Tuesday, April 21, 2009

People-watching for fun and entertainment

An old New York Times article provided inspiration for this post.

I frequently people-watch. Maybe it's a past-time born out of an occupational need to be observant (I'm a research engineer who sometimes designs and runs ethnographic studies), but sometimes I can't help but notice things about people.

Most of the time, it actually takes a real conscious effort for me to direct attention outwards to people-watch. This isn't exactly a surprise; my MBTI type is INTJ, so extraverted sensing happens to be my inferior function (if the MBTI is to be believed at all; yeah, I'm skeptical of anything that so neatly categorizes people). 

But when the time and setting are conducive, I settle naturally into a people-watching mood. This often happens during an occasion of enforced waiting, that is, when I am required to wait and have nothing better to do than to people-watch.

This can happen when I'm meeting an as-yet-to-arrive friend at a restaurant, on a bus or subway, waiting for a speaker at a lecture to begin, or waiting in line to purchase something at a mall.

I sometimes, but not often, people-watch at bus-stops or train stations as well. At those places, I usually calculate the Merc Index instead.

What do I do when I people-watch?

Well, at the lowest level, I observe how they dress, what they're doing, and why they're at that particular place where I'm watching them.

I'm no fashionista, but when I'm people-watching, I'm the rare guy who actually notices when someone matches her belt with her shoes, or decides to pair a bag with her dress. Ditto that for the pendant whose stone is the same exact hue as the nail polish that the girl is wearing.

My observations are not limited to girls, in case you're wondering. I notice the too-short hemlines on the pants that some men wear (if the ankles can be seen, it's way too short). I mentally sniff with derision at the puffed collars of preppy types. I discern which wrist the watch is worn on, and how that correlates with the parting of the wearer's hair (those are usually good indicators of handedness). I also listen for the tell-tale "ding" when someone grasps hold of a metal grab-bar while steadying themselves on a bus or train. That "ding" tells me if they're wearing a ring, which of course is an indicator of marital status.

I'm also discreet at people-watching. The audio cue above from the "ring ding" is a discreet method. Wearing shades to obscure one's focus of gaze is another, and it is the preferred method of some people, but to me, that's too obvious. And it also doesn't work for me as I'm practically blind without my prescription glasses. 

So I resort to other tricks. Reflections are easy enough; bus and subway windows, shop windows, even the mirrored surface of a table or chair backing. Other methods are the left-to-right movie-panning glance (best paired with a simultaneous lift of the right hand to the chin to simulate a contemplative pose), fixing a point of focus slightly to the side and beyond your real object of interest, or if you're with company (like in a restaurant), pretending a look where you look like you're feigning interest in the conversation but are actually looking around for an excuse to leave (not easy to pull off, and don't do this if the person you're with is actually talking directly to you). The last method gives perfect license to look around the strangers in the restaurant, even with eye contact, but you must take care not to offend the people actually sitting with you at the table.

People-watching doesn't stop there of course. The fun part is in imagining what kinds of lives people you're watching lead. I allow my imagination to run wild when I observe people and think about what they do: the "student playing hooky at the shopping mall", the "desperate housewife out for retail therapy", or the "lawyer getting a little on the side with his secretary at the Fullerton during lunchtime".

Heh, they're not all G-rated of course. That would be so restrictive when I'm inventing stories for my own amusement. And of course, it just gets more interesting the more layers I add on to the stories. As is said, variety is the spice of life.


Wednesday, April 15, 2009

"Coral Transplant Surgery Prescribed for Japan"

From The New York Times
Published: April 14, 2009

SEKISEI LAGOON, Japan — Beneath the waves of this sapphire-blue corner of the East China Sea, a team of divers was busily at work. 
Hovering along the steep, bony face of a dying coral reef, some divers bored holes into the hard surface with compressed-air drills that released plumes of glittering bubbles. Others followed, gently inserting small ceramic discs into the fresh openings.

Each disc carried a tiny sliver of hope for the reef, in the shape of fingertip-size sprigs of brightly colored, fledgling coral.

This undersea work site may look like a scene from a Jules Verne novel, but it is part of a government-led effort to save Japan’s largest coral reef, near the southern end of the Okinawa chain of islands. True to form in Japan, the project involves new technology, painstaking attention to detail and a generous dose of taxpayer money.

