SCIENCE, DISCOVERY & MAGNETISM
AND NOW FOR SOME COM
ERENT PH PLETELY DIFF
MASTER OF MINIATURE
A Picasso of probes crafts tools fit for a museum
SAVING CELLS FROM STROKE
With high-field MRI, Capt. Research & team come to the rescue FALL 2019
Field Lines Quick hits on diverse discoveries powered by high-field magnets.
4 FIELD TRIP
Sun Churn In addition to heat and light, our sun cranks out a complex, swirling magnetic field.
The Dirt on Carbon A soil scientist explains that molecules containing carbon are anything but carbon copies.
10 SLOW TRAIN TO SCIENCE
Amazing Haze What’s inside the gas surrounding Titan, and what could that tell us about our own planet’s atmosphere?
Master of Miniature In the hands of Peter Gor’kov, delicate science tools become works of fine art.
Stroke of Genius Capt. Research and team show how scientists using high-field MRI are working to improve recovery in stroke victims.
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FIELD OF VIEW
The Allure of Linearity Physicist Nigel Hussey explains why, in his eyes, a simple straight line is the pinnacle of beauty.
fields is produced at the National High Magnetic Field Laboratory (National MagLab) with the support of scientists around the world. Our goal is to show both doers and lovers of science some of the very cool things researchers discover about our world using high-field magnets.
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Combating Cancer Scientists use powerful magnets to better detect, treat and track the second leading cause of death worldwide.
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Monty Python’s Science Circus Eight high-field physics predictions the famed comedy troupe nailed: Now that’s something different!
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Quick hits on the diverse discoveries powered by high-field magnets.
A Super (Lattice) Surprise
hysicists test different materials in their hunt for new quantum behaviors. Duke University physicist Sara Haravifard, for example, has been studying a crystal made with strontium, copper, boron and oxygen: SrCu2(BO3 )2. She tests it using various scenarios. She might make it really cold, say, or put it inside a high magnetic field or under high pressure. Or she might swap out some of the atoms. Every tweak could be the portal to a new discovery — maybe even a totally unexpected behavior. That’s what happened to Haravifard and her team when they studied their crystals in high fields (up to 60 teslas) at the National High Magnetic Field Laboratory. They chose to study this particular crystal because it features a copper/oxygen layer found in many known superconductors. These materials are a hot topic in physics because they conduct electricity with no resistance and could one day be developed into revolutionary technologies. Theory predicts that SrCu2(BO3 )2 should become superconducting under the right conditions. But in pursuit of superconductivity, Haravifard and her team made an unexpected discovery. In their initial experiment, they tried to generate superconductivity in the crystal by substituting a small percentage of copper atoms with magnesium, a process called doping. This changed the number and location of electrons in the crystal lattice, as well as the number and location of so-called “holes,” which are spots where an electron had been but is currently vacant. Then her team put the material in a powerful magnet to see how field strength affected it (the team also played with temperature and pressure variables). As expected, the scientists did observe a change. But the type and extent of that change took them by surprise. The holes in the copper layer paired up in twos: The behavior of one dictated the behavior of the second. This happened at regular intervals throughout the material, resulting in a kind of
Sz = 2 bound state
Sz = 1 triplet
Image Courtesy of Sara Haravifard
In sheets of copper oxygen, magnesium “holes” formed pairs in intriguing ways, as did pairs of copper electrons, resulting in a super-structure of “bound states,” highlighted here in purple. The green dots indicate where the material was “doped” with magnesium.
“super lattice” pattern on top of the underlying crystal lattice of the compound. That was amazing enough, especially given the very low concentration of the doping, Haravifard said. But in addition, the hole-based super lattice influenced the electrons in the system, causing them to pair off themselves and form their own repeating pattern across the material, a secondary super lattice. These behaviors emerged under the influence of a high magnetic field. “If you didn’t have access to high magnetic fields, you would never discover these things,” Haravifard said. The group’s findings indicated, she added, that if you were to continue to raise the magnetic field above 60 teslas, you would reach a point where this coupling breaks. Keep raising the field, though, and the holes and electrons will again pair up into entirely new, correlated configurations and patterns. “You start doing research,” she said, “and you figure out there is a whole new world out there that you just opened a door to.” - K.C.
Images Courtesy of The Metropolitan Museum of Art
High Fields Form New Picture of Damaged Paintings
he paintings of great artists are their legacies, outliving them for centuries. When exposed to years of fluctuating temperatures, humidity and light, however, these works take on their own artistic expression in a way that would have horrified their creators. That’s because hardened paints aren’t exactly permanent. Instead, they evolve like slow-moving geological processes. When metals — such as lead or zinc, commonly used in pigments — interact with fatty acids present in oil paints, they form heavy-metal “soaps,” gunky, white scum that oozes out through the paint and resembles insect eggs. Rather than keep the art squeaky clean, they can cause the paint to flake off. The mysterious substance has cropped up in many oil paintings, and even rudely interrupted Guercino’s “Samson Captured by the Philistines” and John Singer Sargent’s “Madame X,” just to name two cases at The Metropolitan Museum of Art in New York. It’s enough to haunt any art historian’s nightmares. The good news is that some scientists are trying to untangle the complex interactions causing this soapy sabotage in order to better protect and preserve affected paintings. The 36-tesla Series Connected Hybrid magnet at the National High Magnetic Field Laboratory may be just the tool for the job. Scientists from the University of Delaware, in collaboration with The Met, have used the ultra-high resolution
Lead soaps have formed on the oil painting “Samson Captured by the Philistines” (top). The inset shows the surface texture of rounded protrusions resulting from the formation of lead soaps in the ground layer as it aged.
instrument to shed new light on the reaction between zinc pigments and linseed oil, common components of these problematic paints. Using nuclear magnetic resonance, they can distinguish the zinc in the soaps from the zinc in the pigments and better understand the chemical structure of the soaps. “That simply could not be done at lower magnetic fields,” said University of Delaware chemist Cecil Dybowski, one of the scientists involved in the study. With this new research angle as a blank canvas, scientists can paint more details of how and why the heavy metals continue to react, long after an artist’s final stroke. - Abigail Engleman
Resilient Reefs Photo: Joshua Patterson
lobal threats to our planet’s coral reefs are mounting; more than half of these critical ecosystems have disappeared in recent decades. In hopes of helping coral survive our warming oceans, scientists from the University of Florida recently did some experiments at the National MagLab. The team retrieved tissue from staghorn coral — which is often planted in reef restoration efforts — from a nursery off the Florida Keys. The samples were of three different genotypes — animals (yes, corals are animals) with three distinct genetic makeups. They analyzed the samples using a strong nuclear magnetic resonance magnet to compare the chemical makeup of certain metabolites among the three genotypes.
Their hypothesis: Even among genotypes of the same species growing in the same place they would find variation in important molecules. Some of those variations would better protect the coral from the stress of climate change. The data confirmed the scientists’ hunch. In some samples, for example, they identified a molecule that may protect the coral against nitrogen overload. The team’s work sheds light on the underlying mechanisms that help coral survive and could help future efforts to restore damaged coral reefs. - K.C.
