Annual DIA Meeting Chicago

 

Target Health will again be exhibiting at DIA this year. We will be at Booth 1464 and 1466, as always by the Food Court. This year we will be featuring our full paperless clinical trial suite of software tools and will share some operational results from an ongoing clinical trial under a US IND.A

 

To make appointments and or more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at: www.targethealth.com

Hips Take Walking in Stride, Ankles Put Best Foot Forward in Run

 

In a new study, researchers show that the hips generate more of the power when people walk, but the ankles generate more of the power when humans run.

(Credit: iStockphoto/Mads Abildgaard)

 

 

 

In a first-of-its-kind study comparing human walking and running motions – and whether the hips, knees or ankles are the most important power sources for these motions – researchers at North Carolina State University show that the 1) ___ generate more of the power when people walk, but the ankles generate more of the power when humans run. Knees provide approximately one-fifth or less of walking or running power.

 

The research could help inform the best ways of building assistive or 2) ___ devices for humans, or constructing next-generation robotics, say NC State biomedical engineers Drs. Dominic Farris and Gregory Sawicki. The co-authors of a study on the mechanics of walking and running in the journal Interface, a Royal Society scientific journal, Sawicki and Farris are part of NC State’s Human PoWeR (Physiology of Wearable Robotics) Lab.

 

A long history of previous studies have focused on the biomechanics of human locomotion from a whole-body or individual limbs perspective. But this study is the first to zoom in on the mechanical power generated by specific lower-limb 3) ___ in a single comprehensive study of walking and running across a range of speeds, Sawicki says.

 

The study shows that, overall, hips generate more power when people walk. That is, until humans get to the point at which they’re speed 4) ___ — walking so fast that it feels more comfortable to run — at 2 meters per second. Hips generate 44% of the power when people walk at a rate of 2 meters per second, with ankles contributing 39% of the power. When people start running at this 2-meter-per-second rate, the ankles really kick in, providing 47% of the power compared to 32% for the hips. 5) ___ continue to provide the most power of the three lower limb joints as running speeds increase, although the hips begin closing the distance at faster speeds. “There seems to be a tradeoff in power generation from hips to ankles as you make the transition from walking to 6) ___,“ Sawicki says.

 

Both researchers are interested in how the study can help people who need assistance walking and running. Knowing which part of the lower limbs provide more 7) ___ during the different activities can help engineers figure out how, depending on the person’s speed and gait, mechanical power needs to be distributed. “For example, assistive devices such as an exoskeleton or prosthesis may have motors near both the hip and ankle. If a person will be walking and then running, you’d need to redistribute 8) ___ from the hip to the ankle when the person makes that transition,“ Farris says. Ten people walked and ran at various 9) ___ on a specially designed treadmill in the study; a number of cameras captured their gait by tracking reflective markers attached to various parts of the participants’ lower limbs while the treadmill captured data from the applied force. The study examined walking and running on level ground in order to gauge the differences brought about by increased speed; walking and running on inclined ground is fundamentally different than walking and running on flat 10) ___, the researchers say, and would likely skew the power generation results toward the hips and knees.

 

ANSWERS: 1) hips; 2) prosthetic; 3) joints; 4) walking; 5) Ankles; 6) running; 7) power; 8) energy; 9) speeds; 10) ground

Ancient Egyptian Princess Now Known to Be First Person in Human History With Diagnosed Coronary Artery Disease (1580-1550 BCE)

 

 

Calcification, seen as white, in the right (RCA) and left coronary arteries (LCA), each indicative of coronary artery disease. (Credit: Image courtesy of European Society of Cardiology)

 

 

 

The Egyptian princess Ahmose-Meryet-Amon, who lived in Thebes (Luxor) between 1580 and 1550 BCE, and who is now known to be first person in human history with diagnosed coronary artery disease, lived on a diet rich in vegetables, fruit and a limited amount of meat from domesticated (but not fattened) animals. Wheat and barley were grown along the banks of the Nile, making bread and beer the dietary staples of this period of ancient Egypt. Tobacco and trans-fats were unknown, and lifestyle was likely to have been active.

