Attack in New York City


This week, NYC was attacked again, this time by a deranged van driver, killing 8 people, and injuring many others. Our hearts and prayers go out to the families of those who were killed and injured. When it comes to tolerance, our city is open, gentle, and a true melting pot welcoming all to the American Dream.  Hopefully, the day will come, when Martin Luther King’s dream will become a reality, where we tolerate differences, share ideas, listen to each other and compromise.


Let freedom ring! Freedom Tower has replaced the WTC Towers – © Target Health Inc.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.


Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor



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Study Shows How Memories Ripple Through the Brain


NIH-funded study suggests increased communication between key brain areas during sleep


Posterior and inferior cornua of left lateral ventricle exposed from the side. The hippocampus is located in the medial temporal lobe of the brain. In this lateral view of the human brain, the frontal lobe is at left, the occipital lobe at right, and the temporal and parietal lobes have largely been removed to reveal the hippocampus underneath.

Graphic credit: Henry Vandyke Carter – Henry Gray (1918) Anatomy of the Human Body (See “Book“ section below) Gray’s Anatomy, Plate 739; Public Domain, Wikipedia



The hippocampus (named after its resemblance to the seahorse, from the Greek “seahorse“ from hippos, “horse“ and kampos, “sea monster“) is a major component of the brains of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the 1) ___. The hippocampus belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located under the cerebral 2) ___ (allocortical) and in primates in the medial temporal lobe. It contains two main interlocking parts: the hippocampus proper (also called Ammon’s horn) and the dentate gyrus. The hippocampus is widely thought to turn new information into permanent memories while we sleep


In Alzheimer’s disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage. Short-term memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result from oxygen starvation (hypoxia), encephalitis, or medial temporal lobe epilepsy. People with extensive, bilateral hippocampal damage may experience anterograde amnesia (the inability to form and retain new 3) ___. In rodents as model organisms, the hippocampus has been studied extensively as part of a brain system responsible for spatial memory and navigation. Many neurons in the rat and mouse hippocampus respond as place cells: that is, they fire bursts of action potentials when the animal passes through a specific part of its environment. Hippocampal place 4) ___ interact extensively with head direction cells, whose activity acts as an inertial compass, and conjecturally with grid cells in the neighboring entorhinal cortex. Since different neuronal cell types are neatly organized into layers in the hippocampus, it has frequently been used as a model system for studying neurophysiology. The form of neural plasticity known as long-term potentiation (LTP) was first discovered to occur in the hippocampus and has often been studied in this structure. LTP is widely believed to be one of the main neural mechanisms by which memories are stored in the brain.


Just recently, using an innovative “NeuroGrid“ technology, invented by the study authors, it was showed that sleep boosts communication between two brain regions whose connection is critical for the formation of memories. The NeuroGrid consists of a collection of tiny electrodes linked together like the threads of a blanket, which is then laid across an area of the brain so that each electrode can continuously monitor the activity of a different set of neurons. One of the features of the device, is that it provides for ability to look at multiple areas of the brain at the same time. The study, published in Science, was partially funded by the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, a project of the 5) ___ ___ of ___ devoted to accelerating the development of new approaches to probing the workings of the brain.


Previous work revealed high-frequency bursts of neural firing called ripples in the 6) ___ during sleep and suggested they play a role in memory storage. The current study confirmed the presence of ripples in the hippocampus during sleep and found them in certain parts of association neocortex, an area on the brain’s surface involved in processing complex sensory information. Using the NeuroGrid system, along with recording electrodes placed deeper into the brain, the researchers examined activity in several parts of rats’ brains during NREM or 7) ___-___ ___ ___ sleep, the longest stage of sleep. The team was also surprised to find that the ripples in the association neocortex and hippocampus occurred at the same time, suggesting the two regions were communicating as the rats were 8) ___. Because the association neocortex is thought to be a storage location for memories, the authors theorized that this neural dialogue could help the brain retain information. To test that idea, they examined brain activity during NREM sleep in rats trained to locate rewards in a maze and in rats that explored the 9) ___ in a random fashion. In the latter group of animals, the ripples in the hippocampus and cortex were no more synchronized before exploring the maze than afterwards. In the trained rats, however, the learning task increased the cross-talk between those areas, and a second training session boosted it even more, further suggesting that such communication is important for the creation and storage of memories.


The group hopes to use the NeuroGrid in people undergoing brain surgery for other reasons to determine if the same ripples occur in the 10) ___ brain. The group also plans to investigate if manipulating that neural firing in animals can boost or suppress memory formation in order to confirm that ripples are important for that process. According to the authors, identifying the specific neural patterns that go along with memory formation may provide a way to better understand memory and potentially even address disorders of memory.


The study was funded by NINDS (NS099705, NS090583) and the National Institute of Mental Health (MH107396). The National Institute of Neurological Disorders and Stroke (NINDS) <> is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. References: Khodagholy et al. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science. October 20, 2017. doi: 10.1126/science.aan6203.


ANSWERS: 1) brain; 2) cortex; 3) memories; 4) cells; 5) National Institutes of Health; 6) hippocampus; 7) non-rapid eye movement; 8) sleeping; 9) maze; 10) human


Approximately 65 Years Ago, Eugene Aserinsky Discovered REM Sleep

REM Sleep, outlined in red, above. Below the REM Sleep, are slow EEG waveforms of brain activity during non-REM sleep. – By en:User:MrSandman – Own work, Public Domain,


It was Sigmund Freud who stated, “Dreams are the royal road to the unconscious.”


