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We have had hundreds of short technical talks in the Tuesday get-together called the Millennium Café in the building where I work. Many are interesting. Some are difficult to understand. Today’s talk by a Penn State biology professor was simply mind-blowing.

If Gong Chen’s research pans out, he will likely win a Nobel Prize and be as revered as Jonas Salk or Louis Pasteur. He is working on a technology to turn the scar tissue left in the brain or spine by disease or accidents back into functioning neurons. In the process he believes he can help stroke victims regain their functioning, help Alzheimer’s disease patients to remember, cure diseases like Huntington’s, Parkinson’s, and glioma, a common brain and spinal cord tumor.

So far none of this has been tested on humans, only in mice and in human cells in a petri dish. Many cures that work in mice never end up helping human patients. That’s why he is not polishing his Nobel acceptance speech just yet, he told me.

When the brain is damaged by accident or disease, the neurons die and their space is filled with glial scar tissue. Glia cells provide support for neurons in the brain and the nervous system. When a neuron dies because of a stroke, disease, or an accident, the glia cells called astrocytes form scar tissue that can block the formation of new neurons. For decades, the only therapy was to try to surgically remove the scar tissue; however, that met with little improvement. Then, in 2006, Shinya Yamanaka discovered that mature cells in mice could be reprogrammed to become immature stem cells that could be directed to become any type of specialized cell. He shared the 2012 Nobel Prize in Medicine with John Gurdon, another stem cell pioneer. Gong Chen used this idea to begin his experiments with glia scar tissue, but with some significant differences.

In typical stem cell research, skin cells are taken from a patient, turned into stem cells using chemical cues, reprogrammed to be some other type of cell, and then grown in the lab. They can then be used to test drugs or be injected back into the patient, for instance to grow new blood cells in leukemia patients. Chen’s technique bypasses the stem cell phase and delivers a set of chemicals directly to the glial tissue where they activate a neural transcription factor in glial cells called NeuroD1. The glial cells transform into neural cells and grow into functioning neurons.

One of the risks of stem cells is that they are dividing cells, and cancer arises when cells mutate during division. The same is true of glial cells, which is why brain cancers are called gliomas. However, neurons do not divide, and turning glial cells into neurons actually lowers the risk of cancer.

Gong Chen didn’t offer any timelines on when his technique might be tried in humans. Those kinds of trials require years and millions of dollars. He still needs a reliable method for delivering his chemicals to the right spots in the brain, part of the reason he was giving his talk to materials scientists today. Fortunately, we have people who are experts at packaging and delivering small nanoparticles with cancer fighting chemicals in the body, so I don’t think that will be a significant barrier. We know how to do that.

I would love to see this happen in time to save the great science fiction writer Terry Pratchett, who has early onset Alzheimer’s and is losing the battle. I think most of us know someone who has suffered Alzheimer’s, or had a stroke, or has Parkinson’s disease. It is frightening to lose your memory, or power of speech or movement. There are millions who could benefit, billions of dollars in medical costs avoided each year. All in all, as I said, a mind-blowing concept. Let’s hope its day comes soon.

Gong Chen’s website: http://bio.psu.edu/directory/guc2

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A book landed in our post office box last month, a birthday present that my wife chose for me for reasons that remain obscure, though I have my suspicions.

She is well aware that my general outlook on life tends toward the gloomy. I love the melancholy of autumn and the slant light of October. Contemplating the vastness of the universe, in which the stars are like grains of sand and we are like nits in a flea’s ear, gives me a sense of mordant delight. I tend to distrust the perpetually cheerful, the optimists and true believers of all sorts. So, a book on the science of happiness could be considered a hint. And since I opened it, I have, uncharacteristically, been thinking about what it means to be happy, and what it might be like to pursue happiness.

The book is Flow: The Psychology of Optimal Experience by Mihaly Csikszentmihalyi, sometimes called the father of positive psychology. The field of positive psychology is quite new, originating in the late 1990s, but it builds on insights from the early Greeks, including the Epicureans, Zen Buddhism and modern psychology, such as the well-known hierarchy of needs created by Abraham Maslow in the 1950s. Instead of focusing on curing mental illness, positive psychology tries to understand what constitutes mental health and well-being.

