h+ Media http://hplusmagazine.com Elevating the Human Condition Tue, 31 Mar 2015 01:22:56 +0000 en-US hourly 1 No, Biohackers Did Not Just Discover Eyedrops That Give You Night Vision — And using them might damage your eyesight http://hplusmagazine.com/2015/03/30/no-biohackers-did-not-just-discover-eyedrops-that-give-you-night-vision-and-using-them-might-damage-your-eyesight/ http://hplusmagazine.com/2015/03/30/no-biohackers-did-not-just-discover-eyedrops-that-give-you-night-vision-and-using-them-might-damage-your-eyesight/#comments Mon, 30 Mar 2015 22:31:49 +0000 http://hplusmagazine.com/?p=27342 Currently, there is better scientific evidence that smoking weed improves your night vision than that Ce6 night vision eyedrops do.

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You may have seen the breathless headlines, “See in the dark (for a little bit) with night vision eyedrops”, “California biohackers create night vision eye drops”, “A Team of Biohackers Has Figured Out How to Inject Your Eyeballs With Night Vision”, etc.

Amazing right? Maybe not.

ilyasFirst, importantly, this is a report of a human test of a previously suggested concept and scientific result from a 2006 experiment on mice. That result is due to Dr. Ilyas Washington and his team as documented in a 2007 paper “Chlorophyll derivatives as visual pigments for super vision in the red”

So first, let’s credit the actual inventor Dr. Ilyas Washington. This is not a new discovery and to the extent that it is, it is due to Dr. Washington and his group at Columbia University. Dr. Washington runs the Lab Washington where he and his team work to design and develop approaches modify the course of serious diseases.

He was born in NYC and is an Assistant Professor at Columbia Medical Center in the Department of Ophthalmology. He received a BA in Chemistry from Bard College and received a PhD in Computational Chemistry under Ken Houk from University of California Los Angeles. He is also a co-founder of Alkeus pharmaceuticals a specialty ophthalmology pharmaceutical company using ideas developed from technology originating in his lab.

Dr. Washington is the discoverer of the potential to use Ce6 to gain super night vision but he isn’t a “biohacker” and is he isn’t from California either. In the 2007 paper on the subject he concludes, “This mechanism is shown to enhance vision in a mouse model and perhaps could also do so in humans.”


What Exactly Did the Biohackers Do?

According to the site scienceforthemasses.org, “200mg of Ce6 was mixed with 400 units (4ml) of insulin (70/30 Lantus). To this was added 5.38ml of sterile saline solution (0.9% sodium chloride). The mixture was sonicated briefly (30 seconds) to allow for proper dispersal of the powder into saturated solution and then 625μl of DMSO (Amresco) was added. The solution was sealed with parafilm and sonicated for 150 seconds. The resulting liquid was thin and black in color. Solution was kept in glass aliqouts wrapped in foil at 20°C.”

This is somewhat different application than that described in Washington et al, and the specific formulation is derived from a subsequent 2012 patent. Importantly Washington et al report observed levels of Ce6 in the eye due to dietary consumption of plants roughly 1/10 this amount (2 mg/ml).

Two hours after administering the Ce6 mixture in eye drops, “the subject and 4 controls were taken to a darkened area and subjected to testing. Three forms of subjective testing were performed. These consisted of symbol recognition by distance, symbol recognition on varying background colors at a static distance, and the ability to identify moving subjects in a varied background at varied distances.”

However, apparently, results are really only reported and documented in any detail for the symbol recognition tasks and confusingly in aggregate.

“Symbol recognition consisted of placing a collection of objects with markings on them (numbers, letters, shapes). Subjects were then asked to identify the markings, each viewing the objects from the same location at a distance of 10 meters. The markings were not made prior to the moment of testing. For subject recognition, individuals went moved in a small grove of trees. They were allowed to chose their own location independently. Distances ranged from 25 to 50 meters from observation point”….The Ce6 subject consistently recognized symbols that did not seem to be visible to the controls. The Ce6 subject identified the distant figures 100% of the time, with the controls showing a 33% identification rate.”


Bad Experimental Design

Unfortunately due to the weak design of this experiment we really can not conclude anything conclusively about the true effect of Ce6 on night vision. The results reported are purely anecdotal, although Washington has already shown the idea should work, in the end we still do not know.

SftM reports, “After 2 hours of adjustment, the subject and 4 controls were taken to a darkened area and subjected to testing.” In other words, night vision performance of the subject exposed to the Ce6 was compared to the night vision performance of other individuals. The problem is that these individuals might have different levels of night vision performance for various reasons having nothing to do with the Ce6. For example, the subject was protected from light sources after application of the Ce6 mixture with dark glasses while control subjects were not.

“Black sunglasses were then worn during all but testing, to ensure increased low light conditions and reduce the potential for bright light exposure.”

To perform the experiment correctly, both subjects and control should wear the dark glasses and be isolated from light using the same exact protocol. This eliminates the light isolation protocol as a source of observed differences in night vision performance. We also can not know if the subject had superior night vision performance to the control group before application of the Ce6 since his initial vision performance was never recorded.

This unfortunately undermines the primary result of the experiment. What we really want to know is how the application of a drug enhances the performance of an individual person. The effects of substances can vary and some subjects may respond differently or have adverse side effects. Individual improvements in performance can easily be determined by baselining prior to application of the Ce6. The failure to do baselining is a notable and a pretty unfortunate failure in the StfM experimental design.

Accepting the anecdotal nature of this result, it seems like it worked.  But it isn’t really correct to state that this technique provides “low light amplification in the human eye” as the StfM paper mentions in it’s rather political and unscientific concluding section. This isn’t going to give you night vision like you see in the movies.

What chlorin e6 does is instead to mediate the transformation of light into an electrical signal. The presence of the Ce6 changes the primary event in vision to activation of Ce6, an event which simply does not occur if the Ce6 is not present. The amount of light in the environment remains unchanged and is not “amplified” or increased by this method. These small mistakes all add up when you evaluate the entire experiment as a whole.


Eyedrop Formula is Based on Patent by Discredited Alternative Medicine Practitioner

“In 2012 a patent was filed based in some part on the work of Washington et al. The patent claims that a mixture can be made which, when applied to the eye, will absorb to the retina and act to increase vision in low light. The mixture put forth in the patent is a simple combination of Ce6 and insulin in saline. It is mentioned in the same, that dimethlysulfoxide (DMSO) can be used in place of the insulin. ”

The SftM research references US Patent 20120157377 issued to Totada R. Shantha (aka Totada R. Shanthaveerappa and Dr. Totada R. Shanthawho also holds patents on self heating eyeglasses, efficient lightbulbs, and a wok. He also lost his license to practice medicine in Georgia during a case where Mr. Shantha was shown to have given patients insecticide and weed killer.

Totada R. Shantha and his medical assistant Dan U. Bartoli were indicted on 87 counts of health care fraud and distributing unapproved and misbranded drugs. Shantha was also charged with money laundering. The charges resulted from a clinic Shantha operated in Stockbridge, Georgia under the names “Integrated Medical Specialists” and “Integrated Chemotherapy Specialists.”

One of Shantha’s Web sites offered various pseudoscience methods “for the treatment of cancers and other curable and incurable diseases” and stated “We treat all kinds of chronic, incurable diseases with success!” Shantha’s Georgia medical license was suspended a few days after he was indicted. In 2007,  Shantha pled guilty to one count of health care fraud, agreed to pay a total of $650,000 in asset forfeiture plus restitution, and was ordered to serve five years’ probation followed by three years of supervised release.

Unfortunately the SftM report doesn’t mention any of this information and simply reports the procedure documented in the patent. However the U.S. Patent Office does not evaluate medical devices, drugs or anything else in patent applications for safety.  Therapeutic utility is sufficient under patent law and existence of an issued patent should not be confused with the requirements of the FDA with regard to safety or efficacy of drugs marketed in the United States.

However there are very good reasons to be concerned here, as Mr. Shantha has repeatedly demonstrated a lack of concern for patient safety, well being and health.


Employed Mixture Amplifies Toxicity

The SftM report states at the outset a disclaimer, “The authors of this paper are writing this review for research and informative purposes only. Increased light amplification may have adverse effects on the cellular structure of the eye if improperly used and the some of the materials used in this mixture should not be used on humans or animals.”

That’s good advice because Chlorin e6 releases Reactive Oxygen Species (ROS) that causes cell death and repeated use could damage your eyesight. In fact, Ce6 is used to kill tumor cells in a technique known as photodynamic therapy where a patient is injected with the Ce6 and tumor cells are exposed to a laser light with the appropriate wavelength. This is documented in the SftM report, “Chlorin e6 (Ce6) has been used for many years as a therapy agent in cancer treatment”

But does it damage healthy cells in a normal human eye? In a 2001 analysis , “Retreatment effect of NPe6 photodynamic therapy on the normal primate macula”, macaca fuscata monkeys were given three PDT treatments and then killed. Their eyes were examined for damage and the report concludes that “Repeated PDT of healthy nonhuman primate fundi using a hydrophilic photosensitizer (NPe6) shows preservation of the neurosensory retina components and architecture” with “damage confined to the retinal pigment epithelium and choriocapillaris.”

While Ce6 seemingly doesn’t damage the primary neural structure of the eye, it does have an effect. In monkeys, damage to both the retinal pigment epithelium and choriocapillaris was observed after three treatments using Ce6. While the retinal epithelium was thought to have no role in visual sensory performance, but recent research demonstrates that the epithelium provides multiple functions that are needed for normal photoreceptor function and therefore normal vision. The choriocapillaris consists of the capillaries that provide the retina with oxygen and damage to these structures is associated with various degenerative eye diseases including age related macular degeneration.


The Shantha patent presents a method employing 20 mg of Chlorin e6 in 40 units of Insulin or alternatively the use of dimethlysulfoxide (DMSO). However, in the reported SftM experiment the biohackers used both Insulin and DMSO together, “We propose a combination of the two could lead to the most noted effects. For testing purposes, the mixture from the patent (Ce6, Saline, Insulin) was used with the addition of DMSO for increased permeability.”

The combination probably does increase the effectiveness of the Ce6 but therefore also enhances the toxicity to normal cells.  According to a paper by Chine et all, “Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer”, the addition of DMSO to Ce6 reduces discrimination of tumor cells from application of Ce6 alone. That means that using the Ce6 DMSO combination increases the risk of this technique damaging healthy retinal cells.

This only makes sense since it is the photodynamic effect of the Ce6 that produces the damaging ROS as well the electrical signal that results in the subject seeing something. The better it works, the more damage to the healthy cells in the eye at least potentially.