Eugene Aserinsky (May 6, 1921 – July 22, 1998), a pioneer in sleep research, was a graduate student at the University of Chicago in 1953 when he discovered REM sleep. Aserinsky the son of a dentist of Russian – Jewish descent, like many great scientists, was of an immigrant family. Aserinsky made his discovery after hours spent studying the eyelids of sleeping subjects. Aserinsky and his PhD adviser, Nathaniel Kleitman, went on to demonstrate that this “rapid-eye movement“ was correlated with dreaming and a general increase in brain activity. Aserinsky and Kleitman pioneered procedures that have now been used with thousands of volunteers using the electroencephalograph. Because of these discoveries, Aserinsky and Kleitman are generally considered the founders of modern sleep research.


In 1953, for his Ph.D. in physiology at the University of Chicago, Dr. Aserinsky produced his ground-breaking thesis, ”Eye Movements During Sleep.” His discovery of rapid eye movement, or R.E.M. — the periodic, rapid, jerky movement of the eyeballs under the lids during stages of sleep associated with dreaming — showed that the brain was in a state of some alertness for about 22% of total sleep time. In a long career, he taught at Jefferson Medical College in Philadelphia, Marshall University Medical School and West Virginia University.


Eugene Aserinsky, died on July 22, 1998, when his car hit a tree north of San Diego. He was 77 and lived in Escondido, Calif. Nathaniel Kleitman lived to be 104 years old.


Editor’s note: All the Eugene Aserinsky sources we searched through, were quite limited – dry facts only. Then we discovered a fascinating write-up in the Smithsonian Magazine, by Chip Brown, that is such a fascinating account of Eugene Aserinsky, we have included the whole article, below.


Night after night Eugene Aserinsky had been working late. He’d dragged an ancient brain-wave machine, an Offner Dynograph, from the basement to the physiology lab on the second floor of Abbott Hall at the University of Chicago. He had tinkered with it long enough to think it might not be totally unreliable. And now, late one December evening in 1951, his 8-year-old son, Armond, came over to the lab and sat patiently on an Army cot while his father scrubbed his scalp and the skin around his eyes with acetone, taped electrodes to the boy’s head and plugged the leads into a switch box over the bed. From the adjacent room, Aserinsky calibrated the machine, telling Armond to look left, right, up and down. The ink pens jumped in concert with the boy’s eyes. And then it was lights out, the sharp smell of acetone lingering in the darkness. Armond fell asleep; his father tried not to. Sustained by pretzels and coffee, Aserinsky sat at a desk under the hellish red eyes of a gargoyle-shaped lamp. He was 30 years old, a trim, handsome man of medium height, with black hair, a mustache, blue eyes and the mien of a bullfighter. When he was not in his lab coat, he usually wore a bow tie and a dark suit. He was a graduate student in physiology, and his future was riding on this research. He had nothing but a high school degree to fall back on. His wife, Sylvia, was pregnant with their second child. They lived on campus in a converted Army barracks heated by a kerosene stove. Money was so tight Aserinsky would eventually have to accept a small loan from his dissertation advisor, Nathaniel Kleitman, and then be obliged to feign enthusiasm for the distinguished man’s suggestion that he economize by eating chicken necks.


The hours crept by in the spooky gray-stone gloom of Abbott Hall. While the long banner of graph paper unfurled, Aserinsky noticed that the pens tracking his son’s eye movements – as well as the pens registering brain activity – were swinging back and forth, suggesting Armond was alert and looking around. Aserinsky went in to check on his son, expecting to find him wide awake. But Armond’s eyes were closed; the boy was fast asleep. What was going on? Yet another problem with the infernal machine? Aserinsky didn’t know what to think, standing in bewildered excitement, on the threshold of a great discovery.


The existence of rapid eye movement (REM) and its correlation with dreaming was announced 50 years ago last month in a brief, little-noted report in the journal Science. The two-page paper is a fine example of the maxim that the eye can see only what the mind knows: for thousands of years the physical clues of REM sleep were baldly visible to anyone who ever gazed at the eyelids of a napping child or studied the twitching paws of a sleeping dog. The association of a certain stage of sleep with dreaming might have been described by any number of observant cave men; in fact, if the 17,000-year-old Lascaux cave painting of a presumably dreaming Cro-Magnon hunter with an erect penis is any indication, maybe it was. But scientists had long been blinkered by preconceptions about the sleeping brain. It remains an astonishing anachronism in the history of science that Watson and Crick unraveled the structure of DNA before virtually anything was known about the physiological condition in which people spend one-third of their lives. As Tom Roth, the former editor of the journal Sleep, put it: “It’s analogous to going to Mars with a third of the Earth’s surface still unexplored.“ The REM state is so important that some scientists have designated it a “third state of being“ (after wakefulness and sleep), yet the phenomenon itself remained hidden in plain sight until September 1953, when the experiments conducted in Chicago by Aserinsky were published.


His now-classic paper, coauthored by advisor Kleitman, was less important for what it revealed than what it began. REM opened the terra incognita of the sleeping brain to scientific exploration. Before REM, it was assumed that sleep was a passive state; absent stimulation, the brain simply switched off at night like a desk lamp. After REM, scientists saw that the sleeping brain actually cycled between two distinct electrical and biochemical climates – one characterized by deep, slow-wave sleep, which is sometimes called “quiet sleep“ and is now known as non-REM or NREM sleep, and the other characterized by REM sleep, also sometimes called “active“ or “paradoxical“ sleep. The mind in REM sleep teems with vivid dreams; some brain structures consume oxygen and glucose at rates equal to or higher than in waking. The surprising implication is that the brain, which generates and evidently benefits from sleep, seems to be too busy to get any sleep itself.