 

The coronary arteries of Princess Ahmose-Meryet-Amon as visualized by whole body computerized tomography (CT) scanning – were featured in two presentations at the International Conference of Non-Invasive Cardiovascular Imaging (ICNC) that took place in Amsterdam in May of this year. Both presentations will be based on findings from the Horus study, in which arterial atherosclerosis was investigated in 52 ancient Egyptian mummies. Results have shown that recognizable arteries were present in 44 of the mummies, with an identifiable heart present in 16. Arterial calcification (as a marker of atherosclerosis) was evident at a variety of sites in almost half the mummies scanned suggestive that the condition was common in this group of middle aged or older ancient Egyptians. The 20 mummies with definite atherosclerosis were older (mean 45.years) than those with intact vascular tissue but no atherosclerosis (34.5 years).

 

Although relatively common at other vascular sites, atherosclerosis in the coronary arteries was evident in only three of the mummies investigated, but was clearly visualized in Princess Ahmose-Meryet-Amon (in whom calcification was present in every vascular bed visualized). The CT scan showed that the princess, who died in her 40s, had atherosclerosis in two of her three main coronary arteries. “Today,“ said Dr Gregory S Thomas, director of Nuclear Cardiology Education at the University of California, Irvine, USA, and co-principal investigator of the Horus study, “she would have needed by-pass surgery.“ “Overall, it was striking how much atherosclerosis was found as we think of atherosclerosis as a disease of modern lifestyle. The fact that atherosclerosis also existed 3.500 years ago, calls into question the perception of atherosclerosis as a modern disease. If, however, the princess enjoyed a diet deemed to be healthy and pursued a lifestyle probably active, how could this “disease of modern life“ affect her so visibly? Dr Thomas and his co-principal investigator Dr Adel Allam of Al Azhar University, Cairo, suggest three possibilities.

 

1. First, that there is still some unknown risk factor for cardiovascular disease, or at least a missing link in our understanding of it such as a genetic effect.

2. Second, the possibility that an inflammatory response to the frequent parasitic infections common to ancient Egyptians might have predisposed the princess to coronary disease – in much the same way that immunocompromised HIV cases seem also predisposed to early coronary disease. Nor can a dietary effect be excluded, despite what we know of life in ancient Egypt. Princess Ahmose-Meryet-Amon was from a noble family, her father, Seqenenre Tao II, the last pharaoh of the 17th Dynasty.

 

So it’s likely that her diet was not that of the common Egyptian. As a royal, she would have eaten more luxury foods – more meat, butter and cheese. Moreover, foods were preserved in salt, which may also have had an adverse effect.

 

Despite the suggestion of a genetic, inflammatory or unknown effect, Drs Thomas and Allam were keen not to discount those risk factors for heart disease which we do know about. Indeed, even in the study’s apparent association of atheroma with increasing age, there was a pattern of prevalence consistent with our own epidemiology today.

 

Most of the Horus study research was performed at the National Museum of Antiquities in Cairo and would not have been possible without the availability of non-invasive CT scanning, the focus of the ICNC congress in Amsterdam. CT scanning and nuclear medicine imaging are the cornerstones of modern quantifiable cardiac disease detection, with safe and reproducible results.

Source: European Society of Cardiology (ESC).

Certain Bacteria Render Mosquitoes Resistant to Deadly Malaria Parasite

 

 

According to the World Health Organization, an estimated 225 million malaria cases occur worldwide annually, resulting in about 781,000 deaths. Although the disease is present in 106 countries, most cases occur in sub-Saharan Africa. Insect repellent and bed nets can help prevent transmission of the malaria parasite from mosquitoes to humans, but to control malaria one step earlier, some studies are looking to eliminate infection within the mosquito itself. Normally, when a malaria parasite infects a mosquito, it travels to the insect’s gut, where its chances for survival are slim because the mosquito’s immune system, digestive enzymes and resident bacteria create a hostile environment.

 

According to an article published on May 13 in the journal Science (DOI: 10.1126/science.1201618 2011), a class of naturally occurring bacteria that can strongly inhibit malaria-causing parasites in Anopheles mosquitoes has been identified. In this new study, it was found that among the various types of bacteria in the mosquito gut, Enterobacter – a type of bacteria that occurs in some but not all mosquitoes – effectively blocked infection with the malaria-causing parasite Plasmodium falciparum by 98 to 99%. The finding may have implications for efforts to control malaria. The research was partly funded by the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health.

