Brain Powered

A wave of recent advances shows how the mind affects health in ways we never imagined.

By Dan Ferber, PhD
From Reader's Digest
March 2007


Mice, Maps, and Major Milestones

It's been a very good year for the brain -- that three-pound wrinkled lump of gray matter that directs our movements, thoughts and memories, our loves, hopes and dreams. It's the organ that makes us who we are. It can also make us lose who we are, through degenerative diseases like Alzheimer's, which affects almost half of those who live past 85. And now we know it has far more to do with our overall health than we ever imagined.
A recent wave of breakthrough technologies has yielded unprecedented insight into how our brains work, and a better grasp of how they go wrong. That, in turn, has led to new targeted treatments designed to fix malfunctions. Science is also revealing the surprising power of the mind, when used correctly, to heal the body. Here are some of the mind-boggling findings.

Mapping the Brain
September 2006 marked a major milestone for our noggins, with completion of the Allen Brain Atlas, the first gene map of the brain. It all started in 2002, when billionaire philanthropist Paul Allen, cofounder of Microsoft, gathered some of the world's top scientists and charged them with finding an innovative new way to accelerate our understanding of the brain. From that he committed $100 million and established the Allen Institute for Brain Science in Seattle.
Using custom-built robotics and software, 60 full-time researchers tested 250,000 preserved slices of mouse brain, which resembles the human one enough that most discoveries would also hold true for us. They generated a volume of raw data that revealed where in the brain each of the mouse's 21,000 genes was activated. (Different types of brain cells activate different sets of genes, producing a unique roster of proteins that enables each cell to do its job -- storing memory, directing movement or some other task.)

The map revealed that about 80 percent of the body's genes are turned on in the brain -- more than anyone had expected. That means if pharma companies are not careful, drugs targeted to other organs could have unwanted side effects in the brain. The map also uncovered evidence that could help reveal what goes wrong in complicated brain disorders such as schizophrenia and autism.

The result is a 3-D virtual mouse brain atlas (brain-map.org) that does for neuroscientists what a survey map pinpointing gold deposits does for miners: It lets them hightail it to where the action is and start digging, says David Anderson, PhD, a professor of biology at California Institute of Technology and a project advisor.



Memory Genes
Scientists are already striking gold thanks to the Allen Brain Atlas. Dietrich Stephan, PhD, who directs neurogenomics research at the Translational Genomics Research Institute (TGen) in Phoenix, has used it to learn more about a gene called Kibra, which affects our short-term memory. The Atlas revealed that the gene was activated in the hippocampus, a small sea-horse-shaped brain structure that helps store memories. TGen plans to market drugs to reduce age-related memory loss, including the common short-term sort that causes senior moments and lost car keys.

Progress on Alzheimer's
Today's Alzheimer's drugs improve memory, buying many patients several years of mental clarity, but brain cells still die and patients decline. New experimental drugs, in contrast, are designed to get to the root of the problem, blocking the suspected bad actor, a molecule called beta amyloid, from forming clumps and killing brain cells.

Anna Hickerson, 71, of rural Indiahoma, Oklahoma, already considers one of those drugs a success. Three years ago, she'd lose track of orders in the flower shop she ran with her husband, James Hickerson, 75. She'd forget the day of the week and got lost so often, she quit driving. Ralph Richter, MD, a clinical professor of neurology and psychiatry at the University of Oklahoma College of Medicine in Tulsa, diagnosed her with early-stage Alzheimer's.

In November 2004, Anna enrolled in a Phase III clinical trial for Alzhemed, an experimental drug made by Neurochem, a small drug company in Montreal. The drug seems to have stopped her decline. Today, after more than two years on the medication, she arranges flowers for church services, drives 23 miles on her own to shop in a nearby town, and rarely gets lost. "I'm more clear and I feel better about myself," Anna says. "It's been a real blessing," says her husband.

Researchers reported encouraging Phase II trial results on Alzhemed in a neurological journal last year. Patients, on average, maintained their score on a 30-point standard test of mental function. (Patients on today's medications typically lose three points a year.) Alzhemed also reduced the level of beta amyloid (the bad stuff that kills brain cells) in the cerebrospinal fluid, suggesting that there's less of the bad stuff inside the brain as well. The results of the North American Phase III trial are expected this spring and may provide solid evidence that the drug works. Similar trials of no less than eight different drugs from other companies will finish within two to five years and also look promising.