The project has drawn national attention, coming after alarming reports in the last decade that up to 90 percent of the coral that surrounds many of Okinawa’s islands has died off. This raised a rare preservationist outcry in a heavily industrialized nation whose coastal vistas tend toward concrete sea walls and oil refineries.

The result has been what marine biologists call one of the largest coral restoration projects in the world, begun four years ago. The goal, say biologists, is to perfect methods that could be used around the world to rescue reefs endangered by overfishing, pollution and global warming. 

They say they are using the Sekisei Lagoon Reef, which is named after the broad, shallow lagoon that it created, as a test bed for new techniques that they hope will one day make transplanting coral in the sea as routine as raising tree saplings on land. 

“We have been replanting forests for 4,000 years, but we are only just now learning how to revive a coral reef,” said Mineo Okamoto, a marine biologist at Tokyo University of Marine Science and Technology, who has led development of the palm-size ceramic discs. “We finally have the technology.”

Critics, however, say the project might be wasted effort. They say transplanting is futile without addressing the problems that caused the reefs to deteriorate in the first place, like coastal redevelopment and chemical runoff from terrestrial agriculture. There is also the bigger problem of rising ocean water temperatures, for which there may be no easy fix.

Here in the Sekisei Lagoon, which sits between the tropical islands of Ishigaki and Iriomote, another problem also becomes apparent: the puny size of the efforts to save a reef that stretches as far as the eye can see in almost every direction.

Since 2005, the project has planted around 13,000 pieces of coral, at a cost of some $2 million, said Hajime Hirosawa, a preservation officer at the Environment Ministry who helps oversee the transplanting. This is a far cry, he admits, from the tens of millions of pieces that need to be transplanted in this reef alone, which stretches over an area of about 100 square miles. 

Worse, survival rates have been low, Mr. Hirosawa said. Only a third of the coral sprigs transplanted in 2005 have survived threats ranging from predators like the Crown-of-Thorns starfish to “bleaching,” an ultimately fatal condition caused when rising water temperatures turn coral a sickly white.

“Saving the reef is not something that we can do in three to four years,” Mr. Hirosawa said, “but more like 30 to 40 years.”

Still, say Mr. Hirosawa and others, the techniques have steadily improved, lifting survival rates. One change was to shift from placing new coral on flat sea bottoms, which proved vulnerable to typhoon-driven surface waves that broke off coral, to more protected vertical reef faces. 

Another advance was the ceramic discs, which are baked at 2,700 degrees until hardened, but whose surface contains tiny pores that allow coral larvae to take root. Every spring, a team of a dozen divers has spent up to two weeks drilling holes and gluing in the discs.

While labor intensive, this method offers a more secure footing for the young coral than previous methods, like attaching coral pieces with wire and nails, Dr. Okamoto said. 

The improved transplanting methods have become promising enough that the Environment Ministry says it plans to double the number of coral pieces planted next year, to 10,000. 

While the project’s main goal is environmental, there are also geopolitical motivations. Tokyo plans a much larger and more expensive coral transplantation to try to strengthen the reef protecting Okinotori, a tiny, remote islet that Japan uses to claim economic control of a vast swath of the Pacific Ocean. The government wants to prevent a strong typhoon from wiping away the tiny outcropping, and with it the basis for Japan’s territorial claims, which have already been challenged by China.

There is also a friendly race among global scientists trying to develop the best coral transplantation method. Competing ideas vary from creating coral habitat with large concrete “reef balls” to the use of mild electric current to speed coral growth.

For now, the most common transplanting technique involves breaking off pieces of adult coral and affixing them elsewhere on the reef. Besides damaging the host coral, this method, while quick and easy, also means that most of the transplanted pieces share the host’s DNA, giving the reef a smaller and less healthy gene pool.

In the Japanese method, the discs are stacked underwater for 18 months near a healthy stretch of reef, allowing coral larvae released during spawning to naturally attach and grow on the ceramic surface. This ensures that each disc carries genetically distinct coral organisms, more closely replicating the results of natural reproduction.

“Japan’s methods are expensive and labor intensive, but they also bring more genetic diversity and thus healthy reefs,” said Baruch Rinkevich, a specialist in coral transplantation at Israel’s National Institute of Oceanography in Haifa.