Flow is a very practical book. It is based on surveys the author and his coworkers took from thousands of individuals in which they were asked to write down their emotional states at various random times throughout the day whenever a beeper they carried went off. Those surveyed included athletes and dancers, musicians and surgeons, practitioners of yoga and martial arts, mountain climbers, as well as visual and literary artists. From the surveys they discovered common themes that tend to indicate a path to a heightened sense of life satisfaction.

They found that people who were deeply engaged with a task that required concentrated effort, but that was within their abilities to perform, reported a profound sense of satisfaction. On the other hand, sitting in front of the television or computer screen added little or negative long-term satisfaction, though it might seem pleasurable in the moment.

One commonly reported effect of intense concentration was a kind of time distortion. For athletes and martial artists, time might seem to slow down. For a painter at her easel, hours might pass without notice. I’ve experienced the same lapse of time when concentrating on an enjoyable piece of writing. The minutes slip by while the shadows lengthen. I step out of the stream of time, floating above ordinary existence in a bubble, cut off from self-consciousness or physical sensation. It is just the opposite of being so caught up in the petty irritations of day-to-day existence that minor troubles loom like insurmountable boulders and the mind spins in circles. The boulders are less than pebbles; the mind is calm.

The author calls it flow, because when a person is in that state his skills are matched to the task and the movements of the mind and the body are in harmony. We are not fighting ourselves; the dancer and the dance are one. I’ve been thinking about what it means to pursue happiness in this forest of gloom, and I see that there was a path, only I had forgotten to take it.

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One of the benefits of working on a university campus is that I sometimes get to slip away for an hour to listen to an interesting talk. The other day there were two talks that I wanted to hear, and fortunately, one of them took place over the lunch hour and the other right at the end of the day.

In the noontime talk, a young associate professor of political science, microbiology, and biochemistry spoke on how genetics affect our politics. What recent studies have found is that we are political all the way down to our cellular level.We may think we form our political identities based on the way we were raised, or on careful and thoughtful analysis, but we are more than 60 percent genetically coded to be primarily conservative or liberal. Much of this research is based on twin studies, and especially on identical twins raised apart.
What I found fascinating were the studies that used eye tracking and brain scanning to show that given the same photo, for instance a close up of a woman with a rather frightening spider sitting on her face, self-identified liberals will almost inevitably look first and longest at the woman’s eye, while conservatives will inevitably focus on the spider. Hatemi didn’t offer any particular opinion about what this meant, he just pointed out that it was a very strong difference in results between the two groups. One study found that when it comes to picking a mate conservatives were attracted to the smell of other conservatives, and liberals to liberals. Conservatives in general were repulsed by the smell of liberals, but liberals were neutral to the smell of conservatives. Again, no speculation about the reason or what it said about either group.

Of course, we know we have friends who are on the opposite political spectrum from ourselves, and we are really not repulsed by their smell. I hope that’s the case anyway. But the results were surprising. Hatemi showed that completely different parts of the brain light up in both groups when they hear something scary. Many in the liberal audience wanted him to draw conclusions, hoping, I think, to prove that liberals were more evolved somehow. But he wouldn’t take the bait. An army veteran who served in Iraq, he didn’t give away his own political leanings. Some very interesting food for thought.

The second talk took place in an odd lecture hall in the physics building. You can get vertigo from the steep slope of the seats in the amphitheater style hall. The room slowly filled with professors and graduate students who were there to hear a pretty famous scientist give the annual Marker lectures, named for the Penn State scientist who is considered the father of the birth control pill. I had read about David Awschalom in the course of my day job many times. He is a leader in the study of a futuristic type of quantum computing based on the spin of an electron rather than the flow of electrons as is the case for all computers today.

Spintronics requires the ability to isolate a single electron and flip its spin, like the Earth’s rotation, from up to down and back again. It also requires being able to read back what you’ve done. Since computers are based on zeroes and ones, also called on and off, you only need those two states to make a computer. I won’t begin to get into the quantum weirdness called superposition that will supposedly allow quantum computers to solve some problems incredibly fast.

