Posted by: R. Douglas Fields | November 6, 2014

‘Car Talk’ Host’s Death Illuminates Alzheimer’s

Tom and Ray “Turns out he wasn’t kidding,” said Ray. “He really couldn’t remember last week’s puzzler.” (1) On Monday Tom Magliozzi, co-host of NPR’s ‘Car Talk’ died of Alzheimer’s disease. For his many fans the dreaded disorder suddenly became personal. For many, it comes as a shock to learn that the mind-robbing disease can be fatal.

The passing of Tom Magliozzi, ‘Click or maybe he was Clack’ of NPR’s radio show ‘Car Talk’ is a bitter sweet moment, like the time my 72 VW bus threw a rod returning home to Bethesda, Maryland from a summer at Woods Hole, Marine Biology Lab right after we took a slight diversion to visit the Martin Guitar Factory in Nazareth, PA. Saddened by the abrupt ending, but grateful for the many years of joy and meandering adventures the bus had brought us. Over the years Tom and Ray entertained and enlightened us with their care-free witty banter about ailing cars and just as often faltering human relationships and they did it with obvious brotherly love. These were two guys you wanted to hang out with. They were fun and interesting, and you always seemed to learn something from them. With Tom’s death on Monday, I think he probably enlightened more people than anyone about the fact that Alzheimer’s disease can be fatal. It is perplexing that such a leading cause of death in the United States should be unknown as a potentially deadly disease to so many.

“I like to drive with the windows open. I mean, before you know it, you’re going to spend plenty of time sealed up in a box anyway, right?” (2)

Well, I hope so, but I wouldn’t be surprised if we learn that the practical joking brothers utilized Tom’s Dodge Dart in lieu of a traditional casket. Can you hear that infectious laughter?

If you don’t know Tom and Ray you will rightfully be offended by my unsanctimonious tone. But Tom was a guy who cared about things that mattered and he cared about the science of how things work. This is a guy whose favorite remedy for an idiot light that would not shut off was to cover it with a piece of black electrical tape. Pay attention to the things that matter. And no matter how seemingly ordinary the car repair question might be, Tom loved to take the scientific approach, beginning with first principles of physics to develop a complete understanding of what went wrong. So Tom would want you to know that people do die of Alzheimer’s and to understand how. Ray would groan and wait out the scientific explanation, but here it is:

Everyone knows that Alzheimer’s disease erodes memory, causes confusion, ultimately robs one of their personality and in the end can render them a terrified lost stranger in their own world, but the disease also damages other parts of the brain. This can include parts of the brain controlling vital functions, such as breathing, swallowing, and heartbeat. A study published in the journal Neurology earlier this year concluded that deaths from Alzheimer’s disease were greatly under-reported. The CDC had estimated Alzheimer’s as the sixth most common cause of death, but the new research places Alzheimer’s as the third leading cause of death, behind heart disease and cancer. “You can’t fix it,” Tom would say. There is no cure; not even a treatment that will arrest the disease once it is diagnosed. The odds of getting Alzheimer’s disease at age 85 are 50:50.

Even in leaving us, Tom enlightens.

To Ray, and the many friends and family, we share your loss, but also your blessing. According to the Car Talk website, “The family asks that in lieu flowers, or rotten fruit, fans of Tom make a donation in his memory to either their local NPR station or the Alzheimer’s Association. (3)

Write your condolences on the back of a $20 bill and send them to NPR: http://www.npr.org/stations/donate/ or to the Alzheimer’s Foundation of America: http://www.alzfdn.org/ContributetoAFA/makeadonation.html

References
James, B.D. et. al., (2014) Contribution of Alzheimer disease to mortality in the United States. Neurology 82:1-6.
(1) http://www.npr.org/2014/11/03/357428287/tom-magliozzi-popular-co-host-of-nprs-car-talk-dies-at-77
(2) http://www.cartalk.com/blogs/staff-blog/quotable-tom-magliozzi
(3) http://www.cartalk.com/blogs/staff-blog/tom-magliozzi-1937-2014.
50:50 odds at age 85 see: http://www.alz.org/

Posted by: R. Douglas Fields | October 16, 2014

The Brain’s White Matter–Learning beyond Synapses

Oligodendrocyte forming myelin on axons

Oligodendrocyte forming myelin on axons

Recently scientists have been exploring part of the brain that has been relatively unexplored in learning–white matter, comprising half of the human brain. Here new research is detecting cellular changes during learning that are entirely different from the synaptic changes between neurons in gray matter. A new study shows that learning a new motor skill requires generation of new myelin, the electrical insulation on nerve axons.

Neural computation and information processing take place in the brain’s gray matter, the “topsoil” layer of brain tissue comprised of neurons communicating through synapses, but beneath gray matter billions of nerve axons connect neurons into circuits, much like underground communication cables connecting computers into functional networks over long distances. These dense bundles of cables in white matter held little interest to neuroscientists who were interested in how the brain processes information and learns. These functions were understood to depend on the formation and breaking of synaptic connections between neurons as well as adjustments in the strength of synaptic connections. But as any audiophile knows, cabling is critical to the performance of any communication system. Moreover, while it is important to board a train efficiently–much like signals entering a neuron through its synapses–the time it takes to travel between destinations can be even more important in the optimal function of the network compared with the process of “crossing the gap” into the train car. This concept, that the time it takes to transmit signals over long distances between neurons in the brain is important, has been largely overlooked in neuroscience theories of learning.

The most important factor in determining the maximal rate of impulse transmission through a nerve axon is whether or not the axon is coated with electrical insulation called myelin. Myelin boosts the speed of electrical impulse transmission by at least 50 times. People have always understood that if the myelin sheath breaks down in disease, such as multiple sclerosis, impulses can fail to travel beyond the damaged insulation and the neural circuit fails. In multiple sclerosis, for example, failure of transmission because of myelin damage results in blindness or difficulty walking. But what about the possibility that myelin might influence the proper rate of transmission between relay points in a neural circuit by adjusting the transmission speed so that impulses, like people arriving at appropriate times to catch a connecting flight, arrive at the right time at critical points in the circuit?

Evidence for changes in white matter structure during learning has accumulated in recent years from human brain imaging studies. At the same time, cellular neuroscientists have found that the formation of myelin can be influenced by electrical activity in axons. These two clues suggest that myelin may change during learning to optimize the flow of information through neural circuits. In a study to be published in Friday’s edition of the journal Science, a team of researchers from the laboratory of William Richardson at University College London, and colleagues in Australia, Japan, and Portugal, provide new evidence that learning a motor skill requires new myelin to be formed in the brain.

In the brain and spinal cord, myelin insulation is wrapped around axons by glial cells called oligodendrocytes. These cells develop from immature glia called oligodendrocyte progenitor cells (OPCs). Curiously, these immature glia persist in the adult brain in great numbers. In fact, OPCs are the major class of dividing cells in the adult brain. They comprise 5% of all cells in your brain. Why are these immature glia present in the adult brain long after fetal development?

One possibility is that these immature glia are there waiting to form myelin on bare axons in the adult brain to boost the speed of transmission in a circuit that is engaged in learning a new skill. If so, this would be a non-synaptic mechanism of learning. To test this hypothesis, the scientists studied mice that had been genetically engineered to prevent the OPCs from maturing into oligodendrocytes. They were able to control this block of OPC maturation by giving the mice a drug (tamoxifen) to block this process at any point in the animal’s life. The question they asked is whether or not new myelin is needed to learn a new skill, and by blocking the ability of OPCs to mature into oligodendrocytes, the formation of new myelin would be impaired while leaving myelin on existing fibers intact.

The mice were trained on a running wheel that had some of the rungs missing. At first the mouse stumbled over these missing rungs, but with practice, the animal learned to anticipate the missing rungs and step past them nimbly to run the treadmill with ease. The results showed that the mice that could not make new myelin learned this task much slower than normal mice. So no matter what changes in synaptic communication were taking place in gray matter to help the mouse learn to run on the modified wheel, if new myelin could not form, the animal’s performance would be impaired.