The discovery of REM launched a new branch of medicine, leading to the diagnosis and treatment of sleep disorders that afflict tens of millions of people. It also changed the way we view our dreams and ourselves. It shifted scientists’ focus from the dreaming person to the dreaming brain, and inspired new models in which the chimerical dramas of the night were said to reflect random neural fireworks rather than the hidden intentions of unconscious conflict or the escapades of disembodied souls. By showing that the brain cycles through various neurodynamic phases, the discovery of REM underscored the view that the “self“ is not a fixed state but reflects fluctuating brain chemistry and electrical activity. Many researchers continue to hope that REM may yet provide a link between the physical activity of the brain during a dream and the experience of dreaming itself. It’s hard to overestimate the importance of Aserinsky’s breakthrough, said Bert States, an emeritus professor of dramatic arts at the University of California at Santa Barbara and the author of three books on dreams and dreaming: “The discovery of REM sleep was just about as significant to the study of cognition as the invention of the telescope was to the study of the stars.“


In 1950, when Aserinsky knocked on Nathaniel Kleitman’s office door, Kleitman, then 55, was considered the “father of modern sleep research.“ A Russian emigre, he had received a doctorate from the University of Chicago in 1923 and joined the faculty two years later. There he set up the world’s first sleep lab. The cot where research subjects slept was pitched under a metal hood formerly used to suck out noxious lab fumes. At the time, few scientists were interested in the subject. Despite research on the electrical activity of the brain in the late 1920s, the understanding of sleep hadn’t advanced much beyond the ancient Greeks, who viewed Hypnos, the god of sleep, as the brother of Thanatos, the god of death. Sleep was what happened when you turned out the lights and stopped the influx of sensation. Sleep was what the brain lapsed into, not what it actively constructed. On the face of it, dull stuff.


Kleitman was intrigued nonetheless, and began to explore the physiology of the body’s basic rest-activity cycle. A painstaking researcher, he once stayed up 180 hours straight to appraise the effects of sleep deprivation on himself. In 1938, he and fellow researcher Bruce Richardson moved into Mammoth Cave in Kentucky for more than a month to study fluctuations in their body temperatures and other darkness-engendered changes in their normal sleep-wake cycle – pioneering work in the now booming field of circadian rhythm research. Kleitman backed his fieldwork with formidable scholarship. When he published his landmark book Sleep and Wakefulness in 1939, he apologized for being unable to read in any language other than Russian, English, German, French and Italian. At the office door, Aserinsky found a man with “a grey head, a grey complexion and a grey smock.“ As the younger scientist wrote years later, “there was no joy in this initial encounter for either of us. For my part I recognized Kleitman as the most distinguished sleep researcher in the world. Unfortunately, sleep was perhaps the least desirable of the scientific areas I wished to pursue.“


Aserinsky had grown up in Brooklyn in a Yiddish- and Russian-speaking household. His mother died when he was 12, and he was left in the care of his father, Boris, a dentist who loved to gamble. Boris often had his son sit in on pinochle hands if the table was a player short. Meals were catch as catch can. Aserinsky’s son, Armond, recalled: “Dad once told me he said to his father, ?Pop, I’m hungry,’ and his father said, ?I’m not hungry, how can you be hungry?“ Eugene graduated from public high school at the age of 16 and for the next 12 years knocked about in search of his metier. At Brooklyn College, he took courses in social science, Spanish and premedical studies but never received a degree. He enrolled at the University of Maryland dental school only to discover that he hated teeth. He kept the books for an ice company in Baltimore. He served as a social worker in the Maryland state employment office. Though he was legally blind in his right eye, he did a stint in the U.S. Army as a high explosives handler. By 1949, Aserinsky, married and with a 6-year-old son, was looking to take advantage of the G.I. Bill of Rights to launch a science career. He aced the entrance exams at the University of Chicago and, though he lacked an undergraduate degree, persuaded the admissions office to accept him as a graduate student. “My father was courtly, intelligent and intensely driven,“ says Armond Aserinsky, 60, now a clinical psychologist in North Wales, Pennsylvania. “He could be extremely charming, and he had a fine scientific mind, but he had all kinds of conflicts with authority. He always wore black suits. I once asked him, ?Dad, how come you never wear a sports jacket?’ He looked at me and said, ?I’m not a sport.“


Kleitman’s first idea was to have Aserinsky test a recent claim that the rate of blinking could predict the onset of sleep. But after a number of vexing weeks trying to concoct a way to measure blink rates, Aserinsky confessed his lack of progress. Kleitman proposed that Aserinsky observe infants while they slept and study what their eyelids did. So he sat by cribs for hours but found that it was difficult to differentiate eyelid movements from eyeball movements. Once again he knocked on Kleitman’s door, something he was loath to do because of Kleitman’s austere and formal air. (Ten years after their famous paper was published, Kleitman began a letter to his colleague and coauthor, “Dear Aserinsky.“) Aserinsky had the idea of studying all eye movements in sleeping infants, and with Kleitman’s approval embarked on a new line of inquiry – one that, he would later confess, was “about as exciting as warm milk.“ Significantly, he did not at first “see“ REM, which is obvious if you know to look for it. Over months of monotonous observations, he initially discerned a 20-minute period in each infant’s sleep cycle in which there was no eye movement at all, after which the babies usually woke up. He learned to exploit the observation. During such periods, the fatigued researcher was able to nap himself, certain he would not miss any important data. And he was also able to impress mothers hovering near the cribs by telling them when their babies would wake up. “The mothers were invariably amazed at the accuracy of my prediction and equally pleased by my impending departure,“ he once wrote.


