Sunday, January 26, 2014

Knots and Fluid Flow - Finding Patterns within Turbulence

Could Knots Unravel Mysteries of Fluid Flow?

Irvine Lab
A trefoil vortex knot in water generated by a hydrofoil.

Spaghetti-thin shoelaces, sturdy hawsers, silk cravats — all are routinely tied in knots. So too, physicists believe, are water, air and the liquid iron churning in Earth’s outer core. Knots twist and turn in the particle pathways of turbulent fluids, as stable in some cases as a sailor’s handiwork. For decades, scientists have suspected the rules governing these knots could offer clues for untangling turbulence — one of the last great unknowns of classical physics — but any order exhibited by the knots was lost in the surrounding chaos.

Now, with deft new tools at their fingertips, physicists are beginning to master the art of tying knots in fluids and other flowable entities, such as electromagnetic fields, enabling controlled study of their behavior. “Now that we have these knots, we can measure the shape of them in 3-D; we can look at the flow field around them,” said William Irvine, a physicist at the University of Chicago. “We can really figure out what the rules of the game are.”

Knots and linked loops exist in turbulent fluids like Earth’s outer core because they arise when a rotation coincides with a flow. (As the fluid rotates, the particle pathways, or “streamlines,” get dragged around and entangled in an effect similar to tying a shoelace.) Investigating knotted fluids both on paper and in the lab could provide a much richer picture of how these tangles, once formed, affect the future evolution of the fluids. The researchers say this new means of probing fluid flow could eventually advance the scientific understanding of the plasma rising off the surface of the sun, thermonuclear fusion, Earth’s interior and atmosphere, and other systems embroiled in turbulence.

“This is all a realization of this dream of understanding fluids in terms of the knots and links of the streamlines,” said Randy Kamien, a professor of physics and astronomy at the University of Pennsylvania.
Illustrations of knots and links, including a trefoil knot, top left, in an 1869 paper by Lord Kelvin on his knotted vortex theory of atoms.
Illustrations of knots and links, including a trefoil knot, top left, in an 1869 paper by Lord Kelvin on his knotted vortex theory of atoms. Related Video: Knot Possible?

The dream began in the 1860s with an ingenious knot theory of nature. Lord Kelvin proposed that atoms were knotted vortexes swirling in the ether, an invisible, fluidlike medium believed at the time to fill space. One element would be the simplest knot, called a trefoil, another a figure-eight knot, and so on — and none could transform into another. Though incorrect, Kelvin’s idea spawned the branch of mathematics known as knot theory and ultimately led to the realization that knots do more than passively form in fluids; they can have a pivotal, though as yet poorly understood, influence on turbulent fluid dynamics. In seminal work published in 1969, Keith Moffatt, then a young Cambridge University lecturer, proved that the measure of the total knottedness and linkage in ideal fluids — ones, like liquid helium, that lack viscosity — stays constant over time. In viscous fluids, this measure, called “helicity,” fluctuates, and knots can transform or unravel. But scientists still don’t know when and why helicity dissipates.

“There is a vast literature about what happens to knottedness in fluids, but it has been really hard to do experiments for a long time,” Irvine said. “It wasn’t until recently that we got these great tools for making and measuring things in 3-D, which is essential for knots.”

Earlier this year, Irvine’s team used water displacing objects called hydrofoils, created through 3-D printing, to fashion a trefoil knot out of a water vortex — the first vortex knot ever created in the lab. Using lasers, Kamien’s group constructed a knotlike structure in liquid crystals, the self-aligning fluids found in LCD television screens. And a third group — led by Mark Dennis, a theoretical physicist at the University of Bristol in the United Kingdom — tied knots in filaments of darkness swirling inside laser beams.

Alongside the experimental advances, researchers have also formulated new mathematical descriptions of knotted fluids and fields that can be analyzed on paper rather than in the lab.
Electromagnetic fields — entities that fill space and oscillate at different frequencies, some of which our eyes perceive as light — are mathematical solutions to a set of laws known as Maxwell’s equations. As reported in October in Physical Review Letters, Irvine and his colleagues Hridesh Kedia, Iwo Bialynicki-Birula and Daniel Peralta-Salas discovered a large class of solutions in which the contours of the electromagnetic fields, called “field lines,” twist and turn in knots.

A static, knotted electromagnetic field was derived in the 1990s, but “the new work is much more general,” said Moffatt, now a professor emeritus of mathematical physics at Cambridge. “They provide a technique for finding a really huge variety of knots.”