Can Really You Take Something to Give You Super Night Vision?

The Ce6 mixture employed probably does give some level of enhanced night vision as suggested by Washington in 2007 and reported by Science for the Masses last week.

But it isn’t really viable for this use due to the potential for toxicity and long term damage to normal vision over time.

Other substances have been considered for improving night vision, notably dietary supplements such as bilberry extract and beta carotene. And some Chlorin e6 was demonstrated to be present in the eye after dietary consumption by Washington et al. The effectiveness of these dietary approaches is largely demonstrated, but seemingly fairly limited in scope.

One other substance that has been shown to improve night vision is cannabis. Yes smoking weed apparently improves night vision.

Russo et al heard reports of improved night vision among Jamaican fishermen after ingestion of a tincture of herbal cannabis, so they decided to test this theory with Moroccan fishermen and mountain dwellers who reported an identical improvement after smoking “kif”. They employed a double blind experimental design with placebo and they measured night vision performance using a portable Ganzfeld device, the LKC Technologies Scotopic Sensitivity Tester-1 (SST-1). They conclude the effect is confirmed, “dose-dependent and cannabinoid-mediated at the retinal level.”

Currently, there is better scientific evidence that smoking weed improves your night vision than that Ce6 eyedrops do.

Beyond marijuana, various companies are trying to develop drugs for improving night vision especially due to age related degeneration. Phentolamine mesylate eye drops that improve night vision currently in human trials. Even more extreme, one might consider using CRISPR to make genetic alterations to give human eyes the qualities that maker gecko eyes highly effective night vision cameras.


Conclusion: Do Not Put Ce6 in Your Eyes

Summary, you probably shouldn’t be putting Chlorin e6 in your eyes to get “super” night vision.

If you want to see in the dark, there are better ways than this. The risk is modestly high and unknown especially with repeat use.

While the recent results from California do suggest that the Ce6 eyedrop technique works, they fail to conclusively demonstrate the effectiveness of Ce6. Given the differences in application from other uses of Ce6, the risks remain entirely unknown. It seems from studies in primates, the risks, while not immediately damaging to vision, are not insignificant. It is possible that users could suffer significant degradation of vision over time from repeated use of this substance.

Even if Ce6 works it has to compared with other available alternatives. How much more effective is Ce6 than cannabis for example? What about phentolamine mesylate? Other alternatives?

Here, these experimenters have already defined a solution but failed to identify the problem they are trying to solve. Is this a drug for age related night vision loss? Is the intended use a covert agent infiltrating a secure military base? Is this for hunting?

From conversations online it seems that even raising this issue makes one a “hater” but defining the problem you are trying to solve is a key element of design thinking and it is the first thing you should do when designing an intervention like this. Transhumanism is a strategy for design. Eye drops that give you night vision but make you go blind over time are an example of bad design.

Consider that there might be a way to get a similar or superior result without risking rapid degradation of your normal vision. Even if this process does work and is entirely risk free, it doesn’t come close to the sort of enhancement that is possible with modern GEN IV electronic night vision and thermal imaging equipment. And these devices generally have no or low risk to your normal visual function.


1. A Review on Night Enhancement Eyedrops Using Chlorin e6 Licina, G; Tibbetts, J, retrived from http://scienceforthemasses.org/wp-content/uploads/2015/03/AReviewonNightEnhancementEyedropsUsingChlorine6.pdf

2. http://www.google.com/patents/US20120157377

3. http://www.casewatch.org/doj/shantha/indictment.shtml

4. Retina. 2001;21(5):493-8., Retreatment effect of NPe6 photodynamic therapy on the normal primate macula. Nakashizuka T1, Mori K, Hayashi N, Anzail K, Kanail K, Yoneya S, Moshfeghi DM, Peyman GA.

5. The Retinal Pigment Epithelium in Visual Function, Olaf Strauss, 

6. Eur J Pharm Biopharm. 2008 Aug;69(3):1083-93. doi: 10.1016/j.ejpb.2008.02.013. Epub 2008 Mar 10,Improved formulation of photosensitizer chlorin e6 polyvinylpyrrolidone for fluorescence diagnostic imaging and photodynamic therapy of human cancer., Chin WW1, Heng PW, Thong PS, Bhuvaneswari R, Hirt W, Kuenzel S, Soo KC, Olivo M.

7. J Ethnopharmacol. 2004 Jul;93(1):99-104., Cannabis improves night vision: a case study of dark adaptometry and scotopic sensitivity in kif smokers of the Rif mountains of northern Morocco., Russo EB1, Merzouki A, Mesa JM, Frey KA, Bach PJ.


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Fasting Might Make Our Cells More Resilient to Stress http://hplusmagazine.com/2015/03/30/fasting-might-make-our-cells-more-resilient-to-stress/ http://hplusmagazine.com/2015/03/30/fasting-might-make-our-cells-more-resilient-to-stress/#comments Mon, 30 Mar 2015 18:48:30 +0000 http://hplusmagazine.com/?p=27349 Intermittent fasting (also called alternate day fasting) has become a popular diet. In most versions of intermittent fasting, people fast or eat very little a few days each week and then eat normal amounts during the remaining days.

The post Fasting Might Make Our Cells More Resilient to Stress appeared first on h+ Media.

Intermittent fasting (also called alternate day fasting) has become a popular diet. In most versions of intermittent fasting, people fast or eat very little a few days each week and then eat normal amounts during the remaining days.

Fasting is something that human beings have practiced throughout history, often out of circumstance rather than choice. Our hunter-gatherer ancestors were probably expert fasters, indulging in feasts in times of plenty, and then facing long periods of scarcity in between. With this in mind, it makes sense that our bodies’ cells could perform well under the harsh conditions of feast and famine.

As a group of medical and research students, we wanted to know if fasting causes our cells to become more resilient to damage in the absence of weight loss. And do these benefits depend on the temporary stress that fasting causes in our cells?


Intermittent fasting may have anti-ageing benefits

Scientists have been looking at the possible health benefits of calorie restriction for years.

A prominent theory suggests these health benefits are related to the drop in blood sugar that results from fasting, which pushes our cells to work harder to utilize other forms of energy.

Rhesus monkeys eating only 70% of their normal caloric intake have been shown to live much longer and are much healthier at older ages. These anti-aging benefits have also been seen in animals that are put on an intermittent fasting diet, alternating between days of normal eating and days where calories are restricted. More recently, scientists have discovered some similar effects in humans.

What isn’t clear, though, is why intermittent fasting seems to have a benefit in the fight against aging. This question is complicated by the fact that in all studies performed in people, fasting led to weight loss. The health benefits of weight loss might be overshadowing the other benefits obtained from fasting alone.

Free radicals damage cells, but fasting may help

One way that our cells can become damaged is when they encounter oxidative stress. And preventing or repairing cell damage from oxidative stress is helpful against ageing. This stress happens when there is higher-than-normal production of free radicals, unstable molecules that carry a loosely bound extra electron.

When the free radical encounters another molecule, this extra electron is passed along in a rapid chain reaction from molecule to molecule. When it reaches the end of the chain, it can break apart connections between atoms within important components of the cell, like the cellular membrane, essential proteins or even DNA. Anti-oxidants work by absorbing the unstable electrons before they can do any harm.

Although fasting seems to help our cells combat damage from this process, it isn’t clear exactly how that happens.

Free radicals can be generated by poorly functioning mitochondria (the powerhouses of the cell). The switch between eating normally and fasting causes cells to temporarily experience lower-than-usual levels of glucose (blood sugar), and they are forced to begin using other sources of less readily available energy, like fatty acids. This can cause the cells to turn on survival processes to remove the unhealthy mitochondria and replace them with healthy ones over time, thus reducing the production of free radicals in the long-term.

It might also be true that fasting itself results in a small increase in free radical production early on during fasting.

The cells may respond by increasing their levels of natural anti-oxidants to fight against future free radicals. And although free radicals are commonly seen as harmful because of their ability to damage our cells, they might be important short-term signals for our body in this case, triggering cells to cope better with more severe stresses that may come in the future.


Do fasting and feasting fight aging?

To understand how fasting might make cells stronger, we recruited 24 people and asked them to practice an intermittent fasting diet for two three-week periods. During the first fasting period, participants ate a specially calibrated diet and during the second three week period, they ate that diet and took oral supplements of Vitamin C and Vitamin E, which are both anti-oxidants.

Because we just wanted to focus on how intermittent fasting affected cells, and not weight loss, participants ate 175% of their normal daily calorie intake on feasting days, and 25% of their normal daily intake on fasting days to prevent weight loss. We provided and carefully tracked the volunteer’s food. They ate typical American fare – things like pasta, chicken, sandwiches and desserts like ice cream.

We took samples of blood before they started and just after they ended the diet so we could compare levels of byproducts of oxidative stress and markers of strong cell functioning.

During the first three week period we attempted to see if fasting would increase oxidative stress (free radicals) in each person’s cells and to see if this stress actually led to stronger, more resilient cells.

Then we wanted to see if taking antioxidants in the second fasting period would block the free radicals caused by the fasting, preventing the cells from becoming more resilient. In other words, we wanted to know if Vitamin C and E would shelter the cells to the point that they wouldn’t be ready to stand up for themselves later on.

How did intermittent fasting affect people’s bodies?

We found that in response to fasting every other day, the cells made more copies of a gene called SIRT3, which is part of a pathway that works to prevent free radical production and improve cellular repair processes.

We also found a significant decrease in levels of circulating insulin, a sign that the participants bodies were more responsive to this hormone. This is important because when we become less sensitive to insulin, we are at risk for diabetes.

One somewhat surprising finding is that when participants took daily oral supplements of Vitamin C and E, the benefits from fasting disappeared. It seems that because the cells were relatively sheltered from experiencing any oxidative stress that may have been caused by fasting every other day, they didn’t respond by increasing their natural defenses and improving their sensitivity to insulin and other stress signals.

This suggests that low levels of environmental stress from things like fasting are actually good for our bodies, and that antioxidant supplements, while potentially good at certain times, might actually prevent our normal healthy cellular responses in other situations.

Although our study was relatively small and only had people fasting every other day for a short time period, we were able to pick up on a few important health benefits of fasting that happened even when people weren’t losing any weight at all. We look forward to other studies of intermittent fasting that might show more pronounced, longer-term benefits in larger groups of people.


Douglas Bennion

MD-PhD student and NIH T32 Pre-doctoral Fellow at University of Florida

Martin Wegman

MD-PhD student and NIH TL1 Pre Doctoral Fellow at University of Florida

Michael Guo

MD-Phd student at University of Florida

This article originally appeared here, republished under creative commons license.