Spintronics has been a popular field of research for at least 25 years, but its achievement always seemed to be a decade in the future. It’s just so hard to control a single electron. But Awschalom’s group at the University of Chicago has built devices that can isolate an electron in tiny spaces inside of a diamond, flip the electron’s spin, and read back its condition using laser light. Rather than being something that requires a $10 billion cyclotron the size of a stadium or a supercoiled device near absolute zero, he does it in a little homemade setup in his lab at room temperature. I left the talk with my brain spinning both up and down.

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I’ve been doing some research on the history of computing for an article I’m working on for our materials science magazine. There are some fascinating stories out there dating back more than 2,000 years, of inventors trying to make a calculating machine.  The abacus was an early calculating device used by the Babylonians in 300 B.C. The word calculus derives from the Latin word for pebble, used to represent numbers in the calculation.

According to An Illustrated History of Computers (Kopplin 2002), the first computers were actually the people (mostly women) who performed calculations by hand and had the job title computers. The name was taken over for the earliest devices that could perform the tedious task.

Before the advent of electrical calculating machines, computers were complex amalgams of gears and levers, driven by mechanical means. Child prodigy Blaise Pascal, famous for his later invention of probability theory and his philosophical writings, invented a gear-driven calculator at age 19 in 1642 to help his father who was a tax collector. His Pascaline is still the basis for the automobile odometer.

One of the most elaborate and expensive computers ever designed was the brainchild of genius English inventor Charles Babbage. In the 1820s, Babbage invented a steam-driven calculating machine the size of a room, sponsored by the British government. Called The Difference Engine, his machine was so expensive that after ten years of work, even the British government couldn’t afford to keep funding it. The Difference Engine is the title of a popular science fiction novel by William Gibson and Bruce Sterling that imagines an alternative history if the computer had been completed. The novel went a long way toward popularizing the genre called steampunk, which imagines futuristic technology in a pre-electrified era, usually Victorian, driven by steam.

Babbage kept at it, and invented, on paper, a machine as big as a house that he called the Analytic Engine. Babbage was friends with a young woman, 19 year old Ada Byron, daughter of poet Lord Byron, who was fascinated by his invention and began writing detailed sequences of instructions for the unbuilt Analytic Engine, becoming in the process history’s first programmer.

Another woman programmer, Grace Hopper, was the lead programmer for Harvard’s Mark 1 computer, a behemoth of a calculating machine driven by a 50-foot rotating shaft. Built in the waning days of WWII in collaboration with IBM, the computer had a memory capable of storing all of 72 numbers. Grace coined the term debugging to describe fixing program faults when she fixed an error caused when a dead moth jammed the readout of a punched paper tape in the Mark 1. She also went on to develop the first computer language, the basis for COBOL, a widely used high level computer language.

When I was a teenager, my father often carried around a calculating device called a slide rule, which I never could get the hang of no matter how many times he instructed me on it. Before the handheld calculator was invented, every serious math nerd and professional engineer carried a slide rule. Then the cheap Texas Instruments calculators arrived, and slide rules pretty much disappeared.

I visited my father’s work on the naval base in Key West to marvel at the huge computer that he used to run training simulations for navy pilots. The computer took up an entire house-sized trailer and could run simulations about as complicated as Donkey Kong. In college, my friend Tim became expert at Pong, maybe the earliest commercial computer game. Two paddles and a moving ball was all the animation. The ball moved in slow motion and the player tried to judge the angle and move his paddle to meet it. Tim, as I recall, was the champion Pong player at Ward’s Coffee Shop, after pouring many hundreds of quarters down the slot.

Computers have grown smaller, faster, more ubiquitous. They are the background, and often the foreground of our lives. But I wouldn’t object if The Difference Engine had been built, and we lived in an era of steampunk  technology and steampunk style.

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Ben Hall (left) and Brian Reinhardt in the L4IS office with their laser tomography system

Ben Hall (left) and Brian Reinhardt in the L4IS office with their laser tomography system

Natural color cross section of a bee stinger

Natural color cross section of a bee stinger

Last week I listened to a young man, a former undergraduate student at Penn State, talk about the company he had recently founded based on technology he and two professors developed here. It was one of the fifteen minute talks at the Millennium Café. I was so impressed that I sought him out later that week to hear more about his business.