At home, Aserinsky was under considerable pressure. His daughter, Jill, was born in April 1952. His wife, Sylvia, suffered from bouts of mania and depression. Aserinsky couldn’t even afford the rent on the typewriter he leased to draft his dissertation. “We were so poor my father once stole some potatoes so we would have something to eat,“ recalls Jill Buckley, now 51 and a lawyer in Pismo Beach, California, for the American Society for the Prevention of Cruelty to Animals. “I think he saw himself as a kind of Don Quixote. Ninety percent of what drove him was curiosity – wanting to know. We had a set of Collier’s Encyclopedias, and my father read every volume.“ After studying babies, Aserinsky set out to study sleeping adults. At the time, no scientist had ever made all-night continuous measurements of brain-wave activity. Given the thinking of the era – that sleep was a featureless neurological desert – it was pointless to squander thousands of feet of expensive graph paper making electroencephalogram (EEG) recordings. Aserinsky’s decision to do so, combined with his adapting the balky Offner Dynograph machine to register eye movements during sleep, led to the breakthrough. His son, Armond, liked to hang out at the lab because it meant spending time with his father. “I remember going into the lab for the night,“ Armond says. “I knew the machine was harmless. I knew it didn’t read my mind. The set up took a long time. We had to work out some things. It was a long schlep to the bathroom down the hall, so we kept a bottle by the bed.“ Aserinsky did a second nightlong sleep study of Armond with the same results – again the pens traced sharp jerky lines previously associated only with eye movements during wakefulness. As Aserinsky recruited other subjects, he was growing confident that his machine was not fabricating these phenomena, but could it be picking up activity from the nearby muscles of the inner ear? Was it possible the sleeping subjects were waking up but just not opening their eyes? “In one of the earliest sleep sessions, I went into the sleep chamber and directly observed the eyes through the lids at the time that the sporadic eye movement deflections appeared on the polygraph record,“ he would recall in 1996 in the Journal of the History of the Neurosciences. “The eyes were moving vigorously but the subject did not respond to my vocalization. There was no doubt whatsoever that the subject was asleep despite the EEG that suggested a waking state.“ By the spring of 1952, a “flabbergasted“ Aserinsky was certain he had stumbled onto something new and unknown. “The question was, what was triggering these eye movements. What do they mean?“ he recalled in a 1992 interview with the Journal of NIH Research. In the fall of 1952, he began a series of studies with a more reliable EEG machine, running more than 50 sleep sessions on some two dozen subjects. The charts confirmed his initial findings. He thought of calling the phenomena “jerky eye movements,“ but decided against it. He didn’t want critics to ridicule his findings by playing off the word “jerk.“


Aserinsky went on to find that heart rates increased an average of 10% and respiration went up 20% during REM; the phase began a certain amount of time after the onset of sleep; and sleepers could have multiple periods of REM during the night. He linked REM interludes with increased body movement and particular brain waves that appear in waking. Most amazingly, by rousing people from sleep during REM periods, he found that rapid eye movements were correlated with the recall of dreams – with, as he noted in his dissertation, “remarkably vivid visual imagery.“ He later wrote, “The possibility that these eye movements might be associated with dreaming did not arise as a lightning stroke of insight. An association of the eyes with dreaming is deeply ingrained in the unscientific literature and can be categorized as common knowledge. It was Edgar Allan Poe who anthropomorphized the raven, ?and his eyes have all the seeming of a demon’s that is dreaming.’ “


Aserinsky had little patience for Freudian dream theory, but he wondered if the eyes moving during sleep were essentially watching dreams unfold. To test that possibility, he persuaded a blind undergraduate to come into the lab for the night. The young man brought his Seeing Eye dog. “As the hours passed I noticed at one point that the eye channels were a little more active than previously and that conceivably he was in a REM state,“ Aserinsky wrote. “It was imperative that I examine his eyes directly while he slept. Very carefully I opened the door to the darkened sleeping chamber so as not to awaken the subject. Suddenly, there was a low menacing growl from near the bed followed by a general commotion which instantaneously reminded me that I had completely forgotten about the dog. By this time the animal took on the proportions of a wolf, and I immediately terminated the session, foreclosing any further exploration along this avenue.“ (Other researchers would later confirm that blind people do indeed experience REM.) In any event, Aserinsky wasn’t much interested in the meaning of dreams, said his daughter Jill, adding: “He was a pure research scientist. It always irritated him when people wanted him to interpret their dreams.“


But a future colleague of Aserinsky’s was intrigued. William Dement was a medical student at Chicago, and in the fall of 1952 Kleitman assigned him to help Aserinsky with his overnight sleep studies. Dement recounted his excitement in his 1999 book, The Promise of Sleep. “Aserinsky told me about what he had been seeing in the sleep lab and then threw in the kicker that really hooked me: ?Dr. Kleitman and I think these eye movements might be related to dreaming.’ For a student interested in psychiatry, this offhand comment was more stunning than if he had just offered me a winning lottery ticket. It was as if he told me, ?We found this old map to something called the Fountain of Youth.’ “ By Aserinsky’s account, Dement ran five overnight sessions for him starting in January 1953. With a camera Kleitman had obtained, Dement and Aserinsky took 16-millimeter movie footage of subjects in REM sleep, one of whom was a young medical student named Faylon Brunemeier, today a retired ophthalmologist living in Northern California. They were paying three dollars a night, he recalled, “and that was a lot to an impecunious medical student.“ Kleitman had barred women as sleep study subjects, fearing the possibility of scandal, but Dement wheedled permission to wire up his sweetheart, a student named Pamela Vickers. The only provision was that Aserinsky had to be on hand to “chaperon“ the session. While the sleep-deprived Aserinsky passed out on the lab couch, Dement documented that Vickers, too, experienced REM. Next, Dement says he recruited three other female subjects, including Elaine May, then a student at the University of Chicago. Even if she had not become famous a few years later as part of the comedy team Nichols and May, and had not gone on to write Heaven Can Wait and other movies, she would still have a measure of fame, in the annals of sleep science.