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CRISPR – Technology and Controversy http://hplusmagazine.com/2015/03/30/crispr-technology-and-controversy/ http://hplusmagazine.com/2015/03/30/crispr-technology-and-controversy/#comments Mon, 30 Mar 2015 18:11:02 +0000 http://hplusmagazine.com/?p=27340 A group of leading biologists earlier this month called for a halt to the use of a powerful new gene editing technique on humans. Known by the acronym CRISPR, the method allows precise editing of genes for targeted traits, which can be passed down to future generations.

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Image: Jennifer Doudna/University of California Berkeley

A group of leading biologists earlier this month called for a halt to the use of a powerful new gene editing technique on humans. Known by the acronym CRISPR, the method allows precise editing of genes for targeted traits, which can be passed down to future generations.

With this explainer, we’ll look at where this technique came from, its potential and some of the issues it raises.

Surgical precision

CRISPR stands for clustered regularly interspaced short palindromic repeats, which is the name for a natural defense system that bacteria use to fend off harmful infections.

Bacteria are infected by other microorganisms, called bacteriophages, or phages. The intricate details of the mechanism were elucidated around 2010 by two research groups led by Dr Doudna of the University of California Berkeley and Dr Charpentier of Umeå University in Sweden.

The CRISPR system recognizes specific patterns of DNA from the foreign invaders and decapacitates them by cutting the invader’s DNA into pieces. The way that the bacteria target specific DNA and cleave it gave scientists a hint of its potential in other applications.

In 2013, two research groups, one lead by Dr Zhang of Massachusetts of Institute of Technology and the other by Dr Church of Harvard University, successfully modified this basic mechanism and turned it into a powerful tool that can now cut human genomic DNA at any desired location.

The ability to cut DNA or genes at specific locations is the basic requirement to modify the genome structure. Changes can be made in the DNA around the cleavage site which alter the biological features of the resulting cells or organisms. It is the equivalent of a surgical laser knife, which allows a surgeon to cut out precisely defective body parts and replace them with new or repaired ones.

Tool for gene discovery

Scientists have long sought after this sort of genome editing tools for living cells. Two other technologies, called zinc-finger nucleases and TALEN (transcription activator-like effector nuclease) are available to achieve the same result. However, the CRISPR technology is much easier to generate and manipulate. This means that most biological research laboratories can carry out the CRISPR experiments.

As a result, CRISPR technology has been quickly adopted by scientists all over the world and put it into various tests. It has been demonstrated to be effective in genome editing of most experimental organisms, including cells derived from insects, plants, fish, mice, monkeys and humans.

Such broad successes in a short period of time imply we’ve arrived at a new genome editing era, promising fast-paced development in biomedical research that will bring about new therapeutic treatments for various human diseases.

Jennifer Doudna from the University of California Berkeley, who was one a co-inventor of the CRISPR, recently called for caution in using the gene-editing technology on human cells. US Department of Energy

The CRISPR technology offers a novel tool for scientists to address some of the most fundamental questions that were difficult, if not impossible, to address before.

For instance, the whole human genomic DNA sequence had been deciphered many years ago, but the majority of information embedded on the DNA fragments are largely unknown. Now, the CRISPR technology is enabling scientists to study those gene functions. By eliminating or replacing specific DNA fragments and observing the consequences in the resulting cells, we can now link particular DNA fragments to their biological functions.

Recently, cells and even whole animals with desired genome alterations have successfully been generated using the CRISPR technology. This has proven highly valuable in various biomedical research studies, such as understanding the cause and effect relationship between specific DNA changes and human diseases. Studying DNA in this way also sheds light on the mechanisms underlying how diseases develop and provides insights for developing new drugs that eliminate specific disease symptoms.

With such profound implications in medical sciences, many biotech and pharmaceutical companies have now licensed the CRISPR technology to develop commercial products.

For example, a biotech company, Editas Medicine, was founded in 2013 with the specific goal of creating treatments for hereditary human diseases employing the CRISPR technology.

However, products derived from the use of CRISPR technology are yet to hit the market with FDA approval.

Call for ethical guidelines

With the CRISPR technology, scientists can now alter the genome composition of whole organisms, including humans, through manipulating reproductive cells and fertilized eggs or embryos. Those particular genetic traits are then passed down through generations. This brings hope to cure genetic defects that cause various hereditary human diseases, such as cystic fibrosis, haemophilia, sickle-cell anemia, Down syndrome and so on.

Unlike the current approaches of gene therapy which temporarily fix defective cells or organs through the introduction of corrected or functional genes, the CRISPR technology promises to correct the defect in the reproductive cells, producing progenies that are free of the defective gene. In other words, it can eliminate the root causes of hereditary human diseases.

In theory, then, hereditary features that people consider advantageous, such as higher intelligence, better body appearance and longevity, can be introduced into an individual’s genome through CRISPR mediated reproductive cell modifications as well.

However, scientists do not yet fully understand all the possible side effects of editing human genomes. It is also the case, that there is no clear law to regulate such attempts.

That’s why groups of prominent scientists in the field have recently initiated calls for ethical guidelines for doing such modifications of reproductive cells. The fear being that uncontrolled practice might bring about unforeseen disastrous outcomes in long run.

The guidelines call for a strong discouragement of any attempts at genome modification of reproductive cells for clinical application in humans, until the social, environmental, and ethical implications of such operations are broadly discussed among scientific and governmental organizations.

There is no doubt that the exciting and revolutionary CRISPR technology, under the guidance of carefully drafted and broadly accepted rules, will serve well for the well-being of humankind.


Dr. Shouguang Jin is Professor of Molecular Genetics and Microbiology at University of Florida This article originally appeared here, republished under creative commons license.

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Patenting the Singularity http://hplusmagazine.com/2015/03/27/patenting-the-singularity/ http://hplusmagazine.com/2015/03/27/patenting-the-singularity/#comments Fri, 27 Mar 2015 18:17:52 +0000 http://hplusmagazine.com/?p=27336 What if the Industrial Revolution never ended? What if Da Vinci was not merely a creative genius but had many teachers due to the influx of Greek scholars after the fall of the Byzantium Empire? What if the future is just a stepwise evolution from the nearest-neighbor in systematic composition while directed by correspondence, one recombination after another, pushing along what has already happened while shaped by the pull of the potential?

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“A mathematician, like a painter or a poet, is a maker of patterns. If his patterns are more permanent than theirs, it is because they are made with ideas.”G.H. Hardy

What if the Industrial Revolution never ended? What if Da Vinci was not merely a creative genius but had many teachers due to the influx of Greek scholars after the fall of the Byzantium Empire? What if the future is just a stepwise evolution from the nearest-neighbor in systematic composition while directed by correspondence, one recombination after another, pushing along what has already happened while shaped by the pull of the potential? What if that means that the nearby future is highly predictable and we are living in an era witnessing the emergence of ways of making which continue to shorten the path between idea and actualization?

After several millennia, from the first brick to reusing the same glyphs to simplify writing, to water wheels and lenses, assembly lines, robotic arms and general purpose computing machines, we’re about to enter a phase in our evolution where we will have collectives of machines which can reproduce just about everything, like a CD player can reproduce all sorts of music, an LCD screen can show anything from drawings to movies, and a printer can reproduce any book in the world, written in any language at any time in history. The concept of ‘printing’ holds within itself a maximal potentiality for manufacturing processes. The idea of a printer is interesting as, in theory at least, one can print out the whole range of documented human thought using a printer. Likewise, a nano-circuit printer can spit out a design from any mobile phone company irrespective of the manufacturer of the printer itself. Similar to how computer software works, or how moveable types made the Gutenberg printing press so flexible, a printer will allow for a local maximum of interchangeability, while increased competition will ensure the commoditization of its many parts.

Nowadays we have tools making tools, some even capable of reproducing themselves. Several technical domains are forecasted to advance towards the level of an ‘information science’ during the following two decades. This is a stage where the technological application and technical means reach a ‘general purpose’ state, and the end-result will be determined by a sort of software, a set of instructions on how this ‘general purpose’ tool is to behave, such as lighting up a number of pixels on a screen in a variety of colours so that this text appears on this particular location. The currently identified domains are bio-technology, nano-technology, robotics, information and communication technology and the cognitive sciences. Not only are these different areas evolving in an accelerated pace as information, technology, “feeds back on itself”, but it is also highly exchangeable which is causing a high degree of cross-fertilization amongst these domains, further accelerating its evolution. E.g. Artificial Intelligence is a bio-info-cogno combination, and if we’d mix this with programmable matter it can join nano-robo to the mix.

This is an adequate stage to introduce an intriguing idea concerning “novelty density”, the technological singularity. If we consider the gradual spread and development of ideas since recorded history we are nearing a time where ideas combine and recombine at such a high speed that their application will not have a definitive form anymore but exist in a state of continuous renewal. This is for example very obvious in the case of personalization, where clothes can be made for an exact fit, a medical treatment is composed specific for the person’s condition and habits or a headset is etched and embedded into someone’s favorite glasses. None of these end-products will be the same, at least not intentionally.

When tracing back its origins science and technology used to be two very distinct disciplines. It is even so that the type of persons involved are quite distinct, with engineers tending to be the pragmatic hands-on type of person, and scientist a bit more absorbed in figuring out a tool, machine or procedure. As the term already indicated, an engineer tends to work more with his/her hands while a scientist works more with his/her head. Different tools, different results. Once in a while in history these disciplines come together, combine and fasten the pace of evolution, such as mixing geometry with construction that lead to a jump in ways of building and machine making, using mathematical formula not only as a descriptive framework but in many occasions also as a prescriptive framework. Within the context of information technology the latter is a programming language and in essence you can regard chemical notation as a programming language, or quantum field theory, or optics, or thermodynamics, or mechanics, or musical notation. You get something with the expressive power of a language, with a functional grammar and syntax, and a sort of alphabet.

During the singularity, the combinatorial explosion of both intra-domain and cross-domain advances becomes so fast that we cannot give it a meaningful measure any more. Ideas, procedures, methods, programs, can jump from one language to another, but if they are in bordering fields they can provide new functionality which in turn make the previously impossible possible. For example carbon nanotubes can already be fabricated with a length of one meter, eventhough the individual tubes are so thin they are invisible to the human eye. Once this fabrication process has been improved to the state that it is economically viable, mixing this with weaving techniques will allow for rope, cables, duct tape, wall paper, concrete bricks, rubber or asphalt.