Irvine and coauthors will show in forthcoming work that there are corresponding knotted solutions to Euler’s equations, which govern ideal fluids. Because they have zero viscosity, these fluids flow perfectly smoothly, much like the light fields studied by the researchers. “It illustrates that we can be talking about very different physical systems with the same sorts of solutions,” Dennis noted. This equivalence means that if physicists discover the principles behind knots in Earth’s core, the same rules should apply to the tangled vortexes near an airplane wing.
A Knotty Picture
A rendering of a magnetic field encoding a trefoil knot
To visualize a knotted electromagnetic field, imagine three-dimensional space partitioned into doughnut-shaped tori of a continuous range of sizes, nested like Russian dolls. Collections of field lines (shown above in orange and blue) form the surface of each torus. In the trefoil knot field, each line wraps twice around the perimeter of the torus and three times through the center. As a result, any two lines on the same torus are knotted, and any two lines from different tori are knotted too. “It gives you a way of filling space with knots,” Irvine said. Then, as the field propagates through space and time, “these knots travel with the light.” (Illustration: Irvine Lab)
The knotted light fields that Irvine and his colleagues derived on paper may be realizable experimentally, he said, within a tightly focused and polarized laser beam. By shining the knotted beam onto another material, such as plasma, it should also be possible to “transfer the knottedness onto that thing,” he said, enabling controlled study of knots in a range of settings.

At present, almost nothing is experimentally proven about how knots in fluids and fields evolve over time despite decades of speculation and extensive computer simulations.

“Suppose William [Irvine] made two trefoil knots in a fluid and shot them at each other,” Kamien said. “What do they do? How do they interact? That’s completely beyond the scope of what we understand.” The answers to these seemingly simple questions, he added, are central to “how fluids work.”

For starters, when do knots unravel and when do they not? Moffatt proved that helicity stays constant in zero-viscosity fluids — a law of nature analogous to the conservation of energy in frictionless systems. But just as friction saps energy from a car, particle collisions suck helicity out of viscous fluids like water and plasma. “We know helicity is not exactly conserved, but how is it not exactly conserved?” Kamien asked. “Nobody really knows.”
Flow patterns in Earth's core
Gary A. Glatzmaier, Los Alamos National Laboratory, U.S. Department of Energy
A supercomputer model of flow patterns in Earth’s liquid iron outer core. The fluid’s complex topology is believed to play a central role in the “dynamo effect,” which generates the planet’s magnetic field.

The most pressing question is what happens when knotted or linked vortices in a viscous fluid cross and separate — a common process called reconnection. Some researchers hypothesize that link or knot helicity is converted into “twist helicity,” or faster swirling of the vortices, keeping the total helicity constant. However, preliminary work by Moffatt and Yoshifumi Kimura, a professor of fluid dynamics at Nagoya University in Japan, suggests that helicity dissipates during reconnection. “It’s an open question,” Moffatt said.
Reconnection is central to many turbulent processes, such as feedback between large and small eddies in Earth’s atmosphere, the heating of the solar corona and the generation of Earth’s magnetic field. In thermonuclear fusion — a solar process in which atoms fuse together, releasing massive amounts of energy — a turbulent plasma constantly undergoes reconnection as it relaxes to its minimum energy state. Understanding whether helicity remains constant during this process will help researchers correctly model and replicate fusion in the laboratory. “That’s why it’s an important issue to try to understand,” Moffatt said. “The long-term hope for mankind is to produce energy from fusion.”

Quantities that are “conserved,” or stay constant in time, “give you powerful ways to look at complicated problems,” Irvine explained. “Understanding a new conserved quantity, helicity, could have a huge impact on how we understand flows. It’s one of those holy grails.”

Once the rules of knottedness are established, some scientists say it might be possible to harness them through clever system design to control turbulence. The findings might suggest, for example, a better shape for airplane wings. “Could you braid the turbulence, and would that make it possible for planes to fly closer together?” Kamien asked. “Turbulence appears to be random. But is there some way to keep it from being random?”

Wednesday, January 22, 2014

Discovery of Quantum Vibrations in 'Microtubules' Corroborates Theory of Consciousness

by Staff Writers Amsterdam, Netherlands (SPX) Jan 21, 2014
The recent discovery of warm temperature quantum vibrations in microtubules inside brain neurons by the research group led by Anirban Bandyopadhyay, PhD, at the National Institute of Material Sciences in Tsukuba, Japan (and now at MIT), corroborates the pair's theory and suggests that EEG rhythms also derive from deeper level microtubule vibrations.