Pulsed Magnets Give Gadolinium a Thermal Rush
hen you put things inside a magnetic field, the outcome can be surprising. In some ferromagnetic materials, for example, the temperature changes — a phenomenon called the magnetocaloric effect. Gadolinium sets a benchmark: The rare-earth element exhibits a significant magnetocaloric effect in relatively low fields. When gadolinium is placed in a magnetic field of 2 teslas — about the strength of the magnet in an average MRI machine — its temperature jumps by about 5 degrees Celsius. What would happen if you put the silvery metal in much higher fields? Physicists from the Dresden High Magnetic Field Laboratory at the Helmholtz-
Zentrum Dresden-Rossendorf in Germany decided to look into it. The scientists had the right tools to tackle the question. The lab is home to some of the world’s strongest pulsed magnets, which are electromagnets that generate fields so powerful they only last a few milliseconds. But measuring behavior that happens in the blink of an eye can be tricky. “This is where the biggest challenge lurks for everyone trying to measure this effect: Developing a method that accurately records the temperature change during the brief experiment,” said Tino
Gottschall, the lab’s lead scientist. “To do this, we applied miniaturized thermocouple wires, half as thick as a human hair.” With that unique setup, the scientists detected a whopping 60.5 degrees Celsius temperature change in gadolinium in a 62-tesla field. Just as spectacular, research team members from the Aix-Marseille University in France developed a mathematical model neatly describing the effect. In the future, materials with magnetocaloric properties could be used in magnetic cooling
devices, offering a more sustainable alternative to classical refrigeration. But these devices probably won’t be made with gadolinium, which is expensive. Still, this “gold standard” material for magnetocaloric properties could help us better understand the phenomenon in other materials. Already, the team behind this project (which included researchers at Ames Laboratory in the U.S. and TU Darmstadt in Germany) is planning to study other rare-earth elements in pulsed fields. - Bernd Schröder
Good Neighbors Make Good Science
ne way that scientists study new materials is to expose them to extreme conditions. When they put a sample in a high magnetic field, intense laser light, extreme cold or high pressure, its behavior changes, revealing something new about its properties and what the material could be used for. Sometimes researchers use several of these techniques at once, opening new experimental horizons. This year scientists got access to a unique combination of instruments when a pair of neighboring labs in Nijmegen, the Netherlands, joined forces, both literally and figuratively. At the High Field Magnet Laboratory (HFML), scientists place experiments inside highfield magnets. Right next door at the FELIX Laboratory, scientists expose materials to powerful beams of light, across a wide range of wavelengths available nowhere else, which are generated by free-electron lasers. Now these two international facilities, which have long cooperated, are officially under one roof. Thanks to 80 meters of vacuum tubes, beams of precisely controlled photons generated by FELIX’s free-electron lasers can be guided right into the center of the magnets at HFML. With this “twofer” setup, scientists can expose materials to a uniquely powerful laser and a high magnetic field at the same time, allowing them to drive matter into previously inaccessible states and phases.
Image Courtesy of HFML
“We are entering a whole new scientific area,” said HFML Director Peter Christianen. “You can actually change the properties of the material.” What kinds of new science will this dynamic duo enable? “We hope we can realise a new method of data storage, using six to eight times less energy,” Christianen said, “or trace the origin of hightemperature superconductivity — a mystery since it was discovered in the 1980s — with the aim of making superconductivity at room temperature a reality.” Of course, Christianen added, “It is impossible to predict what we are going to discover exactly — but it certainly will be interesting.” - Marloes Gielen
Image credit: G. Petrie/NSO/AURA/NSF
In addition to heat and light, our sun cranks out a complex, swirling magnetic field. By Kristin Roberts and Claire Raftery
or this field trip, we’re travelling 93 million miles to shine a light on the sun’s magnetic field, a complex phenomenon that a powerful new telescope will soon help us better understand. Similar to our own planet, the sun is like a huge bar magnet with a north and a south pole producing a magnetic field. But the sun’s magnetic field is about twice as strong as the Earth’s and much, much larger, extending well beyond the farthest planet in the solar system. The sun’s field is also a jumbled mess. As the sun rotates, the plasma near the poles rotates more slowly than the plasma near the equator. This off-rhythm spinning causes the magnetic field to get twisted and tangled into massive bundles. As the fields get more and more tangled, they burst through the sun’s surface, leaving marks we know as sunspots. Around a sunspot, the magnetic field can reach as high as 0.4 tesla, which is around 4,000 times stronger than the field at the sun’s poles, but more than 100 times weaker than the massive electromagnets at the National High Magnetic Field Laboratory (see sidebar). If that’s hard to envision, this image from the National Science Foundation’s National Solar Observatory Integrated Synoptic Program can help you out. The program has taken daily images of the sun’s splotchy magnetic field for more than 40 years and uses them to create a model of the magnetic field in the sun’s outer atmosphere, called the corona. In the picture here, the bright solar disk, which is more than a million times brighter than the sun’s outer atmosphere, is blocked out and the modeled magnetic field lines are traced. Solar wind blows outward along the open magnetic field lines (traced in yellow), while the closed field lines (in teal) that loop back onto the sun trap plasma in planet-sized arches called coronal loops.
The sun’s magnetic fields get jolted around by constantly bubbling surface gases. When they come in contact with each other, they create a short-circuit-like effect called magnetic reconnection. Short-circuiting the magnetic field over and over helps the field unwind itself over time, an 11-year process known as the solar cycle. Over the course of the solar cycle, the number and location of sunspots varies, which help scientists predict space weather. Today, the best scientists can do is use models to understand the magnetic field in the corona. However, the NSF is building what will be the world’s most powerful solar telescope, the Daniel K. Inouye Solar Telescope, in Maui. When it comes online later this year, researchers will be able to measure magnetic fields in the corona for the very first time.
MEASURING MAGNETS Here’s how the sun’s field stacks up against other magnets in the solar system as measured in teslas, a unit of magnetic field strength. Earth
1.5 – 3 teslas
Strongest MRI for animal research*
Strongest magnet with continuous-field used in research*
*Located at the National MagLab
DISHING THE DIRT ON CARBON Molecules containing carbon are anything but carbon copies. This soil scientist explains some important differences and what they mean for our environment.
ucy Ngatia, a soil biogeochemist at Florida A&M University in Tallahassee, uses nuclear magnetic resonance spectrometers to study different kinds of carbon found in soils. She gives an overview of her research in this two-minute interview with nonscientist Lee Chipps-Walton. For more details, go to fieldsmagazine.org to watch a second, more technical interview conducted by Faith Scott, a physical chemist at the National MagLab.
LCW: I would love to hear about your research.
LG: Absolutely. My research focuses on three different aspects: phosphorous eutrophication mitigation; carbon sequestration and greenhouse gases; and heavy metals contamination.
You said “sequestration.” What is that?
Carbon sequestration. I work with soils, and sequestration happens when we are able to store an amount of carbon in the soil for a long period of time.
Which sounds like a good thing, storing carbon. Tell me more about that.
Carbon is normally sequestered by plants through photosynthesis. Eventually plants die and deposit parts of their leaves and stems to the ground. When the organic matter gets to the soils, a process called decomposition starts. And in the process of decomposing, the easily decomposable carbon is lost through the atmosphere into greenhouse gases. But we have a form of carbon that is more stable, and it’s stored in the soil for a longer period of time.
Photo: Stephen Bilenky
How do you determine which kind of carbon is which?
That is where we use nuclear magnetic resonance. We take the samples from the field, we prepare them, and we determine the composition using nuclear magnetic resonance. And what we have observed is when we have more alkane carbon, that carbon is stored in the soil for a longer period of time. But when we have n-alkane carbon, itâ€™s easily degraded: Most of it is lost to the atmosphere as greenhouse gases.
Is there a way of increasing the amount of stored carbon?
I think that is more about management practices. For example, what we know for sure is that in anaerobic conditions, like wetlands, the decomposition of organic matter is slower, so we tend to store more carbon in the wetlands. But when we drain the wetlands, we lose a lot of carbon. So itâ€™s more about maintaining our wetlands and focusing on our management practices. This interview has been edited for clarity and brevity.
SLOW TRAIN TO SCIENCE
HOP ON HERE! 1
AMAZING HAZE Using the world’s most accurate molecular scale, a former astronaut wanna-be is studying Titan’s hazy atmosphere, which resembles the ancient chemistry that once surrounded our own planet.
FIRST, PRODUCE A PLASMA. This plasma approximates the outer atmosphere of Titan, and includes the same ingredients that scientists believe make up the gas that gives that moon its characteristic orange haze.
cientists are very interested in Titan, the largest of Saturn’s moons and the second-largest satellite in our solar system. But it’s not just the moon’s size, which is 50% larger than our Earth’s lone satellite, that most intrigues them. Rather, it’s Titan’s outer atmosphere. Scientists believe it has the potential to one day yield life, if paired with the water that is theorized to lie below Titan’s frozen surface.
WHAT’S PLASMA? Plasma is a kind of ionized gas. The sun, lightning and auroras are all plasma.
Because it’s not possible to collect actual samples of that atmosphere, a research team at the Université de Versailles Saint-Quentin-en-Yvelines in Paris, France, cooks up a facsimile in their lab. Maillard, a Ph.D. student working in planetology and mass spectrometry, studies the results in high magnetic fields, looking at the vast array of different kinds of molecules, called tholins, that can be raw materials for life.
WHAT DOES “IONIZED” MEAN?
As much as he’s learning from his imitation atmosphere, Maillard hopes one day to be able to compare his results to the real thing. “Maybe we will be right, maybe we will be wrong,” he said.
An atom or molecule is ionized if it has a negative or positive charge.
METHANE? Methane molecules are made up of one carbon and four hydrogens (CH4). Like nitrogen, it’s a colorless, odorless gas.