It is hard to imagine what it means to have so many materials with the strength of diamond, and what the impact will be of a washing machine or a pair of worker jeans that doesn’t break anymore or glasses that don’t scratch. Surely it will mean the end of the ‘throw away’ culture of mass produced goods that are designed to break. ‘Planned obsolescence’ as it was introduced in the late forties will need to give way to other market forces, like fashion trends. Besides articles that are simply rare or inimitable, what does it mean for other forms of artificial exclusivity, most importantly the protection of intellectual property via copyright and patents? What will the impact be when the chemical signature of the most valuable rare chemical elements on the periodic table can be simulated with a combination of cheap alternatives? What happens when there are so many discoveries that duplicate patents are becoming the norm? How can the language used in a patent ensure its uniqueness? And even if it is unique enough, can simple variations result in the same outcome without being covered by the patent? To what extend will similarities amongst different patents be considered equivalent in favor of the original patent? And is that fair?

Some companies have set up their patents in such a way that a discovery of a possible new area of applications will result in the patent being automatically deconstructed to its elementary building blocks and their join points after which a computer system will start generating variations on the core patent. This can be twenty variations, two hundred or two thousand. This way such a company will try to patent a possible industry. Also, it makes it unclear for their competition what has actually been discovered, so that they can reverse-engineering the same kind of solution. But patents are also meant as a show of muscle, a signpost that this company might be willing to defend their patent in a court of law, but more importantly that they are eager to strike a commercial deal with other companies concerning reusing their patent or even the products described and thereby grow their business. In particular the software industry, it is not really worthwhile to defend patents in court, unless you have an illusionary exclusive company named after a well-known fruit and are eager to bully new entries off of your perceived turf by threatening them with expensive court cases that will bankrupt any start up.

That may sound reasonable when a company has spent years figuring out how something actually works, such as with medicinal treatment, and they are rewarded with this imposed exclusivity with a patent, but there are many bio-tech companies too that have simply patented or copyrighted the gene sequence of a common disease or its healthy form and charge an arbitrary large sum of money for sharing that information. Mapping the human genome has been a collective effort that took quite some years, but with every increase in knowledge the technologies improved and it has essentially become an information science. DNA sequencer machines are simply fed the information of the gene sequence and an exact copy of a disease or the cells of an organ can be reproduced. Even in the commercially oriented US patent system it says that a patent refers to “the right granted to anyone who invents any new, useful, and non-obvious process, machine, article of manufacture, or composition of matter”.

Maybe thirty years ago a gene sequence was non-obvious, but with current technology it is primarily a matter of number crunching an enormous database of research results and trying to find correlations that indicate a causal relation. Likewise, with general purpose robotics, the advances in nano-science, meta-materials and programmable matter, can we still say that descriptive patents are non-obvious? Especially as information technology is reaching a stage where inventions can be automatically deconstructed the same way as patents are and new inventions can be grown using evolutionary algorithms which simulate the act of invention. Computing systems are already used to grow mathematical or chemical formulas, and by 2020 such automated discovery engines will be powerful enough to spit out potential leads on a daily basis.

apple_head_track_patent_largeIf the patent system is becoming increasingly inadequate, what else is there? Well, companies can be secretive about their R&D by simply not sharing it, or sharing only the end-results in a non-obvious way by scrambling, encrypting, obfuscating, cloaking or any other technique that hides the actual invention. Additionally they can opt to protect their intellectual property by treating it as a trade secret, making sure that the vital information remains confidential via non-competition and non-disclosure, but even better is to simply have some “secret formula” that is only known to a handful of people.

Again, referring to the above mentioned company named after a well-known fruit, such secrecy can be applied all throughout the company, to internal projects, to release schedules and marketing campaigns, and any another kind of information about the products so that one can tightly control the impression that the product range has. Added to some previous laws adopted during the Bush era, with the new copyright laws it has become possible to control online media by addressing unwanted news coverage as copyright infringement. As has become the norm, providers are all too aware of the costs of giving this the attention it deserves and they simply remove such articles whenever complaints start spilling over. Be that as it may, such an environment and company culture is often not that welcoming or challenging for top-talent and as a result their R&D will steadily degenerate towards a second-rate copy shop, which may not be that bad for business and considering the advent of automated invention a current head start can provide enough momentum, traction and path dependency to last up to 2020 for sure, maybe even 2025.

Still, full frontal secrecy is only one sort of business model. Cooperation is another. Now, what if it is possible to take the patent system and the trade secret system and mix them? Extrapolating patents towards the nearby future, its description will need to become as specific enough to ensure uniqueness and to meet that requirement the difference between a patented invention and the actual implementation is greatly reduced. Most efficiently it would describe, in the appropriate “programming language” how the invention is realized. On the other hand trade secret can be ensured by an information exchange infrastructure of digital certificates so that information can be securely shared. This infrastructure can be set up in ways that honors such secrecy by avoid any readable display or avoid temporary storage, so that a business partner can use the ‘secret sauce’ on a pay-per-use manner. Again, we can draw upon and extend current systems of electronic data interchange.

There is a definite shift going on, from owning the actual production process and sharing the end result, to owning the rights and sharing the production process, to owning the “secret formula” and sharing the invention itself. What if someone comes up with a universal design exchange language, a sort of MIDI which simply describes the input or output of a machine, but doesn’t tell it how to do it. Enveloping these with a machine-to-machine digital certificate infrastructure, a system can be constructed for when the factory hall turns into a general purpose 3D-printing service station run by self-assembling software robots.

Patents are a legal affair dealt with in a complete outdated modality, relying on procedures and an ineffective, impotent and overly expensive system that is unsuitable to deal with the demands of our future. If it is such a vital aspect of the free market, there are better ways, by automating the patent system and providing an infrastructure that allows sharing its temporary copies. That way the return on a patent is based on actual consumption instead of perceived value, which can lie very much apart. Possibly it has not been automated yet as it is an industry in its own right, but that will soon be over when series of novelty wave reshape the legal landscape. As programming languages go, law itself seems ripe for an overhaul.


Paul Peters is futurist and designer, working through both the tangible and the phantasmal, ranging from common beliefs and common sense, to how people feel, think, motivate and decide, to designing enterprise-wide solutions He has 17 years working background in ICT, involved with some 80 projects of which some 60 with integration technologies. Geographic coverage of some twenty countries, mostly in Europe but including the USA, Turkey and Egypt.

Paul’s main expertise concerns providing strategic and operational consulting services in the areas of multi-layered integration and collaboration, the enabling enterprise architecture frameworks and the technologies involved.

Since late 2009 Paul’s activities have been shifting towards both advisory services as well as early-stage entrepreneurship. Adding to roughly ten years of researching interdisciplinary approaches to evolutionary applications, in recent years I have spent much time self-training in the areas of quantitative analysis, machine learning, robotics, and also Chinese Medicine, cognitive sciences, organizational psychology and a random pick from physics, complexity and theoretical biology. Paul’s aim is to gradually shift towards “resellable formats”, where the valuable concepts are “invented on demand”. The aim for his entrepreneurial work is simply to change the world.

See http://www.fluxology.net/


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Get Tomorrow’s Anti-Aging Therapy — Available Today Outside the U.S. http://hplusmagazine.com/2015/03/26/get-tomorrows-anti-aging-therapy-available-today-outside-the-u-s/ http://hplusmagazine.com/2015/03/26/get-tomorrows-anti-aging-therapy-available-today-outside-the-u-s/#comments Thu, 26 Mar 2015 00:00:56 +0000 http://hplusmagazine.com/?p=27292 BioViva is a new company offering experimental medical services outside US borders.

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biovivaFor people who have a few hundred thousand dollars to spend and are willing to take on the risks of an “early adopter” and travel to South America, options are now becoming available that were inconceivable just a few years ago. A new company is leapfrogging over the time-consuming process of testing and regulatory approval, and offering the best-established and most promising experimental anti-aging technologies in the near future. This is a new vision for combining research with treatment, for treating diseases that have no proven therapies, and for aging itself.

(This column begins with a couple of pages of background.  If you want to cut to the chase, scroll down to BioViva.)

You only have to read Time Magazine to notice that this is the year anti-aging medicine is coming of age.  Promising life extension technologies are being debuted, with potential for preventing many diseases at once, adding decades to the human life span, and restoring youthful function to an aging body. These include telomerase therapies, stem cell therapies, epigenetic reprogramming, removal of senescent cells, plasma transfer, and hormonal therapies inspired by gene expression changes between young and old.

Inevitably, this has brought a surge in the number of companies eager to jump the gun and offer treatments to consumers based on early lab research, before the technology has proved  safe and effective in humans.  In an age of wildcat capitalism, we are well-advised to approach all claims with a skeptical eye, and assume that hucksterism is rampant.  Anyone who considers signing on with a new company that is offering a promising but unproven anti-aging technology had best start with a foundation of second opinions and broad considerations of risk and rewards.

But I stop short of saying, “stay away”.  The field is too important, with too much at stake for us individually and as a human community, to sit on the sidelines, to wait for the research to be sorted out.  Political control of medical research has protected us imperfectly, and has held back life-saving treatments, sometimes for decades.  The system serves pharmaceutical profits more effectively than the public of medical consumers.  Too often, the treatments that are approved are not those that offer the best risk/reward ratio, but those that are patentable and owned by someone who can afford to invest hundreds of millions of dollars in scientific advocacy.

The standard path to regulatory approval respects individual human life, and is “conservative” in the Hippocratic sense of “first do no harm”.  But it is far from the most effective way to move science forward, and probably is not the most efficient way to save the most lives, even in the short run.  Many libertarians, anti-aging enthusiasts and ordinary citizens who find themselves with a condition for which there is currently no effective medical treatment want the freedom to participate in experimental medicine, and experimental medicine certainly wants to try to help them and to learn from successes and failures.

For people who see their options for an active and creative life being closed by age-related disabilities, for people who are willing to take personal risks to help move the science forward, for people who are bold and adventure-seeking, the choice to try experimental anti-aging technologies can be a rational decision.


The Promise of Telomerase Therapies

In my opinion, the best-validated and most promising of the experimental therapies is the direct delivery of telomerase through gene therapy.  This is a technology pioneered in mice by Maria Blasco’s lab in Madrid, with stunning results.  In a ground-breaking 2012 paperby Blasco’s student Bruno Bernardes de Jesus, ordinary lab mice were given gene therapy with an “extra” telomerase gene spread to their cells by a genetically-engineered virus.  the mice lived 13-24% longer, and the experimenters reported “remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging.”

Some strategies work better in mice than in humans, but there is theoretical reason to believe that this technique should work (even) better in humans than in mice.  Untreated mice already have plenty of telomerase, and the telomeres of lab mice are at least 3 times as long as humans’, with shorter life spans in which to lose their telomeres.  Before the above experiment, it was reasonable to think that telomere length was a primary aging clock in humans, but not in mice.  Mice can live up to six generations after their telomerase gene has been knocked out (no telomerase at all), whereas people exhaust their telomere endowment in a single generation.