A review and update of a controversial 20-year-old theory of consciousness published in Physics of Life Reviews claims that consciousness derives from deeper level, finer scale activities inside brain neurons. The recent discovery of quantum vibrations in "microtubules" inside brain neurons corroborates this theory, according to review authors Stuart Hameroff and Sir Roger Penrose.
They suggest that EEG rhythms (brain waves) also derive from deeper level microtubule vibrations, and that from a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions.
The theory, called "orchestrated objective reduction" ('Orch OR'), was first put forward in the mid-1990s by eminent mathematical physicist Sir Roger Penrose, FRS, Mathematical Institute and Wadham College, University of Oxford, and prominent anesthesiologist Stuart Hameroff, MD, Anesthesiology, Psychology and Center for Consciousness Studies, The University of Arizona, Tucson. They suggested that quantum vibrational computations in microtubules were "orchestrated" ("Orch") by synaptic inputs and memory stored in microtubules, and terminated by Penrose "objective reduction" ('OR'), hence "Orch OR." Microtubules are major components of the cell structural skeleton.
Orch OR was harshly criticized from its inception, as the brain was considered too "warm, wet, and noisy" for seemingly delicate quantum processes. However, evidence has now shown warm quantum coherence in plant photosynthesis, bird brain navigation, our sense of smell, and brain microtubules.
The recent discovery of warm temperature quantum vibrations in microtubules inside brain neurons by the research group led by Anirban Bandyopadhyay, PhD, at the National Institute of Material Sciences in Tsukuba, Japan (and now at MIT), corroborates the pair's theory and suggests that EEG rhythms also derive from deeper level microtubule vibrations.
In addition, work from the laboratory of Roderick G. Eckenhoff, MD, at the University of Pennsylvania, suggests that anesthesia, which selectively erases consciousness while sparing non-conscious brain activities, acts via microtubules in brain neurons.
"The origin of consciousness reflects our place in the universe, the nature of our existence. Did consciousness evolve from complex computations among brain neurons, as most scientists assert? Or has consciousness, in some sense, been here all along, as spiritual approaches maintain?" ask Hameroff and Penrose in the current review.
"This opens a potential Pandora's Box, but our theory accommodates both these views, suggesting consciousness derives from quantum vibrations in microtubules, protein polymers inside brain neurons, which both govern neuronal and synaptic function, and connect brain processes to self-organizing processes in the fine scale, 'proto-conscious' quantum structure of reality."
After 20 years of skeptical criticism, "the evidence now clearly supports Orch OR," continue Hameroff and Penrose. "Our new paper updates the evidence, clarifies Orch OR quantum bits, or "qubits," as helical pathways in microtubule lattices, rebuts critics, and reviews 20 testable predictions of Orch OR published in 1998 - of these, six are confirmed and none refuted."
An important new facet of the theory is introduced. Microtubule quantum vibrations (e.g. in megahertz) appear to interfere and produce much slower EEG "beat frequencies." Despite a century of clinical use, the underlying origins of EEG rhythms have remained a mystery. Clinical trials of brief brain stimulation aimed at microtubule resonances with megahertz mechanical vibrations using transcranial ultrasound have shown reported improvements in mood, and may prove useful against Alzheimer's disease and brain injury in the future.
Lead author Stuart Hameroff concludes, "Orch OR is the most rigorous, comprehensive and successfully-tested theory of consciousness ever put forth. From a practical standpoint, treating brain microtubule vibrations could benefit a host of mental, neurological, and cognitive conditions."
The review is accompanied by eight commentaries from outside authorities, including an Australian group of Orch OR arch-skeptics. To all, Hameroff and Penrose respond robustly.
Penrose, Hameroff and Bandyopadhyay will explore their theories during a session on "Microtubules and the Big Consciousness Debate" at the Brainstorm Sessions, a public three-day event at the Brakke Grond in Amsterdam, the Netherlands, January 16-18, 2014. They will engage skeptics in a debate on the nature of consciousness, and Bandyopadhyay and his team will couple microtubule vibrations from active neurons to play Indian musical instruments.
"Consciousness depends on anharmonic vibrations of microtubules inside neurons, similar to certain kinds of Indian music, but unlike Western music which is harmonic," Hameroff explains.
"Consciousness in the universe: A review of the 'Orch OR' theory," by Stuart Hameroff, MD, and Roger Penrose, FRS. The review is freely available online on ScienceDirect.
Commentaries on the review are:
"Reply to criticism of the 'Orch OR qubit'-'Orchestrated objective reduction' is scientifically justified," by Stuart Hameroff, MD, and Roger Penrose, FRS;
"Reply to seven commentaries on "Consciousness in the universe: Review of the 'Orch OR' theory," by Stuart Hameroff, MD, and Roger Penrose, FRS.