TO PLUTO — AND BEYOND! In true astronaut spirit, Maillard and his colleagues are not content to stop at Titan. Venturing to the edges of our solar system, they recently approximated the atmosphere of Pluto (believed to include methane, nitrogen and carbon monoxide) and examined those chemicals in the 21-T as well. What did they learn? That’s an outta-this-world story for another time ...
Enjoy your trip! -K.C.
Nitrogen makes up about three-quarters of the Earth’s atmosphere. Normally, two atoms of the element bind to form dinitrogen (N2).
To find out more, shimmy into your space suit and board our Slow Train to Science. Follow the path that makes the most sense for you, taking as many detours as needed.
FILL ’ER UP. At a laboratory in Paris, scientists fill up a reactor mostly with nitrogen gas, then add a little bit of methane.
NASA’s Cassini mission collected vast amounts of data on Titan, but many of the moon’s mysteries remain unsolved. Chemist Julien Maillard is attacking one of them: What exactly is Titan’s outer atmosphere made of?
What he is learning could shed light not just on the future of Titan, but on the past of Earth: before the chemicals in our atmosphere created tholins, and before those tholins created amino acids, and before those amino acids created the proteins that would be one day assemble into simple organisms and, eventually, into your own body.
3 LET THE SUN SHINE IN. The molecules in the real Titan’s haze don’t exist in a reactor: They are constantly bombarded by the energy of the sun’s UV rays. So Maillard needs to simulate this energy and get the gases in his reactor to socialize. To do this, he adds another kind of energy to his system; it’s kind of like turning up the radio at a lackluster party. In fact, Maillard actually sends radio waves through the reactor. Suddenly, molecules that had been waltzing like couples in a ballroom begin thrashing like teens in a mosh pit, sending electrons flying, ionizing each other, and morphing from a gas into a plasma bearing the same lovely, pink tint as Titan.
A MONSTER MOSH. With all this molecular moshing going on, molecules that bump into each other sometimes bond together into new, larger molecules.
A MEGA MOSH. As time passes, more molecules combine into bigger and bigger structures.
6 WHAT ARE RADIO WAVES? They are a type of electromagnetic radiation with a relatively long wavelength.
POWDER DOWN. After a few days, those growing gas molecules reach a point at which gravity kicks in, and they float down into a waiting beaker in the form of a brown powder that contains the tholins Maillard studies. The longer the process continues, the more complex the molecules become.
7 BRING IN THE BIG GUNS. So Maillard flew to Florida, where the world’s strongest ICR magnet is housed at the National MagLab. Thanks to its 21-tesla field, it could weigh molecules up to 1,200 daltons, more than doubling the number of molecular species Maillard could see. Also, because of the instrument’s higher resolution, Maillard learned that some molecules that the 12-T magnet had identified were actually several different kinds of molecules that had been inaccurately represented by one peak. These details gave Maillard fresh insight into the chemical diversity surrounding Titan.
WHAT’S A THOLIN? These organic molecules form when simple carbon-containing compounds like methane get energized by UV or cosmic rays, often in the presence of nitrogen or other compounds. The outer atmosphere of Titan is full of these tholins, which could be precursors to life in the presence of water.
WHAT’S A TESLA?
THE RIGHT WEIGH. Tholins come in all shapes and sizes, and Maillard’s job is to identify exactly which molecules he cooked up in his replica of Titan’s haze. So first, he puts the molecules inside a 12-tesla ion cyclotron resonance (ICR) magnet located in Rouen, France.
It’s a unit of magnetic field strength. A typical hospital MRI magnet generates a field of about 2 or 3 T.
THE BIG REVEAL. This 12-T instrument identified 15,000 different molecules in Maillard’s powder, each represented by a different peak in his data. But the instrument could only detect molecules up to 800 daltons. To identify the heaviest molecules, he was going to need a bigger magnet.
WHAT’S A DALTON?
Thanks to the 21-T’s stronger field, it could see the molecules in greater detail, and therefore tell the difference between molecules that were very similar in atomic mass.
An atomic-scale unit of mass that scientists use to weigh atoms and molecules. A single proton weighs about one dalton.
These magnets reveal the chemical composition of complex compounds by separating and weighing each of them. Every kind of molecule has a unique weight.
PEAK? As shown here, each peak represents a unique molecular mass that corresponds to a unique molecule.
THE MASTER OF MINIATURE BY KRISTEN COYNE
Photo: Stephen Bilenky
In the hands of Peter Gor’kov, scientific tools become works of fine art.
ou can’t find Peter Gor’kov’s work in the Louvre or The Met. But perhaps you should.
Gor’kov has always had an eye for beauty. As a boy growing up outside Moscow, he admired stylish things, sometimes crafting his own. Later, as a young tourist strolling through the street markets of Venice, he discovered the famed glassblowers of nearby Murano Island. Gor’kov marveled over their wares — some of the most delicate, ingenious and detailed objects he had ever seen. He was mesmerized by the artistry, the intricacy, the shininess. How could they put a glass fish inside a glass cat? How did they layer colors? How did they manage to assemble such beautiful things? As Gor’kov described those fragile masterpieces decades later in his office at the National High Magnetic Field Laboratory, it was as if a little drawer suddenly sprang open in his brain. He framed his head with well-manicured hands, conveying how far beyond the confines of his skull his mind had been displaced by the sculptures. He felt a kinship with the artists who had conjured them. “You want to do something that others around you can’t do or don’t understand how to,” Gor’kov remembered. “You want to be different, basically.” Gor’kov never learned to blow glass. But he ended up an artist nonetheless, creating instruments called magnetic resonance probes that have been likened to Fabergé eggs. Researchers use these high-tech arms to place experiments in the cramped space at the center of magnets and retrieve data from the novel materials, proteins, complex macromolecules and animal models they study. Gor’kov, who has practiced his craft at the National MagLab for two decades, is considered a master. He became one by staking out a magical middle ground at the confluence of all the traits, disciplines and talents his work draws from. He inhabits a unique zone between engineering and science; academia and industry; mechanical and electrical engineering; theory and experiment. Physics, chemistry and biology intersect in this space, where hands and head play equally vital roles. Gor’kov grew up among science luminaries. His father, Lev Gor’kov, was renowned for his work in the field of superconductivity and the recipient of numerous international awards in physics. In graduate school, Peter Gor’kov worked in the labs of another well-known physicist and a Nobel Prize-winning chemist. Yet through this forest of science giants, Gor’kov blazed his own trail, chasing something different, something gleaming, like a firefly’s glint in the trees.
Gor’kov’s groundbreaking “low electric field” probe prevents microwave heating from interfering with sensitive signals from proteins.
Photo: Dave Barfield
They don’t hand out prizes for what Gor’kov does. After all, he’s not the scientist, just one of the people who make the discoveries possible. But in the world where that science happens, Gor’kov’s a rock star. “He’s quite a unique person who is very highly regarded in the field from people in academia as well as industry,” said Tatyana Polenova, a professor of chemistry and biochemistry at the University of Delaware who uses Gor’kov’s probes. His tools are easy to spot, she said, like a particular brand of luxury car speeding down the road. “You open his probes, you can see how impeccably things are put together.”
Make or break an experiment Scientists use strong magnets the same way they use microscopes: to see things they couldn’t otherwise see. A probe is the equivalent of the microscope’s slide — but with a lot more moving parts. “Fields are useless without the probes,” said Bill Brey, a physicist at the National MagLab who leads the instrumentation group in the nuclear magnetic resonance (NMR) spectroscopy and magnetic resonance imaging (MRI) program. “And in some cases, they are a lot more complex than the magnets themselves.” 16
That is especially the case for NMR probes. In NMR, scientists use a combination of magnetic fields and radio frequency (RF) pulses to identify specific atoms in a sample — a huge, intricate protein, for instance. The technique is the same as is used in MRI machines, which send and receive RF pulses from hydrogen atoms in the body to create an image. As magnets have gotten stronger and instrumentation more sophisticated, scientists have gained access to a wider range of isotopes, including sodium, phosphorous and lithium. Thanks to a new world-record instrument at the National MagLab called the Series Connected Hybrid magnet, scientists can now even use NMR to study oxygen, the body’s most biologically active isotope. This capability has opened the door to vast new areas of research. But getting those results requires packing a whole lot of complicated electronics into a soda can-sized container perched at the end of a long pole. Inside this probe, hundreds of tiny parts — pneumatic sample spinners, radio-frequency resonators, heaters, dewars, temperature sensors, fiber optics, screws, cables, capacitors, inductors, resistors — must be fastidiously assembled to allow for clear signals between the scientist and her science. “The probe is where the business side of NMR really happens,” explained Joanna Long, who oversees the National MagLab’s spectroscopy and imaging facility at its University of Florida branch.
