Children of the wilderness

A young girl disappears in the forest while playing with a cousin. The cousin is found several days later, but no one can find the girl. Some time later, stories emerge from the forest about a girl seen walking alongside a tiger, about a wild woman walking around with long hair and nails, but she is never found and the search is eventually abandoned. Thirty-eight years later, she is finally rediscovered at the age of 42, after having wandered through the forests on the borders of three different countries. 

This sounds like a chapter from a magical realist novel, or some fairy-tale fable, but it is the true story of Ng Chhaidy from the district of Mizoram in India, close to the border with Myanmar. Chhaidy’s story is astonishing for the length of time that she has been missing, long enough for her to lose the ability to use language, even though she was fluent in her native Mara when she disappeared as a four-year-old. It seems remarkable to those of us living in the developed and urbanized world, far removed from close contact with forest and wilderness, that such a thing could happen in modern times. 

Giving “junk DNA” the credit that it’s due

When the Human Genome Project was completed over a decade ago, in 2001, many biologists were surprised that the human genome only contains about 20000 to 25000 genes, which occupy less than 1% of the total DNA sequence. This was surprising news: how could such a complex system as a human being be coded for by only 25000 instructions, when a microscopic worm (C. elegans) has 21000, and a bacterium (E. coli) has 5000? And what was the point of carrying all this other DNA around? The term “junk DNA” was coined to refer to these non-protein-coding sequences. Are they really junk — relics of past evolution, gene duplication, viral infection, and other hypothesized mechanisms of sequence accumulation — or do they have a function that we simply haven’t found out about yet?

The ENCODE (Encyclopedia of DNA Elements) project has recently released its first results in a series of publications in Nature and other scientific journals. There was plenty of news surrounding it; not surprising given the $180 million that have already been spent, and the over 400 scientists working on it. Articles appeared in major newspapers and news outlets, but then I got an email from a college friend, who’s not a biologist, asking me what all this fuss was about. He’d read the newspaper articles, which were full of quotes from scientists lavishing praise on the project and its promise, but couldn’t quite figure out exactly what it was about. The generic-sounding name of the project doesn’t give many clues, either. And so, even though I’m supposed to be a microbiologist and not a human geneticist, I thought I’d take a shot at explaining the significance of the ENCODE results.

The idea of the “gene” has been a long and problematic one. It has a peculiar history for a biological concept, because the existence of genes was predicted by theory (the experiments of Mendel and his successors) long before we had any clue of what the physical nature of genes were. Eventually biologists figured out that DNA was the hereditary material, and the Central Dogma took shape: that genetic information stored on DNA was first transcribed to RNA, which was then translated to proteins, and that proteins were the main functioning parts of the cell: the scaffolding, motors, and carriers that performed the business of life. A gene was just the information needed to make a protein, and if asked to define the physical manifestation of a gene, one would have said that it was the stretch of DNA that held the instructions for making that protein.

As we found out more about genes and how they were regulated, however, the story began to get complicated. It wasn’t necessarily true that one gene = one protein: some genes could be spliced in different ways to give different products. Nor was it true that proteins were the only functional pieces of the cell: sure, we’ve known about ribosomal RNAs (rRNA) and transfer RNAs (tRNA) for a long time, but other small RNAs, some with catalytic functions, have also been discovered. Gradually, we’ve also come to appreciate that the complexity of life is not just the result of proteins interacting with other proteins, with DNA sitting passively by; many proteins also interact with DNA, determining which genes are going to be expressed, and which should stay silent. In the classical textbook examples, regulatory elements lie close to the genes which they administer, but it is now known that this isn’t necessarily so. New mechanisms of silencing genes have been discovered, some which work by chemically modifying DNA (methylation), and others which involve a dizzying dance of RNA and protein molecules (RNA interference). Is it time to revise the concept of the “gene”, or should we simply acknowledge that protein-coding genes are not the only significant pieces of a genome?

