BLOG: High expectations for melanoma drug ipilimumab
Monoclonal antibodies light up rat tissue culture
I wrote about the cancer drug ipilimumab last year, which has been hailed as miraculous by some. The drug has been through Phase 3 clinical trials and results will be presented on June 6 at the annual meeting of the American Society of Clinical Oncology (ASCO).
Meanwhile, following announcements of the miracle cure in three men having prostate cancer, ipilimumab has also been show to be modestly effect against lung cancer, according to the company.
Ipilimumab works by targeting an inhibitor of the immune system called CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) and subsequently boosting the response of the killer T-cells. It belongs to the highly promising monoclonal antibody field of therapeutics.
Quote from a press release sounds like the company is excited:
“We are excited by the potential of immuno-oncology, an entirely new paradigm in the treatment of multiple types of cancer in which a patient’s own immune system is activated to fight cancer cells,” said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer and president, Research and Development, Bristol-Myers Squibb.
“We are leading the way with ipilimumab, the most advanced investigational compound in our immuno-oncology portfolio, in testing this new paradigm and we look forward to presenting results from the ipilimumab clinical development program at this year’s American Society of Clinical Oncology Annual Meeting.”
But while the promise of the basic science is cool, it’ll be difficult to draw conclusions about the real-world application of the drug until the results are formally presented and peer reviewed.
BLOG: Need Greater Public Investment in Agriculture
A blog based on ideas fermenting in the DC think tank/ policy sectors
The chicken farm in Food, Inc. reminded me of a poultry farm in a village in Karnataka, India. The chickens in that farm were healthy and caged in separate coops. It was a clinical operation; the neatest farm of any variety I’ve visited in India.
In Food, Inc., the fat birds (they have excess breast tissue) totter about on their feet, unable to carry their own weight before collapsing.
With a burgeoning population and the challenges that agriculture will face in the coming years with changing climate and water scarcity, the question of how to feed everyone is becoming increasingly relevant. The answer doesn’t have to be factory farming controlled by a small number giant corporations. It could be a network of smaller farmers using the best of technology to increase productivity despite smaller land sizes, according to an agricultural expert Gerald Nelson from the International Food Policy Research Institute. He was speaking at a conference in Washington, DC last week.
But to ensure that the control and choice of technology and farming remains in their hands, greater public investment in agriculture is critical. Food, and knowledge of food, needs to move back into the public sphere. The farm to table movement is important, not because it argues for a return to an ancient, unsustainable agriculture, but because it calls for greater transparency.
Not to say the private sector hasn’t made critical advances over the past few years as governments have slashed agricultural spending. But their responsibility to their shareholders makes profit the overarching ideal. They plan with the short-term motive of money in mind without seeing a grand master plan for the planet or the human race.
In Search of Chlamydia
The cement trough yawns below me, an abyss filled with streaming sewage hundreds of feet below. The smell is pungent and faintly urine-like as wastewater from streams and rivers mixes with household waste to create a haven for the bacterium that is my nemesis: Chlamydia.
“You know what’s in the sewage?” asks the beefy engineer at the Woodward Avenue water purification plant in Hamilton, a small city in Ontario once famous for its steel. These days, it is more known for its non-achievements: steel mill layoffs; Ti-Cats football fanatics who shout “Oskie-Wee-Wee! Oskie-Wa-Wa! Holy mackinaw! Tigers…ha! Ha! Ha!” even as their team repeatedly loses; and an underdeveloped downtown core with an overdeveloped pigeon problem.
But Hamilton is also a city of waterfalls and streams, rivers and harbors, all a natural home for Chlamydia. As, of course, is sewage.
“Corn,” the engineer answers himself seriously. “Corn doesn’t get digested. It passes through the intestine intact.”
He hands me five liters of the waste water.
Under a darkening sky, I drive back to my research laboratory at the McMaster University hospital and lug the jugs of water upstairs, past the red zone where just-born infants rest peacefully in plastic incubator cages, under individual yellow bulbs.
Rather like plants.
Children are at great risk of infection by Chlamydophila pneumoniae, which causes pneumonia. Its cousin Chlamydia trachomatis is infamous for causing the sexually transmitted disease Chlamydia, which can result in blindness. Prachlamydia and Simkania cause respiratory illness. Waddlia causes abortion in cows.