From 1955 to 1957, Dement published studies with Kleitman establishing the correlation between REM sleep and dreaming. Dement went on to help organize the first sleep research society and started the world’s first sleep clinic at Stanford in 1970. With a collaborator, Howard Roffwarg, a psychiatrist now at the University of Mississippi Medical Center, Dement showed that even a 7-month-old premature infant experiences REM, suggesting that REM may occur in the womb. Dement’s colony of dogs with narcolepsy – a condition of uncontrollable sleep – shed light on the physiological basis of the disorder, which in people had long been attributed to psychological disturbances. Dement became such an evangelist about the dangers of undiagnosed sleep disorders that he once approached the managers of the rock band R.E.M., seeking to enlist the group for a fundraising concert. The musicians brushed him off with a shaggy story about the acronym standing for retired english majors.


When Aserinsky left the University of Chicago, in 1953, he turned his back on sleep research. He went to the University of Washington in Seattle and for a year studied the effects of electrical currents on salmon. Then he landed a faculty position at Jefferson Medical College in Philadelphia, where he explored high-frequency brain waves and studied animal respiration. In 1957, his wife’s depression came to a tragic conclusion; while staying at a mental hospital in Pennsylvania, Sylvia committed suicide. Two years later, Aserinsky married Rita Roseman, a widow, and became stepfather to her young daughter, Iris; the couple remained together until Rita’s death in 1994.


In the early 1960s, Armond Aserinsky urged his father, then in his 40s, to return to the field he had helped start. Aserinsky finally wrote to Kleitman, who had retired from the University of Chicago. Kleitman replied, “It was good to learn that you have renewed work on rapid eye movements during sleep. The literature on the subject is quite extensive now. I believe that you have ability and perseverance but have had personal hard knocks to contend with. Let us hope that things will be better for you in the future.“ Kleitman also took the opportunity to remind his former student that he still owed him a hundred dollars. In March 1963, Aserinsky went home to Brooklyn to attend a meeting of sleep researchers. “People were shocked,“ his son recalled. “They looked at him and said, ?My God, you’re Aserinsky! We thought you were dead!’ “


Delving into the night again in an unused operating room at the Eastern Pennsylvania Psychiatric Institute in Philadelphia, Aserinsky worked on the physiology of REM and non-REM sleep, but he had prickly encounters with colleagues. He took offense when he did not receive an invitation to a prestigious dinner at a 1972 meeting of sleep researchers. He was often stung when Dement and Kleitman got credit he felt belonged to him. (For his part, Dement said he resented that Aserinsky never acknowledged all the work he did as low man on the lab totem pole. “I was so naive,“ he told me.) In 1976, after more than two decades at Jefferson MedicalCollege, Aserinsky was passed over for the chairmanship of the physiology department. He left, becoming chairman of physiology at Marshall University in Huntington, West Virginia. He retired in 1987. “He could be a deeply suspicious and impolitic person,“ Armond Aserinsky said. Narrating his version of events in the Journal of the History of the Neurosciences, Aserinsky criticized Dement’s contention that the discovery of REM was a “team effort,“ saying, “If anything is characteristic about the REM discovery, it was that there was no teamwork at all. In the first place, Kleitman was reserved, almost reclusive, and had little contact with me. Secondly, I myself am extremely stubborn and have never taken kindly to working with others. This negative virtue carried on throughout my career as evidenced by my resume, which reveals that I was either the sole or senior author in my first thirty publications, encompassing a period of twenty-five years.“ That stubbornness spilled into his family relations as well. Years passed in which he had no contact with Armond. To younger sleep scientists, Aserinsky was only a name on a famous paper, an abstraction from another time. And such he might have remained if not for a license plate and a chance encounter in 1989. Peter Shiromani, then an assistant professor of psychiatry at the University of California at San Diego, had just nosed his Datsun 310 into the parking lot of a Target department store in Encinitas, California. His custom license plates advertised what had been his scientific obsession since his undergraduate days at City College in New York City: REM SLEP. “A woman walked up to me and said, ?I really love your plates! Did you know my father discovered REM sleep?’ “ Shiromani recalled. “I said, ?You must be Eugene Aserinsky’s daughter!’ She was very pleased. I think she felt a lot of pride in her father’s accomplishment, and here was someone who recognized her father’s name. We chatted briefly with much enthusiasm about REM sleep. Fortunately, I had the presence of mind to ask for her father’s address.“ Shiromani passed the address along to Jerry Siegel, a sleep researcher at UCLA and the Sepulveda Veterans Affairs medical center in suburban Los Angeles, who invited Aserinsky to address the June 1995 meeting of the Associated Professional Sleep Societies in Nashville. Siegel was organizing a symposium in honor of Kleitman, who had recently turned 100. “It was very difficult to get Aserinsky to come,“ Siegel recalls. “People who knew him in the early days said, ?Don’t invite him.’ But my dealings with him were very pleasant.“ Despite their rivalry, it was Dement who introduced Aserinsky to the crowd of 2,000 people in the ballroom at the OpryLand Hotel. They gave him a standing ovation. And when he finished a witty, wide-ranging talk on the history of REM, the audience again rose to its feet. “It was one of the high points of his life,“ recalls his daughter Jill, who had accompanied her father to the meeting along with his stepdaughter, Iris Carter. “He wore a name tag, and people would stop and point and say, ?There’s Aserinsky!’ “ says Carter.