The ENCODE project has shown this very clearly. Far from being “junk”, the non-protein-coding sequences in a genome are actually doing something and not just sitting there passively. At least 80% of the genome can be experimentally shown to have some kind of function (recall that less than 1% of the genome codes for proteins), or as the authors put it: a “demonstrable biochemical function”. They may be regulators or promoters, i.e. sequences which control the expression of genes by binding to proteins involved in the machinery of transcription. They could be regions that are controlled by DNA methylation, which silences expression. Or they could be regions which are exposed to transcription factors, instead of being coiled up in histones.

This was a large scale project with many participants. What they did to discover this was a process of systematic cataloging. They used almost 150 different human cell lines in culture (including the famous HeLa cells) and performed different experiments to spot different functions. For example, to see what portion of the DNA was actually being transcribed, they extracted and sequenced RNA en masse, an approach made possible by new methods of nucleic acid sequencing which can sequence huge numbers of small lengths very quickly. To see what sequences bind to known proteins, they performed a method called ChIP, chromatin immunoprecipitation. For a protein which is thought to bind to DNA, antibodies are raised against it. The protein is then exposed to genomic DNA; it seeks out and binds to the specific sequence that it interacts with. A chemical is added to cross-link the protein and DNA, and this complex is fished out using the antibodies developed earlier. The crosslinks are removed, and the DNA is sequenced, to find out what region of the genome this protein interacts with. Other types of experiments were performed to find out which parts of the genome are methylated, are accessible to transcription factors, and so on. They’ve also analyzed how the regulatory elements in a genome interact with each other, and how the three-dimensional folding of the DNA itself affects the interactions between different parts of the genome.

One of the surprising findings was that much of the genome (75%) is actually transcribed to RNA at some point or another, even though most of these don’t end up being translated to proteins. Textbooks usually mention the three classical types of RNA: messenger RNA (mRNA), rRNA, and tRNA (described above), but aside from these workhorses, RNA was usually thought of as a sort of “relic” molecule, doing only these few menial jobs. But recent research is accumulating evidence for the importance of various kinds of small RNAs in the eukaryotic cell, and the ENCODE project could help the task of cataloging them all. 

There are a whole bunch of other sub-projects (or “threads”, as they call them on the ENCODE website) that have been carried out by the ENCODE consortium. As a way of doing science, I think it points the way to the future: big consortia collecting big data and crunching big numbers. For biology, the new sequencing technologies (collectively called “next-generation sequencing”, or NGS) are a tremendous advance over traditional Sanger-type sequencing, which was developed decades ago and still based on the same principles. NGS came into the market just in time for the ENCODE project, allowing them to sequence several times as much DNA for the same cost. We are now reaching the point when you could have your own personal genome sequence for a thousand dollars or even less. The limit on what we can do is imposed instead by our ability to store, transmit, and compute such massive quantities of data. 

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The first batch of papers published by the ENCODE consortium are available via the website of Nature. They’ve also got some snazzy interactive graphics. 

Visiting the Hunterian Museum

I have always been enthralled by dissection and the appearance of well-dissected specimens. It's a strange kind of art form: the structure is already there, formed by the hand of Nature, so the artist's job is not to create something new, but to reveal something hidden. In school I participated in biology competitions where we trained on dissecting earthworms, cockroaches, flowers, and the like, while in college I had a memorable experience cutting open a gravid dogfish with a friend.

But the enthusiastic hacking of amateurs and students is one thing, while the preparation of display specimens is another. The Hunterian Museum is one of the most well-known collections of its kind. It's owned by the Royal College of Surgeons of England, and was originally put together by John Hunter, the famed 18th century anatomist and surgeon, some of whose exploits have been described before on this blog. I recently got to visit the museum because I was in London, and despite it being a relatively small collection (two thirds of the original collection was lost by bombing during World War II), I spent more than 2 hours wandering around. Unfortunately photography is forbidden, so no photos this time.