That business, Long added, is tricky. “You’re putting in all these high-powered pulses, and then you’re trying to get out these ittybitty signals,” she explained. “It’s like hitting a bell with a sledgehammer and waiting for one tiny note to come back. So you have to design something that is very robust and at the same time very sensitive.” There is no one-size-fits-all NMR probe. Different experiments call for different models. Some are for solutions, some for solids; some for one isotope, some for another. There are probes that artfully insulate sensitive biological samples from damaging microwave heat; probes that keep rodents comfortably anesthetized during brain scans; and probes that spin samples around 100,000 times a second so that they emit clearer signals to scientists. Developing and building a state-of-theart probe costs between $100,000 and $200,000, Brey estimated — and it’s worth every penny. “Because magnetic fields are so expensive, it’s important that those probes work really well,” Brey said. “The performance of the probe is just as important to the success of an experiment as the magnet itself.” A hair’s breadth of metal on a probe can make the difference between good and bad data. That’s why building one requires an uncommon mix of tenacity, ingenuity and spatial intelligence that, according to Brey, Gor’kov has in spades. “He is the most detail-oriented and most meticulous person working in his area,” Brey said.
Poking, prodding and blowing stuff up Gor’kov can’t recall a time when he wasn’t itching to get his hands on a project. “When I was a kid I always wanted to do something with my hands,” he remembered. “It started with explosives, of course.” Peter and his young pals creatively sourced ingredients. They dug up decades-old stashes of bullets and artillery powder in the woods around Moscow, pilfered magnesium from retired aircraft used for target practice in war games. Once, while harvesting his shiny booty from an old helicopter,
“When I was a kid I always wanted to do something with my hands. It started with explosives, of course.” he glanced up to see a line of Soviet tanks headed straight his way. Terrified, Gor’kov tumbled to the ground and broke an arm. The soldiers were not pleased, but let him off with a good bawling-out. It wasn’t the only time young Gor’kov’s curiosity ran afoul of the rules. In defiance of his mother (like her husband, a physicist), he tried to repair his grandmother’s watches. After getting one ticking again, he was emboldened to advance to a more valuable Swiss timepiece. “I just opened up and I poked things inside,” Gor’kov remembered. “I unscrewed everything, and I couldn’t put it back together.” Once again, the authorities were not amused; another bawling-out ensued. Luckily, Gor’kov’s Soviet education offered a constructive outlet for his urge to poke. (He began university in Moscow and continued in the U.S., where he and his parents relocated after the Soviet Union dissolved.) He did stints in labs, saw science in action during field trips and took classes in drafting, soldering, machining and general electronics. In one class, students were handed a schematic for a high-frequency amplifier and a bunch of parts. Their instructions: Figure it out. “So you solder, solder, solder,” Gor’kov recalled. “Then you come to the front where the teacher is sitting, and he plugs it in and says, ‘Well, instead of an amplifier, it’s an attenuator.’” The student would slink back to his seat to start over. At the time, Gor’kov admitted, he probably hated the approach. But later in the U.S., when impressed classmates asked where he’d learned all that stuff, he understood its value. “You keep making mistakes, but have to go back to it until it works,” he said. “It was an amazing experience, because you learn it.” fieldsmagazine.org
But Gor’kov was rarely satisfied with just making something work. He also needed to make it look good. He once modified his parents’ rotary phone to look like the latest touchtone models — just because he thought they were cooler. Another time, seeking (unsuccessfully, as it turned out) to win points with a girlfriend, he made snazzy turn signals for her bike out of old car parts. “That’s what I kept doing all the time,” he said. “I saw something that looked nice, and I tried to imitate it.” Gor’kov, however, seemed less gifted in the classroom. In chemistry class, he got a C — and “never did any better,” he said. He fared even worse in physics, bringing home an F after his first course in seventh grade. His inauspicious start in science may have been due to uninspired teaching, a subconscious aversion to subjects at which others in the family excelled, or just not taking schoolwork seriously. Then again, Gor’kov said, “I never learned like other people did.”
“I saw something that looked nice, and I tried to imitate it.” While explaining how he does learn, Gor’kov spoke slowly and softly, as is his practice. Though still heavily accented, his English is precise. You can almost see him gingerly poke about his brain to locate the mot juste, then carefully lower it into position in his sentence. In fact, he conceives of learning spatially, as units you accumulate and store on a “shelf of knowledge” in your head, then retrieve as needed. “I learned only those bits and pieces that were immediately necessary at the moment to complete a particular task,” Gor’kov said. “And I would later learn other pieces elsewhere — the missing pieces. And then I would kind of say, ‘Aha’ — that now this little block falls into place and shows the whole picture.
“I’m still like that,” Gor’kov concluded. “I’m learning by necessity.” And, sometimes, by the lure of beauty.
Small wonders It was beauty, after all, that revised the boy’s opinion about physics. It came in the shape of a blue and gold pin, featuring a bird and the symbol for Planck’s constant, an important quantity in quantum physics. “It was the tiniest pin of all I’d ever seen,” Gor’kov said. “And I wanted it, because you had actually to work for it.” At the time, trading and collecting pins was popular among Soviet school children. To earn the particular pin he coveted, Gor’kov spent a year working on physics problems printed in a youth science magazine. After successfully solving them, the boy who would grow up to be an unassuming wizard of miniaturized circuitry won his bitty prize. “All my friends had pins,” he said. “Nobody had anything as small as this, because pins usually were made to stand out.” For Gor’kov, its very restraint commanded attention. Later, after emigrating to the U.S., Gor’kov eventually completed a master’s degree in physics at the University of Illinois at Urbana-Champaign. But he was about as inspired by his classes as he was by the drab building they were taught in. Where his professors dove deep into theories and equations, he wanted to go broad. Where they focused on book learning, he craved handson work. He felt restless, like an eager student of French who is taught only verb conjugations. “You want to learn the language and go use it,” he said. “You want to have it as a tool and do something with it.” Gor’kov found consolation in the lab of his advisor, internationally recognized physicist and NMR pioneer Charles Slichter. There he learned to build basic NMR tools, he later admitted, “with maybe unnecessary accuracy.” He then moved to the lab of Paul Lauterbur, a chemist later awarded a Nobel Prize for discoveries
One of Gor’kov’s newest creations, the ultra-fast magic-angle spinning probe, helps reveal the structure of complex molecules like proteins.
Photo: Stephen Bilenky
concerning MRI; he learned to build the MRI coils used to generate images of the animals or tissues scanned inside them. Gor’kov took to heart a lesson he said came straight from the laureate’s lips: “If you ever make a device that doesn’t work, make sure it has a good coat of paint.” A few years later, the National MagLab’s Brey lured him to the facility’s headquarters in Tallahassee, Fla., where the senior Gor’kov was already ensconced as a founding scientist. Brey was trying to build up the nascent NMR facility, which featured one of the world’s most powerful NMR machines at the time — an 830 MHz spectrometer for experiments on solids. But the instrument sat largely unused: There were no reliable probes to give scientists access to its 19.6-tesla magnetic field. Gor’kov had spent years working on MRI instrumentation, but had never before built a solidstate probe. So he did what he always does. “I dive in and I learn on the go,” he said.
“Let’s take it apart and see.” One day last spring, MagLab physicist Victor Schepkin walked into the MagLab’s probe workshop clutching a copper-clad canister. Schepkin has helped pioneer a technique called sodium MRI, which tracks the movement of salt in the brain in real time. In this way, using
a world-record MRI machine at the MagLab, he can monitor how rats with brain tumors respond to chemotherapy. If he sees sodium leaving the cancer cells, he knows those cells are dying. If scientists eventually are able to scale this technique to humans, oncologists would know far sooner than is now possible if a patient’s chemotherapy is working. On this day, however, Schepkin complained that his most recent experiment had been a bust. Dark shadows were cropping up on his MRI images: He suspected something was wrong with the RF coil. Now Gor’kov, clad in his usual baggy jeans and plaid flannel button-down, was bent over a workbench in the probe lab, fingering the canister like a Rubik’s cube. To jog his memory, diagrams from the probe’s patent paperwork were spread out on the surface below. After all, this instrument had been created many years and dozens of probes ago, well before the white now halfway across Gor’kov’s ginger beard had made its first incursions. A postdoctoral researcher perched at his left, glued to his every word and move. Gor’kov connected the coil’s tuning mechanism to an analyzer to check its resonance frequency. But on the screen, instead of a single peak corresponding to one frequency, there were two. Gor’kov stared, trying to tune in to the answer floating out in the universe somewhere. He sighed.