 

By observing the interaction between the bacteria and the parasite, the study determined that Enterobacter inhibits parasite growth by producing short-lived molecules known as reactive oxygen species (ROS). Although ROS travel through body fluids in the mosquito, they do not need to be in a mosquito to inhibit parasites. Future research plans include sequencing the Enterobacter genome to better understand how it produces malaria-inhibiting ROS and studying other bacteria that reside in the mosquito gut to learn whether they have similar effects.

 

The authors hope to apply their findings to the field, where they would first modify Enterobacter for use in mosquitoes. The next step would be to strategically place the bacteria in the mosquitoes’ natural environment, such as in their sugar food sources or breeding sites. Although these strategies have not yet been tested in malaria prevention, sugar baits have been used successfully to expose mosquitoes to toxins.

ECOLOGY

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Dual Parasitic Infections Deadly to Marine Mammals

 

 

Toxoplasmosis, the illness caused by Toxoplasma gondii infection, is generally not serious in otherwise healthy people. However the parasites can cause severe or fatal disease in people with compromised immune systems and can also damage the fetuses of pregnant women. The parasites are globally distributed and enter water via infected cat feces. Chlorination does not kill T. gondii, but filtration eliminates them from the water supply. Although Sarcocystis neurona parasites do not infect people, other closely related species of Sarcocystis parasites do.

 

According to an article published online 24 May 2011in the open-access journal PLoS Neglected Tropical Diseases, a study of tissue samples from 161 marine mammals that died between 2004 and 2009 in the Pacific Northwest reveals an association between severe illness and co-infection with S. neurona and T. gondii. S. neurona, is new to the northwest coastal region of North America and is not known to infect people, there was a large outbreak of T. gondii in people in 1995.

 

For the study, over the course of the six-year evaluation period, more than 5,000 dead marine mammals were reported on the coastal beaches of the Pacific Northwest. Some deaths ascribed to parasitic encephalitis (brain swelling) were assumed to be caused by T. gondii, because the parasite can infect most mammals and was well established in the region. For the study, specimens were collected and animal autopsies (necropsies) were conducted by members of the Northwest and British Columbia Marine Mammal Stranding Network on 151 marine mammals with suspected cases of parasitic encephalitis. The mammals included several kinds of seals and sea lions, Northern sea otters, a Pacific white-sided dolphin, porpoises and three species of whale. An additional 10 animals, all healthy adult California sea lions that were euthanized in the Columbia River to protect fish stocks, were included in the study as controls. Brain tissue was examined from 108 animals positive for either S. neurona or T. gondii. The number of parasites in the tissues were measured and combined that with an assessment of the degree of brain inflammation to gauge whether the infection was likely to be the primary, contributing or incidental cause of death.

 

At NIAID, 494 brain, heart, lymph node and other tissue samples were screened with a variety of genetic techniques. The techniques were unbiased in that we do not directly search for any particular species of parasite. Rather, the screens simply reveal evidence of any parasite in the tissue being studied. The team then applied gene amplifying and gene sequencing methods to identify the species and, often, the subtype or lineage of the microbes.

 

Of the parasites found in 147 of the 161 of animals, 32 were infected with T. gondii, 37 with S. neurona and 62 with both parasites. The remaining 16 infections were caused by various other parasites, including several that had not been detected before in any kind of animal. Notably, all 10 healthy animals were infected with either one or both of the parasites.

 

According to the authors, the presence of T. gondii was not surprising, but the abundance of S. neurona infections was quite unexpected. The authors have theorized that S. neurona has been introduced into the Pacific Northwest by opossums, which gradually have been expanding their range northward from California and can shed an infectious form of the parasite in their feces. The ample rainfall in the region provides an easy route for infected feces to enter inland and coastal waterways and then contaminate shellfish and other foods eaten by marine mammals.