Used for both teaching and research, it is notable for its bringing together of both human and non-human (including plants!) specimens in a systematic arrangement. Unlike most museums of the time, which arranged things in a taxonomic layout (according to classification), Hunter arranged his museum to demonstrate his ideas of comparative physiology and anatomy. For example: flowers, eggs, uteruses would be brought together in one case under the heading "organs of reproduction". What struck me was the range of non-human material that was present. I had read about this before, but actually seeing the collection led me to appreciate how deeply Hunter was trying to draw analogies between the different classes of life (before the advent of evolution theory), which is a project that biologists today are still working on.

There were lots of children with their parents, when I was visiting. One would think that a young child would be terrified of seeing recognizable pieces of people (some of the specimens were stained and looked quite lifelike), but I don't think most of them were too put off by it. Perhaps the sheer quantity of stuff to see distracted them from the particularly morbid examples. One case that did give many visitors some pause was the display of human fetuses at various stages of development. I heard one parent mutter "that can't be right...."

Halfway through my visit, the children trooped off to hear a presentation in period costume about 18th century surgeons, and I was left in near-silence again, with a few other people who were sitting on stools and making drawings. In the upper floor of the gallery are the pathological specimens, collected to demonstrate the different diseases and abnormalities that a practicing surgeon might encounter. Some of these show how "nasty, brutish, and short" life was like before antibiotics and modern medicine: skulls devastated by syphilis, spines bent over by tuberculosis. The smallpox exhibit was especially heartbreaking, because it contained half the face of a child victim of smallpox, to illustrate the scarring. It was injected with red dye to stain the arteries, but that also gave a rosy glow to the cheeks.

Another disconcerting thing is seeing specimens that come from named persons: a cancerous tumor from Miss Somebody, a diseased body-part from Lord Someplace. Hunter was a surgical innovator, but that also meant that many patients died anyway, and their body parts would end up in his collection.

Hunter's skill in anatomical preparation, and the care taken by conservators in the years since, have kept much of the collection in very good shape. I marveled especially at the dissections of invertebrates to demonstrate the nervous system: one of the most challenging things to display in a tiny animal. Sadly, the anatomist's art is in defiance of nature: to unveil the concealed, to prevent decay, and to simulate the appearance of life. Even if specimens are well conserved and do not decay, plenty of work is involved, and they are ever prone to destruction because most are highly flammable and fragile. One photograph on display from 1941 shows the aged retired curator Arthur Keith helping to salvage from the wreckage after the bombing, beside a bust of Richard Owen, the 19th century anatomist, poking out from the rubble. An anatomist's lifetime's work could be easily reduced to ashes within minutes, but on reflection, it is the knowledge gained that is most precious. The medical anatomists are fortunate in that their hard-won learning is valuable to society and is therefore carefully passed on. The comparative biology of other organisms, however, suffers from a lack of qualified taxonomists and specialists in many groups. Even today we need more people like John Hunter, who are driven to seek out the connections between the familiar and the unfamiliar, the immediately relevant and the merely philosophical.

(For those who are visiting London: The museum is free, and is open Tuesdays to Saturdays, 10 am to 5 pm. It is located beside Lincoln's Inn Fields; the nearest Tube stop is Holborn.)

Planet Earths' debt ceiling

You may have not noticed it amid all the news on the economy, but on Tuesday we've gone into ecological debt for the year. 27 September was this year's Earth Overshoot Day (via Discover), the day when human consumption and waste emission for the year has exceeded the Earth's annual productivity and ability to absorb waste. The organization responsible for this announcement is the NGO Global Footprint Network, which seeks to raise awareness of environmental sustainability. They've issued a media packet explaining the concept here (pdf). The idea was originally mooted by the UK-based new economics foundation (they do their name in lowercase) in the 1980s as Ecological Debt Day.

From Global Footprint Network website

It sounds like a straightforward calculation of income minus expenditure, but the reality of course is quite complicated. Most of the parameters, such as crop productivity and human greenhouse gas emissions, have to be estimated, so the date is not an exact one. Despite the uncertainties, the calculated date is actually be on the more generous (to humans) end of the scale.

