Australian Stem Cell Scientists go for Fresh Embryos

Australian scientists can routinely create new cell lines from discarded frozen embryos. But scientists say that having access to fresh embryos with genetic damage would allow them to develop treatments for genetic diseases. The fresh embryos, they say, are less likely to be damaged than frozen embryos.

The Australian stem cell scientists are seeking the country's first licenses to use fresh embryos in stem cell research. This highlights the international competition in stem cells. Some countries ban the use of embryos in research, and others, like the US, do not allow government funds to sponsor new embryonic stem cell line creation.

Both embryonic stem cells and adult stem cells will eventually enjoy widespread use, and each has its specific set of advantages and disadvantages. It is important that all ethical areas of stem cell research be pursued.

In the US, university presidents in New York State are demanding that state institutions take a more aggressive role in promoting stem cell research. Governor Arnold Scharzenegger of California has created a local sponsorship for stem cell research inside California. The competition for results from stem cell research is heating up not only between countries, but between regions of the same country.

Despite ethical objections and budgetary constraints, the research will be done, genetic diseases will be treated with gene therapies. Eventually, germ cell lines will be treated genetically and this new knowledge will substantially impact human evolution. The main questions are where, when, and how.

Hat tip to Stem Cell Research Blog

The Face of a Desperado

Take a look at this photograph. This is the face of a desperado--at least what is considered to be a desperado, a grave threat to the state. Publius Pundit has more of the story behind the photograph, and links to more details.

It is sad when a nation's leader feels so threatened by a fragile young woman's voice, that he is willing to put her on trial before a one-man judge/jury/prosecutor, and deny her the right to speak in court at her own trial. That is the sign of a corrupt government. Where do you find such governments in the world? Zimbabwe? North Korea? Iran? Cuba? Well, yes, you do, but this young woman is not being railroaded to decades in prison in any of those countries, simply for being a democracy organiser. Try again.

Once, such injustice might have occurred in Nicaragua, Guatemala, Chile, Argentina. Now, one particular country is perpetrating this type of outrage at a rapid rate, as if to catch up to the failed latin dictatorships of the past.

Connection between Cancer and Alzheimer's Disease

An intriguing finding by researchers at Brigham and Women's Hospital, Harvard Medical School, seems to link neuronal death in Alzheimer's with proteins expressed by some cancers.

Neurons in the brain generally do not divide. It is therefore perplexing that in Alzheimer's disease, and other dementias associated with a protein called tau, dying neurons actually re-express proteins normally seen during cell division or in cancer. It has previously been unclear whether such cell-division proteins cause neuronal death, protect neurons from death, or are irrelevant.

In the present work, the scientists used a fruit-fly model of Alzheimer's disease to examine the relationship of cell-division proteins to neurodegeneration. The power of this model, which recapitulates key features of the human disease, lies in the ability to use genetic tools to establish a causal correlation between a molecular pathway and neuronal death. Khurana and his colleagues found that, as in human disease, abnormal expression of cell-cycle proteins accompanied neuronal death in their fly model. Most importantly, loss of neurons could be prevented when the cell cycle was genetically blocked or when flies were fed anticancer drugs. Cell-cycle activation depended upon a hyperactive cell growth molecule, TOR (target of rapamycin), also known to be abnormally activated in Alzheimer's disease. By establishing these causal connections, this study suggests that anticancer drugs are potential therapies for Alzheimer's disease and related disorders. More broadly, the results point to an intriguing correlation between cancer and dementia, two of the most important diseases in the elderly.

Hat tip to medicineworld.org and sciencedaily.com.

This is a preliminary finding from fruit flies, but a provocative finding nonetheless. Often important discoveries occur in microbes and lower animals before finding their way to human research, and then into mainstream medicine.

Cleaning Up the Environment: Bacteria to the Rescue

In new research from the 1 Feb. issue of Environmental Science and Technology, as described in Physorg.com, microbes have been developed to scavenge metals from spend catalytic converters and electronic scrap disposal, The metal engorged microbes were then used to catalyse and clean industrial waste, converting it to an environmentally friendlier form.

The researchers experimented with the bacteria Desulfovibrio desulfuricans and Escherichia coli. Prior studies revealed that these bacteria could, in the presence of hydrogen gas or the organic molecule formate, take palladium from solution and deposit it as nanocrystals on their cell surfaces.

Mabbett and her colleagues at bioremediation researcher Lynne Macaskie's lab at the University of Birmingham flowed wastewater from spent catalytic converters and electronic scrap disposal operations past the microbes. The resulting palladium crystals, roughly 50 nanometers wide, were half the size of those generated by conventional industrial means. The bacteria also pulled out aluminum, platinum and silver from the waste as nanocrystals.

The researchers then used these dead nanocrystal-coated bacteria in bioreactors where they flowed industrial waste past loaded with a carcinogenic form of chromium known as chromium-VI. These bioreactors were capable of transforming chromium-VI into the non-carcinogenic chromium-III version that could get extracted out. Mabbett and her colleagues published their findings in the Feb. 1 issue of the journal Environmental Science & Technology.

"This research should definitely impact on the mining and scrap metal industries," Mabbett said. "Instead of just implementing methods to clear up their waste end products, these industries could undertake a two-fold process of 'clean up and manufacture,'" and "both industries could potentially make profit from what was once waste." She estimated it could take five to 10 years for such bacterial nanocrystals to reach the market.

The bacterial nanocrystals continued to work even after operating nonstop for three months, while palladium catalyst generated by conventional means lasted for just one week. To achieve such results, the researchers did first have to enrich the wastewater they gave the bacteria with a palladium solution, but the total amount of palladium used to create the bacterial nanocrystals remained less than that used in the conventional catalyst, Mabbett said.