Photo: Stephen Bilenky
was sending heat into their proteins, boiling them like a microwave oven. After months of work and little to show for it, he was mulling the puzzle over in the shower, scanning his mental archives for clues. He retrieved: a random conversation with a spectroscopist at some conference; sound bites from a presentation by a probe manufacturer that he had not understood at the time; and a few pages from a decades-old textbook. The clues snapped together in his brain, leading him to a different arrangement of RF coils for what became Gor’kov probe No. 20. The Low-E probe (the E is for the electric field, the culprit that had been cooking the samples), later commercialized by Bruker Corp., was the tool University of Delaware biochemist Polenova later used to study HIV-1 virus proteins. Because the proteins’ high salt content readily conducts heat, other NMR probes had never worked for Polenova’s research. But this new probe, ingenious and sleek, did the trick for her tricky proteins.
Gor’kov in his workshop “Some asymmetry,” he mused as the postdoc leaned in to catch his words. “Let’s take it apart and see.” Donning a magnifying visor, Gor’kov loosened several tiny screws to free the coil from its casing. He then poked delicately at a millimeter-wide ring of copper tape that scientists could slide up and down the coil to fine-tune its frequency. He spotted a slit in the soldering — a clue, perhaps? “I’m curious what will actually happen if I force the crack,” he pondered. The postdoc fetched a razor blade, and Gor’kov sliced the shiny tape, which fell to the workbench like a curlicue of holiday ribbon. Gor’kov plucked it up, examined it. “I don’t get it,” he murmured. “This was supposed to have a pressure adhesive. Where is that adhesive? Why don’t we replace it and see what happens?” Some years ago, Gor’kov was struggling with another stubborn problem: a probe that, scientists complained, was not sensitive enough and that 20 fields
“We put the sample in, and we were able to get beautiful data,” she said. “It was a game changer.” Gor’kov has recently begun work on two new probes — No. 59 and No. 60 — that pose a whole new level of challenge. They will be for the lab’s new Series Connected Hybrid, which operates at much higher magnetic fields and resonance frequencies than any NMR magnet before it, said Tim Cross, director of the National MagLab’s Tallahassee-based NMR/MRI Facility. Gor’kov, Cross said, is the person for the job. “He’s fantastic at this.” Back in his lab, Gor’kov was trying to get to the bottom of the funky sodium coil. He rose from his stool, went straight to a little plastic drawer labeled “Copper Foil Tapes.” He tugged it open, fished one out to replace the one he had just cut. At that moment, research engineer Steve Ranner walked into the lab. He had had first crack at fixing the coil, but, seeing no obvious problem, asked its inventor to take a look. Now, a bit taken aback, Ranner surveyed its pieces, scattered across the table like shards of Venetian glass. “I asked Peter to help and now it’s all in bits,” he said. “I’m worried maybe I shouldn’t have asked.” But Gor’kov wasn’t worried. He knew, with enough poking, he would sort it all out.
Stroke of Genius
Caroline McNiel Illustrated by
Using high-field MRI, researchers are working to improve recovery in stroke victims.
hen a stroke strikes the brain, neurons die. But danger lingers for days afterward, as low oxygen in the area of the stroke threatens surviving brain cells. Researchers using world-record magnetic resonance imaging (MRI) machines at the National MagLab have been developing a way to save them. The technique involves using adult stem cells retrieved from outside the brain, treating them to promote healing and growth, then sending them through the blood to the site of the stroke.
Sam Grant, a MagLab bioengineer and associate professor at the FAMU-FSU College of Engineering, has been collaborating on the effort with colleagues from his college as well as from the University of South Florida and Tulane University. By labeling the stem cells with contrast agents, the team can track where they go in the brain and how long they stay. Once cells arrive at the stroke lesion, their job is to secrete proteins that will stimulate healing. It’s cutting-edge and potentially life-saving stuff, dramatized below as Capt. Research and his team come to the rescue of endangered brain cells …
Capt. Research, There’s
been an attack on the striatum and cortex. Brain cells are dying without the oxygen and nutrients the blood delivers!
A Stroke has attacked! Emergency!! A blockade is keeping out blood flow!
We need to send a team in quickly or damage will spread.
We need accurate real-time reporting to determine what steps to take next. If this mission fails we’ll need to move to plan B immediately.
The Stem Cell Unit should be able to stabilize the area.
Didn’t we have trouble tracking them last time?
Dispatch Agent Contrast with the team. Then we can monitor the progress over the magnetic field channels.
Team, the area of stroke destruction is growing and brain cells are dying every minute! Remember, time is tissue, so get to work!!
Take the middle cerebral artery to the site of the stroke.
Weâ€™ll track your progress on the MRI.
Agent Contrast here. Weâ€™re on site and the situation is dire, but Stem Cell Unit members are already working on their 4 assignments.
First Weâ€™re resuscitating damaged brain cells by releasing special proteins called trophic factors.
second, We’re getting the lights back on by rebuilding sodium levels.
third, we’ll increase blood flow by opening the vascular highways and building new routes.
N ATTENTIO and finally, We’ll summon
neuroprogenator cells from all over the body to the site of the stroke.
! Captain, the area is starting to stabilize. Neuroprogenator cells have begun to rebuild the area, and even have transformed into new brain cells!
Amazing work team! Let’s share our results with Maj. Publication.
Endangered brain cells have been saved. Blood flow and sodium levels are back to healthy levels. and we’ve learned a lot for a future mission.
Field of View
THE ALLURE OF
LINEARITY BY NIGEL HUSSEY
hen a new material is synthesized, one of the first things scientists do is attach four wires to its surface, cool it down and measure its electrical resistance as a function of temperature. Plotting the data on a graph then tells these scientists how well the electrons flow through the material â€” in other words, whether it is an insulator, a semiconductor, a metal or even, at lower temperatures, a superconductor (a special class of conductor through which the electrons encounter zero resistance). Each of these yields its own telltale line on a graph.
Yet while this is one of the first physical properties we measure, it is very often the last to be understood. Never was this more the case than in an exclusive club of materials known as strange metals. True to their name, these materials exhibit behavior that condensed matter physicists like me (who study solid materials) find nothing short of spectacular. The graph representing that data is equally spectacular, depicting a line rising straight as an arrow across the page that telegraphs an entirely new, mysterious kind of physics at work â€” one we suspect is as elegantly simple as the line itself.
What hides behind the elegantly simple line that describes the relationship between temperature and electrical resistance in certain materials? For some physicists, this is the most compelling question in the field.
E G N A R AL T S T E M TEMPERATURE
This behavior is all the more exciting because the strange metals club includes some very promising materials, such as cuprates and magicangle twisted bilayer graphene. Both of these special materials superconduct at temperatures
far higher than the conventional theory predicts, and it is hoped these “high-temperature superconductors” will ultimately revolutionize superconducting technology. So, what makes that straight line so special? After all, electrical resistance in ordinary metals, like copper or platinum, also varies linearly with temperature. Indeed, this linearity is the precise reason why platinum is used as a thermometer standard.
The thing is, normal metals exhibit this linearity only within a limited temperature range, as shown in the blue region of the line below. In the case of platinum, it’s between zero and a few hundred degrees Celsius. But if we were able to track the resistance over a much wider range of temperature, we would find that this linearity is only one of a host of different behaviors. The shape below shows this, reflecting how the resistance evolves at the quantum level.