Lasers for Innovative Solutions (L4IS) is the brainchild of Ben Hall, along with his business partner Brian Reinhardt. In office space in the TechCelerator program at Penn State’s Innovation Park, Ben and Brian showed me how their laser tomography works. An infrared laser setup occupies a corner of the office with a high speed camera attached. A specimen is positioned on a moving platform that can propel the specimen into the laser beam in micrometer steps, a tiny fraction of the width of a human hair. The laser ablates or vaporizes a slice of the specimen in a nanosecond burst, and the camera captures an image of the next portion of the specimen’s interior. Putting together the captured images in a software program reveals a three-dimensional video of the specimen’s internal structure.

On this particular day Ben had brought in a small insect that looked like a thin walking stick with legs. With his exciting $100,000 toy to play with, he regularly is on the lookout for unusual bugs and plants he can study, and he has learned to identify the internal structures of roots, seeds, and insects, mostly by interacting with experts who come to L4IS for analysis. This insect appeared to be dead, but Ben took no chances. He once unknowingly vaporized a live hornet and watched on the computer monitor as it came awake and struggled. He froze the walking stick with a blast of coolant, and then placed it on the stage. In a few moments we were looking at the internal structure of the walking stick. What I had expected would be a blob of goo – the way bugs make greasy splatters on the windshield – turned out to be more like a complex machine inside.

The genesis of L4IS was a problem that professor of plant nutrition Jonathan Lynch brought to the laser lab in Penn State’s Applied Research Laboratory where Ben Hall was working while going to school. Lynch was studying plant adaptation to drought, especially breeding plants with better root traits to absorb important nutrients and water in soil. In his root lab, an assistant laboriously sliced thin sections of root mechanically to be imaged and phenotyped. At four or five slices per hour, a large number of them damaged, she had a backlog of over 20,000 specimens to prepare. Lynch wondered if a laser could do a faster and cleaner job. After initially thinking it was not possible, Ben developed a system to cut 11 slices per second without damage.

When Ben got tired of carting samples across campus to the root lab to be imaged, he worked out a way to hook a camera to the laser, and instead of slicing the roots, he burned off small slivers of the surface and took pictures of the clean surface while it was being vaporized. A free software program from the National Science Foundation, Image J, compiled the 2-D images into a 3-D structure that could be viewed from any angle, including the interior. The laser beam provided illumination for the photographs, and the natural fluorescence of his samples made the internal structures vividly clear.  These were the stunning still images and videos that he showed at the Millennium Café.

Brian Reinhardt became a part of the company because of his love for video games. He owned a great computer with a powerful video card to play his games on. He also had a degree in physics and was working on a Ph.D. at Penn State when Hall recruited him and his computer. These are a pair of smart young men and Ben in particular seems to have the kind of curiosity-driven motivation that turns college drop-outs into moguls.

But we’ll see. In their bare bones offices they are making 3-D images of plants, bugs, and fungi. A Penn State-related and state of   Pennsylvania funded organization called Ben Franklin Technology Partners has helped them with acquiring a laser and developing a business plan. Penn State is applying for patents in the U.S. and other countries that would be interested in the technology.

The real possibilities of the technology are still unclear. The images are brilliant and in some sense mind boggling. Travelling through the interior of insects and plants is otherworldly, like the sixties science fiction movie Fantastic Voyage, in which a miniaturized submarine was injected into the bloodstream of a scientist.  “We can do lots more than this,” Ben told me. “We just have to think differently. We can do 3-D analysis. Now what else can we do?”

See some of Ben and Brian’s laser tomography videos on YouTube: http://www.youtube.com/user/L4ISLLC

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A pitcher plant N_raffiesiana-ub-hb-wf.jpg: credit: W. Federle, H. Bohn, and Ulrike Bauer

A pitcher plant N_raffiesiana-ub-hb-wf.jpg: credit: W. Federle, H. Bohn, and Ulrike Bauer

For the summer issue of the science magazine I produce, I have been talking to engineers and scientists about taking inspiration from nature to design useful new products. It has been an eye-opening experience.