One July day three years later, Aserinsky, driving down a hill in Carlsbad, California, collided with a tree and was killed. He was 77. An autopsy could not determine the cause of the accident. It’s possible he fell asleep at the wheel.


Today it’s well established that normal sleep in human adults includes between four and six REM periods a night. The first starts about 90 minutes after sleep begins; it usually lasts several minutes. Each subsequent REM period is longer. REM sleep is characterized by not only brain-wave activity typical of waking but also a sort of muscle paralysis, which renders one incapable of acting on motor impulses. (Sleepwalking most often occurs during non-REM sleep.) In men and women, blood flow to the genitals is increased. Parts of the brain burn more energy. The heart may beat faster. Adults spend about two hours a night in REM, or 25% of their total sleep. Newborns spend 50 percent of their sleep in REM, upwards of eight hours a day, and they are much more active than adults during REM sleep, sighing and smiling and grimacing. After 50 years, researchers have learned a great deal about what REM isn’t. For example, it was once thought that people prevented from dreaming would become psychotic. That proved not to be the case; patients with injuries to the brainstem, which controls REM, do not go nuts without it. Still, if you deprive a person of REM sleep, they’ll recoup it at the first chance, plunging directly into the REM phase – a phenomenon discovered by Dement and called REM rebound.


Studies of animals have yielded insights into REM, sometimes. In the early 1960s, Michel Jouvet, a giant of sleep research and a neurophysiologist at the University Claude Bernard in Lyon, France, mapped the brain structures that generate REM sleep and produce the attendant muscle paralysis. Jouvet, who coined the term “paradoxical sleep“ as a substitute for REM sleep, also discovered that cats with lesions in one part of the brainstem were “disinhibited“ and would act out their dreams, as it were, jumping up and arching their backs. (More recently, University of Minnesota researchers have documented a not-dissimilar condition in people; REM sleep behavior disorder, as it’s called, mainly affects men over 50, who kick, punch and otherwise act out aggressive dream scenarios while they sleep. Researchers believe that REM sleep disorder may be a harbinger of Parkinson’s disease in some people.) Paradoxical sleep has been found in almost all mammals tested so far except for some marine mammals, including dolphins. Many bird species appear to have short bursts of paradoxical sleep, but reptiles, at least the few that have been assessed, do not. Jouvet was especially interested in penguins, because they stay awake for long periods during the brooding season. Hoping to learn more about their physiology, he went to great trouble to implant a costly radio-telemetry chip in an emperor penguin in Antarctica. The prize research subject was released into the sea, only to be promptly gobbled up by a killer whale.


In 1975, Harvard’s Allan Hobson and Robert McCarley proposed that many properties of dreams – the vivid imagery, the bizarre events, the difficulty remembering them – could be explained by neurochemical conditions of the brain in REM sleep, including the ebb and flow of the neurotransmitters norepinephrine, serotonin and acetylcholine. Their theory stunned proponents of the idea that dreams were rooted not in neurochemistry but psychology, and it has been a starting point of dream theorizing for the past 25 years. The once-popular description of REM as “dream sleep“ is now considered an oversimplification, and debate rages over questions of what can be properly claimed about the relation of dreaming to the physiology of REM sleep. (In 2000, an entire volume of the journal Behavioral and Brain Sciences was devoted to the debate.) To be sure, you can have REM without dreaming, and you can dream without experiencing REM. But most researchers say that dreaming is probably influenced and may be facilitated by REM. Still, dissenters, some of whom adhere to psychoanalytic theory, say that REM and dreaming have little connection with each other, as suggested by clinical evidence that different brain structures control the two phenomena. In the years to come, new approaches may help clarify these disagreements. In a sort of echo of Aserinsky’s first efforts to probe the sleeping brain with EEG, some researchers have used powerful positron brain-scanning technology to focus on parts of the brain activated during REM.


This past June, more than 4,800 people attended the Associated Professional Sleep Societies’ annual meeting in Chicago. The scientists took time out to mark REM’s golden anniversary. With mock solemnity, Dement echoed the Gettysburg Address in his lecture: “Two score and ten years ago Aserinsky and Kleitman brought forth on this continent a new discipline conceived at night and dedicated to the proposition that sleep is equal to waking.“ But to paraphrase the physicist Max Planck, science advances funeral by funeral. Kleitman died in 1999 at the age of 104, and though he was a coauthor of the milestone REM study, he never really accepted that REM was anything other than a phase of especially shallow sleep. “Kleitman died still believing there was only one state of sleep,“ Dement told me. Aserinsky had his own blind spots; he never relinquished his doubts that sleeping infants exhibit REM. To honor the research done in Kleitman’s lab five decades ago, the Sleep Research Society commissioned a 65-pound zinc plaque. It now hangs in the psychiatry department at the University of Chicago Medical Center, adjacent to Abbott Hall. To be sure, the inscription – “Commemorating the 50th Anniversary of the Discovery of REM Sleep by Eugene Aserinsky, Ph.D., and Nathaniel Kleitman, Ph.D., at the University of Chicago“ – doesn’t speak to the poetry of a lyric moment in the history of science, a moment when, as Michel Jouvet once said, humanity came upon “a new continent in the brain.“ If it’s the poetry of REM you want, you need wait only until tonight.