Gene Deliveries With Promise
Targeted gene therapies could help patients with brain diseases that drugs alone cannot heal. Such therapies deliver healthy genes to parts of the body where faulty ones are wreaking havoc. In the past, gene therapies turned out to be more dangerous than scientists had expected, and the death of an Arizona teenager in a 1999 clinical trial set the field back years. But a new method of gene delivery to the brain, via a harmless virus called adeno-associated virus (AAV), has proved safe in early human trials.
One AAV therapy may ease advanced Parkinson's disease by repairing an overactive brain circuit that causes typical symptoms of slowness and rigidity. That circuit acts like a brick on a car brake, interfering with the patient's ability to move. Brain surgeons currently remove that brick by implanting a pacemaker-like device that overrides this circuit. But the treatment, called deep brain stimulation, requires three months of weekly visits to a specialized neurosurgery facility, which is tough when you live hundreds of miles away, says neurosurgeon Michael Kaplitt, MD, of Weill Cornell Medical College.

Dr. Kaplitt's AAV therapy removes the brick from the brake by delivering a neurochemical called GABA into brain cells. In a safety trial that ended in 2006, the gene therapy proved safe. At the highest levels, it helped patients as much as deep brain stimulation. If this proves effective in a larger trial, someday an advanced Parkinson's patient could have brain surgery, get a gene implanted in precisely the right spot and go home a couple of days later. "Our hope is to bring this type of therapy to a much larger audience of patients in need," Dr. Kaplitt says.

Since his trial, other AAV gene therapies have been used in six early trials: three for Parkinson's, two for lethal pediatric brain disorders and one for Alzheimer's. If they continue to prove safe and show positive results, we'll be able to treat some of the most devastating brain disorders.



Bridging the Blood-Brain Barrier
Scientists have begun to overcome one of the biggest obstacles to treating brain disease: getting drugs into the brain. Ninety-eight percent of candidate drug compounds do not pass from the bloodstream into the brain, even though they move easily into other organs, says William Pardridge, MD, a professor of medicine at University of California, Los Angeles. As a result, good drugs for brain disorders are few and far between.
Would-be drugs fail because the walls of the brain's blood vessels act like border-crossing guards after a code-red terror alert: They allow only molecules that have essential business in the brain to cross. To get his drugs past the hypervigilant guards, Dr. Pardridge turned to smuggling. He uses genetic engineering to link potentially helpful brain drugs to a specific kind of antibody that is welcomed and escorted into the brain.

In a 2006 study, one such hybrid drug reduced brain damage by two-thirds in rats when given two hours after a simulated stroke. The drug contains a normal brain protein that stimulates cells to thrive but is normally too scarce to prevent stroke-induced brain damage. Such brain-cell-saving drugs are desperately needed to protect stroke patients from brain damage, but over the past decade, none have passed muster in clinical trials. ArmaGen Technologies, which Dr. Pardridge founded to commercialize the technology, plans a human safety trial on the new stroke drug in late 2007.

The smuggling strategy could work with any brain drug, Dr. Pardridge says, and ArmaGen is developing drugs for Alzheimer's, Parkinson's and a class of hereditary brain diseases that cause birth defects, mental retardation and other severe problems.



How Your Mind Heals You
In one of brain biology's most amazing advances, scientists have found that our brain may actually help our immune system fight disease. It took 20 years of careful experiments for Kevin Tracey, MD, to see it that way. It also took a very special patient -- an 11-month-old girl named Janice. "She changed my life," says Dr. Tracey, a neurosurgeon, immunologist and director of the Feinstein Institute of Medical Research in Manhasset, New York.
In the spring of 1985, Dr. Tracey was a surgeon in training at New York Hospital, treating patients for such things as gunshot wounds, head injuries and infection, when Janice was admitted. She had been crawling on the kitchen floor of her grandmother's Brooklyn apartment when her grandmother, who was cooking pasta, tripped over her and spilled a ten-quart pot of boiling water onto the baby girl. Dr. Tracey cared for the girl, who had suffered second- and third-degree burns over 75 percent of her body. A week after she was admitted, Janice developed severe sepsis, a condition in which the immune system massively overreacts to a bacterial infection, indiscriminately training its cannons on the body's own tissues.