Nature has solved many of the problems that we humans would like to solve, and often with economy and micro-engineering. For instance, there is a lovely plant found in Asia and other parts of the world, called the pitcher plant because of its bell or pitcher shaped leaf. The tiny structure of the leaf’s surface holds a coating of rainwater. It holds it so tightly that you can turn the plant over and shake it, and the water will not run off. Ants, on the other hand, have an oily substance on their feet to help them climb. Once the ant climbs up the leaf it encounters the film of water on the lip of the plant. As you recall from childhood, oil and water don’t mix. The ant slides down the side of the pitcher plant into the waiting interior where it becomes plant food.

A young scientist who just arrived at Penn State took this idea from nature and improved on it. By taking inspiration from the pitcher plant’s microscopic surface, and reducing the structures by 1000 times to the nanoscale, he and his former colleagues at Harvard University, created a new product called SLIPS. Instead of a coating of water, he uses a liquid that repels almost everything – water, oil, blood. A coating of SLIPS on a window would make water drops roll off and clean the window. In a hospital setting, germs would easily slide off of catheters and counters, maybe solving the difficult problem of hospital acquired infections. A coating of SLIPS inside an oil pipeline would make the oil flow without resistance, saving massive amounts of energy.

Even though I grew up in South Florida and spent many hours on the water near mangrove islands, I never thought about how mangrove trees survive in salt water. Turns out, one of the scientists told me, that if you cut open a mangrove branch you will find water with almost no salt at all. What a marvelous natural desalinization plant. Since the world is running out of fresh, drinkable water, and something like 97 percent of the water on Earth is salty, discovering exactly how the mangrove works and replicating it on a large scale could solve one of the future’s most pressing problems.

It’s a new field, biomimetics, that is starting to take off in a big way. I talked to an engineer who makes a flapping wing based on the exact replication of a dragonfly wing that he wants to put into micro flyers an inch or two across. The little flyers could go places where it is too dangerous for a human to go. Another is trying to wipe out a terrible pest that is killing ash trees across the Northeast by making an exact replica of the emerald ash borer. It looks so lifelike that the bug flies down to mate and can be captured in a kind of flypaper trap.

Nature has perfected the coloring on butterfly wings, the ability of the house fly to see you sneaking up from behind with its compound eyes, the whale’s perfect flippers glide through the water with so little resistance that they are being imitated in the blades of windmills.

It’s a remarkable, and sometimes strange, world out there, and we are just beginning to learn how to take these examples of natural engineering into the lab and back out into the world in a new form to solve our most challenging problems.

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Professor Moriah Szpara discusses the herpes simplex virus

In a few minutes, I will be wandering over to the café area of our science building where on Tuesdays we can hear two researchers tell a group of 80 or 90 faculty and graduate students about their research. Each of them speaks for about 15 minutes, while the audience drinks great gourmet coffees from around the world and munches on pastries.
I enjoy the talks and love the coffee. The speakers are typically filled with enthusiasm for their topics, and though sometimes the jargon can get a little thick, usually I learn something new about the physical world. Today’s speakers include a professor working in the area of biofuels who has made a recent breakthrough in engineering plants that can be much more easily processed into fuel. The second speaker is a biologist researching how to combat Herpes simplex virus, which has infected a majority of the population worldwide, though we are not always aware we are infected. This virus hides in the brain’s neurons and can re-emerge in times of stress.

This huge building where I work is divided into two wings, one side devoted to materials research and the other to life sciences. We have people working on the brain, controlling seizures, implanting probes, and others working on the transmission of deadly diseases. On our side, we have people developing the next advance in miniature electronics, microscopes that can see individual atoms, polymer scientists making artificial muscles out of plastic and others making ultrasound devices small enough to fit inside a pill. These different worlds meet on Tuesdays at the Millennium Café and listen to each other’s ideas. And sometimes, they strike up a conversation and create a new project that crosses over their very diverse backgrounds and disciplines.

They call it interdisciplinary research, and it is definitely the science of the future. I get to watch it unfold right before my eyes, and then write about it in our magazines. Oops, time to go. The coffee and conversations are percolating.

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