The researchers found that when an animal is trained on the running wheel, OPCs started to divide in its brain (in the corpus callosum, which are axon cables connecting the right and left hemisphere). By 4-6 days after training, there was a 40% increase in the number of OPCs that were dividing, and by three weeks there were many newly formed oligodnedrocytes. When this increase in oligodendrocyte production was impaired by genetic manipulation, the ability of mice to learn to run on the wheel was impaired.

An interesting finding was that quite similar increases in OPC cell division were also seen in the brains of control mice that were allowed to run on a standard running wheel, compared with mice kept in a normal cage without a running wheel. Possibly motor functions common to wheel running, such as grasping the rungs, are improved through myelination by running on the normal wheels as well. Alternatively it might be that exercise or novelty increase OPC production in the adult brain, not necessarily learning specifically. This benefit of enriched environments and exercise on OPC production in the adult brain is something that has been noticed in several other studies. This raises the question of whether new myelin is formed by the learning process to speed impulse transmission through the circuit required for the task, or instead there might be a general benefit of capacity for myelination in the adult brain by providing a better network structure for motor learning and performance.

Studies in aged humans show that myelin begins to degrade in aging and that learning new skills improves the integrity of white matter in the brain by slowing loss of myelin (Engvig, et al., (2012). The mice in this study were not aged, but still there might be a constant process of myelin renewal that could be difficult to detect but important for motor performance. This renewal would be undermined by the genetic manipulation blocking the formation of new myelin. In an e-mail, William Richardson agrees that this is an alternative possibility, but he doubts that this is as important as the formation of new myelin on circuits that must improve their performance during motor learning. “There is no detectable loss of oligodendrocytes after one month or three months,” the age at which these studies were performed, he says.

Richardson also offered a peek at what may be on the horizon. In comparing the rates of learning between controls and mice unable to form new myelin they noticed, “That the difference between [experimental and control mice] starts to develop less than 2 hours after first introduction to the wheel. At face value, therefore, myelin…is involved in the early events as well as the later events [of learning].”

This is intriguing because recent brain imaging studies have detected changes in white matter structure in the human brain by magnetic resonance imaging within two hours of training on a race car video game (Hofstetter et al., 2013). “Maybe the early events involve new protein production (Wake et al. 2011), while the later events contribute to long-term memory/consolidation,” Richardson says. (The study he is referring to found that the synthesis of myelin proteins is stimulated by electrical activity in axons, so that oligodendrocytes in contact with axons firing impulses begin to form myelin rapidly on those fibers.)

After a century of research focused on the synapse to understand the cellular basis of learning and memory, neuroscientists are excited to find that there may be much more in store in the neglected white matter regions of the brain involving non-neuronal cells, glia, that have been largely overlooked by most neuroscientists. The questions presented by this elegant new research are fascinating. For example, how do oligodendrocytes know which neural circuit to myelinate during learning, that is, how do they sense electrical activity in axons? What are the molecular mechanisms that control activity-dependent myelination? If these molecules can be identified, new approaches to treating nervous system disorders might be found, because abnormal transmission of information is associated with mental illnesses as well as neurological illnesses. How is this cellular mechanism of learning different from learning based on synaptic plasticity? For example, do improvements in transmission of information through a neural network explain why learning a difficult motor skill, such as riding a bike, takes so much practice, but suddenly everything kicks in and once the training wheels come off, you never forget how to ride a bike the rest of your life?

“Plenty more experiments up ahead!” Richardson exclaims.

More to explore

Bracken, Kassie (2009) The brains behind talent, The New York Times http://www.nytimes.com/video/sports/1194817108368/the-brains-behind-talent.html

Engvig, A., et al., (2012) Memory training impacts short-term changes in aging white matter: a longitudinal diffusion tensor imaging study. Human Brain Mapping 33, 2390-2406.

Fields, R.D. (2008) White Matter Matters, Scientific American (March 2008) 298, 54-61.

http://www.nature.com/scientificamerican/journal/v298/n3/full/scientificamerican0308-54.html

Fields, R.D. (2012) Social interaction in early life affects wiring to the frontal lobes The Huffington Post November 13, 2012

http://www.huffingtonpost.com/dr-douglas-fields/social-interaction-early-life-frontal-lobes_b_1864234.html

Hofstetter, S., Tavor, I., Moryosef, S.T., and Assaf, Y. (2013) Short-term learning induces white matter plasticity in the fornix. J. Neurosci. 33, 12844-50 (2013).

**McKenzie, I., Ohayon, D., Li, H., Paes de Faria, JH., Emery, B., Tohyama, K., and Richardson, W.D. (2014) Motor skill learning requires central myelination. Science, October 17, 2014 issue.

Wake, H., Lee, P.R. and Fields, R.D. (2011) Control of local protein synthesis and initial events in myelination by action potentials. Science 333, 1647-51.

** Reviewed in this article.

Posted by: R. Douglas Fields | October 13, 2014

Ebloa on the Brain

On September 23, 1976, while the nation’s attention was focused on the battle between Gerald Ford and Jimmy Carter for President of the United States, a 42-year-old woman half way around the world was engaged in a personal battle. Outside the limelight of world view, her struggle for life in a remote third world country marked the crossing of a threshold for our species. Rapidly others from her region began to appear in hospital with the same symptoms: fever, sore throat, muscular pains, vomiting, diarrhea, and most shockingly breakdown of the body’s capillaries and small blood vessels, causing internal bleeding. The whites of their eyes turned red with blood seeping into tissue. A disturbingly high percentage of hospital personnel quickly developed the same fatal disease. This was a highly contagious and highly fatal disease unlike any other known.

Specimens from throat swabs, urine, and blood from these patients were sent to labs around the world; first to the Microbiological Research Establishment in England and to the University of Antwerp. Then from the lab in England samples were sent to the Virology Division at the Center for Disease Control in Atlanta, Georgia. Through electron microscopes in these modern laboratories human beings saw for the first time a new virus and a new deadly threat to humanity. The virus particles had a close relation to the Marburg virus, but the envelope encapsulating it was clearly but subtly different. In consultation among the world’s experts they named this new virus Ebola, after a small river flowing westward north of Yambuku in Zaire, past the small village where the first person became ill and provided the sample to isolate this new germ.

The disease is categorized as a hemorrhagic fever, meaning that it is accompanied by bleeding and fever. The virus ravages the body’s organs, liver, spleen, kidney, lungs, testis, and especially the vascular system, but the purpose of this article is to describe how the virus affects the brain. Most of what we know about Ebola comes from animal research on rats, rabbits, guinea pigs, and monkeys.

Clearly the brain is affected in Ebola patients, who quickly lose the ability to walk and suffer convulsions. The assault on the brain comes from two fronts: injury to the brain’s vascular supply and biochemical disruptions in the body as a result of kidney and other organ failure. The blood vessels in the brain become severely congested and some begin to bleed causing brain stroke. Disruption of the normal potassium, sodium, and calcium concentrations, and other biochemical changes in the body from renal failure, disrupt the mechanisms of brain cell communication and ultimately damage brain cells. Primarily, though, the virus replicates in the vascular system, infecting the cells that make the walls of blood vessels, as well as cells flowing in the blood, the lymphocytes and monocytes. As the blood vessels degenerate, blood seeps out into the surrounding tissue. The patient goes into shock caused by severe blood and fluid loss, which makes it impossible for the heart to supply blood to the body’s organs, and they stop working and die. The brain is very vulnerable to loss of blood flow. The brain uses 20% of the body’s energy supply even though it comprises only 5% of body weight.

While you read this article consider for a moment how the world torn as it is by politics and separated by geography is united in biology. And consider that in Dallas, Texas today another woman whose name is not public lays suffering in bed in a hospital room completely isolated. She is a nurse who cared for and comforted Thomas Eric Duncan through the last horrible days of his life. Duncan was the first patient to become ill with Ebola in the United States. He died last Wednesday.

The heroism of service men and women in combat and of the brave first responders who rush into burning buildings to save the life of a stranger that we so justly admire and honor with metals cannot allow us to overlook the silent selfless heroism of nurses and other health care providers who silently and with unwavering commitment risk their own lives for the same cause: to help another human being who is facing death. The courage to risk surrendering one’s own life to save the life of a stranger reflects the noblest character of mankind.