I run through the list, memorized for my upcoming thesis defense. The next sentence in the presentation goes so:
New species of the bacterium are still being found, in places as far-flung and extreme as Antarctic salinity lakes. Wherever they are found, they are pathogenic. And yet, their presence in our environment, in our water sources—rivers, ponds, and lakes—has been largely ignored.
My job is to figure out a way to detect them that lab technicians can employ easily, an amazingly difficult task as I’ve found out over the past four months. I have trudged through forests and swamps and manmade reservoirs located next to deserted hiker’s trails and country roads and highways. I have watched the Red Hill Expressway, intended to cut travel time between Hamilton and Toronto in half, grow from a muddy road to a cemented monster, all the while collecting water from the Red Hill Creek. The different water sources have distinctive fauna and flora that comes to life under a microscope.
A single drop of water is a universe unto itself, inhabited by creatures of reduced proportions. Magical shapes drift in and out under 40 times magnification—translucent amoebas, paramecia, rotifers, sun animalcules (“little animal”) with hair-like flagellum around them like a halo, and other strangely beautiful blobs. These are the visible creatures.
My target is the inhabitant of a world of less than a single micrometer—invisible.
Invisible is what I feel as I pass into the purple zone of the hospital. Fluorescent bulbs cast shadows in the deserted hallway. Graduate students have fled their labs to quell their boredom in alcoholic beverages. I am alone in my quest for what I have come to view as an ethereal creature, my yeti. It exits, but has eluded me repeatedly. I do not know if this is because of human error, or because the water samples lack Chlamydia.
I do not know which answer I would prefer.
So filtering sewage is what it comes down to.
–
Every day, for the past four months I have performed the same set of experiments.
One. Collect sample. Spin sample in a centrifuge at 500 times the speed of gravity. This weighs down all the debris that can be thrown away.
Two. Take the “soup”—the resulting sample—and filter using paper with pore size of 1000 micrometers under strong vacuum. All but the biggest microorganisms will go through.
Three. Filter through a paper with one micrometer-sized pores. Only the smallest organisms will pass through.
Four. Add phenol and chloroform, chemicals that will cause the beautiful, mysterious living blobs to burst open, spilling out their genetic secrets—DNA and RNA—into the water.
Five. Amplify regions of DNA where the four bases—adenine, guanine, cytosine, and thymine—have come together in a sequence that, out of all the organisms in the world, are present only in the Chlamydial genome. The sequence is a signature as unique as a thumbprint, which, after many steps inside the nucleus of the bacterium, results in the “signature protein” CT429. No one knows the function of this protein, one of the thousands that allow these bacteria to grow and multiply and infect.
Six. Amplify regions of DNA that correspond to Heat shock protein 70, a protein present in most organisms on Earth. It helps fold other proteins into shapes that must be painfully conserved for proper function. Misfolded proteins can result in disease—dementia and Lou Gherig’s, for example.
Seven. Separate amplified DNA fragments according to size and charge using agarose gel electrophoresis.
If the heat shock protein amplifies but the Chlamydia protein doesn’t, it means the water sample contained organisms of many varieties, but not Chlamydia.
Or it could mean that there is a glitch in the experimentation.
This uncertainty is ever present in the lab, I have found. Why did something not work? Or why did something work? Was the result an outlier? Could it be possible that the wrong sequence got amplified due to primer mismatch? Perhaps the AGTCCCT primer, instead of attaching to TCAGGGA, attached to a region of the DNA that goes TCACGGA. Now the wrong region is amplified, a size of 600 base pairs instead of the 400 base pairs that I am expecting.
Or perhaps, serendipitously, the wrong region is also 400 base pairs long, creating the illusion of the perfect match. Voila! The protein is found! Chlamydia exists!
But clone the region into a vector and re-amplify. Sequence. The protein sequence is not the same as for CT429. The wrong protein got amplified. Chlamydia doesn’t exist.
–
I pour the sewage into 1000 ml centrifugation bottles. The lab vibrates as the ancient machine spins. I bounce slightly on my toes in rhythm with the rocking cultures of bacteria grown by my colleagues.
This is a world of objectivity, ruled by the gods of precision and accuracy. But much as life itself, the world of experimentation is ruled by uncertainties, with a result true to perhaps a 90th percent of certainty, or 95th percent. There are no final answers.
But there is always the quest.