In Sekisei Lagoon, healthy reefs are increasingly found only along the lagoon’s north side, where most coral still flourishes. This has led scientists to speculate that the north side may have evolved coral species adapted to surviving in warmer oceans. Starting next year, the divers will transplant northern coral to the lagoon’s more decimated southern side, said Shuichi Fujiwara, the diving team leader.

“This is absolutely worth doing,” said one of the team’s divers, Ryo Isobe, 26, who works as a diving instructor during the summer tourist season. “When I think of how colorful these reefs used to be, I know we need to do all we can.”

Monday, April 6, 2009

"Brain Researchers Open Door to Editing Memory"

From The New York Times
Published: April 5, 2009

Suppose scientists could erase certain memories by tinkering with a single substance in the brain. Could make you forget a chronic fear, a traumatic loss, even a bad habit. 

For all that scientists have studied it, the brain remains the most complex and mysterious human organ — and, now, the focus of billions of dollars’ worth of research to penetrate its  

Researchers in Brooklyn have recently accomplished comparable feats, with a single dose of an experimental drug delivered to areas of the brain critical for holding specific types of memory, like emotional associations, spatial knowledge or motor skills. 

The drug blocks the activity of a substance that the brain apparently needs to retain much of its learned information. And if enhanced, the substance could help ward off dementias and other memory problems.

So far, the research has been done only on animals. But scientists say this memory system is likely to work almost identically in people. 

The discovery of such an apparently critical memory molecule, and its many potential uses, are part of the buzz surrounding a field that, in just the past few years, has made the seemingly impossible suddenly probable: neuroscience, the study of the brain. 

“If this molecule is as important as it appears to be, you can see the possible implications,” said Dr. Todd C. Sacktor, a 52-year-old neuroscientist who leads the team at the SUNY Downstate Medical Center, in Brooklyn, which demonstrated its effect on memory. “For trauma. For addiction, which is a learned behavior. Ultimately for improving memory and learning.” 

Artists and writers have led the exploration of identity, consciousness and memory for centuries. Yet even as scientists sent men to the moon and spacecraft to Saturn and submarines to the ocean floor, the instrument responsible for such feats, the human mind, remained almost entirely dark, a vast and mostly uncharted universe as mysterious as the New World was to explorers of the past. 

Now neuroscience, a field that barely existed a generation ago, is racing ahead, attracting billions of dollars in new financing and throngs of researchers. The National Institutes of Health last year spent $5.2 billion, nearly 20 percent of its total budget, on brain-related projects, according to the Society for Neuroscience. 

Endowments like the Wellcome Trust and the Kavli Foundation have poured in hundreds of millions of dollars more, establishing institutes at universities around the world, including Columbia and Yale.

The influx of money, talent and technology means that scientists are at last finding real answers about the brain — and raising questions, both scientific and ethical, more quickly than anyone can answer them. 

Millions of people might be tempted to erase a severely painful memory, for instance — but what if, in the process, they lost other, personally important memories that were somehow related? Would a treatment that “cleared” the learned habits of addiction only tempt people to experiment more widely? 

And perhaps even more important, when scientists find a drug to strengthen memory, will everyone feel compelled to use it? 

The stakes, and the wide-open opportunities possible in brain science, will only accelerate the pace of discovery.

“In this field we are merely at the foothills of an enormous mountain range,” said Dr. Eric R. Kandel, a neuroscientist at Columbia, “and unlike in other areas of science, it is still possible for an individual or small group to make important contributions, without any great expenditure or some enormous lab.”

Dr. Sacktor is one of hundreds of researchers trying to answer a question that has dumbfounded thinkers since the beginning of modern inquiry: How on earth can a clump of tissue possibly capture and store everything — poems, emotional reactions, locations of favorite bars, distant childhood scenes? The idea that experience leaves some trace in the brain goes back at least to Plato’s Theaetetus metaphor of a stamp on wax, and in 1904 the German scholar Richard Semon gave that ghostly trace a name: the engram. 

What could that engram actually be?