More to Explore
Bowen, E.T.W. et al., (1977) The Lancet March 12, p. 571
Pattyn, S., et al., (1977) Isolation of Marburg-like virus from a case of haemorrhagic fever in Zaire. The Lancet, March 12, p. 573
Johnson, K.M., et al., (1977) Isolation and partial characterization of a new virus causing acute haemorrhagic fever in Zaire. The Lancet, March 12, 1977
Baskerville, et al., (1985) Ultrastructural pathology of experimental Ebola haemorrhagic fever virus infection. J. Pathol. 147:199-209.

Posted by: R. Douglas Fields | August 30, 2014

Sharks Use ESP

shark

As beachgoers flock to the ocean over Labor Day, thoughts of “jaws” will inevitably surface. A shark’s ability to home in on the scent of blood is legendary, but many people are surprised to learn that sharks have a stealthy sixth sense to find prey and explore the world around them. Sharks have the ability to sense an electric aura that surrounds all creatures in seawater–including people.

This sixth sense works where vision fails, in murky water, at night, and when prey animals are buried under sand. This extra sense of perception (ESP) is called “electroreception.” Human beings can only imagine what it must be like to “see” a world of electrical auras the way sharks do.

For four hundred million years sharks and their relatives, the chimaeras and rays, have been using a force of nature that our species learned about only recently–electricity. And, sharks knew something about electricity that scientists never imagined until the 1970s: that all organisms in seawater are surrounded by a weak bioelectric field that pulsates and changes with the animal’s movements and physiological activity. With the surprising discovery of bioelectrical fields, a neuroanatomical mystery extending back to the 1600s was finally solved.

If you look closely at the head of any shark or ray you will see that it is stippled with small pores focused around the mouth. The first person to have examined a shark must have seen them, but what are they?

In 1678, anatomist Stephano Lorenzini guessed that they might be the openings of glands to coat the fish with slime. Squeezampullae raying the pores does expel a crystalline jelly substance. But this doesn’t seem quite right. Sharks are not slimy. In fact, the clear gel inside the pores does not resemble any bodily secretion.

Lorenzini had second thoughts. Writing by candle light centuries before electricity was discovered, and he wrote in his notebook that these mysterious openings must have some hidden function; thus calling on scientists of the future to solve this puzzle of Nature.

If the shark’s skin is peeled away carefully you will see that the pores are openings of long clear tubes, some nearly the diameter of a spaghetti noodle and in some cases nearly as long, but most are much smaller. The tube ends in a swelling somewhat like an eyedropper bulb. A slender nerve trails out of the end of the swollen ending. This structure reminded anatomists of Roman long-necked flasks, called ampulla, so these strange tubes found only under the skin of sharks and their close relatives became known as “ampullae of Lorenzini.”

ampullae
Anatomists tracing the nerves from the ampulla saw that they entered the brain through the top side or dorsal surface. This vital clue meant that ampullae of Lorenzini are sense organs, not glands, because sensory input to the brain–touch, temperature, pain, etc., enters through the dorsal side of the spinal cord, whereas nerves that control muscles exit from the ventral (bottom) side of the brain and spinal cord. But what sense could these strange tubes, unlike any other sense organ in any other animal, possibly detect?

Soon after the electronic amplifier was developed early in the 20th century, physiologists began to use them to detect the weak electrical impulses traveling through nerves. Alexander Sand in 1938 found that when he amplified the signals sent out the nerves of the ampullae of Lorenzini the impulses changed their rate of firing depending on the temperature. The organs were extremely sensitive “thermometers,” detecting changes in temperature as small as 0.2 degrees C. Thus, these organs must allow sharks to detect small temperature differences in seawater.

But when R.W. Murray was repeating Sand’s experiments in the 1960’s, he accidentally switched on an electrical stimulator and the ampullae of Lorenzini responded by firing a burst of electrical impulses down the nerve. Startled by this discovery, he did further tests and found that the organs were remarkably sensitive “voltmeters.” Astonishingly they were more sensitive to weak electric fields than all but the most sensitive electrical instruments available to measure voltage.

Further research by Murray and others showed that gently touching the ampullae also caused nerve impulses to fire, and that the salt concentration and pH of a solution applied to the openings also stimulated nerve impulses in the organs. Now neuroscientists faced a difficult question: How is it possible to know which of these stimuli is the natural stimulus for these sense organs? Touch, taste (salt and pH), and temperature are common senses, but other animals cannot sense such weak electricity. Is it possible that these creatures have a 6th sense that other animals do not have? But if the ampullae of Lorenzini were “voltmeters,” why would a shark have sense organs to detect electricity?

The answer came in the 1970s when neuroscientist Adrianus Kalmijn made a surprising discovery. Using very sensitive electronic instruments he found that all animals in seawater have a very weak electrical field surrounding their body. Further behavioral experiments showed that sharks could locate prey by sensing the fish’s bioelectric field, even when hidden beneath the sand. Moreover, electrodes buried in the sand that emitted weak electric fields just like those surrounding any fish, provoked the shark to attack just as if the electrodes were a hidden prey item. This proved that the sense organs were indeed used by sharks in a normal behavior (feeding) to detect weak electric fields.

This bioelectric aura is not mysterious. It is generated just like electricity is produced in an electric battery. When positive and negatively charged ions in a solution are separated by a barrier, the imbalance in charges in the two compartments creates a voltage, simply because positive and negative charges attract. If there is not an equal balance of charges on both sides of the barrier, a small voltage will be created. In animals the barrier of separation is the animal’s skin and the two different salt solutions are the salty ocean outside the skin and the somewhat different salts in body fluids. This creates and extremely weak voltage, but ampullae of Lorenzini are so sensitive, they could detect whether or not a 1.5 V flashlight battery connected across the distance of the Atlantic Ocean was switched on or off.

In research on electroreception studying blue sharks at sea near the Woods Hole Oceanographic Institution, my colleagues and I observed that sharks would follow the scent of bait (ground-up fish that we pumped through a tube), but in the last moment of attack electroreception would take over and the shark would bite electrodes emitting a weak electric field placed a meter away from the food source. This revealed that surprisingly, electroreception is the most important sense a shark uses to orient its jaws in the final moments of attack, even overriding the scent and smell of blood.

I don’t believe that a shark repellent can be made to stop a shark in a feeding frenzy, but from these experiments I can see how we might use electroreception to avoid being attacked by sharks. By trailing a slender wire behind a swimmer or surfer emitting a weak electric field, the shark would attack the decoy electrode instead of chomping down on its intended meal. Like lizards escaping a predator by dropping its tail as a decoy, the electrical decoy could be life-saving.

Interestingly, in 2003, physicists temporarily and mistakenly revived the long-discarded theory that ampullae of Lorenzini are temperature receptors. This was based on an experiment in which they squeezed out some of the clear gel from the ampullae of Lorenzini onto a microscope slide. The researchers put the two electrodes from their sensitive voltmeter into the gel and heated or cooled one end and discovered that a voltage was generated. What they overlooked was something sharks know well. Metal in contact with a salt solution creates a battery, and the probes of the voltmeter were metal. As everyone knows, the amount of voltage a battery generates depends on temperature.

In reality, the salty gel inside the tubes is just a good electrical conductor. It does not generate electricity. The gel conducts the voltage through the tubes acting like an antenna to collect the bioelectrical signals and send them to voltage sensing cells in the bulb-like ending of the organ. This also explains why so many different kinds of stimuli affect ampullae of Lorenzini. This happens because voltages are affected by very many factors. This also illustrates how rich the sense of electroreception must be. Salt concentration, temperature, pH, and many other factors will affect the bioelectric field surrounding an animals, just as light is reflected differently from many different kinds of surfaces, giving us great insight into properties of different materials that we see. Sharks must be able to learn a great deal about the world from their sense of electroreception.

Experiments using food to study shark behavior can lead to an overly simplistic view of the purpose of ampullae of Lorenzini. Like vision or hearing, electroreception does not exist for only one purpose. Electroreception provides sharks with a unique and very sophisticated means of analyzing the world around them. We humans can only imagine what it must be like to see the world through a strange sixth sense.