Raj Rajarathnam’s Bail
Galleon founder Raj Rajaratnam looked unusually charming in person. Surrounded by a troupe of lawyers inside the magisterial courtroom in Manhattan’s Second District Courthouse, he was calm, unflappable and dressed in a uniform black. A newspaper sketch artist hovered around him like a fly, closely studying his sideburns for exact representation in pastels.
The court room was packed in respect for the large sums of money — $100 million, $2.5 million etc.–under discussion. Nothing like white-collar crime to attract the media in New York. I left my cell phone and camera at the office and rode up to the court from the clerks office with a PR rep for Raj. He had a whole retinue of lawyers, media reps and hangers-on.
The Galleon founder was asking the judge to reduce bail. Words flew in measured tones as the defense adopted a submissive stance. The white-haired lawyer John Dowd seemed like he didn’t have a good response to give to the question: why reduce the bail to $25 million?
The obvious answer is that it’s just too much. $100 million dollars. I wonder at which million our comprehension of the extent of that sum breaks down. But this argument lacks logic. Dowd struggled to give a better one. It seems that Rajaratnam had only scrounged up $2.5 million in cash, and paid the rest in securities and property.
The prosecution (comprising 3 from the DA’s office and one FBI agent) was confident in its arguments. They revealed new evidence saying that they had found a senstive IM transmitting information about Polycom (a California based tech company) between Raj and an accomplice. The IM said: “don’t proceed on PLCM until I give further guidance.”
At the end of the hearing, the judge refused to reduce the bail but allowed Raj travel privileges within the United States. Everyone got up and the courtroom cleared to judge once again, stories of more normal and less expensive criminal behavior.
I traveled back down in an elevator filled with chatty Raj hangers-on who quickly shushed themselves upon my arrival.
Read the story here –>
Evolution: A One-Way Street
Since Darwin, evolution has been in vogue. Most scientists take it on principle that accumulation of mutations in DNA over million of years leads to new life forms.
But a question that has intrigued researchers for some time is whether organisms can go back to their ancestral forms. Is evolution is reversible? Conventional wisdom—known in the sphere of evolutionary biology as “Dollo’s law” after pre-eminent dinosaur researcher Louis Dollo—says no. A recent study published in the journal Nature has elegantly confirmed that evolution is a one-way street by studying the process at the molecular level.
As evolution occurs, the changes are so intricate that it becomes nearly impossible for the organism to go back to its original form. Freshwater fishes that live in a dark cave will lose their eyesight over generations. Even if a landslide creates an opening in the cave and lets in some sunshine, it is highly unlikely that the eye will reform.
Dollo’s theory has remained mostly unchallenged, except for a few works that say that evolution is reversible. In 2003, a team of scientists said that they’d found a species of snail that had regained its ability to coil into a loop after having lost the trait in previous generations.
“But their methods were unreliable,” said Boris Igic, a professor of biology at the University of Illinois in Chicago who was not affliated with the study. The snails could either have gone back to their original genetic makeup, or they could have gained new proteins that give it the old coiling.
The problem was that there was no real test to prove these theories. Evolution of organisms takes millions of years, making it difficult for scientists to make any direct observations.
Joseph Thornton, a biology professor at the University of Oregon, and his colleagues went around the problem by examining a single protein that helps humans and vertebrates cope with stress.
Millions of years ago, a fish existed that lacked bones. It is the ancestor to most life forms on earth today. That fish contained a small protein called the glutocorticoid receptor, which became active in the presence of two distinct hormones.
Over the course of the next 40 million years, the receptor evolved and became more specific such that it activated in the presence of only a single hormone—cortisol. It had accumulated 37 changes, but only seven were necessary to make it into the new receptor.
The researchers wanted to find out whether evolution could reverse at the level of the protein. To do so, they reversed the seven changes.
“But to our surprise, we got a dead receptor when we reversed,” said Thornton.
They found that the only way to make the protein reverse completely was to make five extra changes. These five fine-tuned the receptor, but did not give it a new function.
The probability of all five of these changes getting reversed is highly unlikely since they don’t confer a new advantage to the organism. They act like brakes that have to be removed to make evolution a two-way street.
Once the scientists fixed these five, they found that making the seven key changes reversed the protein to the ancestral form. They called the five brakes “ratchets” that prevented reverse evolution.