Y R A N ORDI L A T E M TEMPERATURE
In normal metals, resistance happens because electrons collide with the vibrating atoms in their path, careering off course. The warmer it is, the more the atoms vibrate, and the more often electrons bump into them and scatter. This
scattering grows linearly with temperature over an intermediate temperature range. But when the metal gets extremely cold, there are fewer vibrations and less scattering. So the relationship between temperature and resistance becomes weaker and eventually levels off. There’s a change in behavior at the opposite end of the thermometer scale too. As ordinary metals warm up, their resistance eventually reaches a saturation value at which scattering ceases to increase. So, in ordinary metals, the process that drives the resistance changes several times between absolute zero and its melting point. These individual processes, described in great detail in modern physics textbooks, are reflected in the curvy line shown on the orange graph on this page. Not so in the strange metals! Their resistance continues to decrease linearly with temperature (in some cases down to near absolute zero, where atoms are essentially frozen). And it increases linearly at temperatures far higher than is seen in ordinary metals, reaching values that are way beyond the conventional limit. At first glance, this might imply that electrons are being scattered multiple times between the atoms, violating a fundamental principle of physics. Optical measurements show, however, that this resistance at high temperature must be driven by some other, still unknown process that, in the end, might have nothing to do with the scattering of electrons. What is most remarkable, and totally unexplained, is that across these very distinct temperature regimes, the resistance follows the same perfectly straight line. Such a relentless, unbounded growth in, say, the share price or the profits forecast of a registered company would look extremely attractive to a potential investor. To a scientist like me, such simplicity of form is also a thing of beauty, particularly when it continues to defy all conventional notions!
THE PLOT (LINE) THICKENS
Y R A N L I D OR ETA M
Now the plot thickens, thanks to high magnetic fields. Strange metals also exhibit a conventiondefying linearity in another measurement: magnetoresistance.
Y R A N L I D OR ETA M
MAGNETIC FIELD STRENGTH In strange metals, however, the magnetoresistance varies linearly with field strength over a very wide window. In some reported cases, this linearity reaches up to the very high field of 90 teslas, yielding once again an elegant straight line.
MAGNETIC FIELD STRENGTH What’s more, its slope is independent of temperature. This constancy suggests that magnetoresistance in strange metals, like their resistance in the absence of field, has nothing to do with the scattering we see in normal metals. So in strange metals, the straight-line response in both field and temperature clearly points to something far deeper.
First, let’s look at ordinary metals. When you put a normal metal in a magnetic field, the electrons experience a sideways force (called the Lorentz force) that causes them to follow a helical, rather than straight, trajectory, thereby increasing the material’s resistance. This is magnetoresistance, which in ordinary metals grows as the square of the magnetic field strength. The longer an electron travels before being scattered, MAGNETIC FIELD STRENGTH the longer its curved trajectory relative to its original (straight) path, and the larger the magnetoresistance. So as the metal is cooled and its resistance drops, its magnetoresistance (for the same field strength) grows. The data look like this:
GE N A L R T Finding something is will A S out what Tthat E ultimately require a radically new approach to M our understanding of metallic behavior. I am
among a number of researchers around the globe who are working hard to reconcile these two profound observations within such a single, unifying model. I consider this my greatest challenge as a condensed matter physicist. Such a model, once accepted, will surely herald a new chapter in the study of condensed matter.
MAGNETIC FIELD STRENGTH
While the bottom line to linearity remains to be discovered, one thing is certain: Given that many strange metals are also high-temperature superconductors, the rewards for developing such a model may extend far beyond a simple revision of our textbooks.
Nigel Hussey is a professor of physics at Radboud University and former director of the High Field Magnet Laboratory, both in Nijmegen, the Netherlands. Earlier this year, Hussey was awarded a 2.5 million-euro grant from the European Research Council to study the flow of charge in exotic metals and superconductors under extreme conditions. 26
GE N A L R T S ETA M
More about lines … online Want to know more about linearity? Go to fieldsmagazine.org/linearity.
Combating Cancer Scientists are using powerful magnets to learn how to better detect, treat and track the second leading cause of death worldwide. By Wudan Yan and Kristen Coyne | Illustrations by Caroline McNiel
mong all the ailments the human body may face, cancer is one of the trickiest. It can grow stealthily, evade detection, evolve complex defenses to drugs. Researchers have been studying cancer, and developing drugs to fight it, for decades in hopes of one day stamping out the mutant cells that are constantly outsmarting our immune systems. It is urgent work. According to the U.S. National Cancer Institute, more than one third of all men and women will be diagnosed with cancer at some point during their lifetimes. The disease kills millions worldwide every year, and the number of new cancer cases annually continues to rise, projected to reach 23.6 million by 2030.
DETECT EARLY Cancers often develop undetected. By the time a patient starts to experience symptoms, it might be too late to treat. Researchers are looking at how high-field tools could help. At the National MagLab, analytical chemist Lissa Anderson is collaborating with researchers from the Mayo Clinic in Rochester, Minnesota, to
In this epic health battle, many scientists are turning to high magnetic fields as their weapons of choice, using magnetic resonance imaging (MRI) and other magnet-based techniques. Today, stronger magnets, clearer images, better data resolution and novel techniques are leading to new cancer discoveries on everything from brain tumors to pancreatic cancer to multiple myeloma. At the National High Magnetic Field Laboratory (National MagLab) in Tallahassee, Florida, and similar labs worldwide, scientists are pushing the boundaries of cutting-edge instruments to learn how to better detect, treat and track this deadly disease.
It’s important to find out early when cancer first strikes. But it’s equally critical to detect when a cancer doctors hoped was vanquished makes a comeback. Because of the very high sensitivity of this instrument, Anderson said, it could be used to identify a relapse well before symptoms resurface.
detect multiple myeloma early. Multiple myeloma is a cancer of immune cells called B cells, which produce antibodies that defend against foreign invaders. But when B cells turn cancerous, they proliferate and secrete an overabundance of antibodies. Doctors currently use a technique called gel electrophoresis to detect these excess antibodies (and by extension, multiple myeloma). But this approach can’t identify the exact antibodies being overexpressed: They may or may not be from B cells. Clinicians can also diagnose the disease by a bone marrow biopsy, but that can be both painful and inaccurate. “False negatives are possible because you might not be sampling in an area where there’s an abundance of these transformed cells,” Anderson said. Anderson and her colleagues have used the world’s most powerful ion cyclotron resonance (ICR) mass spectrometer to overcome the limitations of conventional methods. Thanks to its 21-tesla magnet, the instrument can distinguish between molecules that are so similar that weaker machines can’t tell them apart. This allows researchers to differentiate among proteins from various antibodies and identify biomarkers that could help in the early detection and monitoring of multiple myeloma. In fact, the sensitivity of their measurements is 10 times higher than what doctors now get in clinical testing, Anderson said. “With these antibodies, we can see as the cells get transformed further because of the cancer — they’re always undergoing mutations,” Anderson said. “As the disease progresses, we can track the antibodies in the sequence and the number of single amino acid substitutions that are happening. No one has ever even done that, to my knowledge.”
“That hasn’t been done, yet,” she said, “but what we have demonstrated is that that could be done.” Claudio Luchinat, a chemist at the University of Florence in Italy, is using another spectroscopic technique, nuclear magnetic resonance (NMR), to detect relapses of the most common kind of cancer: breast cancer. Mammography detects tumors about a centimeter in size or larger, but is useless when tumors are tinier. Luchinat, however, has discovered that new tumors produce another telltale clue: They affect the metabolites of the host, changes that are detectable in blood. “It seems miraculous that you can tell the presence of a very tiny metastasis by looking at something that seems unrelated,” said Luchinat. When Luchinat took samples of serum from early breast cancer patients and analyzed them using a 600 MHz/14.1-tesla NMR magnet, he found that the set of metabolites in women who, after treatment, remained free from the disease differed from those who eventually relapsed. In fact, Luchinat discovered that the “metabolic fingerprint” was accurate about 80% of the time in predicting if a patient will relapse. In order to demonstrate the applicability of the technique to clinical practice, Luchinat is broadening his research to see if the fingerprint works within different populations. He is also studying whether other cancers generate a similar fingerprint.
TREAT AGGRESSIVELY Once cancer has been spotted, the next step is, of course, to stamp it out. With high magnetic fields, researchers are trying to improve the aim of anticancer drugs.