More to explore
Fields, R.D. (2007) The shark’s electric sense. Scientific American, August, p. 75-81. http://www.scientificamerican.com/article/the-sharks-electric-sense/

Fields, R.D., Fields, K.D., and Fields, M.C. (2007) Semiconductor gel in shark sense organs? Neuroscience Letters, 426, 166-170. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211453/

 

Posted by: R. Douglas Fields | August 1, 2014

Lucy Movie Review and Neuro Fact Check

LucyMoviePoster The premise for the movie Lucy is that 90% of human cerebral capacity goes unused, but that’s only the start of the neuroscience bloopers in this new film.

After becoming an unwilling drug mule Lucy is suddenly able to access the full potential of the human brain when a surgically implanted packet of a new street drug ruptures inside her. From “Flowers for Algernon” to “Limitless,” stories about turbocharging brain power are a genre in themselves, but Lucy busts out beyond all reason to throw in nearly every supernatural power ever conceived. Toss every comic book superhero from Popeye to Superman into a blender and the slurry you get is Lucy, a super girl with the power of super intelligence, super strength, ESP, complete control of all the cells in her body, the ability to control other people’s bodies, supersensory reception, mind reading, telekinesis, the talent to tap into mass electronic communications using only her mind in a way that would make the NSA envious and give Edward Snowden a panic attack.

But wait there’s more! Levitation, antigravity, time travel, morphing her body, generating an impenetrable force field, regenerative healing, controlling TV, radio, and cell phone transmission.

But that’s not all! Superhuman speed and agility, X-ray vision, cyber communication, omnilingualism, astral projection, mental projection, telepathy, precognition, electromagnetic manipulation, self-disintegration, … The list goes on and on, but I’m bored trying to list them. There is not space to consider how each of these superpowers may violate the laws of nature or neuroscience. I’ll pick a few issues related to neuroscience that may have some educational value, but first a quick critique of this new film.

The revenge plot that launches the film quickly fizzles out when a side effect of bulking up her brain causes Lucy to lose all emotion and desire. Then the plot shifts to a quest (for knowledge), propelled by a trite Asian mobster chase scenario. The film is sloppy, with illogical and contradictory sequences and amateurishly distracting visual metaphors. To begin with, after all the mayhem and murder to battle her way to the evil gang leader to seek revenge early in the movie, Lucy gives the gangster a flesh wound. Then she leaves, stepping over a massacre of bloody dead corpses so that he can chase her for the rest of the movie. After seeing Lucy toss his bodyguard thugs around like cheap china, the villain never gets a clue that maybe he should have his henchmen take a snort of the powerful stuff. And why is Lucy running at all? Why doesn’t she just turn the mob chief into a pillar of iodized salt using her god-like powers? There is no character development. Lucy appears out of context in the opening scene as if you had channel surfed your way into the middle of a TV sitcom.

The “tell em what your are going to tell them, then tell them, then tell them what you told them, dialog makes the obvious tedious. Hammered in by repeated scenes of Professor Norman, expounding nonsense pseudoscience lecture as if it were true, the lack of scientific fact checking that went into this movie is astonishing. Couldn’t the screen writers have at least typed “GOOGLE” when they were dreaming up this script?

I don’t want to be a kill joy. Why spoil something like “Jack and the Beanstalk,” with the delightful goose laying golden eggs because the premise for the fantasy is inconsistent with science? It is fine to suspend belief for story telling if this illuminates human nature in a compelling way. But in Lucy, the story does not progress beyond the absurd premise. Look a golden egg! Wow, she laid another one! Look another one and it is even bigger…amazing special effects! A story that never advances beyond the premise is infantile. Lucy lays one egg after another exploiting the same contrivance as former disc jockey Casey Kasem with his hyped-up countdown winding up suspense to hear the top-ten pop songs. Viewers grow anxious to see what will happen when Lucy finally reaches 100% of her brain capacity. When we finally get there, the answer–that the meaning of life is to be found in a thumb drive–is an enormous let-down. The Bible story of the Tower of Babel works the same material as Lucy–man’s quest for god-like knowledge and power, but it does a far better job, and it has a cleaver ending. In return for man’s hubris, God puts lowly humans in their place by dividing them by language. The message in Lucy is trivial: that if we could have god-like knowledge we wouldn’t know what to do with it, other than stick someone else with it.

As for the premise; if you lose 10% or your brain power you will know it. The experiment has been done through disease, injury, intoxication, and prefrontal lobotomy. If you lose 90% of your cerebral cortical function, you will not be able to operate on the remaining 10%. You will be brain dead.

Animals do not use less of their brain than humans. Survival of the fittest sees to it that nature is never wasteful. The human brain uses 20% of the body’s total energy but it represents only 2% of the body’s mass. What would happen if an animal built such a costly organ and let 90% of it go idle?

Dolphins do not use twice as much of their brain as humans do and other animals do not use less of their brains than humans. Humans have superior intellect because of the increased cortical network that sustains more complex information processing. Dolphins are not more intelligent than humans. Whales and dolphins have big brains, but their cerebral cortex—the part that gives humans their incomparable intellect, is much simpler in structure than in primate brains or indeed the brains of many other clever terrestrial mammals including your pet dog. Dolphin cerebral cortex is thin. It has poor layering. Humans, primates, and even rodents, have six layers of cerebral cortex. Contrary to the movie, ecolocation in dolphins is not evidence of superior intelligence. After all, bats do it. So do shrews and some birds. None of these critters are considered Einsteins of the animal world.

Life did not begin 1 billion years ago as the movie says; it began 3.5 billion years ago. Not all animals have brains. Worms, insects, slugs, for example, have clusters of neurons stashed throughout their body where they need them instead of having a brain. Not all life has a nervous system; sea sponges for example, not to mention plants. Single-celled animals like the silvery Paramecia swimming in a drop of pond water, move, find food, avoid dangers, even conjugate (in addition to asexual reproduction) just fine with no nervous system at all.

At least the cliché 1950’s premise for super human abilities, radiation exposure, had some biological plausibility from genetic mutations, but the way the drug, CPH4, is supposed to allow Lucy to utilize 100% of her brain is dumb. CPH4 is supposed to be a growth factor stimulating cell division. How a growth factor could give a drug addict an instant high is unclear. Run away cell division is cancer. How cerebral metastasis enables Lucy to obtain supreme knowledge is a bit murky. The entire movie is supposed to have taken place in 24 hours, but this is about how long it takes one mammalian cell to divide in two. Supposedly this growth factor is supplied by the mother’s body and it acts like “an atomic bomb” to energize the formation of fetal bones. Had anyone bothered to fact check this they would have found these developmental facts of life are about as inaccurate as the evolutionary history Professor Norman expounds in his inane lecture. At six weeks gestation the human fetus has no bones. Only the size of a pencil eraser it doesn’t even have limbs yet. It looks like a cashew.

Lucy’s ability to remember suckling on her mother’s breast is impossible. Moreover an increase in brain cells could work to produce amnesia. Recent research indicates that birth of new neurons in the growing brain of young children is one of the reasons we can’t remember events from when our head was still expanding to its adult size. The new neurons disrupted the existing connections between neurons holding memories. Actually, children and infants do learn and remember–the sound of their mother’s voice, how to walk, recognize distinct sounds in their native language. What we lack from our early life experience is declarative memory, which is the memory of facts and events, but this requires understanding. Experience and awareness are necessary to form a “schema,” which is a complete and coherent combination of meaningful events, emotions, in temporal sequence and in relation to what is already stored in the mind to make a declarative memory. Infants are still just trying to make sense of the world. Moreover, human beings are born long before their brain is fully formed. The brain develops after birth so that environmental experience can help guide the process of wiring together our 100 billion neurons properly.

Icarus crashing to earth when his wax wings melt from flying too close to the sun makes an eloquent point with lovely unforgettable imagery, but Lucy is mind-numbing. On a scale of 1 to 5 neurons, a neuroscientist would rate Lucy “one neuron” because the science is abysmal. Filmgoers and literary types will concur because of the juvenile plot and lazy production. Philosophers will rate it two neurons in appreciation of the eastern philosophy patina, especially in the nirvana-like final scene. Those who spend their time staring semi-comatose at reality TV will find the car-chase scenes in Lucy much more exciting than watching fishermen land crabs or realtors flip houses, so they will give Lucy 3 neurons. Taking the mathematical mean, I give Lucy a rating of two neurons– but not cortical pyramidal neurons; just small inhibitory interneurons.

