Thursday, December 24, 2015

Through The Looking Glass: Can A Cheap, Portable Microscope Revolutionize Global Health?

Alan: Gregory Bateson observed that "Natural History is the antidote for piety."

I would build on Bateson's observation by saying that scientific enterprise aspires to make the invisible -- or, what once would have been called "the spirit world" -- visible.

I am a firm believer in revering the Magnum Mysterium but unless a person lacks the mental ability to learn science, I am opposed to any form of religious piety that focuses people on "the spirit world" to the exclusion (or even the diminishment) of one's ability to bring "the invisible" to the light of day.

It is not our human "purpose" -- or even our innate "directionality" - to remain in uterine darkness but to bring full consciousness to Light.

I have always admired the indwelling wisdom of language and within this frame note that the most colloquial way to say "give birth" in Spanish is "dar a luz" --- "to give to light."

On this Christmas Eve when Christians commemorate the coming of New Light into the world, may we see fit to radiate all the light that is in us.

Fiat lux.

Arguing against those who said that natural philosophy was contrary to the Christian faith, (Aquinas) writes in his treatise "Faith, Reason and Theology that "even though the natural light of the human mind is inadequate to make known what is revealed by faith, nevertheless what is divinely taught to us by faith cannot be contrary to what we are endowed with by nature. One or the other would have to be false, and since we have both of them from God, he would be the cause of our error, which is impossible."
"Aladdin's Lamp: How Greek Science Came to Europe Through the Islamic World" by John Freely

St. Thomas Aquinas, Natural Law, And The Common Good
Aquinas Quotations

Annals of Science 


Through the Looking Glass

Can a cheap, portable microscope revolutionize global health?


Antoni van Leeuwenhoek wrote a letter to the Royal Society of London, in 1683, announcing the discovery of something extraordinary in his mouth. He was a haberdasher by trade, in the Dutch city of Delft, but he was known for his enthusiastic work with microscopes, which he made himself. By modern standards, Leeuwenhoek’s devices were rudimentary, and fickle in their operation. They were nearly flat, consisting of a tiny magnifying glass sandwiched between metal plates, with an adjustable spit to hold the sample being viewed. But they could be effective, particularly when an unsqueamish eye was at the peephole. Leeuwenhoek had already examined eels’ blood, dogs’ sperm, and the bile of elderly rabbits, among other substances. Now he had turned his attention to dental plaque.
Leeuwenhoek had an intensive routine of oral prophylaxis, which involved rubbing salt on his teeth each morning and buffing his molars with a cloth after meals. Nevertheless, he wrote, the plaque lay “thick as if  ’twere batter.” He scraped some off, mixed it with rainwater, deposited a droplet on one of his microscopes, and held it up to the light. The sample was teeming with “many very little living animalcules, very prettily a-moving.” When he reproduced the experiment with the plaque of an old man, he found even wilder specimens, which “bent their body into curves.” Leeuwenhoek had revealed a world that few of his contemporaries were willing to believe existed. As he lamented to another microscopist in 1680, “I suffer many contradictions, and oft-times hear it said that I do but tell fairy-tales about the little animals.”