“This is not to say that the ancestral function cannot be re-acquired,” said Igic. But the function will come from forward evolution rather than a reversal. When whales evolved from a four-legged terrestrial ancestor, they evolved new proteins that resulted in fins. It was a reversal in function toward an ancestor of tetrapods that could swim, but in biochemistry, it was a movement forward.
Natural selection can take numerous paths during evolution but once those paths are chosen, reversal is highly unlikely. This is the first study of its kind, but Thornton does not expect this to be a rare case.
That an experiment at the molecular level can deliver a decisive conclusion about higher-order evolution is testament to the elegance of life.
“Everything that makes us who we are is stored in DNA,” said Ortlund, a biochemistry professor at Emory University, and co-author of the study. “Changes at the macroscopic scale have to start at the molecular level.”
Elixer Of Old Age
The indigenous people of the Ryukyu Islands have, it seems, the elixir of old age. They live on average for 110 years.
They longevity has been tied to their eating habits, and termed the Okinawa diet by commercial interests. The islanders consume only 1 calorie per gram of food, primarily through green and yellow vegetables, grains and very little sugar. Essentially, they are eating a nutrient-rich, low-calorie diet that triggers a stress response within their cells.
The years of low calorie consumption leads to a long, healthy life, say the proponents of the diet. A recent article by Dr. Sandy Westerheide and colleagues in the journal Science provides support for this theory, although in organisms several orders of magnitude less complex than humans.
The nematode Caenorhabditis elegans responds similar to human cells in times of calorie restriction. Within the millions of cells that make up the tiny nematode, there are specific pathways that act in concert to keep the organism going.
In response to stress such as reduced calorie intake, the cells adapt by changing their pathways, according to Dr. Westerheide. They do so in tiny increments that, in the way of life, have amplified results—in this case, increased longevity.
The key players in the pathway that get changed are highly conserved proteins that are the master controllers of the microscopic world of the cell.
They are called transcription factors. They tell the cell whether to grow, divide, fight invaders, specialize, or commit suicide. Their functions are as ubiquitous in humans as the nematode, although small differences in sequence may exist.
Dr. Westerheide focused on two proteins, the enzyme sirtuin 1 (SIR1) that increases the production of the second protein, heat shock factor 1 (HSF1). Both increase in concentration within cells when the body consumes fewer calories.
The ultimate result is an increase in HSF1 production. This protein works entirely by binding to DNA, and sending signals that promote growth.
In aging individuals, there is less SIR1, and in the absence of this protein, HSF1 can no longer bind DNA. There is no growth. Instead, there is aging, and eventually, death.
But in an individual who meticulously controls his or her calorie consumption, a stress response is triggered. These responses, learnt early in evolution, are protective mechanisms that allow cells to remain alive in the face of harsh conditions—thermal stress faced by single-celled bacteria on hot sulfur springs, oxygen toxicity faced by the lung cells of scuba divers, and calorie restriction faced by cells in Ryukyu islanders.
In the nematode, the stress response increases the levels of SIR1. This leads to increased binding by HSF1 to DNA, leading to growth signals even in an aging cell.
That is the secret of the long life of the healthy nematode. Whether HSF1 has a part in the response in higher organisms remains to be seen, but SIR1 looks important.
And given that cancer cells have strong stress responses, Dr. Westerheide’s work indicates a role for HSF1 in forming tumors, something that has been hinted at already by other researchers.
Small proteins have big roles in the elixir of the Ryukyu islanders.
PricewaterhouseCoopers and Rivals are Recruiting More M.B.A.s
Sept 11, 2009 – PricewaterhouseCoopers is ramping up its hiring of M.B.A.s, with plans to recruit 75 to 100 business-school graduates in 2010.
The Big Four accounting firm planned to bring on 60 to 90 graduates from master’s degree in business programs in 2009, up from 40 last year.
“We’ve found that we have excellent return value from M.B.A. hires,” said Margaret Burke, human-resources leader for the advisory practice based in New York. “They are able to make an impact quickly.”
Crack 03.09
March, 2009—Amy Keenan, 25, sat in her faded denim jacket and blue jeans as the cold March wind blew. Her fair skin was pockmarked — red spots surrounded her forehead and mouth. She picked at her face when she smoked crack cocaine sitting on the rooftops of the Van Dyke projects in Brooklyn.