The Symphony of Life, Revealed - and it is Vibratory

by Staff Writers Buffalo NY (SPX) Jan 21, 2014

Using a new imaging technique they developed, scientists have managed to observe and document the vibrations of lysozyme, an antibacterial protein found in many animals. This graphic visualizes the vibrations in lysozyme as it is excited by terahertz light (depicted by the red wave arrow). Such vibrations, long thought to exist, have never before been described in such detail, said lead researcher Andrea Markelz, a UB physicist. Credit: Credit: Andrea Markelz and Katherine Niessen.
The strings on a violin or the pipes of an organ, the proteins in the human body vibrate in different patterns, scientists have long suspected. Now, a new study provides what researchers say is the first conclusive evidence that this is true.
Using a technique they developed based on terahertz near-field microscopy, scientists from the University at Buffalo and Hauptman-Woodward Medical Research Institute (HWI) have for the first time observed in detail the vibrations of lysozyme, an antibacterial protein found in many animals.
The team found that the vibrations, which were previously thought to dissipate quickly, actually persist in molecules like the "ringing of a bell," said UB physics professor Andrea Markelz, PhD, wh0 led the study.
These tiny motions enable proteins to change shape quickly so they can readily bind to other proteins, a process that is necessary for the body to perform critical biological functions like absorbing oxygen, repairing cells and replicating DNA, Markelz said.
The research opens the door to a whole new way of studying the basic cellular processes that enable life.
"People have been trying to measure these vibrations in proteins for many, many years, since the 1960s," Markelz said. "In the past, to look at these large-scale, correlated motions in proteins was a challenge that required extremely dry and cold environments and expensive facilities."
"Our technique is easier and much faster," she said. "You don't need to cool the proteins to below freezing or use a synchrotron light source or a nuclear reactor - all things people have used previously to try and examine these vibrations."
The findings will appear in Nature Communications on Jan. 16, and publication of information on the research is prohibited until 5 a.m. U.S. Eastern Time on that day.
To observe the protein vibrations, Markelz' team relied on an interesting characteristic of proteins: The fact that they vibrate at the same frequency as the light they absorb.
This is analogous to the way wine glasses tremble and shatter when a singer hits exactly the right note. Markelz explained: Wine glasses vibrate because they are absorbing the energy of sound waves, and the shape of a glass determines what pitches of sound it can absorb. Similarly, proteins with different structures will absorb and vibrate in response to light of different frequencies.
So, to study vibrations in lysozyme, Markelz and her colleagues exposed a sample to light of different frequencies and polarizations, and measured the types of light the protein absorbed.
This technique, developed with Edward Snell, a senior research scientist at HWI and assistant professor of structural biology at UB, allowed the team to identify which sections of the protein vibrated under normal biological conditions. The researchers were also able to see that the vibrations endured over time, challenging existing assumptions.
"If you tap on a bell, it rings for some time, and with a sound that is specific to the bell. This is how the proteins behave," Markelz said. "Many scientists have previously thought a protein is more like a wet sponge than a bell: If you tap on a wet sponge, you don't get any sustained sound."
Markelz said the team's technique for studying vibrations could be used in the future to document how natural and artificial inhibitors stop proteins from performing vital functions by blocking desired vibrations.
"We can now try to understand the actual structural mechanisms behind these biological processes and how they are controlled," Markelz said.
"The cellular system is just amazing," she said. "You can think of a cell as a little machine that does lots of different things - it senses, it makes more of itself, it reads and replicates DNA, and for all of these things to occur, proteins have to vibrate and interact with one another."