The answer, previous research suggests, is that brain cells activated by an experience keep one another on biological speed-dial, like a group of people joined in common witness of some striking event. Call on one and word quickly goes out to the larger network of cells, each apparently adding some detail, sight, sound, smell. The brain appears to retain a memory by growing thicker, or more efficient, communication lines between these cells. 

The billion-dollar question is how?

In the decades since this process was described in the 1960s and 1970s, scientists have found scores of molecules that play some role in the process. But for years the field struggled to pinpoint the purpose each one serves. The problem was not that such substances were so hard to find — on the contrary. 

In a 1999 paper in the journal Nature Neuroscience, two of the most prominent researchers in brain science, Dr. Jeff W. Lichtman and Joshua R. Sanes of Harvard, listed 117 molecules that were somehow involved when one cell creates a lasting speed-dial connection with a neighbor, a process known as “long-term potentiation.” 

They did not see that these findings were necessarily clarifying the picture of how memories are formed. But an oddball substance right there on their own list, it turned out, had unusual properties.

A Helpful Nudge

“You know, my dad was the one who told me to look at this molecule — he was a scientist too, my dad, he’s dead now but he had these instincts — so anyway that’s how it all started,” Dr. Sacktor was saying. He was driving from his home in Yonkers to his laboratory in the East Flatbush neighborhood of Brooklyn, with three quiches and bag of bagels bouncing in the back seat. Lunch for the lab.

The father’s advice led the son, eventually, to a substance called PKMzeta. In a series of studies, Dr. Sacktor’s lab found that this molecule was present and activated in cells precisely when they were put on speed-dial by a neighboring neuron. 

In fact, the PKMzeta molecules appeared to herd themselves, like Army Rangers occupying a small peninsula, into precisely the fingerlike connections among brain cells that were strengthened. And they stayed there, indefinitely, like biological sentries.

In short: PKMzeta, a wallflower in the great swimming party of chemicals that erupts when one cell stimulates another, looked as if it might be the one that kept the speed-dial function turned on.

“After that,” Dr. Sacktor said, “we began to focus solely on PKMzeta to see how critical it really was to behavior.”

Running a lab is something like fielding a weekend soccer team. Players come and go, from Europe, India, Asia, Grand Rapids. You move players around, depending on their skills. And you bring lunch, because doctoral students logging 12-hour days in a yellowing shotgun lab in East Flatbush need to eat.

“People think that state schools like ours are low-key, laid back, and they’re right, we are,” said Robert K. S. Wong, chairman of the physiology and pharmacology department at SUNY Downstate, who brought Dr. Sacktor with him from Columbia. “You have less pressure to apply for grants, and you can take more time, I think, to work out your ideas.”

To find out what, if anything, PKMzeta meant for living, breathing animals, Dr. Sacktor walked a flight downstairs to the lab of André A. Fenton, also of SUNY Downstate, who studies spatial memory in mice and rats. 

Dr. Fenton had already devised a clever way to teach animals strong memories for where things are located. He teaches them to move around a small chamber to avoid a mild electric shock to their feet. Once the animals learn, they do not forget. Placed back in the chamber a day later, even a month later, they quickly remember how to avoid the shock and do so.

But when injected — directly into their brain — with a drug called ZIP that interferes with PKMzeta, they are back to square one, almost immediately. “When we first saw this happen, I had grad students throwing their hands up in the air, yelling,” Dr. Fenton said. “Well, we needed a lot more than that” one study.

They now have it. Dr. Fenton’s lab repeated the experiment, in various ways; so has a consortium of memory researchers, each using a different method. Researchers led by Yadin Dudai at the Weizmann Institute of Science in Israel found that one dose of ZIP even made rats forget a strong disgust they had developed for a taste that had made them sick — three months earlier. 

A Conscience Blocker?

“This possibility of memory editing has enormous possibilities and raises huge ethical issues,” said Dr. Steven E. Hyman, a neurobiologist at Harvard. “On the one hand, you can imagine a scenario in which a person enters a setting which elicits traumatic memories, but now has a drug that weakens those memories as they come up. Or, in the case of addiction, a drug that weakens the associations that stir craving.” 

Researchers have already tried to blunt painful memories and addictive urges using existing drugs; blocking PKMzeta could potentially be far more effective.