Sickle Cell Treatment Safe for Young Children

 

 

Sickle cell disease is an inherited blood disorder that affects approximately 100,000 Americans. It is most prevalent in persons of African, Hispanic, Mediterranean, and Middle Eastern descent. People living with this disease have two copies of an altered gene responsible for producing hemoglobin, the protein in red blood cells that transports oxygen throughout the body. Those with sickle cell disease produce hemoglobin that changes shape and becomes stiff after releasing its oxygen. The transformation, which can cause normally round and flexible red blood cells to become misshapen and sticky, slows the flow of blood to the tissues. These changes contribute to fatigue and pain, which are among the hallmarks of this disease. There is no widely available cure for sickle cell disease, though bone marrow transplants have cured some younger patients. Those who live with the disease have life-long anemia due to the rapid destruction of red blood cells in the body. Some people with sickle cell disease undergo periodic blood transfusions to increase the number of healthy red blood cells.

 

Hydroxyurea was originally developed as a cancer treatment, but has been successful in reducing episodes of severe pain, known as pain crises, in adults with sickle cell disease. The drug is intended to raise levels of fetal hemoglobin, a form of hemoglobin everyone produces before birth and during the first few months of life. As time goes on, this fetal hemoglobin almost disappears from a person’s system as production of adult hemoglobin takes over. Increasing fetal hemoglobin levels for people who have sickle cell disease is helpful because fetal hemoglobin reduces the tendency of sickle hemoglobin to change the shape of the red blood cells.

 

Results of a study, The Pediatric Hydroxyurea Phase III Clinical Trial, known as Baby HUG, appearing in the May 14 edition of the Lancet has shown that a drug now used to treat adults who have sickle cell disease appears to be safe for children aged 8 to 19 months. The drug, hydroxyurea, reduced pain episodes and improved key blood measurements. According to the authors, there are now strong reasons for health care professionals to consider starting children who have sickle cell disease as early as possible on hydroxyurea.

 

The study was designed to determine whether hydroxyurea could protect spleen and kidney function in very young children who have sickle cell disease. Loss of spleen function is associated with increased risks of serious bacterial infections. The study also sought to determine whether hydroxyurea treatment would reduce the frequency of other complications, including pain events and hospital stays.

 

The study enrolled 193 children, making it the largest trial to test hydroxyurea treatment in very young patients, randomly assigned 96 participants to a group taking hydroxyurea and 97 participants to a control group taking a placebo. Results showed that the children who were given hydroxyurea fared about the same as those children not given the drug based on scans of the spleen and examination of the kidney’s filtering capacity, the main tests used to evaluate the treatment. However, the children given hydroxyurea showed improvements in other tests of spleen and kidney function. Most importantly, hydroxyurea also was shown to decrease the occurrences of pain episodes. Those in the hydroxyurea group experienced half as many pain events, 177 events spread among 62 participants, versus 375 events spread among 75 participants in the placebo group.

 

The treatment also lowered the risk of dactylitis, which is pain in the hands and feet often accompanied by swelling. Children treated with hydroxyurea also experienced fewer episodes of acute chest syndrome (eight instances, compared with 17 in the placebo group), needed fewer hospitalizations (232, compared to 324 in the placebo group), and needed fewer blood transfusions, which are sometimes given to increase red blood cell counts. Acute chest syndrome is a pneumonia-like infection that can be life-threatening.

 

As in adults, the children taking hydroxyurea in Baby HUG showed elevated levels of fetal hemoglobin compared to the children receiving a placebo.

 

While results of the primary spleen and kidney function tests did not differ in the two groups, it is possible that improvements may arise in future years. The study plan to follow study participants through 2016, when the children will be between 9 and 13 years of age, to look at the long-term effects of the treatment. The extended study will test brain, heart, kidney, lung, and spleen function; examine growth as well as psychological and social development; and provide information about the predictive value of blood tests.

TARGET HEALTH excels in Regulatory Affairs and Public Policy issues. Each week we highlight new information in these challenging areas.

FDA Approves Treatment for Clostridium difficile Infection

 

People at risk of developing the bacterial infection include the elderly, patients in hospitals or nursing homes, and people taking antibiotics for another infection. The most effective way to prevent CDAD is thorough handwashing with soap and warm water.

 

 

Clostridium difficile (C. difficile) is a bacterium that can cause diarrhea and lead to colitis, other serious intestinal conditions, and death in severe cases. C. difficile bacteria are found in the stool of an infected person, and others can become infected if they touch items or surfaces contaminated with the bacteria or spores and then touch their mouths.