I’ve written in the past about telomere length as one of the body’s primary aging clocks.  Very little telomerase is expressed in human adults.  As our stem cells divide during a lifetime, telomeres get progressively shorter with age.  Some results include the most important symptoms of aging:

  • fewer functioning stem cells to replenish the stock of blood and skin cells
  • more senescent cell, each sending out distress signals that promote the body’s hyper-inflamed state
  • decline of the immune system, as new white blood cells form more slowly
  • a cascade effect, as cells with short telomeres senesce and then trigger senescence in neighboring cells
  • higher cancer rates, as the chromosomes in cells with short telomeres become unstable, and the immune system sentinels that nip cancer in the bud go AWOL.

Yes—higher cancer rates result when telomeres get short.  There is a theory that our bodies withhold telomerase in order to prevent cancer, but it is an idea with no experimental support.  Fear of cancer has held back telomerase therapy, and this is a red herring, based on misunderstanding of evolutionary biology.  All evidence suggests that telomerase therapies will lower cancer risk.



BioViva is a new company offering experimental medical services outside US borders.  Their team includes

  • a lab that provides genetically modified viruses with a gene payload, made to order.  (This has now become a reliable and predictable technology.)
  • A doctor who has experience with experimental gene therapy, and who had the courage to experiment on himself five years ago, with good outcome thus far.
  • Sites in Colombia and Mexico where doctors will administer therapies for which there is not yet FDA approval.
  • Most important, a Scientific Advisory Board that includes two of the most prominent, senior biochemists who developed the science of telomerase in the 1990s and before.  They are Bill Andrews and Michael Fossel.

What they offer is gene therapy with hTERT and a proprietary myostatin inhibitor “in the same family with GDF-11,” according to CEO Elizabeth Parrish.

Parrish stresses that AAV gene therapy is a mature technology and has already passed FDA tests for safety.  “AAV has become increasingly common as a vector for use in human clinical trials; as of [2008], 38 protocols have been approved by the Recombinant DNA Advisory Committee and the Food and Drug Administration (FDA).” [ref] The uncertainties are no longer about safety, but about whether the virus will be destroyed by the body’s immune system before their payload can be delivered.  The rejuvenation benefit is likely to be systemic, and will have ripple consequences that we can only learn with human subjects.

In a surprise marketing move, Parrish has offered a guarantee for Patient #1 only.  If results for the first patient are disappointing, and Bioviva learns to avoid pitfallss and do a better job over the next 2 years, Patient #1 will be re-treated without cost, using the updated technology.


How Gene Therapy Works with AAV

AAV stands for Adeno-Associated Viruses, and there are several types in use.  This virus makes its living by

  • slipping its payload of DNA into a human cell (shedding its protein shell at the cell wall)
  • finding its way to the cell nucleus
  • copying itself into a specific place on Chromosome 19,
  • from where it manufactures copies of its own DNA, and also of the proteins that it needs to replicate, to penetrate other cells.

In therapeutic applications, the AAV DNA strand is modified to include a payload of therapeutic DNA, and to eliminate the genes coding for proteins that AAV needs in order to reproduce.  In this form, the modified virus can infect a cell, but once inside it cannot reproduce, infect more cells, reproduce there, and spread, causing disease.  It becomes a one-trick pony.  Each individual virus can infect one cell only, and then it has shot its wad.  No way this infection can “go viral”.

AAV therapy has been studied for over 25 years, and there is some reason to expect that the payload gene can remain active for a long time.  So this is a permanent change in the DNA of some cells in the body, though it is not a permanent infection.  Though AAVs are common in the environment, 80% of us have a naive immune response, so the treatment can be effective.  (For the other 20%, temporary immune suppression may be necessary.)  Repeat treatments are sometimes possible.  Here is a good semi-technical introduction to the subject.

Adeno-associated viruses, from the parvovirus family, are small viruses with a genome of single stranded DNA. These viruses can insert genetic material at a specific site on chromosome 19 with near 100% certainty. There are a few disadvantages to using AAV, including the small amount of DNA it can carry (low capacity) and the difficulty in producing it. This type of virus is being used, however, because it is non-pathogenic (most people carry this harmless virus). In contrast to adenoviruses, most people treated with AAV will not build an immune response to remove the virus and the cells that have been successfully treated with it.

Different AAV viruses can be customized to infect different cell types, and of course the place where the virus is injected is the most likely place for the virus to take root.  Viruses used in previous generations of gene therapy tended to disrupt the body’s own DNA by inserting at sites that are essential, and cancer rates were raised by some early forms of gene therapy.  AAV is favored because its target site seems to be safe, and its insertion harmless.



Therapies with hTERT and Myostatin Inhibitor

hTERT is only half the telomerase molecule, but it is the half that is in short supply, and hence the bottleneck for production of telomerase.  Of course, the DNA in our every cell contains the hTERT gene, but it is covered up and remains un-expressed almost all the time.  The new copy on Chromosome 19 is active, and in tests in cell cultures and live mice, telomeres have been lengthened.

I believe that telomerase is the closest thing we have at present to a cure for aging.  Bill Andrews and others have a long-term goal of developing drugs that will signal the body to activate its own telomerase gene, but these seem to be a few years off.  For now, adding an extra gene for hTERT may be the most promising generalized anti-aging intervention.  An important issue is that a large viral dose may be needed to saturate the body’s stem cells with the gene payload.  This is because a small minority of cells with the shortest telomeres is the source of some of the body’s biggest problems.  We’ll learn about the body’s response—if we are lucky, a rejuvenated immune system will itself eliminate the residual senescent cells without the need to lengthen telomeres in every senescent cell.

The myostatin strategy grows from (of all things) body-enhancement strategies for muscle-builders.  Myostatin is a member of the TGF-β family, is also called GDF-8*, and is a gene that inhibits muscle growth.  So if myostatin can be tied up, there is less inhibition and more muscle growth.  In the last several years, creatine has become a popular supplement for body-builders, and it works directly at the level of the gene, by inhibiting expression of myostatin=GDF-8.  Later in life, expression of the myostatin gene increases, and it is thought, logically enough, that this is a cause of the loss of muscle mass (sarcopoenia) that is almost universal with aging (though it is mitigated by exercise).  Bioviva offers gene therapy for a myostatin inhibitor (the specific gene is not disclosed), and it has been tried by one of the team members, experimenting on himself 5 years ago, with good results in ayounger man.  Here is an article that offers a balanced view of reasons to believe this might or might not work for age-related sarcopoenia.

Perhaps more important, the same gene has been found to clear blocked arteries, with expected reduction of the risk for heart disease and stroke.  There is rodent data and good theoretical reason to expect this will work, and there has been one heart patient who has received the AAV/myostatin treatment it with excellent results.  Blocking myostatin is also expected to reduce the progression of insulin resistance that is a driver of many age-related diseases.


Alzheimer’s Disease

There is a well-supported theory of AD that it has its roots in the microglial cells of the brain.  These are not nerve cells, but they act as a kind of immune system for the brain, protecting it from inflammation and cleaning up plaques.  Their secretions promote growth and repair.  Unlike nerve cells, microglia are continually replicating, and so they lose telomere length over time.  On the theory that restoring telomeres in the microglia will reverse dementia, Bioviva is offering gene therapy with hTERT in the brain as treatment for AD.  Direct evidence that this might work comes from a 2011 experiment from the de Pinho lab at Harvard Med School, in which brains atrophied in mice deprived of telomerase, and the brains actually regrew when telomerase was provided.


The Bottom Line

Experimental treatments are, by definition, at the wrong end of the learning curve.  But there is so much to be gained, and the people involved are such experts, that I am deeply hopeful about Bioviva’s work, and the prospect of a fast track to meaningful anti-aging therapies.


* Myostatin is GDF-8, not to be confused with GDF-11, which has also been recently in the news.  Both are in the TGF-ß family.  GDF-8 inhibits muscle cell growth, while GDF-11 inhibits nerve cell growth.  Curiously, Bioviva’s anti-aging strategy is to suppress GDF-8but last year’s headline-making paper from Harvard found benefits in  promoting GDF-11.


This article originally appeared in Josh’s Aging Matters blog here. Republished with permission of the author.

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Mesoscopic Brain Dynamics for Mind Uploading http://hplusmagazine.com/2015/03/25/mesoscopic-brain-dynamics-for-mind-uploading/ http://hplusmagazine.com/2015/03/25/mesoscopic-brain-dynamics-for-mind-uploading/#comments Wed, 25 Mar 2015 22:22:11 +0000 http://hplusmagazine.com/?p=27288 Mesoscopic brain dynamics usually refers to the neural activity or dynamics at intermediate scales of the nervous system, at levels between neurons and the entire brain.

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Mesoscopic brain dynamics usually refers to the neural activity or dynamics at intermediate scales of the nervous system, at levels between neurons and the entire brain. It is commonly considered to relate to the dynamics of cortical neural networks, typically on the spatial order of a few millimeters to centimeters, and temporally on the order of milliseconds to seconds. It is usually the type of dynamics that can be measured by methods such as ECoG (electrocorticography), EEG (electroencephalography), LFP (local field potentials) or MEG (magnetoencephalography). Indeed, the terminology can be used in relative terms, where “meso” just indicates that the scale of interest is in between the “micro” and the “macro”.


In science in general, e.g. in physics, chemistry and biology, but also in the social sciences, it is common to distinguish between two levels that may be referred to as “microscopic” and “macroscopic”, respectively. Intermediate or “mesoscopic” levels are less commonly considered, but are becoming increasingly in focus (Ingber, 1992; Imry, 1997; Freeman, 2000; Haken, 2005). For example, in lasers and certain chemical reactions, spatio-temporal patterns emerge at scales much larger than the constituent atoms or molecules. The formation of such patterns, which is highly relevant to mesoscopic physics, chemistry and biology has been intensely studied by Hermann Haken and co-workers within the field of synergetics (Haken, 1983, 2002).

Mesoscopic brain dynamics is intermediate between microscopic and macroscopic neurodynamics. What is microscopic could be considered processes and systems studied with a microscope or microelectrodes. It could refer to ion channels or single neurons. The macroscopic scale, on the other hand, could be considered corresponding to the largest scales possible to measure with regard to brain activity. This would be the dynamics related to maps, or systems, such as cortico-thalamic, or cortico-cortical interactions, usually measured with PET, fMRI, or other brain imaging techniques, capturing the dynamics associated with blood flows and metabolism. Also scalp EEG may capture this type of dynamics (Bressler & Menon, 2010).