Yet any such drug, Dr. Hyman and others argue, could be misused to erase or block memories of bad behavior, even of crimes. If traumatic memories are like malicious stalkers, then troubling memories — and a healthy dread of them — form the foundation of a moral conscience. 

For those studying the biology of memory, the properties of PKMzeta promise something grander still: the prospect of retooling the engram factory itself. By 2050 more than 100 million people worldwide will have Alzheimer’s disease or other dementias, scientists estimate, and far more will struggle with age-related memory decline.

“This is really the biggest target, and we have some ideas of how you might try to do it, for instance to get cells to make more PKMzeta,” Dr. Sacktor said. “But these are only ideas at this stage.”

A substance that improved memory would immediately raise larger social concerns, as well. “We know that people already use smart drugs and performance enhancers of all kinds, so a substance that actually improved memory could lead to an arms race,” Dr. Hyman said.

Many questions in the science remain. For instance, can PKMzeta really link a network of neurons for a lifetime? If so, how? Most molecules live for no more than weeks at a time.

And how does it work with the many other substances that appear to be important in creating a memory?

“There is not going to be one, single memory molecule, the system is just not that simple,” said Thomas J. Carew, a neuroscientist at the University of California, Irvine, and president of the Society for Neuroscience. “There are going to be many molecules involved, in different kinds of memories, all along the process of learning, storage and retrieval.”

Yet as scientists begin to climb out of the dark foothills and into the dim light, they are now poised to alter the understanding of human nature in ways artists and writers have not.

Friday, April 3, 2009

"Heart Muscle Renewed Over Lifetime, Study Finds"

From The New York Times
Published: April 2, 2009

In a finding that may open new approaches to treating heart disease, Swedish scientists have succeeded in measuring a highly controversial property of the human heart: the rate at which its muscle cells are renewed during a person’s lifetime.

Tests of nuclear weapons in the atmosphere, which lasted until 1963, generated a radioactive form of carbon, carbon-14. The carbon-14 in carbon dioxide is breathed in by plants, turned into glucose (see equation) and enters the human diet. In the body, the carbon-14 is incorporated into new DNA, and once a new cell is made, its DNA does not change. The level of carbon-14 in the atmosphere has dropped each year since 1963 (see graph), so the exact amount in a cell marks the year the cell was born. From a cell's birth date, researchers can calculate how quickly different tissues such as the intestine, brain and heart are renewed. 

The finding upturns what has long been conventional wisdom: that the heart cannot produce new muscle cells and so people die with the same heart they were born with.

About 1 percent of the heart muscle cells are replaced every year at age 25, and that rate gradually falls to less than half a percent per year by age 75, concluded a team of researchers led by Dr. Jonas Frisen of the Karolinska Institute in Stockholm. The upshot is that about half of the heart’s muscle cells are exchanged in the course of a normal lifetime, the Swedish group calculates. Its results are to be published Friday in the journal Science. 

“I think this will be one of the most important papers in cardiovascular medicine in years,” said Dr. Charles Murry, a heart researcher at the University of Washington in Seattle. “It helps settle a longstanding controversy about whether the human heart has any ability to regenerate itself.”

If the heart can generate new muscle cells, researchers can hope to develop drugs that might accelerate the process, since the heart fails to replace cells that are killed in a heart attack. 

The dogma that the heart cannot generate new muscle cells has been challenged since 1987 by a somewhat lonely skeptic, Dr. Piero Anversa, now of the Harvard Medical School. Dr. Anversa maintains that heart muscle cells are renewed so fast that a person dying at age 80 has replaced the heart four times over. Many other researchers have doubted this assertion.

Cell turnover rates can easily be measured in animals by making their cells radioactive and seeing how fast they are replaced. Such an experiment, called pulse-labeling, could not ethically be done in people. But Dr. Frisen realized several years ago that nuclear weapons tested in the atmosphere until 1963 had in fact labeled the cells of the entire world’s population. 

The nuclear blasts generated a radioactive form of carbon known as carbon-14. The amount of carbon-14 in the atmosphere has gradually diminished since 1963, when above-ground tests were banned, as it has been incorporated into plants and animals or diffused into the oceans. 