For the next two and half weeks, Janice lay clinging to life in her hospital bed, as Dr. Tracey and his colleagues tried one heroic measure after another to revive her. She recovered enough to celebrate her first birthday in the burn unit with her parents, her grandmother and the medical staff, and was expected to be discharged soon. Then, the next day, her heart stopped suddenly and she died. "She's the only patient I ever had nightmares about," Dr. Tracey says. "She shouldn't have died."

No one knew then what caused severe sepsis, so, inspired by Janice, Dr. Tracey set out to learn. Two decades later, his work is paying off. In a series of studies since 2000, he's shown that stimulation of the vagus nerve -- a major nerve that runs from our brainstem to our belly and regulates our heartbeat, breathing and intestines--stops severe sepsis. It does so by using neurochemicals to signal immune cells, which prevents them from releasing alarm molecules that spur inflammation and cause damage. In a 2006 study, he discovered a brain circuit that could stimulate the vagus nerve to switch off inflammation.

Taken together, the studies demonstrated a hard-wired connection between the brain and immune system that Dr. Tracey calls the "inflammatory reflex." Normally, when inflammation spreads, the brain tells the immune system to turn it down. In patients like Janice with severe sepsis, that reflex fails.

Drugs that activate the reflex could one day reduce chronic low-grade inflammation--the kind that causes Crohn's disease and rheumatoid arthritis, and contributes to heart disease. Meditation might help, too, says Dr. Tracey. People can learn to slow their heartbeat by modifying vagus nerve activity, which suggests they might be able to control their own brains to calm inflammation and fight disease. "It's the most exciting thing I've ever worked on," he says.

Calming the mind and body might even slow the spread of some cancers. The stress hormone norepinephrine can spur lab-grown cancer cells to release two compounds that help them move through the body and then metastasize, according to a study in the November issue of Cancer Research by virologist Ronald Glaser, PhD, of Ohio State University Medical Center. A third compound that's released helps supply growing tumors with nutrients. So reducing stress may prove a cancer fighter.



Buff Up Your Brain
Studies like Glaser's and Dr. Tracey's have "given credibility to mind-body approaches, which had been rejected and ignored by the scientific and medical communities," says Esther Sternberg, MD, director of the Integrative Neural Immune Program at the National Institute of Mental Health. Now scientists and doctors have begun taking the next step, harnessing the immense powers of the human brain to help people heal themselves.
For example, using special fMRI scanners and software that allowed patients to see their own brain activity, scientists at Stanford University and Omneuron, a biotech company, trained participants to reduce chronic pain by just visualizing it and learning to control it. Some were able to decrease it by more than 40 percent, says pain expert Sean Mackey, MD, one of the study leaders.

Dr. Mackey foresees a day when doctors might use such imaging to train us to ease depression, battle addiction or overcome phobias. And years from now, he says, we may head to a real-time brain-imaging center the way we go to the fitness center today, and buff up parts of our brain that improve performance, memory and even intelligence. Now, that would be a real no-brainer.

www.brain-map.org

http://www.armagen.com/

http://www.armagen.com/about-bbb.php#drugs
for full page info - go to the link above

Why is the blood-brain barrier problem so central to CNS drug development?

If practical solutions to the BBB problem were available, the global CNS drug market would be the fastest growing sector of the pharmaceutical industry, because the following drug development pathways would be enabled:

development of protein-based large molecule drugs, including peptides, recombinant proteins or enzymes, and monoclonal antibodies
development of non-viral gene medicines for the brain
expansion of the small molecule drug base to include water soluble drugs

Facts about the BBB


There are 100 billion capillaries in the human brain, and the endothelial walls of these capillaries form the BBB. The density of the capillary network in the brain is shown in the adjacent figure.