 

This week, the FDA approved Dificid (fidaxomicin) tablets for the treatment of Clostridium difficile-associated diarrhea (CDAD). The safety and efficacy of Dificid were demonstrated in two trials that included 564 patients with CDAD that compared Dificid with vancomycin, a common antibiotic used to treat CDAD. The clinical response was similar in the Dificid group compared with the vancomycin group in both studies, however. a greater number of patients treated with Dificid had a sustained cure three weeks after treatment ended versus those patients treated with vancomycin. The most common side effects reported with Dificid included nausea, vomiting, headache, abdominal pain, and diarrhea.

 

Dificid, a macrolide antibacterial, should be taken two times a day for 10 days with or without food. To maintain the effectiveness of Dificid, and to reduce the development of drug-resistant bacteria, the drug should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile.

 

Dificid was developed by San Diego-based Optimer Pharmaceuticals Inc.

 

For more information about our expertise in Medical Affairs, contact Dr. Mark L. Horn. For Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr. Glen Park.

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Science Weekly Podcast: Climate science, transparency and harassment

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Sir Paul Nurse talks to Alok Jha about the misuse of Freedom of Information requests to harass climate scientists

Kandel at Lange Nacht der Wissenschaften (Long Night of Science) in Austria in 2006

 

 

 

Born November 7, 1929 to Present
Vienna, Austria
Fields psychiatrist and neuroscientist
Institutions Columbia University College
of Physicians and Surgeons
Alma mater New York University Medical School
Harvard University
Known for physiology of memory
Notable awards Nobel Prize in Physiology or Medicine 2000

Life is Learning (and a good sense of humor) – A Genius Checks Out the iPad

 

 

 

Eric Richard Kandel (born November 7, 1929) is an American neuropsychiatrist who was a recipient of the 2000 Nobel Prize in Physiology or Medicine for his research on the physiological basis of memory storage in neurons. He shared the prize with Arvid Carlsson and Paul Greengard.

Kandel is professor of biochemistry and biophysics at the Columbia University College of Physicians and Surgeons and a Senior Investigator in the Howard Hughes Medical Institute. He was also the founding director of the Center for Neurobiology and Behavior, which is now the Department of Neuroscience at Columbia. Kandel authored In Search of Memory: The Emergence of a New Science of Mind (WW Norton), which chronicles his life and research. The book was awarded the 2006 Los Angeles Times Book Award for Science and Technology.

Kandel was born in 1929 in Vienna, Austria, in a middle-class Jewish family. His mother, Charlotte Zimels, was born in 1897 in Kolomyya, Pokuttya (modern Ukraine), and came from a well-educated middle-class family. At that time Kolomyya was in Eastern Poland (he used to joke “as with all bright people, my roots are in Poland.” His father was born in 1898 into a poor family in Olesko, Galicia (then part of Austria-Hungary). At the beginning of World War I his parents moved to Vienna where they met and married in 1923, shortly after Hermann Kandel, Eric’s father, had established a toy store. They were a thoroughly assimilated and acculturated family, who had to leave Austria after the country had been annexed by Germany in March 1938. Aryanization (Arisierung) started; attacks on Jews escalated; Jewish property was confiscated. Eventually, when Eric was 9, he and his brother Ludwig, 14, boarded the “Gerolstein” at Antwerp in Belgium and joined their uncle in Brooklyn on May 11, 1939. Later his parents succeeded in moving to the US.

When Kandel won the Nobel Prize in 2000, it was claimed in Vienna that he was an “Austrian” Nobel, something he found “typically Viennese: very opportunistic, very disingenuous, somewhat hypocritical.” Afterwards, he received a letter from Austria’s President Klestil asking, `”How can we recognize you?” Kandel then proposed to have a symposium on the response of Austria to National Socialism.[1])

After arriving in the United States, and settling in Brooklyn, Kandel was tutored by his grandfather in Judaic studies, and was accepted at the Yeshivah of Flatbush, graduating in 1944. He attended Brooklyn’s Erasmus Hall High School, a Public high school.