In the body, carbon-14 in the diet gets into the DNA of new cells and stays unchanged for the life of the cell. Because the level of carbon-14 in the atmosphere falls each year, the amount of carbon-14 in the DNA can serve to indicate the cell’s birth date, Dr. Frisen found.

Four years ago he used his new method to assess the turnover rate of various tissues in the body, concluding that the average age of the cells in an adult’s body might be as young as 7 to 10 years. But there is a wide range of ages — from the rapidly turning over cells of the blood and gut to the mostly permanent cells of the brain.

Dr. Frisen has successfully applied his method to the heart muscle cells, but had to navigate a series of technical obstacles created by the special behavior of the cells. Many have two nuclei, instead of the usual one, and within these double nuclei the DNA may be duplicated again. “I was really impressed at the level of rigor they put into this analysis,” Dr. Murry said, calling it a “scientific tour de force.”

The finding that heart muscle cells do regenerate, though at a considerably slower rate than Dr. Anversa predicted, is a “reasonable conclusion to a hotly contested issue,” Dr. Murry said. “Anversa went out on a limb, and I think he was partly right.”

Dr. Loren Field, a heart expert at the Indiana University School of Medicine, said he had found that heart muscle cells regenerated in mice at the same rate that Dr. Frisen had found in people. Despite the controversy created by Dr. Anversa’s claims, there has long been agreement that there is a low but detectable rate of cell renewal in the heart, Dr. Field said. The goal now, in his view, is “to try to tickle the system to enhance it.”

Dr. Anversa, for his part, said he was “ecstatic” at Dr. Frisen’s confirmation of his view that the heart could generate new muscle cells, but suggested that the new measurements might have underestimated the rate at which new cells are formed. Since heart muscle cells contract 70 times a minute, they seem likely to need renewing more often than Dr. Frisen’s measurements suggest, he said. “Now let’s discuss the magnitude of the process, and that will let us think about how we can apply this concept to heart failure,” Dr. Anversa said.

Dr. Frisen said he did not agree that the rate of regeneration had been underestimated. He said it would now be worth trying to understand how the regeneration of heart muscle cells was regulated. 

A zebrafish, for instance, can regenerate large regions of its heart after injury, and possibly a similar response could be induced in people. It could also be that the heart does generate many new muscle cells after a heart attack but that the cells fail to establish themselves. Drugs that kept any such new cells alive could be helpful, Dr. Frisen said.

Wednesday, April 1, 2009

"Centre to focus on rare diseases"

The Singapore Experimental Therapeutics Center is focusing on rare diseases.

That's actually not a bad idea at all. Given our lack of resources, focusing on niche areas will reduce the level of competition while raising the likelihood of success. That's because unknown to most lay people, Phase III clinical trials for new drugs involves showing improved clinical outcome of the experimental drugs vis-a-vis the existing gold standard for treatment. If the existing treatment is "nothing" or something purely palliative, then passing Phase III is practically a cinch if the new drug actually works.

Incidentally, knowledge of how the clinical trial process works is also why I'm always deeply skeptical whenever our local media reports (always in 'breathless tones') on how compound X is now being tested by Singapore company Y in clinical trials (invariably Phase I and II). I'm like, yeah, whatever, hit the snooze button and get back to us after they've passed Phase III please. 

In addition, it might come as a shock to most people that it's distressingly often that articles like this get published. The truth is that coming up with a revolutionary new treatment that dramatically improves the clinical outcome for patients is as rare as a ... revolution. Many pharmaceutical companies are motivated to engage in all kinds of research chicanery in order to get their drugs approved, make them look like real performers, and then rake in the money while their drugs are still on patent. 

So developing drugs for rare diseases is, in a way, less susceptible to temptations of intellectual dishonesty. Certainly, the market for such drugs is smaller and less lucrative, so the temptation is correspondingly less.

However, Alex Matter is right in saying that "Once you publish these results, other scientists and doctors will sit up and take notice, and they will soon find that the drug can treat other diseases as well." What Matter is referring to, termed off-label use, can substantially boost the profitability of a drug. He mentions Glivec as an example. I can immediately think of another, Latisse, which I suspect might be a real money-spinner.

Finally, with climate change now gathering force, tropical diseases that were nearly as ignored as rare diseases may rise in economic importance. Focusing on drug discovery and development in this related area could well be an excellent investment as well.