What's scarier is that the date has been moving forward every year: from sometime in early November in 2001, to late September now, about 3 days a year. Even scarier, this ignores the cumulative effect of previous times when we've gone into debt. This crisis mirrors the financial one: in some heavily indebted countries, politicians are happy to report when they've simply slowed down the rate of debt increase.

This is a good way of getting people's attention, because of all the headlines that the poor economy has been grabbing lately. Even non-economists, like myself, have become acquainted with concepts like debt ceilings, defaults, and bailouts (though what a "tranche" is still remains opaque to me). Environmentalists and sustainability scientists are also working on figuring out how to put an economic price on ecosystems and the environment, to make the importance of preserving the environment more "real" to those who think in dollars and cents, such as policymakers and industry. Examples include factoring in the cost of ecosystem services into environmental impact assessments, or selling carbon credits, or swapping habitat protection for debt forgiveness. All of these schemes have their critics, but I like to think of them as experiments in progress, as people try to figure out what's a workable way to account for the environmental impact of our economic decisions.

"Mismeasure of Man" Revisited

Stephen Jay Gould's 1981 book, The Mismeasure of Man, made the case against 'scientific racism'. He opened the book with an attack on the 19th-century physical anthropologists, the craniologists, who measured skulls as a way to classify different races as superior or inferior. Later on, he examined the origins of the IQ test and argued against its validity and statistical basis. In 1996, the book was reissued with a set of new essays, in response to the controversial 1994 book The Bell Curve. This was welcomed by those who opposed the Bell Curve's revival of biological determinism in intelligence.

Fifteen years on, Gould's book is back in the news but to criticism, rather than acclaim. One of the bodies of work that he analyzed and apparently refuted was that of Samuel George Morton, an American craniologist who amassed a large collection of skulls from around the world. Gould claimed that Morton's measurements exhibited bias, unconscious or not, that bolstered the preconceived notion that Europeans should have larger brain volumes than other, 'inferior' races. Morton supposedly fudged his analysis by selective reporting (see my previous blog post on other ways to fudge your science) and improper measurement. However, Gould did not remeasure the skulls himself, basing his criticism only upon his re-analysis of the published data. Now, a study by anthropologists who painstakingly remeasured Morton's skull collection has absolved Morton of misconduct. There was no mismeasurement, contradicting Gould's thesis that unconscious bias had influenced Morton's scientific methodology. The research team says: "Ironically, Gould's own analysis of Morton is likely the stronger example of a bias influencing results."

Read more at the New York Times, and the original article in PLoS Biology.

Reference:
Jason E Lewis et al. 2011. "The Mismeasure of Science: Stephen Jay Gould versus Samuel George Morton on Skulls and Bias." PLoS Biology 9(6): e1001071. doi:10.1371/journal.pbio.1001071

Rebirth of Bird Watching

"Bird watching" sounds like such a back-to-nature pursuit: just me and my binoculars, hiding behind a bush and waiting for the birds to come out. But with digital cameras making high-quality photography cheap and accessible, and the Internet making sharing those pictures and swapping tips so much easier, birding has become a hobby for the technologically savvy too.

Today, there are crowd-sourced bird-mapping tools, birding packages that double as vacation getaways, birding blogs, birding iPhone apps, and remote-birding Web sites that don't require watchers to be present in the landscape at all. A few old-fashioned birders may still practice their hobby in isolation with binoculars and field guides, but the birding community, these days, has moved on to gather, check, and share sightings across great distances using the fruits of technological industry and the jumbo jet. 

This is from an amusing article about the different kinds of birders and the kinds of communities that they form. What the writer calls "privileged aloneness"–getting up to go birding before other people are even awake–seems like a good way to describe the attitude that many birders have.

The way I see it, it's as much about the birds as it is about immersing yourself in the community and its special culture. Just like hardcore runners (or cyclists, or computer geeks) have their own magazines, fashions, gear fads, the same with birders.

Those birds don't stand a chance.

Melting Glaciers Reveal Plane Wrecks in Andes

A bizarre and somber side-effect of retreating glaciers in the Andes mountains: decades-old aircraft wrecks and dead climbers, as well as older Inca mummies and 'icemen', are being revealed by the thaw:

"Some discoveries are personal, allowing families closure after years of mourning loved ones who appeared to have vanished. Others have added alluring clues into the history of human migration, diet, health and ethnic origins..."