Mesoscopic brain dynamics refers typically to the dynamics of neuronal populations, networks or columns within cortical areas. It is characterized by its high complexity, often involving oscillations of different frequencies and amplitudes, perhaps interrupted by chaotic or pseudo-chaotic irregular behaviour. The mesoscopic brain dynamics is affected by the activity at other scales. For example, it is often mixed with noise, generated at a microscopic level by spontaneous activity of neurons and ion channels. It is also affected by macroscopic activity, such as slow rhythms generated by cortico-thalamic circuits or neuromodulatory influx from different brain regions.

The possibility to measure, in greater detail, the electrical part of brain activity with external electrodes was discovered and used by Berger in the early 20th century (Berger, 1929). One of the first experiments to demonstrate stimulus-induced activity in the mammalian central nervous system was made by Adrian (1942), showing oscillatory activity in the olfactory system of hedgehog.

Figure 1: Mesoscopic brain dynamics as EEG from rat olfactory cortex (data courtesy of Leslie Kay). The x-axis shows milliseconds, and the y-axis is in microvolts.

Figure 2: Simulated EEG with a model of olfactory cortex (as seen in Fig. 3).

Generation of Mesoscopic Brain Dynamics

Mesoscopic brain dynamics are partly a result of neuronal thresholds and the summed activity of a large number of neuronal elements interconnected with positive and negative feedback. This kind of neural dynamics is often characterized by oscillatory synchronous neuronal population behaviours, which underlie the rhythmical EEG waves in the cortex. Synchronization among groups of neurons were first discovered in the olfactory system (Adrian, 1942; Freeman, 1959), but has also been demonstrated in other brain structures, such as thehippocampus (Green and Arduini, 1954; Buszaki et al., 1992), thalamus (Steriade and Llinás, 1988), and the visual cortex (Eckhorn et al., 1988; Gray and Singer, 1989), where the oscillations tend to synchronize in phase. Synchronous oscillations can occur in nearby neurons, but also over considerable distances across spatially separate columns (Gray et al., 1989) and even between cortical areas (Eckhorn et al., 1988; Engel et al., 1991).

Neural oscillations may be due to intrinsic properties of certain pacemaker cells (Lllinas, 1988) or due to network effects (Traub & Miles, 1991). A population of neurons might fire together either because it responds to an afferent oscillatory input or because of cellular/synaptic interactions. An understanding for how such synchronous groups of neurons may be formed was first given by Donald Hebb (1949), who proposed that representations of sensory or motor patterns should consist of assemblies of cooperatively interacting neurons. Such assemblies could form according to a so called Hebbian synaptic modification, which depends on the co-occurrence of pre- and postsynaptic activity. The finding and analysis of cooperating neural assemblies is facilitated by triple recording from microelectrodes, which simultaneously can detect single unit spike trains, in addition to neural mass signals, such as multiple unit spike activity (MUA) and local slow-wave field potentials (LFP).

Events and processes at the microscopic level of neurons and molecules have an effect on the meso- and macroscopic levels of networks and systems, through their interactions via synaptic and non-synaptic connections. At the same time, the network or ensemble dynamics constrain the constituent neurons, engaging them in a self-organizing and coordinated activity. The higher level dynamics “enslaves” the lower levels, according to the theory of synergetics, providing an example of circular causality of complex systems (Haken, 1983, 2002).

The Olfactory Cortex as a Model System

While mesoscopic brain dynamics is observed in many brain structures, the mammalian olfactory system (primarily bulb and cortex) is often used as a model system, much due to the pioneering work of Walter Freeman and his co-workers since the 1960s (Freeman, 1959; 1975; 2000). In particular, theta and gamma rhythms are observed, as well as spatiotemporal waves of activity moving across the bulbar and cortical surfaces. Also chaotic-like behaviour has been observed and characterized (Freeman, 1987). Furthermore, the structure of this system is well characterized, and Freeman and others have successfully studied and described how structure, dynamics and function are related in this system.

Computational models have contributed to elucidate these relationships, where simulations have been able to closely mimic the dynamics, as captured by LFPs (local field potentials), ECoG, or intracranial EEG (Freeman, 1987; Li and Hopfield, 1989; Liljenström, 1991; Wilson & Bower, 1992). An intracranial EEG trace from the rat olfactory cortex (Fig. 1) is closely reproduced by a simulated EEG (Fig. 2) generated by a neural network model (Liljenstrom, 1991) of the three-layered olfactory cortex (Fig. 3). In this case, the output of several neighbouring network units, representing the average membrane potential of neuronal populations, was summed and weighted to mimic the electrical activity at an electrode located above the network surface. In Fig. 4 spatio-temporal patterns of activity, representing the neural response to an odorous input signal, is shown as color-coded positive and negative “mean membrane potentials” of the network nodes. A specific odor input results in a specific spatio-temporal pattern in the network activity, resulting in learning or recall (see below).

Figure 3: A neural network model of the three-layered olfactory cortex. The middle layer corresponds to excitatory pyramidal cells, whereas the top and bottom layers correspond to feedforward and feedback inhibitory interneurons, respectively. Nerve bundles (LOT) from the olfactory bulb reaches the two top layers. (Liljenström, 1991)

Figure 4: The spatio-temporal activity pattern in the olfactory cortex model resulting from an artificial odor input. The top frame shows the color-coded simultaneous activity in the three layers, whereas the bottom frame shows a number of snapshots of the middle, excitatory layer activity.

Transitions in Mesoscopic Brain Dynamics

Cortical neurodynamics is constantly changing, due to internal fluctuations, neuromodulation, and sensory input. Many factors influence the dynamical states, such as the excitability of neurons and the synaptic strengths between them. A number of neuromodulators affect these neural properties, including acetylcholine (ACh) and serotonin (5-HT). The concentration of these neuromodulators in the cortex seems to be directly related to the arousal ormotivation of the individual (Freeman, 2000).

The state of arousal or attention may change the macro- and mesoscopic brain dynamics considerably, and even induce phase (state) transitions that could affect the functional efficiency of cognitive processes (Liljenström, 2010). Visual attention has several effects on modulating cortical dynamics, in terms of changes in firing rate (McAdams & Maunsell, 1999), as well as gamma- and beta-band coherence (Fries et al., 2001). With attention, there is a reduction in low-frequency synchronization and an increase in gamma-frequency synchronization. Generally, it is believed that lower frequency bands are generated by global circuits, whereas higher frequency bands are derived from local connections (Gu & Liljenström, 2007).

Electrical stimulation may also induce transitions in cortical dynamics. When studying the dynamical properties of the olfactory cortex, Freeman and coworkers stimulated the lateral olfactory tract (LOT) of cats and rodents with electric shock pulses of varying amplitude and duration, and recorded the neural response via intracranial EEG (Freeman, 1959; 1964). A strong pulse gives a biphasic response with a single fast wave moving across the cortical surface, whereas a weak pulse results in an oscillatory response, showing up as a series of waves with diminishing amplitude. When a short pulse is applied to the LOT input corner of the network model, waves of activity move across the model cortex, consistent with corresponding global dynamic behaviour (c.f. Fig. 4).

Figure 5: Simulated effect of anaesthetics. The dynamics of a network, where K channels are increasingly blocked by anaesthetics. The two upper time series show the activity of single excitatory and inhibitory neurons, respectively, while the lower time series is the network mean activity (Halnes et al., 2007)

Another way of artificially inducing phase (state) transitions in cortical network dynamics is by using neuroactive drugs, such as certain kinds of anesthetics and anti-epileptics, which clearly can induce transitions between mental states, characterized by different oscillatory modes and frequencies (see Fig. 5). An important principle in the action of these drugs is selective blocking or activation of ion channels, which will have different neurodynamical effects, depending on the relative selectivity and the intrinsic network activity (Århem et al., 2003, 2007; Halnes et al., 2007).

Functional relevance and computational models

A fundamental question in neuroscience concerns the functional significance of mesoscopic brain dynamics, including the observed phase transitions between various oscillatory states and chaotic or noisy states. The electrical activity of the brain, as captured with EEG is considered by some to be an epiphenomenon, without any information content or functional significance, but there exists contrary evidence that mesoscopic brain dynamics at least to some degree reflects mental states and processes (Wright & Liley, 1996; Freeman, 2000).

Most cognitive and mental functions presumably involve larger “macroscopic” brain areas or even networks of interconnected cortical areas, but the mesoscopic dynamics of such an area may still reflect some aspect or part of the mental activity. For example, different conscious states, such as drowsiness, sleep or alertness may result in similar type of dynamics, such as alpha or gamma waves across several areas, and detectable at mesoscopic spatial scales. Similarly, some aspects of a “macroscopic” phenomenon such as face recognition or eating behaviour may be reflected in the “microscopic” activity of single neurons (c.f mirror neurons).

Figure 6: The attractor dynamics during recognition of an unknown input pattern. After an initial semi-chaotic period, the system converges to a near-limit-cycle attractor (40 Hz), corresponding to the recognized odor. Cholinergic modulation facilitates learning and increases pattern recognition efficiency. The activity of three arbitrary network nodes are plotted against each other in arbitrary units.

In order to elucidate the significance of mesoscopic brain dynamics, computational methods are used to supplement experimental methods. For example, there is strong computational, as well as experimental support for a population (relational) coding in cortical networks, where mesoscopic brain dynamics apparently play a functional role (Singer, 1994). Such a coding principle implies that information is contained not only in the activation level of individual neurons but also in the relations between the activities of distributed neurons.

Computer simulations with cortical neural network models support the view that complex dynamics makes neural information processing more efficient, providing a fast and accurate response to external stimuli or in associative memory tasks (Liljenström, 1995; Liljenström & Hasselmo, 1995). For example, with an initial chaotic-like state, sensitive to the input signal, the system can rapidly converge to a limit cycle attractor memory state, see Fig.6 (Wu & Liljenström, 1994). Perhaps the most direct effect of cortical oscillations could be to enhance weak signals and speed up information processing, but they may also reflect various cognitive functions, including segmentation of sensory input, learning, perception, and attention. Phase transitions in mesoscopic brain dynamics can reflect transitions between different cognitive and mental levels or states, for example corresponding to various stages of sleep, anesthesia or wake states with different levels of arousal, which in turn could affect the efficiency and rate of information processing (Liljenström, 2010).

Simulations also show that mesoscopic network dynamics can be shifted into, or out of, different oscillatory states by small changes in ion-channel densities or by changing connection strengths in a network model (Halnes et al., 2007). It is demonstrated that the blocking of specific ion channels, as a possible effect of some anesthetics, can change global brain activity from high-frequency (awake) states to low-frequency (anesthetized) states, as apparent in the recorded and simulated EEG (See Fig. 5).