The surface area of human BBB is about 20 square meters.
There are about 400 miles of capillaries in the human brain.
The total volume of all the endothelial cells in the human brain is about 5 mL.
Every neuron is virtually perfused by its own blood vessel; therefore, the delivery of drugs or genes through the BBB (the 'trans-vascular' route to brain) places the drug or gene at the 'doorstep' of every neuron in the brain.
The BBB is very tight and excludes the brain uptake of all large molecule drugs and >98% of small molecule drugs. A misconception about BBB drug transport is that all small molecules readily cross the BBB. In fact, most small molecules do not cross the BBB. In order to cross the BBB in pharmacologically significant amounts, the drug must have the following characteristics:

(a) lipid soluble

(b) have a molecular weight < 400 Daltons

(c) not be a substrate for a BBB active efflux transporter.

Example of restricted drug transport at the BBB


The nearby figure is a body scan of a mouse following the intravenous injection of a small molecule (molecular weight only about 100 Daltons). The scan shows the small molecule drug readily crosses the porous capillary barrier in all organs, but does not enter the brain or spinal cord--the drug does not cross the blood-brain barrier or the blood-spinal cord barrier. This drug cannot be further developed as a neurotherapeutic, unless the BBB problem is solved. At this point the brain drug developer has only 2 options: either terminate the drug development program, or attempt to use one of the traditional approaches for dealing with the BBB problem.


What are the traditional approaches for solving the BBB problem?
If a CNS drug developer has a lead candidate that does not cross the BBB, the traditional approaches for solving the BBB problem are:

Craniotomy-based drug delivery. The drug or gene is implanted into either the brain directly via an intra-cerebral implant, or into the cerebrospinal fluid (CSF) via an intra-cerebroventricular (ICV) infusion. The problem with this approach, apart from the expense of the neurosurgical procedure, is that the drug is not delivered to the brain. Owing to the limitations of drug diffusion (diffusion decreases with the square of the distance to be traveled), the drug either resides at the depot site, in the case of intra-cerebral implants, or binds to the ependymal epithelium, in the case of ICV infusion. In addition, the invasive placement of foreign particles in the brain can lead to neuropathological changes
BBB disruption. The endothelial cells may be transiently disrupted by the intra-carotid arterial infusion of either hyper-osmolar solutions or vasoactive drugs. The problem with this approach, apart from the expense of the interventional radiologist who accesses the carotid artery, is that the BBB stays open for only a short time. In adddition, BBB disruption allows plasma proteins to enter the brain, and these proteins are toxic to the brain. BBB disruption leads to chronic neuropathologic changes in the brain.
Lipidation. A water soluble drug that does not cross the BBB may be attached to a lipid soluble drug carrier. However, the 'lipidation' of the drug increases the uptake in all organs, which causes a proportionate decrease in the plasma area under the concentration curve (AUC). The decreased AUC offsets the increase BBB permeation leading to little change in the brain uptake of the drug. That is, increasing the lipid solubility of the drug, with either lipid carriers or with medicinal chemistry, has an adverse effect on the plasma pharmacokinetics of the drug. For this reason, there are few, if any, examples in clinical practise today whereby lipidation strategies of a water soluble drug provided practical solutions to the BBB problem.
Cationic import peptides. A water soluble drug or peptide may be 'cationized', i.e, take on positive or cationic charge, by attachment of the drug to a cationic import peptide. Such cationic peptides enter the endothelium via absorptive-mediated endocytosis based on electrostatic interactions with anionic sites on the BBB. The limitation of this approach is similar to lipidization of small molecules. The attachment of the cationic peptide to the drug results in a marked decrease in the plasma AUC leading to little change in brain uptake. The rapid removal from blood necessitates the administration of very large doses of the cationic peptide carrier, and this can lead to toxicity associated with cationic peptides.

Why most CNS drug development programs end in termination
Most CNS drug development programs end in termination, because

(a) the lead drug candidate does not cross the BBB
(b) the existing solutions to solving the BBB problem are difficult to implement
(c) no BBB drug targeting program is available to the CNS drug developer.
A new model for brain drug development

ArmaGen Technologies' model to brain drug development is to develop effective BBB drug or gene targeting technologies first, and then start specific CNS drug or gene development programs. In each case, the specific CNS drug or gene is formulated to enable transport across the BBB via one of the endogenous catalyzed transport systems that normally function at the brain endothelial wall. The brain is richly perfused by a complex capillary network (see above Figure). There are about 100 billion capillaries in the human brain, and every neuron is virtually perfused by its own blood vessel.