Kandel’s initial intellectual interests lay in the area of history. (History and Literature was his undergraduate major at Harvard University.) He wrote an honors dissertation on “The Attitude Toward National Socialism of Three German Writers: Carl Zuckmayer, Hans Carossa, and Ernst Jünger.” While at Harvard, a place dominated by the work of B. F. Skinner, Kandel became interested in learning and memory. It should be noted, however, that while Skinner championed a strict separation of psychology, as its own level of discourse, from biological considerations such as neurology, Kandel’s work is essentially centered on an explication of the relationships between psychology and neurology.

The world of neuroscience was first opened up to Kandel through his interactions with a college girlfriend, Anna Kris, whose parents were Freudian psychoanalysts. Freud, a pioneer in revealing the importance of unconscious neural processes, was at the root of Kandel’s interest in the biology of motivation and unconscious and conscious memory.

Medical school and early research

In 1952 he started at the New York University Medical School. By graduation he was firmly interested in the biological basis of the mind. During this time he met his future wife, Denise Bystryn. Kandel was first exposed to research in Harry Grundfest’s laboratory at Columbia University. Grundfest was known for using the oscilloscope to demonstrate that action potential conduction velocity depends on axon diameter. The researchers Kandel interacted with were contemplating the technically challenging idea of intracellular recordings of the electrical activity of the relatively small neurons of the vertebrate brain.

After starting his neurobiological work in the difficult thicket of the electrophysiology of the cerebral cortex, Kandel was impressed by the progress that had been made by Stephen Kuffler using a much more experimentally accessible system: neurons isolated from marine invertebrates. After becoming aware of Kuffler’s work in 1955, Kandel graduated from medical school and learned from Stanley Crain how to make microelectrodes that could be used for intracellular recordings of relatively large crayfish giant axons.

Karl Lashley, a well-known American neuropsychologist, had tried but failed to identify an anatomical locus for memory storage in the cortex at the surface of the brain. When Kandel joined the Laboratory of Neurophysiology at the National Institutes of Health in 1957, William Beecher Scoville and Brenda Milner had recently described the patient HM, who had lost explicit memory storage following removal of the hippocampus. Kandel took on the task of performing electrophysiological recordings of hippocampal pyramidal neurons. Working with Alden Spencer, electrophysiological evidence was found for action potentials in the dendritic trees of hippocampal neurons. They also noticed the spontaneous pace-maker-like activity of these neurons and a robust recurrent inhibition in the hippocampus. With respect to memory, there was nothing in the general electrophysiological properties of hippocampal neurons that suggested why the hippocampus was special for explicit memory storage.

Kandel began to realize that memory storage must rely on modifications in the synaptic connections between neurons and that the complex connectivity of the hippocampus did not provide the best system for study of the detailed function of synapses. Kandel was aware that comparative studies of behavior, such as those by Konrad Lorenz, Niko Tinbergen, and Karl von Frisch had revealed conservation of simple forms of learning across all animals. Kandel felt it would be productive to select a simple animal model that would facilitate electrophysiological analysis of the synaptic changes involved in learning and memory storage. He believed that, ultimately, the results would be found to be applicable to humans. This decision was not without risks since many senior biologists and psychologists believed that nothing useful could be learned about human memory by studying invertebrate physiology.

In 1962, after completing his residency in psychiatry, Kandel went to Paris to learn about the marine mollusc Aplysia californica from Ladislav Tauc. Kandel had realized that simple forms of learning such as habituation, sensitization, classical conditioning, and operant conditioning could readily be studied with ganglia isolated from Aplysia. “While recording the behavior of a single cell in a ganglion, one nerve axon pathway to the ganglion could be stimulated weakly electrically as a conditioned [tactile] stimulus, while another pathway was stimulated as an unconditioned [pain] stimulus, following the exact protocol used for classical conditioning with natural stimuli in intact animals.” Electrophysiological changes resulting from the combined stimuli could then be traced to specific synapses. In 1965 Kandel published his initial results, including a form of pre-synaptic potentiation that seemed to correspond to a simple form of learning.