This is an expanded version of my review of this movie first published on the World Science Festival Website:

http://www.worldsciencefestival.com/2014/07/cinema-peer-review-lucy/

Posted by: R. Douglas Fields | June 12, 2014

Why Girls Like Guys Who Kayak

Hazard_Creek_Kayaker She’s checking out your on-line profile.

“I am a scientist who enjoys bird watching and canoeing.”

“Interesting!” she thinks.

Then she scrolls to the next profile; also a scientist:

“I enjoy white water kayaking, and I study alligators in the wild.”

She passes on you with your canoe, and in eager anticipation sends the kayaker an electronic “wink.”

This, according to a study by psychologist John Petraitis, is what most women will do, but why?

John Petraitis limped painfully into his office with his left foot in a black knee-high Velcro cast. His right wrist was wrapped in a matching black cast to stabilize his thumb tendon recently repaired by surgery.

“Skiing deep in the trees makes me come alive.” He says enthusiastically gazing at the gorgeous snow covered mountains surrounding his office in the Department of Psychology at the University of Alaska, at Anchorage.

That explains the snapped Achilles tendon and hand surgery. Many guys are drawn to danger. Whether aggressive skiing, motorcycle racing, or rock-climbing, why are men and boys attracted to risky activities?

Part of the answer, according to John Petraitis’ latest research, together with co-authors Claudia Lampman, Robert Boeckmann, and Evan Falconer, is supported by an experiment analyzing responses to on-line profiles in a mock electronic dating service. A lady’s choice for a first date may be swayed by factors extending back in time to when sharp stones, rather than Sharp computers, were the most advanced technology.

Petraitis was investigating the psychology of adult substance abuse when he was struck by the conspicuous differences in risk-taking behavior between the sexes. The highest rates of cigarette use, heavy alcohol use, binge drinking, and illicit substance use are seen in young people between the age of 15 and 25. Males have higher rates of all these risky activities, and males show up at emergency rooms in much higher numbers with traumatic injuries. They die at higher rates in outdoor accidents such as skiing and car accidents, and they are more often victims of homicide.

Part of the answer could be cultural. Boys are encouraged to display dominance and courage, accept dares and take risks, whereas girls tend to be socialized to be cautious, social, and to show concern for others. Girls play with dolls. Boys play with “action figures.” But the preference for risk-taking behavior in males is seen across all cultures, suggesting something more than socialization may be at work in drawing men and boys to risky pursuits.

The research team suspects that gender-specific behaviors that have been favored over eons of evolution in the battle for survival have left their imprints in our DNA and they are still guiding our mate choices today. As every biologist knows, evolution is about sex. When it comes to sex, females are the ones who make the decision about mates. Males audition.

Consider the garish male peacock with such ridiculously showy tail feathers that actually make it hard to fly and easier for predators to spot them. The male birds strut about displaying their showy tail feathers to impress the peahens in hopes of mating with them. The females, seeing the handsome bird with such a dangerously showy plumage think, “This guy must be amazingly fit to have survived with those dazzling tail feathers.” Genetic fitness, superior ability to survive in the face of dangers and handicaps, that’s what females are seeking in selecting their mates. A mate that can survive great risks must be exceptionally good at avoiding predators and acquiring food.

Many modern women will object to having their mate choices reduced to the pea-brained level of a bird, but have a look at the data. The researchers devised a list of 101 pairs of behaviors in a mock dating service in which each question paired a higher-risk option with a lower-risk choice. For example: Do you prefer a person who enjoys canoeing vs. white water kayaking? The choices included many more subtle risks, such as whether one prefers hot or mild hot sauce. The questionnaire was given to both men and women, and what the results showed is that women greatly preferred guys who engaged in the higher risk behaviors. Guys, in contrast, did not show any preference for women based on their risk-taking profile.

But here’s the really cleaver part. Half of the paired questions dealt with the sort of risks that human beings would have faced thousands of years ago, and the other half dealt with modern risks, such as driving while talking on a cell phone. Neither guys nor gals cared a whit about modern risks in selecting first dates; in fact, these modern risks were likely to be viewed as unattractive and foolish.

Females could care less about a guy who enjoys sticking forks in toasters. There was no electricity in the Stone Age. The risk-taking behaviors women prefer are the ones that deal with overcoming gravity, dealing with wild beasts, crossing water, being indifferent to nasty or dangerous foods, and engaging in human conflict. These are what the research team calls “hunter/gatherer risks,” the kind of risks our cave-man ancestors would have had to deal with. Modern risks, like playing with electricity, fooling with deadly chemicals, taking risks of identity theft, or driving without a seatbelt, did not impress the ladies one bit.

Why is risky behavior so pronounced in young males? Again, the answer is sex.

“Female fertility is a rare commodity,” Petraitis explains. Males remain fertile into old age, but not so for females. “A 20-year-old male competes with a 60-year-old male” [for attractive women]. The two age groups use different strategies to attract younger women. “Younger males are faster, stronger; they can bounce back from injury or adversity. Older males have more resources to provide for women.” So each group competes for young women in arenas in which they are more likely to win. “Young males are greater risk takers and adventurers to demonstrate their fitness,” he says.

He cites statistics on the biological facts of life to make his case. Males are fertile for 60 years, or 22,000 days. Females are only fertile half as many years, and they are only fertile 26 days/year whereas males are fertile every day. Do the math and in an entire lifetime, women are fertile only 850 days compared to 22,000 days for men. Also, women’s investment in fertility is much greater, considering the 9 months of pregnancy and years devoted to rearing a young child. Women have to be choosy.

Human behavior is complex and one important insight, such as the hunter/gatherer risk appeal identified in this new study, cannot explain everything about male risk taking. Petraitis suspects that males may also engage in risky activities to elevate status among other males. These new findings also do not explain why many women engage in risky activities, but he is devising experiments to investigate these questions.

For guys this research provides revealing insights into our male urge to risk life and limb in tests against gravity, water, fire, wild beasts, and dangerous food, but if you are thinking that taking risks is how to impress women, you are missing an important point. Male fertility is cheap. If a peacock with an outrageous tail gets eaten, well…there are plenty others. Likewise if a guy gets trampled by charging bulls in Pamplona, Spain.

Energetic and fit with a neatly trimmed greying beard, one might easily imagine Petraitis as the kind of guy who would eagerly attempt a 720 with a half-twist off the halfpipe to impress his lady (who happens to be one of the co-authors on the paper). But maybe he shouldn’t.

Reference:
John M. Petraitis, Claudia B. Lampman, Robert J. Boeckmann, and Evan M. Falconer (2014)
Sex Differences in the Attractiveness of Hunter-Gatherer and Modern Risks Journal of Applied Social Psychology 44: 442-453.

Posted by: R. Douglas Fields | May 28, 2014

The Lone Wolf Delusion

wolfAnguish grips the country with news of another horrific mass murder. From local police to the Secret Service, law enforcement worry about the “lone wolf.” These are individuals with no criminal record, feeling alienated and angry, plotting spectacular murder and violence in secret. “Experts” lament that there is no way to track lone wolf killers, but nothing could be farther from the truth. The lone wolf is perhaps the easiest of all potential murderers to identify and stop before they act.

The pop psychology argument says that there is no way to recognize the lone wolf, but that assertion is invalidated by the obvious–the defining feature of the lone wolf, their isolation. The recent mass murders in Santa Barbara were committed by an individual who was angry because no women would accept him. That is because they all knew. Something was off about him and women could sense it. Apparently most people could recognize this as reports state that he had few friends. Even his family knew. And so it is with so many other lone wolves. Such isolation and alienation is something that nearly everyone can plainly see, but too often choose to ignore. It is a common feature of mental illnesses. Isolation is no different from any symptom of a physical illness that appears long before the disease becomes deadly. The clear signs of illness must be acted upon effectively. Lone wolves should be viewed as medical failures. Unless disorders of the mind are addressed as fervently as disorders of the body, the disease will fester like any disease neglected.