Friday, January 17, 2014

Grandma's Experiences Leave a Mark on Your Genes

By Dan Hurley|Tuesday, June 11, 2013
Alison Mackey/DISCOVER

Darwin and Freud walk into a bar. Two alcoholic mice — a mother and her son — sit on two bar stools, lapping gin from two thimbles.
The mother mouse looks up and says, “Hey, geniuses, tell me how my son got into this sorry state.”
“Bad inheritance,” says Darwin.
“Bad mothering,” says Freud.
For over a hundred years, those two views — nature or nurture, biology or psychology — offered opposing explanations for how behaviors develop and persist, not only within a single individual but across generations.
And then, in 1992, two young scientists following in Freud’s and Darwin’s footsteps actually did walk into a bar. And by the time they walked out, a few beers later, they had begun to forge a revolutionary new synthesis of how life experiences could directly affect your genes — and not only your own life experiences, but those of your mother’s, grandmother’s and beyond.
The bar was in Madrid, where the Cajal Institute, Spain’s oldest academic center for the study of neurobiology, was holding an international meeting. Moshe Szyf, a molecular biologist and geneticist at McGill University in Montreal, had never studied psychology or neurology, but he had been talked into attending by a colleague who thought his work might have some application. Likewise, Michael Meaney, a McGill neurobiologist, had been talked into attending by the same colleague, who thought Meaney’s research into animal models of maternal neglect might benefit from Szyf’s perspective.
Michael Meaney, neurobiologist.
Owen Egan/McGill University
“I can still visualize the place — it was a corner bar that specialized in pizza,” Meaney says. “Moshe, being kosher, was interested in kosher calories. Beer is kosher. Moshe can drink beer anywhere. And I’m Irish. So it was perfect.”
The two engaged in animated conversation about a hot new line of research in genetics. Since the 1970s, researchers had known that the tightly wound spools of DNA inside each cell’s nucleus require something extra to tell them exactly which genes to transcribe, whether for a heart cell, a liver cell or a brain cell. 
One such extra element is the methyl group, a common structural component of organic molecules. The methyl group works like a placeholder in a cookbook, attaching to the DNA within each cell to select only those recipes — er, genes — necessary for that particular cell’s proteins. Because methyl groups are attached to the genes, residing beside but separate from the double-helix DNA code, the field was dubbed epigenetics, from the prefix epi (Greek for over, outer, above).
Originally these epigenetic changes were believed to occur only during fetal development. But pioneering studies showed that molecular bric-a-brac could be added to DNA in adulthood, setting off a cascade of cellular changes resulting in cancer. Sometimes methyl groups attached to DNA thanks to changes in diet; other times, exposure to certain chemicals appeared to be the cause. Szyf showed that correcting epigenetic changes with drugs could cure certain cancers in animals. 
Geneticists were especially surprised to find that epigenetic change could be passed down from parent to child, one generation after the next. A study from Randy Jirtle of Duke University showed that when female mice are fed a diet rich in methyl groups, the fur pigment of subsequent offspring is permanently altered. Without any change to DNA at all, methyl groups could be added or subtracted, and the changes were inherited much like a mutation in a gene.
Moshe Szyf, molecular biologist and geneticist.
McGill University
Now, at the bar in Madrid, Szyf and Meaney considered a hypothesis as improbable as it was profound: If diet and chemicals can cause epigenetic changes, could certain experiences — child neglect, drug abuse or other severe stresses — also set off epigenetic changes to the DNA inside the neurons of a person’s brain? That question turned out to be the basis of a new field, behavioral epigenetics, now so vibrant it has spawned dozens of studies and suggested profound new treatments to heal the brain.
According to the new insights of behavioral epigenetics, traumatic experiences in our past, or in our recent ancestors’ past, leave molecular scars adhering to our DNA. Jews whose great-grandparents were chased from their Russian shtetls; Chinese whose grandparents lived through the ravages of the Cultural Revolution; young immigrants from Africa whose parents survived massacres; adults of every ethnicity who grew up with alcoholic or abusive parents — all carry with them more than just memories. 
Like silt deposited on the cogs of a finely tuned machine after the seawater of a tsunami recedes, our experiences, and those of our forebears, are never gone, even if they have been forgotten. They become a part of us, a molecular residue holding fast to our genetic scaffolding. The DNA remains the same, but psychological and behavioral tendencies are inherited. You might have inherited not just your grandmother’s knobby knees, but also her predisposition toward depression caused by the neglect she suffered as a newborn. 
Or not. If your grandmother was adopted by nurturing parents, you might be enjoying the boost she received thanks to their love and support. The mechanisms of behavioral epigenetics underlie not only deficits and weaknesses but strengths and resiliencies, too. And for those unlucky enough to descend from miserable or withholding grandparents, emerging drug treatments could reset not just mood, but the epigenetic changes themselves. Like grandmother’s vintage dress, you could wear it or have it altered. The genome has long been known as the blueprint of life, but the epigenome is life’s Etch A Sketch: Shake it hard enough, and you can wipe clean the family curse.