In the last few years, T-cell therapies have emerged as a promising form of cancer treatment. But many questions remain about how they work and how to improve them. Likai Song, a biophysicist and medical doctor at the National MagLab, is tackling that question by collaborating with researchers at the Dana Farber Cancer Institute in Boston. Together, they study how T-cells, frontline defenders of our immune system, get activated. For this work, Song and his colleagues paired a technique called electron magnetic resonance (EMR) with NMR. (While NMR targets atoms’ nuclei to identify the structure of molecules, EMR gleans information from the electrons.) With this dynamic magnet duo, they study how proteins on the surface of T-cells react to their environment, thereby triggering the T-cell to attack. The team has determined the molecular structure of parts of the protein and observed how that structure changes when T-cells are activated. Knowing these specific shapes, Song said, will help scientists to design new therapies, such as
small-molecule drugs with a complementary structure that fits these sites like a set of keys. Doctors could then fine-tune the T-cell response, amping it up or dialing it back to fit the specific requirements of individual patients. But even the best cancer drug is useless if it never hits the bull’s-eye. That’s why Edward Agyare, an associate professor of pharmaceutics at Florida A&M University in Tallahassee, has been testing a way to verify that drugs intended to zap pancreatic cancer reach their target. Pancreatic cancer has the lowest five-year survival rate of any leading cancer and is projected to become the second leading cause of cancer-related deaths in the United States next year. These tumors are challenging to treat because they’re surrounded by a lot of dense, fibrous tissue. Agyare is trying to get around this defense by developing nanoparticles with a one-two punch. They contain both gemcitabine, a drug used to treat the cancer, and gadolinium, a contrast agent that researchers can track in the body using MRI. These nanoparticles are also coated with a protein designed to bind to tumor cells. Contrast agents are typically metabolized by an animal’s system; packaging them into the same vehicle used to deliver drugs could one day help doctors verify if those drugs make it all the way to their destination. Agyare has been testing this approach in animal models using the National MagLab’s 21.1-tesla MRI machine, the strongest MRI machine used for small animal research in the world. Part of this research, which Agyare conducts with collaborators at the University of Florida, the University of Southern California and the National MagLab, involves DNA sequencing.
The team sequences the genomes of tumors removed from human patients, implants those tumors in mice, treats the rodents with Agyare’s nanoparticles (loaded with drug and contrast agent), then observes the varying results using MRI and other tools. “We want to see how the tumors with different genetic makeups are forming and how they respond to tumor suppression,” said Agyare. What the team learns may help physicians in the future better design and adapt treatments for individual patients based on the genetics of their specific cases.
TRACK CLOSELY It’s a big victory when a drug connects with its target, but that doesn’t guarantee doctors will win the cancer war. Magnetic fields, once again, are helping them master the long game. Duane Mitchell, a physician and immunologist at the University of Florida, studies immunotherapies such as adoptive cell transfer. In ACT, researchers take immune cells from a patient, modify them to enhance their ability to fight cancer, and then deliver those cells back to the patient. Specifically, he and his colleagues have used iron oxide-loaded nanoparticles to deliver dendritic cell vaccines (a type of ACT) to mice bearing invasive melanoma and brain tumors. By packaging the vaccines with MRI-sensitive iron oxide, the researchers could trace them in a strong MRI machine at the National MagLab. After following the paths of these particles, they could tell, within just two days, if the mice were responding to the treatment. “We’ve shown you can use MRI at very early time points after treatment to reliably predict successful treatment and differentiate responding from non-responding subjects,” Mitchell explained. This promising research has advanced to multiinstitutional clinical trials. Mitchell and his colleagues have found that glioblastoma patients treated with dendritic cell vaccines were more
likely to survive when the vaccines travelled successfully to a patient’s lymph nodes, a part of the body’s immune system where immune cells mature. The researchers’ goal is to identify biomarkers that correlate to successful treatment and improve existing therapies. In earlier clinical studies, Mitchell used radioactively labelled cells and SPECT/CT scans to follow the cells in the body. But MRI offers numerous advantages: It’s more widely available, is better for following the fate of cells over longer periods of time, and doesn’t involve potentially damaging radiation. Sam Grant, a biomedical engineer at the National MagLab, uses a technique called chemical exchange saturation transfer (CEST) to study the progression of glioma. Glioma is a brain tumor that typically has a median survival time of about 15 months, even after a patient has received surgery and treatment. CEST allows scientists to detect structures or processes in the body that traditional MRI can’t visualize. MRI scanners are typically used to detect the hydrogen in the body’s water; that information generates an image of structures in the body. In CEST, hydrogen atoms from specific molecules interchange with hydrogen atoms in free water within the body, highlighting the interactions of those target molecules in MRI scans. Grant and his colleagues have been optimizing the technique for experiments in the MagLab’s 21.1 tesla MRI magnet. Using CEST, they can identify metabolites, neurotransmitters and other molecules involved in tumor progression. “Looking at the chemical exchange allows us to identify fairly unique patterns in the spectra
that correspond to a tumor that is changing dynamically as it’s growing,” said Grant, who is also an associate professor at the FAMU-FSU College of Engineering.
“People know that tumors may develop resistance to therapy,” Schepkin said. “But in our experiments, we can actually see the changes in tumor resistance during therapy and quantify them.”
Over the last several years, the researchers have discovered metabolites and lipids that specifically correspond to glioma progression in rat models. They believe these metabolites could one day serve as biomarkers to help detect glioma early.
In fact, Schepkin has discovered that the dose of chemotherapy can influence whether cancer cells evolve to resist it. Two separate, smaller doses of a drug slow a tumor’s growth rate (but don’t shrink it), and don’t affect the tumor’s resistance to chemo. On the other hand, one combined dose might initially shrink the tumor, but what remains becomes more resistant to therapy. So the larger, single dose actually leads to future tumor resistance.
Tumors can evolve to outsmart therapies. But it’s still difficult to predict whether a tumor will become resistant. Here again, powerful magnets can help. MagLab biophysicist Victor Schepkin uses the lab’s 21.1-tesla MRI system to track sodium in tumors. After initiating chemotherapy in rodents with brain tumors, Schepkin performs brain scans that, thanks to the magnet’s high field and special instrumentation, can detect how sodium concentration changes in the rodents’ brains. If the drug works, the intracellular sodium in the dead cells will increase, a process detectable on MRI.
His most exciting discovery, Schepkin said, is that sodium MRI can detect if a tumor is resistant even before the chemotherapy is initiated. The research suggests that, one day, physicians could use sodium MRI to individualize cancer therapy for their patients. Tracking sodium using MRI requires a strong magnetic field, Schepkin said, because the sodium signal is several thousand times weaker than that of hydrogen, MRI’s conventional target. Taking this technique into the clinic will require time, as high-field MRI for humans is still far in the future. Still, magnetic fields, in the shape of different tools and techniques, are proving increasingly useful across a wide swath of cancer research. “Despite its relatively recent development, MRI is considered among the top 10 medical discoveries of all time — up there with the thermometer, the stethoscope and eye glasses,” said Lucio Frydman, chief scientist for chemistry and biology at the National MagLab and a professor in the Department of Chemical and Biological Physics at the Weizmann Institute of Sciences in Israel. “But in fact we have only scratched the surface of how magnetic resonance methods, and high-field magnetic resonance methods in particular, are poised to revolutionize the ways in which we see, better understand, treat and eventually defeat this hideous disease.”
BY KRISTEN COYNE | ILLUSTRATIONS BY CAROLINE MCNIEL
SOMETHING COMPLETELY DIFFERENT A N D N O W FO R 8 HIGH-FIELD PHYSICS PREDICTIONS THAT MONTY PYTHON NAILED
alf a century ago, a group of wacky Englishmen appeared in the first episode of an unconventional comedy series that would, with its irreverent, boundary-pushing humor, soon attract a cult following. With its absurd scenarios, racy sight gags, silly accents and garish graphics, “Monty Python’s Flying Circus” entertained, shocked and inspired audiences worldwide. Over the course of 45 episodes and several movies, the outfit introduced the world to things like silly walks, singing lumberjacks and treeclimbing sheep — images that shall live forever in our hearts, popular culture and, of course, on YouTube. Less well known, however, is the fact that many of the skits written and performed by the Python posse foretold important milestones of high magnetic field research. The troop’s funny façade belied an uncanny ability to see ahead decades into the future of physics. Here we list just a few instances of this Pythonic brilliance, showing how the comedians predicted discoveries about electron behavior such as superconductivity (when electrons travel through materials without any resistance, in contrast to the conventional conductivity) and about new world-record electromagnets that made those discoveries possible. Share your own observations of “Flying Circus” science soothsaying on Twitter, Instagram, or Facebook @NationalMagLab #montypython #Python50.
The Bridge Keeper From: “Monty Python and the Holy Grail”
SYNOPSIS: Accompanied by his knights, King
Arthur approaches a bridge spanning the Gorge of Eternal Peril. To gain access, each must answer three questions posed by a humpbacked ogre; an incorrect answer results in a one-way trip to the bottom of the gorge. That is precisely where some of the ill-fated knights end up when, after acing two softballs, they stumble on the third question, an unexpected curve ball. (King Arthur, of course, tricks the trickster, successfully overcoming yet another obstacle.)