Bewilderment about lone wolf murders stems from talking heads babbling on TV, mixing hidden agendas with fear, sensationalism, and ignorance. It is hard to imagine that the best medical experts are loitering outside TV studios waiting for the chair to next to the news anchor to vacate. Mental health experts are not baffled by the lone wolf. They are not baffled by suicide or by the depths of human depravity, cruelty, and suffering that are incomprehensible to most of us. They see these things every day. They understand what has gone wrong in the mind of lone wolves and the steps that must be taken to deal with the underlying disorder.

I will not use their names, but you will know them: Aurora, Sandy Hook, Virginia Tech, the Navy Yard, the Columbia shopping mall near my home, the Federal Building in Oklahoma City, Rep. Gabrielle Giffords, John Lennon’s passing, and now Santa Barbara. The person who took John Lennon from us carried a list of alternative potential targets. All that mattered was their celebrity. Being the agent of a prominent person’s death elevates the assassin’s identity to equal celebrity with their victim by forever interlinking their two names. In a twisted way they exchange their despicable self-identity with the envious identity of the prominent person they slay. Sensational mass murders are no different. Sensationalism is the key word–they seek mass recognition. How else can one explain the manifestoes, YouTube videos, selfie photos and letters mailed to the media? And the media eat it up, incubate and disseminate the pathology. Too often it is not about information and analysis. It is about attracting eyeballs to ogle in astonishment. If Barnum and Bailey were alive today they would invest in cable not canvass. If this were physical illness rather than mental illness the media would be charged with spreading disease.

The names of juvenile criminals are often withheld in the press, as are the names of victims of sexual assault. This is done to prevent further injury. Why, if the lone wolf acts in violent desperation for recognition and infamous glory should the media promote that illness and spread it? This irresponsibility should be condemned just as vigorously as would knowingly spreading tuberculosis or HIV. The names and images of lone wolves and mass murders should not be allowed to reach public notoriety. Report the news, but as in cases of rape, leave out the names.

People fault the police who interviewed the recent murderer at his home before the attack at the request of his mother who was concerned that her son’s deteriorating mental state could lead to self-harm or result in harm to others. This mother’s action should have been effective if systems were in place to respond appropriately. The system failed. It should not have fallen to the police to respond and diagnose this situation in the absence of a crime. They did what they could within the bounds of their authority and knowledge. Would you fault the police if they responded to a man in cardiac arrest and failed to undertake open heart surgery? Would you send a cardiac surgeon into a gun battle with bank robbers?

Consider, instead, the possible outcome if the police had been accompanied by a psychiatrist? Would the psychiatrist have been fooled by the man’s facade?

“How are you feeling?”

“Tell me about your friends.”

“How about your girlfriends?”

“Do you own any guns?”

The answers, body language, questions unanswered, are as revealing to a psychiatrist as a blood test is to a general practitioner. There are civil liberty concerns and potential abuses of authority to protect against, but there are public welfare issues and issues of compassionate treatment of the ill that have to be dealt with as well. All of these same issues are present and have been managed in areas of public health related to communicable illness that threatens individuals and the public at large. Most of those suffering mental illness–and there is no doubt that their illness inflicts intense and prolonged suffering– want to get better. Others will deny that they have any metal illness at all, but psychiatrists are familiar with both types. It is important to appreciate how many similar tragedies unhatched are prevented by mental health professionals at work every day, because their successes do not become news bulletins.

The answer to this horrendous situation must include regarding illnesses of the mind just as directly and vigorously as we do illnesses of the body, and to institute effective ways to recognize and treat those who are ill. No human being is meant to live isolated like a lone wolf. Any time that happens it is a warning sign that must be recognized and acted upon. Psychiatrists cannot cure every one of their patients any more than any doctor can predict who will be cured and who may die from any serious condition, but the difference is that every measure possible is recognized to deal with physical illnesses, while mental illness too often goes ignored. Even all the power and influence of a senator is useless, as the futile efforts of Senator Deeds to obtain mental health assistance for his son hours before he was nearly killed when his son knifed him viciously in the face before committing suicide. The same response by a hospital if applied to an urgent life-risking physical disorder would constitute criminal negligence.

If only the solution were as easy as eliminating access to weapons which is often the direction discussion of these tragedies turns. Weapons cannot be permitted to reach the hands of children or anyone with an unstable mind, but it is obvious that these tragic mass murders happen in states with the strictest gun laws in the country. They occur in countries like China where guns are not available. That debate is a distraction and it overlooks the fact that half of the victims in Santa Barbara were butchered with a knife and he ran down at least one person with his vehicle. Regardless of one’s views on the need for new laws restricting guns, the simple truth is that no one in their right mind could point a gun at another human being, loaded or unloaded, unless their own life or someone else’s life was at stake. Loan wolves will find other ways: knives, cars, nitrate fertilizer, fireworks and pressure cookers. The root problem, the disease itself, must be recognized and treated.

References and Resources

CDC Mental Health Program: http://www.cdc.gov/mentalhealth/about-us.htm

National Institute of Mental Health: http://www.nimh.nih.gov/index.shtml

C. Weber and A. Chang. Experts say violent action by loners is difficult to predict. The Washington Post May 26, 2014 http://www.washingtonpost.com/politics/experts-say-violence-by-loners-is-difficult-to-predict/2014/05/26/fb8e61ea-e522-11e3-afc6-a1dd9407abcf_story.html

Va. senator recalls son’s attack, mental illness. The Washington Times, Jan 27, 2014 http://www.washingtontimes.com/news/2014/jan/27/va-senator-recalls-sons-attack-mental-illness/?page=all

Posted by: R. Douglas Fields | May 26, 2014

Cerebral Storms

LightningI awoke this morning to a ferocious lightning storm. The house shook from thunderous booms. The predawn darkness blanched in blazing white flashes. Lightning is impressive; especially in contrast to the feeble bioelectricity generated by the body’s nerve cells. Or is that just an illusion? Neuroscientist Michael Persinger has done some back-of-the-envelope calculations that may surprise you.

A neural impulse (action potential) is only a tenth of a volt. About the same as a very dead flashlight battery, this voltage is far too feeble to sense. But, that action potential voltage spans across a microscopic distance of a cell membrane (about 10 nm), so scaled up to real world dimensions in which you and I and lightning operate, this neural impulse is equal to 100,000 V/meter! On the microscopic scale inside a cell, that is a lightning bolt. The molecular and cellular components of a cell will experience a neural impulse the way you experience a lightning bolt.

Now consider the minuscule charge carried by a single action potential of only 1.6 X 10^ -19 Coulombs. In terms of energy, this is a vanishingly small 1.9 X 10^ -20 Joules. But now consider that there are 10^10 neurons in your cerebral cortex and that they are happily firing away at an average frequency of about 1 Hz. Do the math and you’ll find that the total energy per second in your gray matter is 10 ^-10 J/s. Now proportion this to the 1330 cc volume of your brain (assuming it is average…maybe a bit bigger than average if you are reading this), and the result is an energy density of 10 ^-7 J/s.m^3.

A typical lightning strike drives a flow of about 10 Coulombs of electrons across a potential difference of 10^8 V, resulting in 10^9 Joules of energy. Impressive. Now if you figure that there are about 70-100 lightning strikes per second world-wide, this results in lightning generating about 10^11 J/s of energy. That is 100 gigawatts of power! But you already knew this:

Dr. Emmett Brown (frantically): 1.21 gigawatts! 1.21 gigawatts! Great Scott!

Marty McFly: What the hell is a gigawatt?

…flash:
Emmett Brown: Marty, I’m sorry, but the only power source capable of generating 1.21 gigawatts of electricity is a bolt of lightning!

…Off to the clock tower and back to the future…

cerebral storm
Now lightning discharges within a narrow shell of atmosphere about 2 km thick, multiply that times the 6,378 km radius of the earth, and this is a volume of 1 X 10^18 m^3. You guessed it. The energy density of all the world’s lightning is 10^-7 J/s>m^3, and that is the same energy density as inside your head.