Fifty years ago, Eugene Aserinksy discovered rapid eye movement and changed the way we think about sleep and dreaming



Sources: Smithsonian Magazine, October 2003, By Chip Brown;;; Wikipedia

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For your sheer pleasure, British tenor, John Owen-Jones sings, Music of the Night, from Phantom of the Opera.


CHAPLE Disease and Possible Treatment With a Repurposed Drug


CHAPLE disease is also known as CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy. The disease is a form of primary intestinal lymphangiectasia (PIL), or Waldmann’s disease, and was first described in 1961 by Thomas A. Waldmann, M.D., an NIH Distinguished Investigator at the National Cancer Institute, at NIH. Children with the condition can experience severe gastrointestinal distress and deep vein blood clots. No effective treatments are available to ameliorate or prevent these life-threatening symptoms. Now, 56 years later, a genetic cause and potential treatment strategy for a CHAPLE disease has been identified.


In a study published in the New England Journal of Medicine (2017; 377:52-6), genes were analyzed from 11 children with CHAPLE disease and their families. Results showed that each child had two copies of a defective CD55 gene that prevented them from producing a cell surface protein of the same name. The CD55 protein helps regulate the immune system by blocking the activity of complement, a group of immune system proteins that can fight infections by punching holes in the cell membranes of bacteria and other infectious agents. However, complement also can damage the body’s tissues. The study found that in CHAPLE disease, uninhibited complement resulting from a lack of CD55 protein damaged blood and lymph vessels along the lower digestive tract, leading to the loss of protective immune proteins and blood cells. In many patients, this process caused a range of symptoms, such as abdominal pain, bloody diarrhea, vomiting, problems absorbing nutrients, slow growth, swelling in the legs, recurrent lung infections, and blood clots.


After discovering that complement hyperactivity was driving these severe symptoms, the authors tested drugs already approved by the U.S. Food and Drug Administration for the treatment of other diseases to see if they block this process in samples of patient immune cells. The authors found that complement production decreased when cells were exposed to eculizumab, a therapeutic antibody approved to treat another rare condition called paroxysmal nocturnal hemoglobinuria. The NIAID team and their collaborators plan to study eculizumab in people with CHAPLE disease with the hope that the therapeutic could become the first effective treatment for the disorder.


CAPTION: This light microscope image shows the gut tissue of a child with CHAPLE disease. The large white areas in the bottom right corner are enlarged lymphatic vessels, which can contribute to intestinal distress.



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Experimental HIV Vaccine


According to the results from an early-stage clinical trial called APPROACH, presented at the 9th International AIDS Society Conference on HIV Science in Paris, an investigational HIV vaccine regimen was well-tolerated and generated immune responses against HIV in healthy adults. The APPROACH findings, as well as results expected in late 2017 from another early-stage clinical trial called TRAVERSE, will form the basis of the decision whether to move forward with a larger trial in southern Africa to evaluate vaccine safety and efficacy among women at risk of acquiring HIV. The ongoing TRAVERSE trial is comparing Ad26-based regimens containing three mosaic antigens (trivalent) with Ad26-based regimens containing four mosaic antigens (tetravalent).


The experimental vaccine regimens evaluated in APPROACH are based on “mosaic“ vaccines designed to induce immunological responses against a wide variety of HIV subtypes responsible for HIV infections globally. Different HIV subtypes, or clades, predominate in various geographic regions around the world. The Ad26-based mosaic vaccines were initially developed by scientists at NIAID and Janssen Pharmaceuticals. In pre-clinical studies, regimens incorporating these mosaic vaccines protected monkeys against infection with an HIV-like virus called simian human immunodeficiency virus (SHIV). The most effective prime-boost regimen reduced the risk of infection per exposure to SHIV by 94% and resulted in 66% complete protection after six exposures. The vaccine-induced immune responses that correlated with this protection were identified and characterized.


APPROACH involved nearly 400 volunteers in the United States, Rwanda, Uganda, South Africa and Thailand who were randomly assigned to receive one of seven experimental vaccine regimens or a placebo. APPROACH found that different mosaic vaccine regimens were well-tolerated and capable of generating anti-HIV immune responses in healthy, HIV-negative adults. Notably, the vaccine regimen that was most protective in pre-clinical studies in animals elicited among the greatest immune responses in the study participants. However, further research will be needed because the ability to elicit anti-HIV immune responses does not necessarily indicate that a candidate vaccine regimen can prevent HIV acquisition.


In APPROACH, study participants received four vaccinations over 48 weeks: two doses of an initial, or “prime,“ vaccine, followed by two doses of a booster vaccine. The experimental regimens all incorporated the same vaccine components in the prime vaccination, known as Ad26.Mos.HIV. The vaccine uses a strain of common-cold virus (adenovirus serotype 26, or Ad26), engineered so that it does not cause illness, as a vector to deliver three mosaic antigens created from genes from many HIV variants. The booster vaccination included various combinations of the Ad26.Mos.HIV components or a different mosaic component, called MVA-Mosaic, and/or two different doses of clade C HIV gp140 envelope protein containing an aluminum adjuvant to boost immune responses. Following the third vaccination, most APPROACH participants had developed antibody and cellular immune responses against HIV. The different boost vaccines altered the magnitude and character of these immune responses, with the regimen that showed greatest protection in monkey studies also eliciting among the greatest immune responses in humans. The anti-HIV immune responses increased after the fourth vaccination.


Mutual Recognition of Manufacturing Facilities


Some drugs approved in the U.S. are either fully manufactured overseas or made in the U.S. but contain some foreign ingredients. All drugs approved in the U.S., regardless of where they are made, must comply with applicable U.S. regulations. One way the FDA oversees drug manufacturing is by routinely inspecting domestic and foreign drug manufacturing plants for compliance with manufacturing standards that assure quality and product label requirements.