HIGH-FIELD PREDICTION: This sketch is
clearly an allegory for the scientific quest for knowledge, and how we can be duped into believing we fully know something when, in fact, we only dimly understand. Take superconductivity, for example. The scientists who, in the mid 1950s, finally explained the behavior of electrons in superconductivity (first observed in 1911) were later honored by the Nobel Prize. But Mother Nature threw a curve ball a few decades later with the discovery of high-temperature superconductivity (HTS), a phenomenon the 1957 theory could not explain. Once again, scientists found themselves in the Bleak Pit of Ignorance. Ever since, using high magnetic fields and other tools, they have labored to pinpoint the physics behind HTS, which occurs at much warmer (read: practical) temperatures than conventional superconductivity. Is it charge order? Spin order? Electron nematicity? Physicists are busy testing theories, but aren’t ready to bring them to the Bridge Keeper quite yet.
Spam From: “Monty Python’s Flying Circus,” Season 2, Episode 12
SYNOPSIS: Mr. and Mrs. Bun visit a café popular among Vikings. Inquiring about the menu, they learn that everything includes at least one side of spam. Some items include multiple portions, and one consists of nothing but spam. Unlike the
other customers, Mrs. Bun is no fan of spam. Her husband, a spam devotee, offers to eat her portion.
HIGH-FIELD PREDICTION: This sketch predicts
the invention of a special magnet that, like Mrs. Bun, spurns spam. In the sketch, spam is clearly a metaphor for what magnet scientists call “noise.” The most powerful electromagnets in the world today generate undesirable noise, or fluctuations in the magnetic field, that result from fluctuations in the power source and can muddy data. But, as the Pythons prognosticated, the National MagLab in 2016 debuted a special kind of magnet, the 36-tesla Series Connected Hybrid magnet, that yields a very high field with relatively little spam — er, noise. Mrs. Bun would be proud.
Society for Putting Things on Top of Other Things From: “Monty Python’s Flying Circus,” Season 2, Episode 18
SYNOPSIS: At a fancy meeting of this exclusive
group, tuxedo-clad gentlemen praise the achievements of members who have succeeded to — well — place some things on top of other things.
HIGH-FIELD PREDICTION: This sketch clearly
presages the advent of van der Waals heterostructures, which are made up of two or more layers of one-atom-thin materials such as graphene. Physicists have been experimenting with different combinations of wafer-like materials, stacking them strategically, arranging them at varying angles atop one another, and exposing them to extreme environments such as high fields and high pressures. Adjusting these parameters often yields exciting quantum behaviors such as superconductivity. Scientists
generally don’t wear formal attire when working with heterostructures. However, the materials may one day lead some of them to a Nobel Prize ceremony, where tuxes and evening gowns are de rigueur.
Theory on Brontosauruses From: “Monty Python’s Flying Circus,” Season 3, Episode 31
SYNOPSIS: Paleontologist Anne Elk is
interviewed on a television show about her theory of brontosauruses. After much throatclearing and repeated proclamations that the theory is, indeed, her theory, she finally spits it out: “All brontosauruses are thin at one end, much, much thicker in the middle and then thin again at the far end.”
HIGH-FIELD PREDICTION: This sketch divines
the dome of superconductivity, which is shaped very much like the brontosaurus of Elk’s theory. This dome is an area on a graph that depicts the specific conditions under which a material becomes a high-temperature superconductor. When you connect the data points, a dome shape emerges: The temperature at which superconductivity occurs rises as a second parameter (typically pressure, magnetic field strength or manipulating the atomic makeup of the material through a process called doping) increases. After reaching a zenith, the superconducting temperature drops off again, creating a telltale hump reminiscent of a grazing brontosaurus. While the giant, Jurassic-era herbivore is extinct, its noble profile lives on in physics!
Holy Hand Grenade of Antioch From: “Monty Python and the Holy Grail”
SYNOPSIS: After some of his knights are taken
out by a killer rabbit, King Arthur and his remaining entourage deploy the Holy Hand Grenade of Antioch against the brutal bunny. The weapon, intended to “blow thy enemies to tiny bits,” hits its mark, allowing the heroes to proceed on their noble quest.
HIGH-FIELD PREDICTION: This sketch clearly foretells the creation of a research magnet so powerful that it explodes with every use. Socalled “single-turn” magnets, found at labs in France, Japan, Germany and the United States, create enormous fields in the hundreds of teslas that last mere microseconds before exploding. The sample that scientists put inside the magnet to study under high-field conditions, however, remains intact. Although the magnet ends up in “tiny bits” in these controlled explosions, the real enemy defeated by the blast is ignorance, as valiant scientists build knowledge with every experiment.
The Pet Shop From: “Monty Python’s Flying Circus,” Season 1, Episode 8
SYNOPSIS: An unhappy customer tries to return
a recently purchased Norwegian Blue parrot. He insists that the bird is deceased and would not revive even if 4,000 volts were passed through it. The pet shop owner begs to differ: Although
the bird is immobile, it is actually “stunned” and “pining for the fjords.”
HIGH-FIELD PREDICTION: This sketch prophesies
both the theory (1976) and experimental evidence (2013) of a stunning physics phenomenon known as Hofstadter’s butterfly, for which the parrot (another winged creature) is clearly a stand-in. Studying specific twodimensional materials in a high magnetic field, physicists working at the National MagLab observed the predicted fractal energy pattern; plotted on a graph in the same vivid blues as the parrot, the data resemble butterfly wings. The landmark discovery is expanding scientists’ understanding of the basic physics of electrons in a magnetic field. It’s no wonder the parrot/ butterfly of the sketch pines for fjords — code for fields, as in high magnetic fields — because only under those extreme conditions (and with an electrostatic gate to apply the “reviving” voltage) can this “butterfly” be brought to life, observed and understood.
Mosquito Hunters From: “Monty Python’s Flying Circus,” Season 2, Episode 21
SYNOPSIS: A pair of hunters armed to the teeth with machine guns, bazookas and even a tank pursue the tiniest of prey: mosquitos. After much shooting, booming and blasting, they succeed in annihilating their quarry.
HIGH-FIELD PREDICTION: This sketch augurs
the creation, still decades in the future, of a massive magnet used by physicists to study very tiny things. Weighing more than 31,000 kg, the 45-tesla hybrid magnet, housed at the National MagLab, opened to scientists in 1999, allowing them to observe teensy-tiny electrons and the crazy things they do when subjected to extreme environments such as high magnetic fields, high pressures and temperatures colder than Pluto. As in the sketch foretelling its creation, the tool may seem inordinately large compared to its wee prey. In this case the size
is justified by the energy requirements of so powerful an instrument. The 45-T magnet remains the strongest continuous field magnet in use in the world, giving researchers an unparalleled view of quantum behavior in a wide variety of materials.
Ministry of Silly Walks From: “Monty Python’s Flying Circus,” Season 2, Episode 1
SYNOPSIS: An employee of the Ministry of Silly Walks makes his way to work along London’s sidewalks, exhibiting a variety of ridiculous gaits while maintaining an exceedingly straight face. Arriving in his office he encounters a gentleman, keen to request a grant to develop a new silly walk. HIGH-FIELD PREDICTION: It is almost eerie how clearly this skit portends the careers of many a condensed matter physicist in the late 20th and early 21st centuries. These scientists were eager to explore the many ways electrons travel through different materials and under different conditions such as high fields, their behaviors as myriad as the silly walks performed in this skit. And like the grant-seeker in the sketch, these researchers often seek government funding to explore the surprising, perplexing and (some might say) even silly ways electrons mosey through materials. But make no mistake: Their work is anything but silly, paving the way to faster electronics, more energyefficient solar cells and more powerful diagnostic tools for doctors. See more Pythonian physics predictions at fieldsmagazine.org. Thanks to the Society of Silly Science for advising on this story: Ryan Baumbach, Greg Boebinger, Bill Brey, Scott Crooker, Scott Hannahs, Marcelo Jaime, Tim Murphy and Steve Ranner.
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Read how powerful magnets fight cancer, the story behind a master of science instrumentation, and how Monty Python presaged key advances in...
Published on Sep 24, 2019
Read how powerful magnets fight cancer, the story behind a master of science instrumentation, and how Monty Python presaged key advances in...