crowd, experiencing the dynamic artistry on the stage, instilled in me an instant addiction. Live concerts for the hell of it are sometimes fun: I was the only person in the crowd at a Counting Crows concert in Johannesburg who had not heard Mr. Jones before they actually played it onstage. I'm still not a fan, truth be told. But to attend a concert as a fan, with like-minded friends, is one of life's biggest pleasures. Encore!
8. People are confused by the name of this blog. It's long and no-one knows what it means, apparently. However, it captures the reasons why I blog perfectly. There are several meanings here, all intertwined like the roots of orchids growing in the cloud forest. Orchids are epiphytes. Epiphytes are plants that grow on other plants. Epiphytes are not parasites, they simply use the bigger plants as perches, as support, as a means to get closer to the light and the air. I love orchids and all things horticultural and botanical. This blog hopes to provide support for the many eclectic and diverse things I'm passionate about, bringing them out of the dark corners of my brain and into the light of the blogosphere. The blog is a platform for my opinions, my creative outlet. I post short pieces I'd like to believe are at times witty or humorous, not exactly epigrams of course, but you get the idea. I only write about things I'm interested in or passionate about. Things that move me. Electrophoresis is the movement of charged molecules - such as DNA - in the presence of an electric field, thereby separating them and revealing their true nature. Do you understand now? Eclectic Epiphytes and Electrophoretic Epigrams is an ever-evolving collection of posts about the thrill of existing in the 21st century. The things that have grown on me. The things that move me.That's it, I suppose. Now to tag some other victims, erm... bloggers. I'm only tagging four of you though (to leave more people to tag later on, see?). Let's go with Adam, who I think is always up for the job; Mike, who is bound to make it revealing; Arcadia, who is sure to make it beautiful; and Twanji, who actually reveals less of himself than I do.
13 September 2007
A certain ambivalence
Since I love making lists, and my last proper list on this blog was posted in May, I thought it would be diverting to list some of my recent discoveries in the form of a comparative analysis with my home country. But instead of slagging off one country as these lists usually go, I'll focus on the good things about both the USA and the RSA. I cannot say that it's worse or better here. What i can say is that it's definitely different.
- Technology. Access to broadband internet in the US is excellent, cheap and ubiquitous. The whole Downtown Fort Collins is rigged up for wireless, as is the whole university campus. On the other hand, I do miss the cellular communications systems in South Africa. SIM cards, GSM networks, number porting between service providers, and consumer choice of handset as wide as you can imagine. Come back Vodacom, all is forgiven! The winner: the USA, by several Kbps.
- Food. US supermarkets are stocked with the most amazing variety of products. From the seventy kinds of peanut butter, ninety flavours of ice cream and thousand formats of Coca-Cola, to the incredible selection of south-of-the-border treats like blue corn chips and chipotle salsa. On the other hand, I miss South Africa's supreme cornucopia of fresh produce: Cape apples, cling peaches, avocadoes by the bag, litchis by the box, papayas from Nelspruit farm stalls, spotless potatoes from Fruit-n-Veg City. Where's a Woolworths when you need one? The winner: sunny South Africa, by a head of cabbage.
- Nature. Colorado is an amazingly beautiful place, sporting snow-covered mountains, valleys covered in pines and aspen trees, and fast flowing rivers stocked with trout. It's a place where you can walk out of your front door and find squirrels and red foxes co-existing in the suburbs. On the other hand, South Africa has a particular beauty all it's own: once experienced it is never forgotten. It is unique and precious; it is the landscape of my spirit.** The winner: South Africa, by a mountain that looks like a table and some wild horses wearing stripey pajamas.
- Society. Americans are easily the friendliest, most helpful people I've ever met. Folks have no qualms with striking up an anonymous conversation on the bus, and everyone seems genuinely interested in where I come from and what I'm doing here. Online purchases are delivered to my door, and actually stay there - untouched - until I return home in the evening! On the other hand, South Africa is the only place where people really know how to do a proper barbecue -it's called a braai, folks. South Africans have a wonderful sense of humour and know how to laugh at themselves. It's the only place where people get what the word lekker means, which says a lot. The winner: The USA, by a white picket fence, patient drivers and a host of friendly store clerks.
So in the end, there is no real winner here. Some aspects of living in a new country are exciting, some are infuriating, some are delicious, some are fattening, some are confusing, some are gorgeous, some are quite scary. But better or worse? Hmm, I just can't tell you yet...
*Ooh, that last part was so twee, I think I just threw up a little as I was typing it.
** Urgh. I think I did it again.
9 September 2007
Suburban conspiracy theory
Once there were parking lots
Now it's a peaceful oasis
This was a Pizza Hut
Now it's all covered with daisies
I miss the honky tonks
Dairy Queens and 7-Elevens
And as things fell apart
Nobody paid much attention
Some of the residential streets look like Agrestic a la Weeds. All taken, it pretty much represents a generic kind of suburban sprawl. It's comforting, somehow. But somebody at town planning must have had a sense of humour. There's a street - very close to where I live - called John F. Kennedy Parkway (or JFK Pkwy for short). It's a busy street, home to banks, supermarkets and the post office. Several other streets in this college town are named after famous universities, like Stanford, Cornell, Princeton, Oxford, Rutgers, Monroe, Columbia, Yale, Pitkin, Cambridge, Baylor and many others. Right where I catch the number 1 bus to campus is the intersection between JFK and Monroe.
So, although Monroe Ave. is obviously named after Monroe College in New York state (itself named after U.S. president James Monroe)... you kind of have to wonder. It's just too beautiful a coincidence. Could they have snuck a secret reference to Marylin Monroe in there? While waiting for the bus one day, this is exactly what went through my mind. A nice little conspiracy theory, all my own, which I now share with you. I haven't yet figured out exactly what the conspiracy is, though. Maybe you could come up with some suggestions?