The endogenous BBB transport systems are localized to the endothelial plasma membranes that form the BBB in vivo. There is a luminal endothelial membrane (on the blood side of the capillary), and an abluminal endothelial membrane (on the brain side of the capillary). The luminal and abluminal membranes are separated by about 300 nm of endothelial cytoplasm; therefore, transport through the BBB is a process of transport through 2 membranes in series.

Within the luminal and abluminal membranes are the endogenous BBB transporters, and these are classified into 3 general groups of transporters:

Carrier-mediated transport (CMT)
Active efflux transport (AET)
Receptor-mediated transport (RMT)

The 3 types of endogenous transporters are shown in the adjacent Figure. The CMT systems generally mediate the transport of small molecules in the blood to brain direction. Examples of the CMT systems include the GLUT1 glucose transporter, the LAT1 large neutral amino acid transporter, and many other CMT systems. The AET systems generally mediate the active efflux of small molecules in the brain to blood direction. The model AET system at the BBB is P-glycoprotein; however, there are many other BBB AET systems other than p-glycoprotein. The RMT systems mediate the transport in either the blood to brain or the brain to blood direction of endogenous peptides and proteins. Examples of the BBB RMT systems include the insulin receptor .

BBB drug and gene targeting technology platforms are built from knowledge about the endogenous transport systems within the BBB. The endogenous transporters can be used ccessed to deliver drugs and genes to the brain via a route of administration no more invasive than an intravenous or subcutaneous administration. See Targeting Protein Drugs, Targeting Non-Viral Genes, and Targeting Small Molecules.

Protein drug delivery technology

ArmaGen Technologies' molecular Trojan horses deliver protein neurotherapeutics to the brain

POTENTIAL OF PROTEIN-BASED THERAPEUTICS IN THE TREATMENT OF BRAIN DISEASES

Many disorders of the brain have proven refractory to small molecule therapeutics, and could be treated with protein therapeutics. Indeed, many protein lead drug candidates have been identified for brain diseases, but these proteins do not enter CNS drug development, because the proteins do not cross the blood-brain barrier (BBB). Instead, attempts are made to isolate small molecule peptidomimetics. However, it is very difficult to produce small molecule peptidomimetics. Moreover, in the rare case that a small molecule agonist is identified, this lead drug candidate most likely will not cross the BBB. Those small molecules that have a molecular weight > 400 Daltons, or form even a few hydrogen bonds, will not cross the BBB in pharmacologically significant amounts. (See Targeting Small Molecules). An alternative strategy is to re-formulate the protein drug candidate to enable transport across the BBB in vivo. This is done by genetically engineering a novel fusion protein, wherein the protein drug is fused to ArmaGen Technologies' molecular Trojan horse (MTH). The MTH part of the fusion protein triggers transport across the BBB via an endogenous receptor-mediated transport system. The following Table is a partial list of protein drug candidates for brain disease:

http://www.armagen.com/protein-drugs.php
go to page for entirety

AGT-190

A neuroprotection drug for stroke or Parkinson's disease

AGT-190 is a genetically engineered fusion protein that is comprised of a human neurotrophin that causes neuroprotection in the brain, and is indicated acutely for the treatment of stroke, and chronically for the treatment of Parkinson's disease (PD). The neurotrophin forming AGT-190 is a large molecule, which does not cross the blood-brain barrier (BBB), and cannot enter the brain following peripheral administration. The neurotrophin is fused to another protein that undergoes receptor-mediated transport across the human BBB; the second protein acts as a molecular Trojan horse to ferry the therapeutic neurotrophin across the BBB into brain from blood. The AGT-190 fusion protein is a bi-functional molecule: it both attaches to a receptor on the human BBB, to cause transport into the brain from blood, and it attaches to a specific neurotrophin receptor on brain cells to protect the cells from cellular damage. AGT-190 is the first neurotrophin treatment specifically engineered to cross the BBB for the long-term treatment of PD.