Ahh, but the current is enormous in a lightning bolt. It can vaporize a tree instantly. That is true. A lightning bolt carries a whopping 100 Amps. But, that electric current is carried through a pretty narrow channel as we can plainly see when the bolt of lightning scores a direct hit the hands of the clock tower. The current in a lightning bolt flows inside a channel of about 1 cm in diameter. Dividing the current in a lightning bolt by the diameter of this channel gives remarkably the same current density as dividing the current generated by an action potential flowing through an axon. So even though the current is much larger in a lightning strike because of its absolute size factor of 10 ^10 larger, the “minuscule” current density driven by an action potential is comparable to a lightning bolt through the cross sectional area of an axon.

Bedazzled by lightning in the predawn hours a cerebral storm of corresponding electrical power blazes away in the world inside your head. When scaled up in proportion from the extreme miniaturization of cellular components in your brain, the neural electrical storm inside your skull is equal in power to all the lightning in the world. The dazzling display of electricity in the howling storm is matched by an even more amazing electrical storm in your brain as your imagination wanders, trying to cook up reasons to stay in bed just a bit longer.

References
Persinger, M.A. (2012) Brain electromagnetic activity and lightning: potentially congruent scale-invariant quantitative properties. Front. Integrative Neuroscience, vol 6 article 19, p. 1-7.

Posted by: R. Douglas Fields | January 2, 2014

Ladies out of Luck: FDA Blocks “Female Viagra”

womanGuys who need it have Viagra; Ladies with the similar needs have nothing now that the FDA has denied approval of a new drug, flibanserin, which would treat sexual dysfunction in women. What’s interesting from a neuroscience perspective is how the drug works. What’s interesting from a social perspective is how difficult it is to address this medical concern in women pharmacologically.

The FDA denied the new drug application by Sprout Pharmaceuticals in October, 2013 asking for more proof that flibanserin treatment works. It’s pretty simple to prove that Viagra works. That drug acts on the vascular system to boost vapid hydraulics in the penis. But it is not so simple to prove a libido lifting drug works for females. Human sexuality is difficult to model in animal experiments. Even in clinical studies it can be difficult to design human experiments that lead to clear conclusions because human sexual behavior is complex, especially so in woman most would agree. In contrast to Viagra, what exactly would a drug target in women whose biological sexual response is a bit more complicated than boosting blood flow? Flibanserin is not a hormone. It does not target the body at all. It targets the brain.

Women with hypoactive sexual desire disorder (HSDD) simply experience no desire for sexual activity, which can undermine wellbeing and interpersonal relationships just as impotence does for men. Flibanserin acts on neurotransmitters that are involved in sexual desire and pleasure, stimulating actions of the neurotransmitters dopamine and norepinephrine and reducing serotonin activity. If you follow the logic behind this pharmaceutical, it is suddenly quite obvious that a person with deficiencies in these neurotransmitter systems could have problems with sexual function. Indeed, sexual desire in people is complex and it can be quite fragile to stresses of many types. Sexual dysfunction is also associated with many mental illnesses and mood disorders. Moods are, after all, the product of specific neurotransmitters acting on circuits in the brain that control emotion. So what’s the recent published experimental evidence say about flibanserin in promoting increased libido in females?

Simon et al, at George Washington University School of Medicine, reported in November, 2013 in the journal Menopause, on flibanserin acting as a serotonin receptor 2A antagonist and serotonin 1A agonist to treat HSDD. The study included 468 premenopausal women receiving the drug and an equal number receiving a placebo for 24 weeks. The results show a statistically significant improvement in number of satisfying sexual events in women treated with the drug; the size of the effect, however, was quite small. There were also adverse side effects reported, including dizziness, sleepiness, nausea, and headache.

A study published this month in the journal Psychopharmacology by Galez et al, from the University of Versailles Saint-Quentin-e Yvelines, France, tracked the action of the drug in the brains of female rats. A gene called c-fos is a well-known marker of neural activity. Simply staining brain tissue in the appropriate way to see if c-fos is turned on in cells allows researchers to determine if a particular neuron is firing actively. The study shows that the drug increased activity in several brain regions, including the nucleus accumbens, arcuate hypothalamic nucleus, locus coeruleus, and other areas known to be active in females during sexual arousal. These brain regions belong to the mesolimbic dopaminergic pathway and hypothalamic structures that integrate sexual cues and influence sexual motivation. The problem is that this result simply shows that the drug acts on the neurotransmitter receptors that it is known to interact with chemically. The behavioral consequences were not studied.

In a review article published in 2012, Fooladi and Davis, at the Monash University, Melbourne, Australia, examined the literature on a wide range of potential drug treatments for female sexual dysfunction, including data on flibanserin available at the time. They found no non-hormonal drugs, including flibanserin, that are clearly beneficial.

They did conclude that systemic testosterone, however “has been demonstrated to be effective for the treatment of HSDD and have a good safety profile.” This is encouraging because there are already testosterone pharmaceuticals approved for treating males. In fact, two million prescriptions for testosterone treatment have been written for women in 2006 and 2007, according to the article, representing approximately 21% of all testosterone prescriptions (that are intended for males). The FDA has not approved testosterone use in women for treating HSSD. “This provokes the question as to who the regulators are most concerned about protecting?” the authors ask. The experts see a contradiction when the compound is approved for men but it raises serious safety issues when used for women, even though women represent 21% of the people who are taking the drug today without adverse health issues. (Testosterone is a naturally occurring hormone in females too.)

According to the CBS news article by Castillo, two large studies failed to show a benefit of testosterone patch or gels for women and the European Medicines Agency withdrew marketing authorization for it in 2012, leaving women with no approved medication that is effective in treating this medical condition.

References
Castillo, M. CBS News December 11, 2013, 2:06 PM http://www.cbsnews.com/news/manufacturers-of-female-viagra-flibanserin-appeal-fda-denial/

Fooladi, E., and Davis, S.R. (2012) An update on the pharmacological management of female sexual dysfunction. Expert Opin Pharmacother. 13:2131-42.

Gelez, H., (2013) Brain neuronal activation induced by filbanserin treatment in female rates. Psychopharmacology, 230:639-52.

Simon, J.A., et al., Efficacy and safety of flibanserin in postmenopausal women with hypoactive sexual desire disorder: results of the SNOWDROP trial. Menopause, Nov 25 e-pub ahead of print.

See also Sprout Pharmaceuticals Appeals FDA Decision On New Drug Application For Flibanserin To Treat Hypoactive Sexual Desire Disorder In Premenopausal Women

http://www.prnewswire.com/news-releases/sprout-pharmaceuticals-appeals-fda-decision-on-new-drug-application-for-flibanserin-to-treat-hypoactive-sexual-desire-disorder-in-premenopausal-women-235380991.html

First published on BrainFacts.org

http://blog.brainfacts.org/2013/12/ladies-out-of-luck-fda-blocks-female-viagra/#.UsV8k_RDun8

Posted by: R. Douglas Fields | December 17, 2013

23andGUVMT– Health and Safety or What? An Antiestablishment Perspective

Is the recent FDA action blocking access to the personal gene analysis services of the company 23andMe really about health and safety? This controversy may instead be more about fear of the future and protecting special interests. What we could be seeing is the usual Luddite paranoia arising at every historic advance in technology, but this time it seems, fear is being exploited by the powerful establishment who may see their dominion at risk. For many, this is fundamentally an issue of civil rights.

The argument being made by the FDA is that people who receive the results are not equipped to interpret the medical implications of the data. By law, analysis of health data is something that only a medical doctor can do, and the FDA enforces that system. Secondly, anyone dispensing medical advice without a doctor’s license must be stopped. On that point, there is no disagreement, but is this what 23andMe is doing?

23andMe provides customers not only their personal gene analysis; they also distill and organize the data according to the known functions of the relevant gene variants published in the scientific literature. What does the scientific literature say about a particular cholesterol gene, for example, and how do combinations of genes having similar biological effects alter the mathematical odds of acquiring a certain biological result? These biological results range broadly from tracing a person’s ancestry back 5 generations, to predicting your ability to taste certain flavors, to indicating how efficiently certain drugs–caffeine or Plavix–for example, will be broken down in your body, to isolating how much of your genome retains traces of DNA inherited from Neanderthals. This is fascinating stuff and very useful. If you are not interested in any of these things, you will not want to use the services of 23andMe, but if you are interested, why should the government prevent you from having it?