It can further be demonstrated that “microscopic” noise can induce global synchronous oscillations in cortical networks and shift the system dynamics from one dynamical state to another (Liljenström & Wu, 1995; Liljenström & Århem, 1997; Basu & Liljenström, 2001). This in turn can change the efficiency of the information processing of the system, e.g. system performance can be maximized at an optimal noise level, analogous to the case of stochastic resonance (Wiesenfeld & Moss, 1995), and spontaneous activity can facilitate learning and associative memory (Liljenström, 1996).

Mesoscopic brain dynamics and consciousness

As briefly discussed above, low frequencies in mesoscopic brain dynamics correspond to low mental activity, drowsiness or sleep, whereas higher frequencies are associated with alertness and higher conscious activity. In particular, oscillations in the gamma frequency band, around 40 Hz, have long been associated with (visual) attention, initially based on experiments on cats (Eckhorn et al., 1988; Gray & Singer, 1989; Engel et al., 1991). It was this phenomenon that triggered the boost of studies on neural correlates of consciousness, as e.g. suggested by Crick & Koch (1990; Koch, 2004) and contributed to opening the field of neuroscience to consciousness studies.

The complex neurodynamics at a mesoscopic level of the brain seems significant for the macroscopic phenomena of cognition and consciousness (Århem & Liljenström, 2007). It has been related to perception, attention and associative memory, but also to volition and activity in the sensory and motor areas of the brain. Even though many details are still unknown, it is obvious that there is an interplay between the neurodynamics of the sensory and motor systems, essential for the interaction with our environment in a perception-action cycle (Cotterill, 1998; Freeman, 2000).

Associated with the perception-action cycle are the dual aspects of consciousness, attention and intention (Liljenström, 2011). Attention is primarily related to the sensory/perceptual pathways and brain areas, whereas intention is more related to the motor areas and pathways. In particular, the supplementary motor area (SMA), but also the parietal cortex, show early signs of intentional motor activity (Eccles, 1982; Libet 1985; Desmurget et al., 2009). EEG measurements from these areas reflect mesoscopic brain dynamics, apparently correlating to various conscious states and events.


Mesoscopic neurodynamics can be seen as resulting from the dynamic balance between opposing processes at several scales, from the influx and efflux of ions, inhibition and excitation etc. Such interplay between opposing processes often results in (transient or continuous) oscillatory and chaotic-like behaviour. Indeed, brain activity is constantly changing, due to neuronal information processing, intrinsic fluctuations, neuromodulation, sensory input, and internal state shifts. An essential feature of mesoscopic brain dynamics is spatio-temporal patterns of activity, appearing at the collective level of a large number of neurons. Waves of activity move across the surface of sensory cortices, with oscillations at various frequency bands. This kind of activity is often associated with mental processes and states, which can be characterized by the specific patterns involved.

A combination of mathematical analysis and computational modeling can serve as an essential complement to clinical and experimental methods in furthering our understanding of neural and mental processes. In particular, when concerning the inter-relation between structure, dynamics and function of the brain and its cognitive functions, this method may be the best way to make progress. The study of phase transitions in mesoscopic brain dynamics could be one of the most fruitful approaches in this respect (Steyn-Ross & Steyn-Ross, 2010). In fact, relating different spatial and temporal scales in the nervous system, and linking them to mental processes may be seen as one of the greatest challenges to modern neuroscience.


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Recommended reading – books

  • Arbib M A, Erdi P and Szentagothai J (1998) Neural Organization – Structure, Function and Dynamics. Cambridge: MIT Press.
  • Arhem P, Liljenström H & Svedin U, eds. (1997) Matter Matters? – On the Material Basis of the Cognitive Activity of Mind. Heidelberg: Springer.
  • Arhem P, Blomberg, C & Liljenström H, eds. (2000) Disorder Versus Order in Brain Function. London: World Scientific.
  • Freeman WJ (1975) Mass Action in the Nervous System. New York: Academic Press. © 2004: (online)
  • Freeman WJ (2000) Neurodynamics – An Exploration in Mesoscopic Brain Dynamics. London: Springer.
  • Haken H (2002, 2008) Brain Dynamics – An Introduction to Models and Simulations. Berlin: Springer.
  • Liljenström H & Århem P (2007) Consciousness Transitions – Phylogenetic, Ontogenetic and Physiological Aspects. Amsterdam: Elsevier.
  • Liljenstrom H & Svedin U, eds. (2005) Micro – Meso – Macro: Addressing Complex Systems Couplings. London: World Scientific.
  • Moss F & Gielen S (2001) Neuroinformatics and Neural Modelling. Handbook of Biological Physics (ed. A J Hoff) Vol 4. Amsterdam: Elsevier.
  • Perlovsky L I & Kozma R, eds. (2007) Neurodynamics of Cognition and Consciousness. Berlin: Springer.
  • Steyn-Ross DA & Steyn-Ross ML, eds. (2010) Modeling Phase Transitions in the Brain. New York: Springer.

Scholarpedia references

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Pierre Teilhard de Chardin: Universal Progressive Evolution http://hplusmagazine.com/2015/03/25/pierre-teilhard-de-chardin-universal-progressive-evolution/ http://hplusmagazine.com/2015/03/25/pierre-teilhard-de-chardin-universal-progressive-evolution/#comments Wed, 25 Mar 2015 17:56:53 +0000 http://hplusmagazine.com/?p=27284 Is evolution a theory, a system or a hypothesis? It is much more: it is a general condition to which all theories, all hypotheses, all systems must bow and which they must satisfy henceforth if they are to be thinkable and true. Evolution is a light illuminating all facts, a curve that all lines must follow.

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Pierre Teilhard de Chardin (1881 – 1955), a Jesuit priest trained as a paleontologist and geologist, was one of the most prominent thinkers who tried to reconcile evolutionary theory, religion, and the meaning of life. In his magnum opus,The Phenomenon of Man,  he sets forth a sweeping account of cosmic unfolding.

While Teilhard’s philosophy is notoriously complex, the key notion is that cosmic evolution is directional or teleological. Evolution brings about an increasing complexity of consciousness, leading from an unconscious geosphere, to a semi-conscious biosphere, and eventually to conscious sphere of mind. The arrival of human beings on the cosmic scene is particularly important, signaling that evolution is becoming conscious of itself. As the process continues, the human ability to accumulate and transmit ideas increases along with the depth and complexity of those ideas. This will lead to the emergence of what Teilhard calls the “noosphere,” a thinking layer containing the collective consciousness of humanity which will envelope the earth. (Some contemporary commentators view the World Wide Web as a partial fulfillment of Teilhard’s prophecy.)

Not only does evolution explain how mind arose from matter, it is also the key to all metaphysical understanding, if such understanding is to be based on a firm foundation.

Is evolution a theory, a system or a hypothesis? It is much more: it is a general condition to which all theories, all hypotheses, all systems must bow and which they must satisfy henceforth if they are to be thinkable and true. Evolution is a light illuminating all facts, a curve that all lines must follow.[i]

Teilhard recognized this evolutionary worldview, with its oceans of space and time, as a source of disquiet for minds previously comforted by childlike myths. Anxiety begins when we reflect, and reflection on the nature of the universe clearly discomforts.

Which of us has ever in his life really had the courage to look squarely at and try to ‘live’ [in] a universe formed of galaxies whose distance apart runs into hundreds of thousands of light years? Which of us, having tried, has not emerged from the ordeal shaken in one or other of his beliefs? And who, even when trying to shut his eyes as best he can to what the astronomers implacably put before us, has not had a confused sensation of gigantic shadow passing over the serenity of his joy?[ii]

Yet psychic troubles derives from this evolutionary worldview. “What disconcerts the modern world at its very roots is not being sure, and not seeing how it ever could be sure, that there is an outcome—a suitable outcome—to that evolution.”[iii]But alas the source of our discomfort is also the fount of our salvation. For if the future is open to our further development, then we have the chance to fulfill ourselves, “to progress until we arrive … at the utmost limits of ourselves.[iv]

The increasing power and influence of the noosphere or world of mind will culminate in the Omega Point—a supreme consciousness or God. At that point all consciousness will converge, although Teilhard argues that individual consciousness will somehow still be preserved. While the Omega point is extraordinarily difficult to describe, it must be a union of love if it is to be a sublimely suitable outcome of evolution. Here Teilhard waxes poetic:

Love alone is capable of uniting living beings in such a way as to complete and fulfill them, for it alone takes them and joins them by what is deepest in themselves. This is a fact of daily experience. At what moment do lovers come into the most complete possession of themselves if not when they say they are lost in each other? In truth, does not love every instant achieve all around us, in the couple or the team, the magic feat, the feat reputed to be contradictory, of personalizing by totalizing? And if that is what it can achieve daily on a small scale, why should it not repeat this one day on world-wide dimensions?[v]

In Teilhard’s vision, all reality evolves toward higher forms of being and consciousness, which includes more intense and satisfying forms of love. Thus spirit or mind, not matter or energy, ground the unity of the universe; they are the inner driving force propelling evolution forward. (This is Teilhard’s god.) Teilhard found meaning and purpose in this sweeping epic of cosmic evolution in which the endpoint of all evolution will be the highest good.

(Note – I do have doubts about some of Teilhard’s esoteric ideas and concepts. A lot of what he says is profound, but some of it is probably nonsense. For the most devastating critique of Teilhard ever penned see the great biologist P. B. Medawar’s “Review of the Phenomenon of Man” (1961).


[i] Teilhard de Chardin, Pierre,  The Phenomenon of Man (New York: Harper Collins, 1975), 219.
[ii] Teilhard de Chardin, The Phenomenon of Man. 227.
[iii] Teilhard de Chardin, The Phenomenon of Man, 229.
[iv] Teilhard de Chardin, The Phenomenon of Man, 231.
[v] Teilhard de Chardin, The Phenomenon of Man, 265.


John G. Messerly, Ph.D taught for many years in both the philosophy and computer science departments at the University of Texas at Austin. His most recent book is The Meaning of Life: Religious, Philosophical, Scientific, and Transhumanist Perspectives. He blogs daily on issues of futurism and the meaning of life at reasonandmeaning.com

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Silver Shines as Antibacterial for Medical Implants http://hplusmagazine.com/2015/03/24/silver-shines-as-antibacterial-for-medical-implants/ http://hplusmagazine.com/2015/03/24/silver-shines-as-antibacterial-for-medical-implants/#comments Tue, 24 Mar 2015 20:03:42 +0000 http://hplusmagazine.com/?p=27277 Infection continues to be a major complication associated with implantable devices.