Faculty member at New York University Medical School

 

Kandel in 1978

Kandel took a position in the Departments of Physiology and Psychiatry at the New York University Medical School, eventually forming the Division of Neurobiology and Behavior. Working with Irving Kupferman and Harold Pinsker it was possible to develop protocols for demonstrating simple forms of learning by intact Aplysia. In particular, the now famous gill-withdrawal reflex, by which the tender Aplysia gill tissue is withdrawn from danger, was shown to be sensitive to both habituation and sensitization. By 1971 Tom Carew joined the research group and helped extend the work from studies restricted to short-term memory to additional experiments that included additional physiological processes required for long-term memory.

By 1981, laboratory members including Terry Walters, Tom Abrams, and Robert Hawkins had been able to extend the Aplysia system into the study of classical conditioning, a finding which helped close the apparent gap between the simple forms of learning often associated with invertebrates and more complex types of learning more often recognized in vertebrates. Along with the fundamental behavioral studies, other work in the lab traced the neuronal circuits of sensory neurons, interneurons, and motor neurons involved in the learned behaviors. This allowed analysis of the specific synaptic connections that are modified by learning in the intact animals. The results from Kandel’s laboratory provided solid evidence for the mechanistic basis of learning as “a change in the functional effectiveness of previously existing excitatory connections.”

Molecular changes during learning

Starting in 1966 James Schwartz collaborated with Kandel on a biochemical analysis of changes in neurons associated with learning and memory storage. By this time it was known that long-term memory, unlike short-term memory, involved the synthesis of new proteins. By 1972 they had evidence that the second messenger molecule cyclic AMP (cAMP) was produced in Aplysia ganglia under conditions that cause short-term memory formation (sensitization). In 1974 the Kandel lab moved to Columbia University as founding director of the Center for Neurobiology and Behavior. It was soon found that the neurotransmitter serotonin acting to produce the second messenger cAMP is involved in the molecular basis of sensitization of the gill-withdrawal reflex. By 1980, collaboration with Paul Greengard resulted in demonstration that cAMP-dependent protein kinase (PKA) acted in this biochemical pathway in response to elevated levels of cAMP. Steven Siegelbaum identified a potassium channel that could be regulated by PKA, coupling serotonin’s effects to altered synaptic electrophysiology.

In 1983 Kandel helped form the Howard Hughes Medical Research Institute at Columbia devoted to molecular neural science. The Kandel lab took on the task of identifying proteins that had to be synthesized in order to convert short-term memories into long-lasting memories. One of the nuclear targets for PKA is the transcriptional control protein CREB (cAMP response element binding protein). In collaboration with David Glanzman and Craig Bailey, CREB was identified as being a protein involved in long-term memory storage. One result of CREB activation is an increase in the number of synaptic connections. Thus, short-term memory had been linked to functional changes in existing synapses, while long-term memory was associated with a change in the number of synaptic connections.

Experimental support for Hebbian learning

Some of the synaptic changes observed by Kandel’s laboratory provide examples of Hebbian learning. One article describes the role of Hebbian learning in the Aplysia siphon-withdrawal reflex.

The Kandel lab has also performed important experiments using transgenic mice as a system for investigating the molecular basis of memory storage in the vertebrate hippocampus.  Kandel’s original idea that learning mechanisms would be conserved between all animals has been confirmed. Neurotransmitters, second messenger systems, protein kinases, ion channels, and transcription factors like CREB have been confirmed to function in both vertebrate and invertebrate learning and memory storage.

Kandel is also well known for the textbooks he has helped write such as Principles of Neural Science. Kandel has been a member of the National Academy of Sciences, USA, since 1974. His 2006 autobiographical book, “In Search of Memory: The Emergence of a New Science of Mind,” is a popularized account of his life and career.

Continuing work at Columbia University

Kandel actively contributes to science as a member of the Division of Neurobiology and Behavior at the Department of Psychiatry at Columbia University. In 2008, he and Daniela Pollak discovered that conditioning mice to associate a specific noise with protection from harm, a behavior called “learned safety,” produced a behavioral antidepressant effect comparable to medications. This finding, reported in Neuron, may inform further studies of the cellular interactions between antidepressants and behavioral treatments. Kandel has been at Columbia University since 1974, and lives in New York City.

Awards

He is a member of the prize committee for neuroscience of Kavli Prize.

 

 

 

Videos On Memory with Eric Kandel MD

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