In September, a biophysicist named Manu Prakash examined some of his own plaque, at high magnification, in honor of the anniversary of Leeuwenhoek’s letter. Prakash, who is thirty-five, is slightly built, with curly brown hair, a beard, and a birthmark like a child’s thumbprint over the bridge of his nose. He doesn’t floss, and perhaps for that reason he found that his plaque contained spirochetes, bacteria that bend their bodies into curves when they move—what Leeuwenhoek observed in the old man. Prakash has his own laboratory in Stanford University’s bioengineering department, and he is best known for having invented a microscope, which was inspired by Leeuwenhoek’s. He has a passion for what he calls the “microcosmos,” meaning all things infinitesimal. “It’s not good enough to read about it,” he told me. “You have to experience it.”
One major difference between the two microscopes is that Prakash’s is made almost entirely from a sheet of paper. He calls it the Foldscope, and it comes in a kit. (Mine arrived in a nine-by-twelve-inch envelope.) The paper is printed with botanical illustrations and perforated with several shapes, which can be punched out and, with a series of origami-style folds, woven together into a single unit. The end result is about the size of a bookmark. The lens—a speck of plastic, situated in the center—provides a hundred and forty times magnification. The kit includes a second lens, of higher magnification, and a set of stick-on magnets, which can be used to attach the Foldscope to a smartphone, allowing for easy recording of a sample with the phone’s camera. I put my kit together in fifteen minutes, and when I popped the lens into place it was with the satisfaction of spreading the wings of a paper crane.
The Foldscope performs most of the functions of a high-school lab microscope, but its parts cost less than a dollar. Last year, with a grant from Gordon Moore’s philanthropic foundation (Moore co-founded Intel), Prakash and some of his graduate students launched an experiment in mass microscopy, mailing fifty thousand free Foldscopes to people in more than a hundred and thirty countries, who had volunteered to test the devices. At the same time, they created Foldscope Explore, a Web site where recipients of the kits can share photos, videos, and commentary. A plant pathologist in Rwanda uses the Foldscope to study fungi afflicting banana crops. Maasai children in Tanzania examine bovine dung for parasites. An entomologist in the Peruvian Amazon has happened upon an unidentified species of mite. One man catalogues pollen; another tracks his dog’s menstrual cycle.
With my Foldscope, I looked at peach flesh, pinkie cuticle, Himalayan sea salt, and grime from a subway pole. (The last of these resembled a Klimt painting stripped of color.) Prakash likes to abet this sort of observation, and he engages in it himself, contributing to Foldscope Explore frequently, even though he has seventy thousand unopened e-mails. A video of his teeth scrapings is there, as are photos of “the gazillion little things” that sprayed from his mouth one night during a coughing fit.
One of Prakash’s interests is biomimicry—understanding how and why certain organisms work so well, and using that knowledge to build new tools. “Plants, insects, tiny bugs under the sink, bacteria, day after day, accomplish things that no scientist anywhere in the world knows how to do,” he has said. Among insects alone, about nine hundred thousand species have been named, but millions more remain to be identified and described. The Foldscope increases Prakash’s reach. “I now have eyes and ears around the world looking at small things,” he told me.
Prakash’s hope is that those eyes and ears will make discoveries of their own. He and his chief collaborator on the project, Jim Cybulski, plan to make the Foldscope available for purchase by the summer. Prakash is particularly keen on getting kits to people who live without electricity or modern sanitation, and who have likely never observed the microcosmos directly. In October, India committed to rolling out a countrywide Foldscope program. Prakash is travelling there to demonstrate the instrument to teachers, students, health-care workers, and forest rangers. (It isn’t yet clear how the Foldscope will help the rangers, who are mainly concerned with the survival of the one-horned rhinoceros.) “There’s a very deep connection between science education and global health,” Prakash told me. “Unless you get people curious about the small-scale world, it’s very hard to change mind-sets about diseases.”
MICROCOSMOSManu Prakash discusses the beauty of the microscopic world.

The idea for the Foldscope crystallized when Prakash was in Thailand, in 2011. “I found myself at a field station that had a really expensive microscope,” he said. “Everyone was afraid of it. It was worth five times the salary of the person trying to operate it. It just made no sense, out there in the jungle.” Three years later, with a prototype Foldscope in hand, he and Cybulski, who was then his student, went to Nigeria to conduct studies at a malaria research center in Lagos. One day, they drove north from the city to find a school. The students had just finished classes for the day, but Prakash persuaded them to stay so that he could show them the Foldscope. They caught a mosquito that was feeding on one of the children and mounted it on a paper slide, which they inserted into the Foldscope. Prakash passed it to the boy, who raised it to his eye and looked through the lens, using a small L.E.D. (also included in the kit) as his light source. “For the first time, he realized this was his blood, and this little proboscis is how it feeds on his blood,” Prakash said. “To make that connection—that literally this is where disease passes on, with this blood, his blood—was an absolutely astounding moment.” The exercise had its intended effect. The boy said, “I really should sleep under a bed net.”
Prakash sees the Foldscope as his main contribution, so far, to frugal science, the endeavor to create low-cost, easy-to-use tools that address serious problems, primarily in the developing world. In recent years, an increasing number of researchers at élite institutions have devoted their time to such inventions. Among the more ingenious are a centrifuge made from a salad spinner; a method for turning farm waste into charcoal briquettes using an oil drum; and a solar-powered sterilizer for surgical instruments, built from pocket mirrors and a pressure cooker.
George M. Whitesides, a chemistry professor at Harvard, works at the more complex end of the frugal-science spectrum, in microfluidics. He and his collaborators have created a series of paper-based medical tests, each about the size of a postage stamp. The tests are printed with lines of liquid-repellent wax, which separate a single drop of blood or saliva into small streams. The streams are then drawn across the paper, like red wine on a napkin, and mixed with an array of chemicals to produce a color-coded result. One test diagnoses liver toxicity, a common side effect of treatment for H.I.V., tuberculosis, diabetes, and heart disease. Another is being developed to determine whether a patient has been successfully inoculated against tetanus or measles. This year, a company that Whitesides co-founded registered the liver-toxicity test with the U.S. Food and Drug Administration, and it has recently started shipping the test overseas.