Voodoo Genetics 
Twenty years after helping to set off a revolution, Meaney sits behind a wide walnut table that serves as his desk. A January storm has deposited half a foot of snow outside the picture windows lining his fourth-floor corner office at the Douglas Institute, a mental health affiliate of McGill. He has the rugged good looks and tousled salt-and-pepper hair of someone found on a ski slope — precisely where he plans to go this weekend. On the floor lays an arrangement of helium balloons in various stages of deflation. “Happy 60th!” one announces. 
“I’ve always been interested in what makes people different from each other,” he says. “The way we act, the way we behave — some people are optimistic, some are pessimistic. What produces that variation? Evolution selects the variance that is most successful, but what produces the grist for the mill?” 
Meaney pursued the question of individual differences by studying how the rearing habits of mother rats caused lifelong changes in their offspring. Research dating back to the 1950s had shown that rats handled by humans for as little as five to 15 minutes per day during their first three weeks of life grew up to be calmer and less reactive to stressful environments compared with their non-handled littermates. Seeking to tease out the mechanism behind such an enduring effect, Meaney and others established that the benefit was not actually conveyed by the human handling. Rather, the handling simply provoked the rats’ mothers to lick and groom their pups more, and to engage more often in a behavior called arched-back nursing, in which the mother gives the pups extra room to suckle against her underside.
“It’s all about the tactile stimulation,” Meaney says.
In a landmark 1997 paper in Science, he showed that natural variations in the amount of licking and grooming received during infancy had a direct effect on how stress hormones, including corticosterone, were expressed in adulthood. The more licking as babies, the lower the stress hormones as grown-ups. It was almost as if the mother rats were licking away at a genetic dimmer switch. What the paper didn’t explain was how such a thing could be possible. 
"What we had done up to that point in time was to identify maternal care and its influence on specific genes,” Meaney says. “But epigenetics wasn’t a topic I knew very much about.”
And then he met Szyf.

Alison Mackey/DISCOVER

Postnatal Inheritance 
“I was going to be a dentist,” Szyf says with a laugh. Slight, pale and balding, he sits in a small office at the back of his bustling laboratory — a room so Spartan, it contains just a single picture, a photograph of two embryos in a womb.
Needing to write a thesis in the late 1970s for his doctorate in dentistry at Hebrew University of Jerusalem, Szyf approached a young biochemistry professor named Aharon Razin, who had recently made a splash by publishing his first few studies in some of the world’s top scientific journals. The studies were the first to show that the action of genes could be modulated by structures called methyl groups, a subject about which Szyf knew precisely nothing. But he needed a thesis adviser, and Razin was there. Szyf found himself swept up to the forefront of the hot new field of epigenetics and never looked back.
Until researchers like Razin came along, the basic story line on how genes get transcribed in a cell was neat and simple. DNA is the master code, residing inside the nucleus of every cell; RNA transcribes the code to build whatever proteins the cell needs. Then some of Razin’s colleagues showed that methyl groups could attach to cytosine, one of the chemical bases in DNA and RNA. 
It was Razin, working with fellow biochemist Howard Cedar, who showed these attachments weren’t just brief, meaningless affairs. The methyl groups could become married permanently to the DNA, getting replicated right along with it through a hundred generations. As in any good marriage, moreover, the attachment of the methyl groups significantly altered the behavior of whichever gene they wed, inhibiting its transcription, much like a jealous spouse. It did so, Razin and Cedar showed, by tightening the thread of DNA as it wrapped around a molecular spool, called a histone, inside the nucleus. The tighter it is wrapped, the harder to produce proteins from the gene. 
Consider what that means: Without a mutation to the DNA code itself, the attached methyl groups cause long-term, heritable change in gene function. Other molecules, called acetyl groups, were found to play the opposite role, unwinding DNA around the histone spool, and so making it easier for RNA to transcribe a given gene.
By the time Szyf arrived at McGill in the late 1980s, he had become an expert in the mechanics of epigenetic change. But until meeting Meaney, he had never heard anyone suggest that such changes could occur in the brain, simply due to maternal care.
“It sounded like voodoo at first,” Szyf admits. “For a molecular biologist, anything that didn’t have a clear molecular pathway was not serious science. But the longer we talked, the more I realized that maternal care just might be capable of causing changes in DNA methylation, as crazy as that sounded. So Michael and I decided we’d have to do the experiment to find out.”
Actually, they ended up doing a series of elaborate experiments. With the assistance of postdoctoral researchers, they began by selecting mother rats who were either highly attentive or highly inattentive. Once a pup had grown up into adulthood, the team examined its hippocampus, a brain region essential for regulating the stress response. In the pups of inattentive mothers, they found that genes regulating the production of glucocorticoid receptors, which regulate sensitivity to stress hormones, were highly methylated; in the pups of conscientious moms, the genes for the glucocorticoid receptors were rarely methylated.
Methylation just gums up the works. So the less the better when it comes to transcribing the affected gene. In this case, methylation associated with miserable mothering prevented the normal number of glucocorticoid receptors from being transcribed in the baby’s hippocampus. And so for want of sufficient glucocorticoid receptors, the rats grew up to be nervous wrecks.
To demonstrate that the effects were purely due to the mother’s behavior and not her genes, Meaney and colleagues performed a second experiment. They took rat pups born to inattentive mothers and gave them to attentive ones, and vice versa. As they predicted, the rats born to attentive mothers but raised by inattentive ones grew up to have low levels of glucocorticoid receptors in their hippocampus and behaved skittishly. Likewise, those born to bad mothers but raised by good ones grew up to be calm and brave and had high levels of glucocorticoid receptors.
Before publishing their findings, Meaney and Szyf conducted a third crucial experiment, hoping to overwhelm the inevitable skeptics who would rise up to question their results. After all, it could be argued, what if the epigenetic changes observed in the rats’ brains were not directly causing the behavioral changes in the adults, but were merely co-occurring? Freud certainly knew the enduring power of bad mothers to screw up people’s lives. Maybe the emotional effects were unrelated to the epigenetic change.
To test that possibility, Meaney and Szyf took yet another litter of rats raised by rotten mothers. This time, after the usual damage had been done, they infused their brains with trichostatin A, a drug that can remove methyl groups. These animals showed none of the behavioral deficits usually seen in such offspring, and their brains showed none of the epigenetic changes.
“It was crazy to think that injecting it straight into the brain would work,” says Szyf. “But it did. It was like rebooting a computer.”