November 8, 2007. Intravenous RNAi of the brain with targeted siRNA.RNA interference (RNAi) enables the knock down of pathologic genes with short interfering RNA (siRNA) duplexes. The limiting factor in the translation of RNAi therapeutics from cultured cell systems to the in vivo state is the siRNA delivery system. Anionic siRNA molecules are generally formulated as a polyplex with a cationic molecule. ArmaGen Technologies has developed a new siRNA delivery system that does not use cationic formulations. In the December, 2007, issue of Pharmaceutical Research, Armagen Technologies achieves intravenous RNAi in intra-cranial brain cancer in vivo with the intravenous injection of targeted siRNA. The breakthrough combines RNAi technology with 2 delivery technologies: receptor-specific molecular Trojan horses and avidin-biotin technology. The mono-biotinylated siRNA is bound with very high affinity to a conjugate of streptavidin and a receptor-specific monoclonal antibody (MAb) that both crosses the blood-brain barrier (BBB) and the tumor cell membrane. Avidin, and streptavidin, bind biotinylated ligands with a dissociation half time of 3 months, and these complexes are highly stable in vivo. ArmaGen technologies has genetically engineered an avidin-MAb fusion protein, AGT-3 (see Products), for the in vivo delivery of siRNA in humans.

It’s no secret that researchers in both the commercial pharma and academic neuroscience communities are intent on designing new medicines to treat the growing populations of patients afflicted with central nervous system disorders such as Alzheimer’s disease, Parkinson’s disease, stroke, and brain tumors. And it’s also no secret that the biggest obstacle to the successful delivery of these specialized drug therapies is the blood brain barrier – a unique network of tightly packed endothelial cells that protects the brain from the many chemicals flowing within the blood.

What’s surprising, however, is that the blood brain barrier continues to be significantly disregarded as an essential area of focus within both Big Pharma and the academic neuroscience establishment. And the unfortunate byproduct of this neglect is a substantial over funding of neuroscience research projects that produce few commercially viable therapies that can effectively address the growing threat of many age-related neurological conditions.

In this program, we speak with Dr. William Pardridge, Professor of Medicine at the UCLA Brain Research Institute and founder of ArmaGen Technologies. Join us for an eye-opening discussion of the science and politics of blood brain barrier drug delivery, and learn more about some of the fascinating new areas of research and development in this critical, but very often overlooked, area of neuroscience.

Direct download: NeuroScene_Podcast_Dr._William_Pardridge_082507.mp 3
Category: Cognition -- posted at: 10:36 PM

http://www.neuroscene.com/index.php?post_id=255049

http://www.dana.org/news/danapressbo...l.aspx?id=3272

go to link to read entire subjects: the book is called - BRAIN WARS...

On the Strategic Advantages of Enhancing the Brain and Nervous System

In a sense, all warfare ultimately happens between our ears. If opponents believe they have been defeated, then that becomes the reality, hence the military’s investment in psychological operations, such as propaganda leaflets and disinformation, despite their uncertain payoffs. But if targeted interventions are made possible by the greatly enhanced knowledge of the brain and nervous system now being generated at a feverish pace in our top neuroscience labs, complemented by ingenious new engineering and pharmacologic products, the battle of the brain will have truly begun.

The powers that can claim the advantage and establish a ‘neurotechnology gap’ between themselves and their adversaries will establish both tactical and strategic advantages that can render them dominant in the twenty-first century.



On the Conflict Between Objective Scientific Research, Government Aims, and Highly Classified Conditions

The relationship between science and the national security state in the context of a war on terror is still unfolding. Unlike the post-World War II era, when scientists who had eagerly joined the war effort saw military-related funding as a continuation of their previous employment, today significant distance lies between much of the scientific establishment and defense organizations. First, science has many other funding sources, including venture capital, that were not important players in the 1950s. Second, cultural differences between scientists and military officials bring with them a degree of mutual skepticism, if not outright suspicion, that was not the case fifty years ago, before Vietnam and Watergate. Third, unlike the experience of physics with the atomic and hydrogen bomb projects, the life sciences have not had much experience with operating under highly classified conditions. Many important researchers and their institutions chafe under security constraints, including not only sequestering their data but also tightening rules on the handling of pathogens in their labs and limiting visas for graduate students from abroad.