Analysis of genetic data is an enormous undertaking, and this is very well done at 23andMe from what I have seen–even providing hotlinks directly to the scientific papers on the gene in question. The company distills the data so that the individual can take the results and any concerns they may have to their personal physicians to use in managing their health. Simply giving a person a list of hundreds or thousands of genes would be useless for most people. The data analysis that 23andMe provides their customers is vital. If that’s practicing medicine, arrest my librarian. (Note to FDA: Don’t mess with librarians. They are smart, organized, and know where things are.)

The second argument the FDA makes is that ordinary citizens do not have the ability to interpret the results and a person might act inappropriately on the basis of the information. Someone might panic if informed that they carry a gene variation with a propensity for a deadly disease, for example.

But this is nothing new. The same argument could be made with respect to a high cholesterol reading or an HIV test. Having a genetic risk does not mean that you will get the disease, just as having high cholesterol does not diagnose that you will have a heart attack or stroke. People understand this and they manage to cope with having access to their cholesterol readings or HIV test result by acting in any way they see fit to do.

The technology being used is well established and reliable–I use it in my own laboratory research and have done so for over a decade. Of course there will be errors–false positives and false negatives in any genetic screen. Name a test (medical or otherwise) that does not have these. Most of us can handle the befuddlement of the engine warning light flashing on in our car. Often it is a false signal, but that’s fine. It is important for the driver to have the information to decide what to do. An essential distinction between genomic analysis and the engine light on your dashboard is that if the warning light stresses you, there is little you can do to avoid it, but 23andMe customers requested the information. They understand that with thousands of genes being assayed, the result of any genomic analysis is not a diagnosis; it is a screen.

In effect, the argument the FDA makes is that people are too ignorant or irresponsible to have access to information about their own body. This is the heart of the issue, and it is a troubling argument. The underlying question that people should be asking is why should the FDA be taking this patronizing view?

As citizens of a free society all of us must be concerned anytime the government acts to withhold information from its citizens. When government censorship concerns information about one’s own body, the abridgment of freedom is even more alarming, because the information is personal and vital to an individual’s right to pursue life and happiness:

We hold these truths to be self-evident, that all men are created equal, that they are endowed by their Creator with certain unalienable Rights, that among these are Life, Liberty and the pursuit of Happiness. –That to secure these rights, Governments are instituted among Men, delivering their just powers from the consent of the governed.–That whenever any Form of Government becomes destructive of these ends, it is the Right of the People to alter or to abolish it.

Those are revolutionary remarks of a bunch of radicals. Today we are much more enlightened. We understand that the government knows what is best for us. The role of government is to protect us from our own bad judgments.

“No, you may not have a large soda.”

The revolutionary genetic pioneers paying 23andMe for genetic screening refuse to acquiesce to this well-intentioned government censorship. They cannot seem to understand that government’s role is to know what is best for us, and to regulate what personal information about ourselves we should have. In their distorted zeal to embrace the future, these people see the FDA action as fundamentally at odds with the founding principles of our society. As these wackos would have it, the role of a free government is to serve the people and secure personal liberty. These fanatics eschew the rightful relationship of dominion and subservience citizens should have to government and the power establishment. In their radical view, the FDA action is government censorship of information that concerns personal information that an individual desires to have, is willing to pay their money to obtain, and to use it for their own personal benefit. We simply can’t have that–right?

People are naturally wary of anything new and so they more likely to swallow any argument maintaining the status quo. 23andMe breaks the corporate/government establishment in health care by giving individuals direct access to information about their own body. The issues about security of the genetic data, misuse of it, and whether or not a person can utilize it appropriately in their own health, are not new. The same arguments apply to any of the current types of medical laboratory analyses and records. By that logic, a person should not get an HIV test because, my God! What if that information were to become public?

Scientific progress has already undermined the strangle hold on direct access to personal health data, and the FDA and medical industry are having a difficult time keeping pace with the advances. The FDA’s action in approving home pregnancy tests or glucose monitors, for example, invalidates their argument about people being able to understand and utilize personal genome analysis responsibly.

Those arguing against 23andMe are using fear mongering tactics. They suggest hidden and subversive motives, and damn the company by association with the likes of Google. “They are mining my personal data!” Google is scary. Try searching the internet for “baldness” or “PMS” and see what pop-ups sprout at the edge of your screen. You understand how this works–right? Data mining is what fuels the internet, which has propelled a revolution that has changed in the world, and it has only gotten started. Are you worried about the Safeway grocer analyzing your shopping list to get the low-down-and-dirty on you? Some folks are, but they are not going to be the ones using 23andMe anyway. Change and the unknown–whether radiation, genetic engineering, or almost anything new–is what gives some people goose bumps.

That mad man, Henry Ford, proposes to replace the normal means of transportation with a “horseless carriage.” What few people realize is that the hazardous contraption carries up to 20 gallons of a highly explosive mixture of hexane and octane on board! Even breathing the smoke out of the engine’s smokestack will kill you. That’s a fact. Do you want something like that in your corral! This thing is dangerous, and who needs it anyway? Is there any place you cannot go on your horse?

Yes, looking back we can see the quaint phobias of those who came before us. We are smarter today, though.

I hear tell one of them ‘lectric vehicles ran over a hunk of metal and burnt up! I hope they put them Tesla guys out of bidness!

But this time, it appears to many, that the fear mongering is being exploited by the powerful establishment. The 23andMe debate has exposed the extent to which personal access to one’s data about their own health is blocked by government regulation. If you wanted to know your cholesterol level, for example, you cannot obtain it directly. You would have to call and make an appointment with a doctor. Wait until he could see you. Tell him in person you want the test and pay the doctor to write you a prescription authorizing you to go to a laboratory to have the analysis done. You need to make an appointment at the laboratory and go there to have the test performed. The lab sends the results–not back to you–they send it to your doctor. In a few weeks you can go back for your follow-up appointment and the doctor will read you the cholesterol concentration from the lab report. That’s how the health industry works in this country today. The very expensive and inefficient process fuels an enormous industry of insurance, real estate, doctor office staff, and the pharmaceutical industry. The results of tests go to the doctor, not to you, and that’s the way “they” like it. Even though you may simply want to know the HDL and LDL cholesterol readings in your own blood, you cannot have the information without paying a doctor as the middleman. This is the issue.

Hey! It’s my cholesterol. I made it. I only what to know how much I made. My genes are no different. Who has the right to tell me I can’t look at my genes? There’s no problem with a fortune teller measuring your lifeline. Walk into any drugstore and there are tons of health supplements and vitamins to treat everything from dementia to impotence–almost none of it backed by clinical studies showing that they work. But we cannot have access to the latest in scientific technology for our own personal use. Smoking, gun control, immunization, however you feel about it, do have consequences for society at large. There is a necessary balance between personal choice and public good, but looking at your own genes is personal. What justifies the government extending its reach into a persons genes?

At one time anyone in this country could purchase cocaine and opiates legally. But then at one time it was illegal to purchase alcohol. The pendulum swings, and it is pretty clear which way it is swooshing these days.

Bill Gates, who is devoting his philanthropic activities to improving health in the developing world, has a broader view of health care from his global perspective. “By far, most people on the planet are born, live their entire lives and die without ever seeing a doctor,” he said last week in a speech at the NIH. This perspective shows how extreme healthcare has become as a business in the United States. If you want to see your own body, you need the government’s permission. Then if access is granted, you will be permitted to see it only through the eyes of a doctor who will describe it to you. The great irony is that people in the underdeveloped world lack access to the most modern medical science because of poverty, whereas people in the developed world lack access to it because of politics.

Imagine! What if a person could know what genes they have that could affect their health. It’s not science fiction. It is political fiction.

This has been modified from an earlier publication on Huffington Post:

http://www.huffingtonpost.com/dr-douglas-fields/genetic-testing_b_4421313.html

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