Despite such seemingly overwhelming evidence, when the pair wrote it all up in a paper, one of the reviewers at a top science journal refused to believe it, stating he had never before seen evidence that a mother’s behavior could cause epigenetic change.
“Of course he hadn’t,” Szyf says. “We wouldn’t have bothered to report the study if it had already been proved.”
In the end, their landmark paper, “Epigenetic programming by maternal behavior,” was published in June 2004 in the journal Nature Neuroscience.
Meaney and Szyf had proved something incredible. Call it postnatal inheritance: With no changes to their genetic code, the baby rats nonetheless gained genetic attachments due solely to their upbringing — epigenetic additions of methyl groups sticking like umbrellas out the elevator doors of their histones, gumming up the works and altering the function of the brain.

The Beat Goes On
Together, Meaney and Szyf have gone on to publish some two-dozen papers, finding evidence along the way of epigenetic changes to many other genes active in the brain. Perhaps most significantly, in a study led by Frances Champagne — then a graduate student in Meaney’s lab, now an associate professor with her own lab at Columbia University in New York — they found that inattentive mothering in rodents causes methylation of the genes for estrogen receptors in the brain. When those babies grow up, the resulting decrease of estrogen receptors makes them less attentive to their babies. And so the beat goes on. 
As animal experiments continue apace, Szyf and Meaney have entered into the next great step in the study of behavioral epigenetics: human studies. In a 2008 paper, they compared the brains of people who had committed suicide with the brains of people who had died suddenly of factors other than suicide. They found excess methylation of genes in the suicide brains’ hippocampus, a region critical to memory acquisition and stress response. If the suicide victims had been abused as children, they found, their brains were more methylated.
Alison Mackey/DISCOVER
Why can’t your friend “just get over” her upbringing by an angry, distant mother? Why can’t she “just snap out of it”? The reason may well be due to methyl groups that were added in childhood to genes in her brain, thereby handcuffing her mood to feelings of fear and despair. 
Of course, it is generally not possible to sample the brains of living people. But examining blood samples in humans is routine, and Szyf has gone searching there for markers of epigenetic methylation. Sure enough, in 2011 he reported on a genome-wide analysis of blood samples taken from 40 men who participated in a British study of people born in England in 1958. 
All the men had been at a socioeconomic extreme, either very rich or very poor, at some point in their lives ranging from early childhood to mid-adulthood. In all, Szyf analyzed the methylation state of about 20,000 genes. Of these, 6,176 genes varied significantly based on poverty or wealth. Most striking, however, was the finding that genes were more than twice as likely to show methylation changes based on family income during early childhood versus economic status as adults.
Timing, in other words, matters. Your parents winning the lottery or going bankrupt when you’re 2 years old will likely affect the epigenome of your brain, and your resulting emotional tendencies, far more strongly than whatever fortune finds you in middle age. 
Last year, Szyf and researchers from Yale University published another study of human blood samples, comparing 14 children raised in Russian orphanages with 14 other Russian children raised by their biological parents. They found far more methylation in the orphans’ genes, including many that play an important role in neural communication and brain development and function. 
“Our study shows that the early stress of separation from a biological parent impacts long-term programming of genome function; this might explain why adopted children may be particularly vulnerable to harsh parenting in terms of their physical and mental health,” said Szyf’s co-author, psychologist Elena Grigorenko of the Child Study Center at Yale. “Parenting adopted children might require much more nurturing care to reverse these changes in genome regulation.”
A case study in the epigenetic effects of upbringing in humans can be seen in the life of Szyf’s and Meaney’s onetime collaborator, Frances Champagne. “My mom studied prolactin, a hormone involved in maternal behavior. She was a driving force in encouraging me to go into science,” she recalls. Now a leading figure in the study of maternal influence, Champagne just had her first child, a daughter. And epigenetic research has taught her something not found in the What to Expect books or even her mother’s former lab. 
“The thing I’ve gained from the work I do is that stress is a big suppressor of maternal behavior,” she says. “We see it in the animal studies, and it’s true in humans. So the best thing you can do is not to worry all the time about whether you’re doing the right thing. Keeping the stress level down is the most important thing. And tactile interaction — that’s certainly what the good mother rats are doing with their babies. That sensory input, the touching, is so important for the developing brain.” 