As she took a drag out of her pipe, she surveyed the scene from atop the building. The Brownsville neighborhood of Brooklyn lay before her—multi-story brown housing with off-white blankets stuffed into rectangular window panes; gray cement roads filled with old model SUVs; the yard of a pipe-manufacturing plant; a metal salvage yard with a three-storey-tall pile of rusted hubcaps and the backbones of schoolroom chairs; black polythene bags caught in the barbed wire fences; faded graffiti on the walls; a memoriam to a young man named “Peanut Head”.
Her hair was tightly tied back and ended in a bunch of small blonde curls sticking up around the top of her head like a crown. Her eyes were cyan-blue, big and glazed. Her lashes were long—she had pretty eyes. They helped her turn tricks in the primarily non-white neighborhood. They got her attention from the cops—hefty white men who hung out two to a block on street corners. When they saw an unkempt white girl walking down the street, they knew she was either an addict or a prostitute.
Amy was both. She wanted to be so much more, but she didn’t know how. She was stuck between her past, and the lack of a future. Crack, and sometimes dope, and sometimes whatever she could get—angel dust, tranquilizers—helped her turn away from a past of sexual abuse she said she had suffered at the hands of her older brother in her middle-class duplex home in Vermont.
When the cops moved away, the dealers occupied the same corners—two or three outside La Crema Deli or the Dominican restaurant. They knew her, too.
They knew she’ll “bust a head”—“bust head” is the new term for a “crack head because they will meaning service men for cheap—for $20 or a crack hit. Especially when she was on a binge. They tempted her.
“Hey, you want something?”
Sometimes, she ignored them, shouting, “Leave me alone.”
Most times, she took whatever drug or money was offered. With her income she supported Eric Irizarry, 33 (or “Eddie Machete”), her boyfriend of seven years, and their landlord—a phantom-like man who shared his living space with them for $10 a day and whatever amount of crack she could give him. She didn’t like sharing, but didn’t have much of a choice—it was better than being homeless.
She shared her crack pipe, her STDs—Hepatitis C, gonorrhea, syphilis; she used to share her needles when she had done heroin. She didn’t have HIV despite sharing a barely-sterilized needle with a HIV-positive man.
She sat at the edge of the roof, staring down, cocaine smoke rising around her. She had not been home in three days. She was in the middle of a crack binge, selling her body to satisfy the cravings of her mind.
Four days ago, she hadn’t smoked crack for a few days in a row. If she didn’t smoke in the morning, she’d be clean for the entire day. But Eddie had become impatient for money. The next day, he’d placed a crack pipe below her nose and woken her up. She’d smelled the drug and had to smoke. Then she’d left in search of highs bigger than the previous hit.
She knew she shouldn’t be with him, but she had nobody else. And ultimately, using drugs was her choice. She dragged him down as well, tempting him when he tried to stay clean. They dragged each other down.
Amy Keenan is one of approximately 2.1 million current users of cocaine aged 12 and older in America, and 8.5 million lifetime users in 2007, a number three times larger than the number of heroin injectors[1] [2]. Crack cocaine is widely available on the streets and is cheap. Although its popularity among the younger generation has declined since the late 1980s, about 350,000 people aged 12 and older smoked it for the first time in 2007.[3] And research has revealed that consistent users of crack persist with their addiction for a decade or longer.[4]
[1]2007 National survey on Drug Use & Health < http://www.oas.samhsa.gov/NSDUH/2k7NSDUH/tabs/Sect1peTabs1to46.htm#Tab1.1A>
[2] Substance Abuse and Mental Health Services Administration, Office of Applied Studies (2008). Results from the 2007 National Survey on Drug Use and Health: National Findings (NSDUH Series H-34, DHHS Publication No. SMA 08-4343). Rockville, MD: http://www.oas.samhsa.gov/nsduh/2k7nsduh/2k7Results.cfm#TOC
[3] Substance Abuse and Mental Health Services Administration, Office of Applied Studies (2008). Results from the 2007 National Survey on Drug Use and Health: National Findings (NSDUH Series H-34, DHHS Publication No. SMA 08-4343). Rockville, MD: http://www.oas.samhsa.gov/NSDUH/2k7NSDUH/tabs/Sect8peTabs1to42.htm#Tab8.30A
[4] Falck, R. S., Wang, J., & Carlson, R. G. (2007). Crack cocaine trajectories among users in a midwestern American city . Addiction , 102, 1421-1431.