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There have been growing concerns in the global health care system about the eradication of pathogens in hospitals and other patient-care environments. Overuse of antibiotics and antimicrobial agents has contributed to the emergence of antibiotic-resistant superbugs – such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) – which are difficult to kill. Lower immunity of sick patients coupled with the escalating problem of antibiotic-resistant pathogens has driven increased rates of infection in hospital and surgical environments.

It’s become crucially important to find ways to control infection in these settings. My research has focused on ways we can do so using alternative antibacterial materials such as the heavy metal silver. I’ve been working on a technique that electrically activates silver to create an antimicrobial surface. We can use this technology to create touch-contact and work surfaces – for instance, door knobs, push plates, countertops – that would help control the transmission of infections, primarily in health care environments. And now we’re experimenting with using silver in medical implants.

Silver takes the gold in fighting bacteria

Silver has long been known for its antibacterial properties. A variety of medical products including ointments, bandages, surgical tools and catheters employ silver-based technologies to prevent or fight infection.

But just an inert lump of silver isn’t going to do much. To be effective, it must first ionize. Research has shown that it’s silver in its ionic (Ag+) and not elemental form that is antibacterial. An atom of silver has a neutral charge; we need to ionize it – take away a negatively charged electron – to transform it into its positively charged ionic form. Silver-based antibacterial surfaces must release silver ions directly into the pathogenic environment to be effective.

Silver ions have antibacterial properties for a few reasons. They can interfere with with cell DNA and affect their ability to procreate. They can inhibit enzymes involved with respiration, essentially suffocating the bacteria cells. And they can react with sensitive thiol groups on bacterial proteins to destroy normal biological activity of the protein. The multi-modal activity also makes it difficult for bacteria to develop resistance in the same way they do to specific antibiotic medications.

Taking silver to inner space

Particularly with our aging population, the number of joint replacement surgeries is growing in the US. And with more surgeries, the associated risks of infection go up too. Now my work with my student George Tan is focused on taking the bacteria-fighting power of silver ions inside the body.

Schematic diagram of silver ions dispersing from the implant and fighting pathogens. Rohan Shirwaiker, CC BY-NC-ND

We are engineering ways to apply a low-intensity electrical charge to a silver-titanium orthopedic implant. Our technique releases silver ions that kill or neutralize bacteria on and around the implant. The power source, which could be a strong watch battery, can potentially be integrated into the implant design. The body’s own fluids act as a conducting medium between the titanium and silver, enabling the low-level electrical current necessary to create and release the silver ions into the environment which might contain pathogens.

Clear zones around the implant’s silver electrodes show that it’s stopping pathogens from growing nearby. Rohan Shirwaiker, CC BY-NC-ND

Click to enlarge

This technology has the potential to dramatically reduce infections which negatively affect patient health, quality of life and health care costs. Our in vitro lab testing has shown a 99% decrease in bacteria growth on and around implants after 24 hours and an infection-free environment after 48 hours.

One of the engineering challenges is to precisely control the level of silver that is released so that no healthy cells are compromised; silver can be toxic. In future, we may explore the possibility of a smartphone app to control the power source and the release of silver ions remotely. Perhaps we could also devise a way to track the biophysical activity around the implant area. Broad application of the system could result in a significant advancement in the fight against infection, with the potential to be incorporated into any type of surgical implant.

Infection continues to be a major complication associated with implantable devices. Although rates vary, an average annual infection rate of approximately 5% (at least 100,000 cases/year) associated with orthopedic procedures involving fracture fixation devices and joint prostheses costs the US healthcare system over $1.5 billion annually. Treatment may require surgical procedures including implant removal, debridement of infected tissue, implant replacement and 6–12 weeks of antimicrobial therapy. Innovations in silver microbial technology could eventually have a wide-ranging impact on patient outcomes as well as on the health of the medical economy.


Dr. Shirwaiker’s research endeavors are focused on implantable medical device and tissue-engineered technologies. His work primarily addresses interdisciplinary design and manufacturing engineering challenges that arise during their product development and scale-up. His research group collaborates with clinicians, biologists and other engineers to develop or advance new implantable product solutions to address musculoskeletal clinical needs that currently lack appropriate alternatives. His current work includes the design and analysis of electrically activated antimicrobial silver coatings for orthopaedic implants, and the development and characterization of 3D-printing processes for knee joint tissues and the trachea. In 2014, Dr. Shirwaiker was awarded the Best Young Investigator Research Poster Award at the American Academy of Orthopaedic Surgeons (AAOS) – Orthopaedic Research Society (ORS) Conference on musculoskeletal infections.

Article originally appeared here, republished under creative commons license.

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PoSeidon Point of Sale Malware Spotted in the Wild http://hplusmagazine.com/2015/03/24/poseidon-point-of-sale-malware-spotted-in-the-wild/ http://hplusmagazine.com/2015/03/24/poseidon-point-of-sale-malware-spotted-in-the-wild/#comments Tue, 24 Mar 2015 19:48:38 +0000 http://hplusmagazine.com/?p=27272 Cisco's Security Team has spotted in the wild a new Point-of-Sale malware dubbed PoSeidon that is more sophisticated than any previously detected PoS malware.

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Kill Senescent Cells Before They Kill You http://hplusmagazine.com/2015/03/24/kill-senescent-cells-before-they-kill-you/ http://hplusmagazine.com/2015/03/24/kill-senescent-cells-before-they-kill-you/#comments Tue, 24 Mar 2015 19:39:21 +0000 http://hplusmagazine.com/?p=27268 I’m betting that the search for strategies that differentially kill senescent cells will soon lead to better drugs than quercetin or dasatinib.

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cells aging

Several readers have asked me to comment on the press release and preprint that came out of the Mayo Clinic this week.  Researchers searched for ways to eliminate cells in the body that have become senescent and destructive.  Their tests in cell cultures and in genetically-modified mice turned up two substances, one natural and cheap, the other patented and dear.  I think theirs is a promising approach, and will soon offer substantial life extension in humans with minimal side-effects, but my guess is that the particular cocktail they have found will be left in the dust.

Here’s the Theory

Our stem cells divide through a lifetime, renewing our muscles, blood vessels, and especially skin and blood cells that turn over rapidly.  But in the process, chromosomes in those stem cells lose their telomeres.  When its chromosomes have telomeres that are too short, a cell becomes “senescent.”  Senescent cells are not just sluggish and moribund, they actually poison the nearby tissue (creating more senescent cells) and poison the body with chemical signals (cytokines) that fan the flames of inflam-aging.  This is called SASP, for “senescent-associated secretory phenotype”.  A tiny number of senescent cells can do a great deal of damage.

Would we be better off without senescent cells?  It was the insight of the Mayo Clinic’s Jan van Deursen to ask this question with an experiment four years ago.  He genetically modified mice in such a way that senescent cells had a bomb and a trigger attached.  By feeding the mice a molecule that matched the trigger, he could cause the senescent cells to self-destruct, leaving normal cells intact.  He did a controlled experiment, comparing the same genetically-modified mice, with and without pulling the trigger.  The result was eye-popping life extension in the mice that had their senescent cells removed.  20 to 25% increase in life span from a single treatment, fairly late in life [ref].

Just a decade ago, such discoveries would remain languishing in the lab for a maddeningly-long time.  But it is a sign of the times that venture capital and even Big Pharma are investing in longevity science.  Van Deursen’s discovery was quickly seized by half a dozen different labs around the world (including a for-profit spinoff by van Deursen himself).  What they are looking for is a drug that will attack the 0.01% of senescent cells while leaving 99.99% of non-senescent cells unharmed.


The Research Strategy

The research group at Mayo/Scripps started with gene expression profiles for senescent cells, comparing them to profiles for non-senescent cells.  This was used to identify targets for the drug.  Van Deursen had used p16 to identify senescent cells.  P16 is a gene that keeps senescent cells alive when they really should be eliminating themselves.  The Mayo/Scripps team identified several other drug targets, but did not use p16.  They used RNA interference to silence these genes, one at a time, to help identify effective strategies for differentially targeting the senescers.  Then they screened 46 compounds to see which would best attack the targets they had identified.

The result was two drugs: quercetin seemed to work best for endothelial cells (in arteries), and dasatinib was best for fat stem cells.  Quercetin is cheap and found in many herbs and berries; dasanatib is a patented chemotherapy agent, sold for a scandalously high price by Bristol Myers Squib.  The team tested the combination Q+D for short-term health effects in mice, and found encouraging results.

Q + D

Quercetin is a common flavonoid, polycyclic, found in black currents, cilanthro, red onion, watercress, cranberries, and smaller amounts in many fruits and herbs.  It is an anti-oxidant, but you know I’m not much impressed by that. Though it is natural, it is a mutagen, which means it breaks DNA. Substances like this would never be approved by the FDA, if they had to be approved by the FDA, but they don’t because they escape regulation as GRAS — “generally recognized as safe”.  This is not to damn the stuff–many toxins have a beneficial effect in small doses.  This is hormesis, a paradoxical but common and well-documented fact of longevity science.

But in the case of quercetin, it has been tried in longevity tests with mammals, and the results are not promising.  In 1982, the first published study showed no life extension, and perhaps a slight shortening of life span in male mice. Stephen Spindler, our reality check for life extension claims, found that quercetin had zero effect on mouse life span in a 2013 study.

Dasatinib is a chemotherapy agent, sold by Bristol-Myers Squibb as Sprycel at thousands of dollars per dose for treatment of leukemia.   Dasaitinib has been tested for toxicity but never for life extension.


To put this in perspective…

The gold standard for a life extension drug is that it works to extend life span in rodents.  That’s because it’s too easy to extend life span in simpler lab models like worms and flies, but tests in humans overtax our patience.  Even for mice, the test requires three years and hundreds of thousands of dollars, so researchers are motivated to screen different compounds with tests that can be done in a petri dish, or with short-term studies of physiological changes in live mice.  This is exactly what the Mayo/Scripps team did, and it should have yielded good candidates for life extension drugs.  But the result was a “good candidate” that had already been tried, and didn’t do so well.

The reason that short-term benefits to the metabolism are not a good indicator of what might increase longevity is that body chemistry is complicated.  Life span is tightly regulated, with a mind of its own.  Some substances have short-term benefits, and the body over-compensates with a shorter life span.  Anti-oxidants are a good example.  Other substances do short-term damage, and again the body over-compensates and the result is a longer life span.  Look at the way paraquat affects life span in worms!


The Bottom Line

I’m betting that the search for strategies that differentially kill senescent cells will soon lead to better drugs than quercetin or dasatinib.

This article originally appeared here, republished with permission.

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