Inventors of frugal-science tools sometimes have trouble anticipating the problems that they will encounter in the developing world. Early on, Whitesides’s group was obliged to change the protective packaging of one of its microfluidics inventions. The test had been designed for use in an air-conditioned American lab, but the Indian lab in which it was being implemented was cooled with ceiling fans. In 2008, Christopher Charles, a Canadian researcher working in Cambodia, met with a similar hurdle. He had been exploring a way to reduce the incidence of iron-deficiency anemia, a serious local health problem, by placing small iron ingots in cooking pots. But Charles had trouble persuading people to use them. When he learned that fish are a symbol of good luck in Cambodia, he redesigned the iron lump as a smiling fish. After that, the ingots were more readily adopted, and the anemia rate fell forty-six per cent.
Prakash is aware of the difficulties inherent in transforming a lab-proven invention into a practical tool. He grew up in India and, as a child, was infected with latent tuberculosis, like a third of the Indian population. Keeping costs down, he told me, is especially important with the Foldscope. “This one-dollar number is not random,” he said. “When something goes from one dollar to ten to one hundred, people will fall off your scale.” Another essential element is cultivating a sense of ownership among the people and the organizations using it. “The fact that it’s such a modular tool—you can break it apart, you put it together—is very important,” he said. He cited the example of the Raspberry Pi, a credit-card-size computer that enables do-it-yourself programming and costs as little as five dollars. Prakash hopes to scale up his invention using aspects of what the Raspberry Pi Foundation has done—“starting small and focussing on the community of users, so that they get the best possible experience.”
It isn’t clear, though, whether his dreams for the Foldscope will be realized. Whitesides called it “quite a neat idea,” with definite promise as an educational tool, but he said that its utility beyond the classroom remained to be seen. (While Prakash and Cybulski were in Lagos, they discovered that the Foldscope, as it was then designed, could not be used to diagnose malaria, because its lens was too simple to reveal the telltale horseshoe-shaped parasite that causes the disease.) Kentaro Toyama, a professor at the University of Michigan School of Information and the author of “Geek Heresy: Rescuing Social Change from the Cult of Technology,” was similarly circumspect. He noted that the success of a tool like the Foldscope depends on how its users implement it, something over which Prakash ultimately will have little control. “What allows people to earn more—at least, in our current globalized economy—are skills that the market will pay for,” Toyama said. “It’s not the innovative tech doing the magic; it’s the effort to build human capacity.”

A cautionary tale might be that of One Laptop Per Child, a nonprofit founded in 2005. The company’s goal was to produce a low-cost, low-energy computer that organizations and the governments of developing nations could buy and distribute in schools. But teachers often didn’t know how to integrate the machines into their lessons, and many struggled with glitchy software. Studies of the laptop’s impact in Peru, Nepal, and Uruguay (the only country to buy enough units for all its primary-school students) found that it had no effect on reading or math skills. The company never succeeded in meeting its price point of a hundred dollars. In 2009, it cut its staff by half. Prakash noted that the Foldscope is quite different in concept from a cheap computer—simple, analog, and geared toward experience rather than information—but he praised O.L.P.C. for inciting new ways of thinking. As Wayan Vota, the founder of a Web site that tracked the project in the news until last year, has said, “The first person charging up the hill always gets gunned down.”
Manu Prakash’s grandfather taught him to swim by throwing him into a canal off the Ganges River in Mawana, the remote sugarcane town where he was born. “It was not all picturesque,” Prakash said. “There were fields full of trash.” But Mawana was where he first fell in love with insects, especially aquatic ones. He built his first microscope at the age of seven, using his brother’s glasses. Three years later, his mother, Sushma, accepted a job teaching political science at a community college in Rampur, five hundred miles away. (“The town is known for the Rampuri chaku,” Prakash said. “It’s a kind of knife—what gangsters use in Bollywood movies.”) His father, Brij, stayed behind to run a real-estate business, so Sushma rented an apartment for herself and the two boys.

“Don’t fall for it, Dogman!”