The FDA has determined that it will recognize eight European drug regulatory authorities as capable of conducting inspections of manufacturing facilities that meet FDA requirements. The eight regulatory authorities found to be capable are those located in: Austria, Croatia, France, Italy, Malta, Spain, Sweden and the United Kingdom. This achievement marks an important milestone to successful implementation and operationalization of the amended Pharmaceutical Annex to the 1998 U.S.-European Union (EU) Mutual Recognition Agreement (MRA) that enables U.S. and EU regulators to utilize each other’s good manufacturing practice inspections of pharmaceutical manufacturing facilities.


According to FDA, beginning November 1, it will take the unprecedented and significant step forward in realizing the key benefits of the Mutual Recognition Agreement with its European counterparts in that FDA will now rely on the inspectional data obtained by these eight regulatory agencies. FDA added that the progress made so far puts it on track to meet our goal of completing all 28 capability assessments in the EU by July 2019.


In June 2017, the European Commission determined that the FDA “has the capability, capacity and procedures in place to carry out GMP inspections at a level equivalent to the EU.“ The completion of these capability assessments enables the FDA and the EU to avoid duplication of drug inspections and allows regulators to devote more resources to other manufacturing facilities in countries where there may be greater risk. Ultimately, this prioritization of inspections will help identify potential drug quality problems more quickly and prevent poor quality drugs from entering the U.S. market.


Sea Scallops With Figs and Butternut Squash Sauce


When I heard about a luscious scallop dish my husband had during his business trip this week in Philadelphia, I got a little jealous and decided to compete by creating a recipe for him to try upon returning home.


Figs are still available, at a local farmer’s market, and today the scallops were sold (Dean & Deluca) within 24 hoursof being caught (harvested?) and couldn’t be fresher. I decided to combine seafood and fresh fruit and here, below, is what I came up with. Serve these delicious flavors with an icy white Bordeaux (we get most of our wines from Sherry-Lehmann here in Manhattan) served in chilled glasses and lovely warm French bread to sop up any juices left on the plate. Or, join us – we’ve recently fallen into a Bellini groove.


Sizzling Scallops MMmmmmm ©Joyce Hays, Target Health Inc.


Serve warm bread to sop up the delicious sauce. ©Joyce Hays, Target Health Inc.


Along with the scallops, we had a new recipe I’m experimenting with, Curried Cauliflower. ©Joyce Hays, Target Health Inc.



8 Fresh Figs

2 teaspoons or more sugar-free apricot jam

1 Tablespoon Sugar-free maple syrup

1 Butternut Squash

1 pound Sea scallops

Pinch Salt and pepper (or no salt)

Very fine balsamic vinegar

2 teaspoons extra-virgin olive oil

1 cup arugula

Annie Chun roasted seaweed for garnish



1. Peel and roast the butternut squash. Then puree it in food processer and add the sugar-free maple syrup and pepper to your taste. Salt if you wish. Keep warm and set aside

2. Wash figs, remove stems, and halve lengthwise. Dip the cut side of the figs in the sugar-free apricot jam and set aside.

3. Wash arugula very well and drain. Then dry on paper towel. Put in small bowl and toss with about 1 Tablespoons of olive oil and a few drops of the balsamic.

4. Heat a skillet over medium heat and add 1 tablespoon of olive oil, so the surface is lightly coated. Add a little sugar-free apricot jam and on it, put the figs cut side down until lightly caramelized.

5. Flip figs and cook for an additional 30 seconds, remove from pan, and reserve. Add one drop (we keep a regular medicine dropper in the kitchen) of balsamic to each fig half and put them aside, trying to keep them warm.

6. Wash scallops and dry with paper towel. Cut each Sea scallop in half and lightly coat with almond flour.

7. Season scallops lightly with black pepper and salt, if you wish.

8. Use the same pan, with oil and jam left in it. If you need more olive oil, add it lightly and mix it with the remaining jam.

9. Add scallops and cook for 1 to 3 minutes (until a golden color). Turn the heat up, but be sure to constantly swirl the pan so that the scallops are rolling around and don’t get tough or burnt.

10. Get ready to serve. Put the arugula on each plate. Now place half of the scallops on the arugula and then a fig half on top of the scallop.

11. To the pan juice, add the butternut squash puree and heat and stir it with all the pan juices until nice and warm. If the squash is not the consistency of a sauce, slowly add some chicken broth until there is the desired thinner sauce. Now spoon this butternut squash sauce over the scallops and figs and serve. Crush the seaweed and sprinkle it over the sauce and serve.

12. One option: At the last stage, when you’re stirring the butternut squash with the pan juices, consider adding 1 or 2 Tablespoons of cream sherry. Do this slowly so you can taste before adding a second Tablespoon.

13. Another option: If you’re pressed for time, consider using a frozen package of Birds Eye Southland frozen butternut squash. Thaw and warm it up, taste, and consider adding sugar-free maple syrup or cream sherry. If not, use as is to pour over the scallops and figs. Crush the seaweed and sprinkle over the scallop/figs.


Consider serving rice or quinoa or orzo, or not. For dessert we had another recipe I’m experimenting with, that I call Mango Mousse.


We buy the bottled pre-mixed Bellinis from Sherry-Lehmann, which is quite good. Sometimes, we add more vodka or more champagne or Blanc de Blancs. ©Joyce Hays, Target Health Inc.


Another good pairing with the scallops and curried cauliflower. ©Joyce Hays, Target Health Inc.



From Our Table to Yours

Bon Appetit!