Read more (NY Times)

John Hunter and the Giants

This isn't the name of a band. John Hunter, the great 18th century surgeon whose anatomical collection now forms the Hunterian Museum of the Royal College of Surgeons, was fascinated by 'freaks' of nature. Among them, the Irish giant Charles Byrne, who measured 2.34 meters in height and became a celebrity when he showed up in London.

Hunter met Byrne in life, and had designs to acquire the giant's skeleton after his death, for his museum. However, Byrne tried to thwart Hunter's plans, and after he died at the age of 22, he had made his friends promise to bury him at sea. Hunter's hired hands, unfortunately for Byrne, managed to bribe or intoxicate the funeral party, or so the story goes, and stole the body away to Hunter's back door in the upmarket Leicester Square neighborhood, where in his basement the body was boiled down to a skeleton.

According to the Guardian, an endocrinologist named Márta Korbonits at London's Barts hospital has found a possible genetic cause for Byrne's gigantism. His growth spurt (and subsequent early death) was due to an excess of growth hormone produced by the pituitary gland. Pituitary tumors are the most common cause of gigantism, and today is treated by surgical removal of the tumor.

She studies a genetic condition called familial isolated pituitary adenoma, which is caused by a mutation in a gene called AIP (Aryl Hydrocarbon Receptor Interacting Protein). According to her work, Byrne's mutation (discovered by sequencing DNA from his teeth) came from a common ancestor as a population of people bearing the AIP mutation in Ireland today. As the article says:

Both Holland and McCloskey [a FIPA survivor and film-maker] came from Tyrone and were fascinated by the number of actual giants in the area, and by the way they figured in Irish folklore not as freaks, but as kings, seers and poets.

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John Hunter himself was also a colorful character, living in a colorful age. He might be called the prototype of the 'brash surgeon', more interested in showing off their surgical chops (and in Hunter's case - acquiring specimens for his collection) than the comfort of their terrified patients.

A good recent biography of him is Wendy Moore's The Knife Man. In his time (and indeed until the modern age), there was no clear line between medicine and natural history, and many of his famous experiments and observation concern the latter subject.

He was one of the first to experiment with surgical grafting. Among the grafts he performed was that of a freshly-pulled human incisor onto the comb of a rooster. We are told that this required repeated trials–I wonder who donated all those teeth! Eventually, the graft did 'take', and he sacrificed the animal, in order to bisect its comb to see how it connected to the tooth. He found that blood vessels from the rooster had indeed penetrated the tooth pulp: "The uniting of parts of different animals when brought into contact he attributed to the production of adhesive instead of suppurative inflammation, owing to their possession of 'the simple living principle.' " (Encyclopedia Britannica).

After his death, his anatomical collection found its way to the Company of Surgeons. It suffered damage during World War II, but is still on display today in London.

Prehistoric Human Remains found in Java

Via our fellow SE Asian science blog SEAArch, the Southeast Asian archaeology newsblog, comes a report from Indonesian newspaper Tempo Interaktif on remains of prehistoric humans found in the Tata and Bonjong caves in Java.

Unfortunately, there is no further information in the article, nor has the research (apparently) been published yet, so there's not much more to say. Java, though, is where the celebrated skullcap of 'Java Man', a specimen of Homo erectus erectus, was found in 1891 by Eugene Dubois on the banks of the Solo River. Also in Java, close to the Java Man site, is the Sangiran Early Man site, which has been declared a UNESCO World Heritage Site, and has yielded many more hominid fossils and ancient tools.

Book Review: The Art Instinct

Book reviewed -- Denis Dutton. The Art Instinct. New York: Bloomsbury Press. 2009.