U.S. come under criticism for swine flu vaccine policy
Given that swine flu vaccines are in short supply ahead of a predicted fall epidemic, U.S. plans to use the vaccines in their raw form, without ingredients to swell supplies, has come under criticism.
The additives, called adjuvents, were recommended by the World Health Organization to increase global supplies of the vaccine. They also boost immunity by increasing the strength of the antigen by as much as 10-fold.
But the U.S. health department has said that it won’t use adjuvents if it has enough of the antigen supply to vaccinate residents.
“Adjuvent use would be contingent upon showing that it was needed or clearly beneficial,” said Jesse Goodman, acting chief of the Food and Drug Administration on July 17.
The medical journal Lancet criticized the policy in its editorial, saying that it is irresponsible, given the low supplies of vaccine globally. The problem is that H1N1 viruses don’t grow well in eggs, and the strains yield only 30% to 50% of antigen as compared to other flu strains.
The U.S. will test flu adjuvents and “review all clinical data to inform our decision on their potential use,” said Bill Hall, a spokesman for the Health and Human Services Department to Bloomberg News.
Madurai’s memoir: a Canadian refugee remembers Sri Lanka
Protests in Toronto (photo from Flickr under CC license)
Names have been changed to protect identity.
February 2009: Madurai’s longing for the country she would never again know had become a sharp pain. That morning, she had gone to Toronto to become part of a human chain protesting the Sri Lankan civil war. She, like many others, had desperately wanted to fly the flag of the Tamil Tigers in solidarity, but couldn’t, since Canada had labeled the rebels terrorists. About 45,000 people had shown up for the protest according to Canadian media, a human chain linking a mass of people to a fragile cause being blown away, bit by bit, by the army.
The same had happened in 1994.
—
Rumors had abounded for weeks, faint whispers that the army is nearby. But the people stayed on, feeling safe under the protection of the Tigers.
Then one day in 1994, under a darkening sky that poured spikes of rain, a column of civilians left Jaffna.
M was 10, a small girl. She had already traveled much of northern Sri Lanka on foot. Born on the small fisherman’s island off the northwestern coast called Velanai, her family had fled in the middle of the brutal second Eelam War of the early 90s.
Velanai had been safe until 1990, when the bombs started falling. The planes had different sounds, depending on altitude, remembered M. They would come close to the ground to bomb, and there would be great noise. M’s family would hurriedly open the bunker below the kitchen floor and escape into the basement darkness to wait it out.
In that year, a census revealed that 22,000 people had lived around Velanai. Following military operations by the Sri Lankan Army and Navy, 14,000 Tamils left the region, a mass exodus in search of protection with Tigers.
M’s mother left the island without food, with 25 rupees, and three young children—M, her elder sister Vimali, and younger brother Arasan. They began their trek southwards to Jaffna, a hub of the Tamil Eelam.
Jaffna was an important city to the rebels, a showpiece to prove to the world that the Tigers are capable of forming their own nation. The rebels set up alternative administrative systems—police stations, banks, and schools where children learned to design models of mini-Eelams with clay.
M first came face-to-face with the Tigers in Jaffna. They lived in three camps behind her aunt Lakshmi’s house and helped her with her homework. It was a brief lull of piece in a wartime characterized by unending violence.
One day came the all too familiar noise of low-altitude planes scouting the region, a sign of bombing to come. M ran swiftly through streets of Jaffna toward home, until she met one of the ubiquitous stray dogs that littered the streets. Frightened by the whirr! of the planes, the dog bit her.
She heard later that an elementary school had been bombed.
Soon after, M and her family left Jaffna in a long cavalcade of displaced refugees. They carried food and clothing in small packages, balanced precariously on bicycles. They pushed the cycles along, even as the hard rain poked into their eyes. They moved east, to Chavakachcheri, a town 10 kilometers from Jaffna.
They went through a small forest and crossed a flooded bridge in an intense darkness created by the storm. M was submerged to her knees but her family was preoccupied with helping her 70-year-old grandmother cross the junction. They reached a bumpy road that cut through vast empty spaces and, after a single day’s trek, arrived in Chavakachcheri.
By 2009, Chavakachcheri no longer existed. In 2002, intense bombing by the army had left the town a mere shell of what M witnessed in 1994. Bombed out shops and hospitals served as a testament to a once-bustling town.