Robots as Soldiers: Science Fiction or the Reality of the Future?

Here’s a science fiction scenario: an army of robots capable of movement nearly as precise as that of a human soldier, each controlled by an individual hundreds or even thousands of miles away. These automata could undertake actions that would be foolhardy for human beings but worth the tactical risk for machines; because they are controlled by people, they would have the benefit of creativity that might limit even the most advanced android. But the old-fashioned remote control scenario would have the operator pushing buttons or moving levers while seeing on a monitor what the robot is seeing, a method that would be far too clumsy for the instantaneous reactions often required in combat. What is wanted is a technology that would allow the robot to respond as soon as the distant operator does. . . . Ultimately, decades from now, human abilities could be augmented so that combat soldiers could have vastly more powerful and faster robotic arms and legs, and pilots could control vehicles through intentional thought alone. Warfighters, intelligence offers, medics, and rescuers could wirelessly manage legions of robots through direct communication between the human brains and on-board artificial brains.



On Creating the Perfect Soldier: The 21st-century Warfighter

“The human being is the oldest instrument of warfare and also its weakest link. Although astonishing and terrifying “improvements” have been made in the devices of conflict over the millennia, soldiers are still basically the same. They must eat, sleep, detect danger, discern friend from foe, heal when wounded, and so forth. The first state (or nonstate actor) able to build better soldiers using medical enhancement technologies will have taken an enormous leap in the arms race. The concept of “an army of one” and the recent shift from soldier to “warfighter” in the military lexicon . . . are tied into the goal of building a more self-sufficient individual warrior. However better soldiers are built – and there’s good reason to believe that the warfighter of the late twenty-first century will be enhanced – the fighter’s brain will have been the object of great interest...

Should we build better soldiers through ‘artificial’ enhancements? Is there even a valid distinction to be drawn between artificial and ‘natural’ enhancements such as exercise and discipline? Aren’t we just trying to gain whatever advantages we can as nations have always tried to do, or are these techniques cheating nature? Can we manage the consequences, or are the risks for the individual and for our society too great?



Forgive and Forget?: On Increasing the Brain’s Capacity to Remember

The introduction of a new memory storage system and bypassing our evolutionarily developed hippocampus raise the question whether our usual ability to slough off unneeded memories will be threatened, resulting in a cacophony of useless data that could drive one to distraction. Forgetting is often annoying but mostly adaptive, even a great relief. In the film Eternal Sunshine of the Spotless Mind, ex-lovers undergo a high-tech brain-erasing procedure to forget about the pain of their breakup. In a literally touching moment in Star Trek, Mr. Spock engages in an (unconsented) Vulcan mind-meld with Captain Kirk to help him forget a tragic love affair. Less romantically, undercover agents would benefit from the ability to lose their memories upon capture. Neuropsychologists have already found that deliberate memory loss among victims of parental abuse is both a demonstrable phenomenon (they are not “lying” when they say they don’t recall) and a very effective defense mechanism. As the philosopher Bernard Williams has put it, “Forgetting is the most beneficial process we possess.”



On Disarming Opponents Through Disruption of the Human Brain

Proponents of “nonlethal” weapons (NLWs) claim that they will obviate the need to kill or maim. These weapons are actively being sought by all branches of the U.S. military and come in a dazzling variety of forms: calmatives or “incapacitants” – chemicals that put people to sleep; acoustic and light-pulsing devices that disrupt cognitive and neural processes; odors so disgusting they sicken; sudden colored fog that creates panic; optical equipment that causes temporary blindness; and mechanisms that stimulate nerve endings as though they are fire, among dozens of others. A striking fact about this list is that all are related to the human brain and nervous system.... Growing concerns about terrorism have fed interest in NLWs. Contemporary arms and stockpiles have typically been designed for fighting between nation-states. The use of conventional nonnuclear and nuclear weapons in the places terrorists like to operate would result in high levels of noncombatant casualties that may be politically as well as morally unacceptable

But please not so fast ..at your rate of presentation, I (and may be some of us) will not have a chance in a million to catch up

hello dear imark,

Just sit back and slowly read what you wish at your own pace,
you are very intelligent!