The previous tenant had been a chemistry teacher. “He was running a science lab in the house, but he didn’t pay his rent,” Prakash said. “The landlord evicted him, confiscated his lab, and didn’t know what to do with it, so he dumped all the equipment in the back.” Prakash and his brother developed an interest in combustion; one experiment involved building and then blowing up a ten-foot-tall wire-mesh effigy of Ravana, the Hindu demon king. Other projects were more practical. Xerox had a plant in Rampur, and sponsored an annual model-making contest. Prakash led teams to victory four years in a row, bringing home the grand prize—a teapot or a box of fine cutlery—to Sushma. His entries included a replica of the Exxon Valdez, the oil tanker that ran aground off the Alaskan coast in 1989, and an anatomically accurate rabbit skeleton made from the stinking corpses of two rabbits. (“They have about as many bones as a human,” Prakash said.) His classmates would approach him a year in advance, asking to be on his Xerox team. “I was the boss, even though I was a foot shorter than everyone,” he said.

At eighteen, Prakash enrolled at the Indian Institute of Technology, in Kanpur, where he majored in computer science. One day in 2001, Neil Gershenfeld, a professor at the Massachusetts Institute of Technology, came to give a lecture. Two students buttonholed him, expressing interest in continuing their studies in the United States. Gershenfeld discussed their cases with the head of the university. “I thought I was going to take the charming, eloquent, articulate one,” Gershenfeld said. “He advised me to take the other one. That was Manu.”
Prakash arrived at M.I.T. in 2002. He did most of his Ph.D. research at Gershenfeld’s Center for Bits and Atoms, an interdisciplinary program with generous funding and a stable of manic inventor prodigies—“a place where Manu can be Manu,” as Gershenfeld put it. Prakash made a name for himself in the area of microfluidic bubble logic, by demonstrating that water droplets could be made to store, carry, and process information, as electrons do in a computer circuit. While at the center, he met two people whose work later helped inspire elements of the Foldscope. The first was Erik Demaine, the youngest professor in M.I.T.’s history, who established the field of computational origami. The other was John Bush, a mathematician, who co-authored several papers with Prakash, including two on the feeding mechanism of the red-necked phalarope, an Arctic shorebird. As it eats, the phalarope moves its beak in a rapid tweezing motion, transforming food-laden droplets of water into aspherical shapes that are propelled up into its mouth. Prakash built an artificial version of the beak, which he is now developing to mold polymers into lenses for the Foldscope.
By 2008, he had racked up thousands of dollars in late fees at the library, and M.I.T. refused to grant him a degree. Nevertheless, he was awarded a post at the Harvard Society of Fellows, where he met Sophie Dumont, a biophysicist from Quebec. She loaned him money and her car so that he could return all the books he could find; M.I.T. gave him his Ph.D. Three years later, in Delhi, he and Dumont got married.
Their life is one of constant work, or constant play, depending on your perspective. She is a professor at the University of California, San Francisco, where she studies the mechanics of cell division. On weekdays, they are both at their labs. On weekends, at home, they work on independent research projects. “The kitchen is a lab now,” Dumont told me. “The dining-room table is a lab. The bathroom is also a lab. Well, it was always a lab.” They are hard pressed to name unscientific forms of leisure. “We don’t know anything about music,” Prakash said one afternoon, over brunch. He was wearing Crocs studded with a little rubber caterpillar and bumblebees, and he had ordered the chili scramble. “The last concert we went to, which was also the first, was Bon Jovi.” His wife corrected him: “Not Bon Jovi. Billy Joel!”

Dumont carries ziplock baggies in her purse to store the specimens that Prakash recovers—a spittlebug from the conifers near their apartment, a winged insect from a chili scramble. His constant Foldscoping, she told me, sometimes invites unwanted attention. On several occasions, he has had to do Foldscope demonstrations for airport security personnel. “At first, when I said they were microscopes, they were, like, ‘What the hell are you talking about?’ ” he said. “Then, by the end, they were so excited.” Dumont mentioned other incidents, like the time Prakash was asked to leave a park in San Francisco after someone reported him for suspicious behavior. “In general, the attitude toward science is not where it needs to be,” he said.
Earlier this year, Prakash took a phone call from his lawyers. He was in his office, beneath Stanford’s Science and Engineering Quad, an expanse of sandstone and Mexican fan palms on the school’s central campus. Although his lab was brand new, it already looked well used. The black countertops were covered with flotsam—pliers, tubes, clamps, an aquarium filled with light corn syrup. In Prakash’s office, a dead sea sponge sat on a table, like a big glob of soap foam. The lawyers wanted to know what he was calling the independent company that would oversee the scaling up of Foldscope manufacturing and, eventually, other frugal-science tools. They also wanted a mission statement. Prakash floundered. “One sentence that explains everything we’re doing!” he said.
In the lab, Laurel Kroo, a mechanical-engineering student, was researching the compound eyes of fossilized trilobites, a group of extinct marine arthropods, in the hope of improving the Foldscope’s lens design. Haripriya Mukundarajan, another mechanical engineer, was elbow-deep in a translucent box of live mosquitoes. With Prakash, she is working on an early-warning system for disease outbreaks. It uses a postcard that is covered in beads of chemical gel, which hungry mosquitoes mistake for human flesh. As the insects feed on the gel, they leave behind traces of whatever pathogens they are carrying—malaria, for instance, or the dengue virus. “When they bite you, they are essentially spitting into you,” Mukundarajan said. Volunteers leave the postcards outdoors for a week, then drop them in a mailbox to send them to a lab. Prakash and Mukundarajan are planning to set up the first field study, in Kenya, next year.
Another student, George Korir, was working on a prototype for a five-dollar hand-cranked chemistry set. Its base is a Kikkerland music box, which works like a player piano, with songs encoded on perforated rolls of paper. In Korir’s adapted version, the perforations tell the box what chemicals to dispense—each note prompts a pump of liquid. Given the right perforations and chemicals, it can detect contamination in water or soil. Korir, who is from Kenya and has been at Prakash’s lab since 2012, is also experimenting with ways to use the box to test for malaria in remote areas. (So far, he hasn’t been successful.)