From Chavakachcheri, M left for the Vanni district, of which Killinochi is the capital. There she caught malaria, but medical help was far away. Her family waited for her to get cured before moving, once again to the south, to Colombo.
From Colombo, they arrived as refugees of the Sri Lankan civil war in Canada where her father was stationed.
—
M, 24, felt like one of ‘them’—the Tigers who had given up so much to fight for her language, her culture. Arriving in Canada at the age of 12, she had been full of hope and childish excitement at a future in the great West. But soon her excitement gave way to a longing, amplified by the absence of any connection with her birthplace. Everyone in Velanai had moved away.
But in a way typical of immigrants who are ever in danger of losing their roots, M became a preserver of Tamil custom. Even after living in Canada for 12 years, she spoke English uncomfortably, with a heavy accent, as though it was not quite her native tongue. Often, she would use Google Maps to zoom into the little island and locate her home. It was next to the hospital and the elementary school, just as she remembered it. It had survived the years of war, through the Allaipiddy massacre in 2002, when masked gunmen killed 13 Tamils in their homes in her island.
Then in October 2008, the government began the final offensive against the Tigers. Intense fighting led to the capture of rebel-held towns of Killinochi and Jaffna. Today, most of the Tamil Eelam fought for by the Tigers over the past three decades has been won over by the government. For the refugees who fled, their sense of helplessness knows no bounds.
There are some 250,000 Tamils left in northern Sri Lanka, according to aid groups. They are trapped in a small area by the intense fighting between the army and the Tigers. When M tried to contact her cousins, they couldn’t discuss the war for fear of being overheard. Indiscrete people who challenge the government are often gunned down under mysterious circumstances.
“There are so many people trapped within, they don’t know where to go,” said M. “Before when we had the big displacement, we were able to move from Velanai to Jaffna to Vanni, but now they don’t have any places. They don’t have food and medicines. They don’t have proper shelter.”
The media has been restricted in airing footage, but M has different sources for news. She relies on underground Tamil television channels that broadcast footage from the warzone. These are picked up and rebroadcast through YouTube, an underground channel of communication watched by refugees throughout host countries that have labeled the Tigers and their cause terrorism.
It is through that network that M found out that only 26 Tamils had taken refuge in a 35-square kilometer safe zone created by the government. It was a good thing too, for the army soon bombed the area.
“People there don’t trust the government,” said M. “They want to be with the tigers.”
“If you know the tigers from inside, rather than from outside, you’ll know that what we want to do is fight for freedom and actually run a country,” she added, forgetting for a minute that she was not actually a Tiger.
Aid agencies have estimated that hundreds of civilians have been killed so far in the army’s offensive. Hospitals and ambulances have been hit. The United Nations chief in Sri Lanka labeled the situation as a “very grave abuse of human rights.”
But M is not without hope.
“Right now, it looks like the government will take over,” said M. “But it doesn’t mean that the Tigers are going to vanish forever. I think they are going to fight back when unexpected.”
She paused.
“That’s the hope.”
Miracle prostate cancer drug not so miraculous?
The Mayo clinic reported over the weekend in its news section that two men with late-stage prostate cancer were successfully treated with a monoclonal antibody treatment (one of the most promising areas of research for cancer drugs) developed by Medarex Inc. Shares increased by 20% on Monday. An article by the AP pointed out at the time that the news must be treated with caution.
Mayo has not included a summary of Phase 2 clinical trials of the drug in its news, as pointed out in Seeking Alpha. The Phase 2 results were presented at the Memorial Sloan-Kettering Cancer Center on May 29-June 2, 2009.
In their report, researchers said that of the 45 patients had been treated with the drug (16 with Ipilimumab alone, 15 with the Ipilimumab + other drugs, and 14 with Ipilimumab + other drugs + chemotherapy).
Antibody declines of 50% or greater were seen in 10 out of the 45 patients, or 22%. Only one patient who was solely treated with Ipilimumab demonstrated complete resolution of lesions.
Alas, the drug may not be so successful as the hype suggests. Why did the researchers release the results of just two patients, with no reference to the larger study presented at the conference? Something shady. Others agree.
Songs About Time
From The Rentals website
Came across a blog post in BBG about Fuji Film giving The Rentals 365 limited edition black-and-white film to capture the making of their new album Songs About Time.
You can see the photo diary here: pretty cool.