The Mark Of Cain 
The message that a mother’s love can make all the difference in a child’s life is nothing new. But the ability of epigenetic change to persist across generations remains the subject of debate. Is methylation transmitted directly through the fertilized egg, or is each infant born pure, a methylated virgin, with the attachments of methyl groups slathered on solely by parents after birth? 
Neuroscientist Eric Nestler of the Icahn School of Medicine at Mount Sinai in New York has been seeking an answer for years. In one study, he exposed male mice to 10 days of bullying by larger, more aggressive mice. At the end of the experiment, the bullied mice were socially withdrawn. 
To test whether such effects could be transmitted to the next generation, Nestler took another group of bullied mice and bred them with females, but kept them from ever meeting their offspring. 
Alison Mackey/DISCOVER
Despite having no contact with their depressed fathers, the offspring grew up to be hypersensitive to stress. “It was not a subtle effect; the offspring were dramatically more susceptible to developing signs of depression,” he says.
In further testing, Nestler took sperm from defeated males and impregnated females through in vitro fertilization. The offspring did not show most of the behavioral abnormalities, suggesting that epigenetic transmission may not be at the root. Instead, Nestler proposes, “the female might know she had sex with a loser. She knows it’s a tainted male she had sex with, so she cares for her pups differently,” accounting for the results.
Despite his findings, no consensus has yet emerged. The latest evidence, published in the Jan. 25 issue of the journal Science, suggests that epigenetic changes in mice are usually erased, but not always. The erasure is imperfect, and sometimes the affected genes may make it through to the next generation, setting the stage for transmission of the altered traits in descendants as well. 

What’s Next?
The studies keep piling on. One line of research traces memory loss in old age to epigenetic alterations in brain neurons. Another connects post-traumatic stress disorder to methylation of the gene coding for neurotrophic factor, a protein that regulates the growth of neurons in the brain.
If it is true that epigenetic changes to genes active in certain regions of the brain underlie our emotional and intellectual intelligence — our tendency to be calm or fearful, our ability to learn or to forget — then the question arises: Why can’t we just take a drug to rinse away the unwanted methyl groups like a bar of epigenetic Irish Spring? 
The hunt is on. Giant pharmaceutical and smaller biotech firms are searching for epigenetic compounds to boost learning and memory. It has been lost on no one that epigenetic medications might succeed in treating depression, anxiety and post-traumatic stress disorder where today’s psychiatric drugs have failed. 
But it is going to be a leap. How could we be sure that epigenetic drugs would scrub clean only the dangerous marks, leaving beneficial — perhaps essential — methyl groups intact? And what if we could create a pill potent enough to wipe clean the epigenetic slate of all that history wrote? If such a pill could free the genes within your brain of the epigenetic detritus left by all the wars, the rapes, the abandonments and cheated childhoods of your ancestors, would you take it?