Prakash and the lawyers concluded their phone call without settling on a name or a mission statement. He began filling a cardboard box with equipment for an experiment at home—coils of black rubber tubing, a vacuum pump—and then, noticing the time, he called, “Who wants to play soccer?,” and rushed out the door. The lab’s Friday game had already started.
At the field, I sat on the sidelines under a mulberry tree with Jim Cybulski, who has done more Foldscope studies overseas than any other member of Prakash’s lab, including Prakash. He looked exhausted. He was defending his dissertation, on frugal science, in a few weeks, and had recently returned from Kenya, where he had been experimenting with a new Foldscope adapted for diagnostics. He said that there had been problems with the original Foldscope when he had used it to screen for schistosomiasis in Ghana, in 2014. The illness, which affects more than two hundred million people worldwide, is caused by parasitic flatworms. Their eggs are detectable with a Foldscope, in urine samples, but it had been too difficult to try to prevent contamination, Cybulski said, and too tiring on the eyes to squint through a pinhole all day long. The new medical Foldscope, which would cost ten dollars, included a built-in projector, so that a team of health workers could view a slide together, without bringing it near their faces. Cybulski’s results from the Kenya test had revealed that fifty-four children, about half the study group, were infected with schistosomiasis, but he reported this as hopeful news. “With a diagnosis, now they will get treated,” he said.
Cybulski is sometimes obliged to play Sancho Panza to Prakash’s Don Quixote. Although Prakash likes to rhapsodize about how a Foldscope kit is the best way to teach germ theory, it can be difficult to see anything much smaller than two microns in size with the standard lens, and bacteria often measure less than one micron. Last year, at a school in Tanzania, Cybulski persuaded the director of a sanitation-and-hygiene program not to have students use the Foldscope to look for microbes on their hands. He worried that the children would fail to see anything, and that this might lead them to conclude that their hands were perfectly clean. (This is less of a concern when the sample is of something with a greater density of bacteria, like, in some cases, dental plaque.) At the same school, Cybulski noted another problem: the teachers treated the Foldscopes as precious, fragile objects, collecting them from students after each classroom use—the opposite of what he and Prakash had intended.
The sun disappeared behind the mountains and the scrimmage ended. Prakash came running over, holding something. “Wait until you see this,” he said. “Do you have your Foldscope?” I got mine out. He placed a tiny object on one of my slides, inserted it under the lens, and handed the device to me. I held it up to my eye.
“What do you think it is?” he asked.
Unmagnified, it might have been a grain of sea salt. But, when the illuminated circle came into view, so did a ghostly, elongated skull, swaddled in a bundle of bent, silvery stalks. The word “unsprung” came to mind.
“I’m still looking. I see lots of legs. Is it a spider egg?”
“You’re close,” Prakash said. “It’s definitely an arthropod. Let’s look at it together.” He attached my Foldscope to his phone with the magnets, precisely aligned the lenses, and turned on his camera.
“There’s something really incredible here,” he said, as the image came into focus. Cybulski leaned over to see. Prakash panned slowly across the creature. “It’s a baby ant,” he said. “This is where ants come from. That’s the gut. Those are the legs. We can watch it develop into a real ant, right here.”
We didn’t wait around. Prakash was late for a date with Dumont. As we made our way back to the lab, he pointed out a parade of ants crossing our path. They were most likely not moving house, he said, since none of them were carrying larvae in their mouths. He crouched down to study them. Then, remembering that he was in a hurry, he stood up and walked on. 

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