Modern humans have a profound fascination with our Pleistocene past, in part because many of us, disillusioned by technology and modernity, find something more authentic and natural in the ways of hunter-gatherers. A recent post by fellow Refugee, Alvin, highlights research suggesting that barefoot running may be better for our bodies. For some people, the 'Paleolithic Diet' is becoming fashionable, while even literary theorists are looking to Darwin and the hunter-gatherer psyche to explain the ins and outs of literature. Can other human endeavors, like art and music, be explained by our evolutionary past in the same way?

Not the Bambi Effect...

Why do we find some animals ugly? Conservationists have long known about the Bambi Effect - where cute animals with big eyes (or majestic miens) attract the most funding and attention. Scientists are also trying to understand why certain animals seem the opposite way and repulse us instead. It seems that animals which look uncannily like us - but not quite - seem to elicit disgust, as well as those which appear like they might be diseased (e.g. mottled, hairless skin).

More generally, psychologists are increasingly interested in the topic of disgust, and how this primitive emotion might affect even higher-order judgments and decisions that we make.

The Story of Maize

The story of how maize (or corn) was domesticated by human beings is a fascinating mix of biology (both classical and modern) and archaeology. It's a tale of careful observation and empirical reasoning that began not in the past century but over 9000 years ago:

"These people were living in small groups and shifting their settlements seasonally. Yet they were able to transform a grass with many inconvenient, unwanted features into a high-yielding, easily harvested food crop."

Cool fact from the article: George Beadle, of Beadle and Tatum fame, was the first modern biologist to suggest that teosinte was the wild ancestor of domesticated maize.

Delusory Parasitosis

"I knew I’d been crazy during that period, but I didn’t know I’d been crazy with a condition that had a name, and that although it wasn’t common, it was well known in psychiatric literature. Not just psychiatric literature. Delusory parasitosis is where psychiatry meets academic entomology and pest control."

Author Jenny Diski writes about delusory parasitosis, also called Ekbom Syndrome, a psychiatric syndrome where a person imagines that he or she is being invaded by tiny invisible bugs. As she tells it, it's something that the unsuspecting entomologist or pest control specialist will be unnerved to encounter for the first time!

The entomologist whom she cites, Nancy Hinkle, has written a review of Ekbom Syndrome for Annual Review of Entomology (2010, vol 55: 77-94, doi:10.1146/annurev.ento.54.110807.090514).

(Scratching cat photo: Pavel Ševela / Wikimedia Commons)

Cleaning Oil-Slick Birds

More than just a scrub with soap is needed to save birds affected by oil spill. The deadly Deepwater Horizon oil rig disaster on 22 April is spreading a huge oil slick over the Gulf of Mexico, which may soon reach land.


Oil slick at bottom right (Picture source: BBC)

Cleaning oiled birds is a complicated process, and this Popular Mechanics article describes how. One important step is when they are dried after washing; rescuers have to make sure that their feathers are all aligned, the way that birds normally do when they preen themselves, so that they can remain water proof.

More information on wildlife impact from the BBC.

(Via Arts and Letters Daily)

Neaderthal Genome Sequenced

The Neanderthal genome has been sequenced, using high-throughput pyrosequencing technology, by a consortium largely based at the Max-Planck Institute for Evolutionary Anthropology in Germany.

They conclude from their analysis that Neanderthal and human populations diverged around 270,000 and 440,000 years ago, depending what age one accepts for the chimpanzee-human split. Also, they found that Neanderthals are closer to non-African (i.e. Eurasian) humans than Africans, suggesting that gene flow from Neanderthals to Eurasian humans occurred before the divergence of the Eurasian populations of humans.

The methods which they use to reduce contamination from non-Neanderthal DNA (human DNA which might be mistaken for Neanderthal, and bacterial which is in great abundance) are also very interesting, as is how they dealt with the problem of deamination of C nucleotides in ancient DNA.

What made me raise an eyebrow, though, is how Roche, the company which manufactures the 454 sequencing platform used in this project, sponsored the publicity campaign for this project. One would like to think that in science, the results which receive the most publicity are those which have the most scientific merit, but it may not always be so. In this case the interest of the subject matter is fairly obvious, but one needs to be wary of special interests and commercial agendas.