Even before this latest discovery,microbes have had a growing role in environmental cleanups. Other key processes involved in microbial cleanup are fairly well known and described at the above link.

Adenovirus Forced to Evolve as Gene Therapy Vector

Scientists from UC Berkeley and Ohio State University have forced an adenovirus to evolve in order to make it a better vector for gene therapies. The immune systems of most people are capable of recognising an adenovirus invader and neutralising it before it is able to accomplish its task of inserting therapeutic genes into target cells.

UC Berkeley's David Schaffer, associate professor of chemical engineering and a member of the Helen Wills Neuroscience Institute, with colleagues Narendra Maheshri, James T. Koerber and Brian Kaspar, decided to speed up the process of viral evolution and direct the change in a way that would allow the virus to slip past the body's immune defenses, making it a more viable vehicle for gene therapy. In essentially two generations of accelerated evolution, requiring about two months of lab work, they succeeded.

Schaffer and his team at UC Berkeley and at Ohio State University report their success in the current issue of Nature Biotechnology.

"Directed evolution has mainly been done to change the activity of an enzyme - to make it more effective toward a new substrate or better able to catalyze a reaction, for example - or to make antibodies better binders against specific targets," said Schaffer, who also is an affiliate of the UC Berkeley wing of the California Institute for Quantitative Biomedical Research (QB3). "In the viral realm, this approach is essentially untapped."

This technique could be used to improve many other characteristics of AAV to make it a better delivery vector for genes.

"We think there are a huge variety of new problems we could address as well, such as targeting the virus to cells it is ordinarily not good at getting into, or speeding its transport through the body," he said.

My first thought on reading about this discovery, was concern that these techniques would make it easier to create viruses engineered for germ warfare. Dr. Shaffer was asked about this possiblity.

Though Schaffer acknowledges that the technique could be used to help pathogenic viruses evade the human immune system, potentially making them more virulent, he said that other and easier techniques already allow this frightening possibility. He did not elaborate on those easier techniques.

How did they do it?

AAV consists of two genes enclosed within a ball, or capsid, of proteins. The capsid proteins are what antibodies recognize, and as a result were the target of directed evolution. To provide the raw material for evolution - the genetic variation from which nature selects the best-adapted organism - the researchers created mutant viruses by introducing small variations in the genes through an error-prone polymerase chain reaction (PCR) coupled with a test tube recombination technique. After reassembling the mutant viruses inside their capsids, they introduced them to blood serum pooled from rabbits immunized against AAV, and thus containing many types of antibodies to AAV. Only the mutant viruses good at evading antibodies to AAV survived the serum.

After passing the viruses three times through increasingly more potent serum, they isolated the survivors and subjected them to another round of PCR that introduced more mutations. After passing this second generation through serum three times, they isolated viruses that could survive AAV antibodies much better than the original strain of AAV. One strain of virus was 96 times more effective than the wild AAV, and two evolved strains survived injection into mice with nearly 1,000 times the level of antibodies required to neutralize the wild virus.

By sequencing the survivor strains, the researchers discovered that the capsid proteins of the survivors differed from those of the original strain by only seven amino acid building blocks, two of which were responsible for most of the altered interaction with antibodies.

"Starting from scratch, just trying to rationally decide which two amino acid changes to make on the virus, there is no way you would have guessed those two," Schaffer said. "Using the same algorithm as nature came up with - evolution - to solve the problem, is the best way to do it."

Since each generation takes about a month, Schaffer predicted that many types of new and improved strains could be created in a few months' time, and certainly in less than a year. He is pursuing experiments now using pooled human blood serum.

Read the entire article for more information. I am not entirely comforted by Dr. Schaffer's assurances of safety, but to be honest, the cat is certainly out of the bag. Genetic engineering techniques may ultimately be more dangerous than nuclear weapons technology, and are being taught to anyone interested at most universities around the world. The incredible promise of benefits comes along with daunting dangers. That is the nature of our world.

Here is an interesting general overview of gene therapy, from the US NIH.

Robot Surgeons: For Prostate Cancer and Gastric Bypass?

Robotic surgeons may seem like science fiction, but they are routinely helping human surgeons perform surgeries across the world, especially North America. Prostate cancer surgery is benefitting immensely from robotic surgeons, since the robots can be more precise in nerve-sparing, allowing men to retain important functions of elimination control and sexual performance that can easily be lost during such surgery performed by a human surgeon.

At the USC Center for Pancreatic and Biliary Diseases, surgeons perform increasingly complex procedures on the liver, pancreas, and associated ductal systems.

The world experience on the use of the Da Vinci Robotic System for surgery on the pancreas, bowel duct, and liver is limited. We have developed experience with this robotic system for the following surgical procedures:

* Bile duct reconstruction
* Hepaticojejunostomy (suturing an obstructive bile duct to the intestine to provide drainage to a bile duct blocked by tumor or other cause)
* Distal pancreatectomy
* Reconstruction of the gastrointestinal tract after a Whipple operation
* Laparoscopic cholecystectomy
* Laparoscopic adrenalectomy
* Pancreaticojejunostomy and the Peustow procedure (suturing the jejunum to the pancreatic duct to provide drainage of pancreatic juice into the intestine in patients with obstruction of the pancreatic duct).

Many more procedures of increasing complexity are being researched for these robotic systems. Read more from "Howstuffworks" and "Futurefeeder":

The first generation of surgical robots are already being installed in a number of operating rooms around the world. These aren't true autonomous robots that can perform surgical tasks on their own, but they are lending a mechanical helping hand to surgeons. These machines still require a human surgeon to operate them and input instructions. Remote control and voice activation are the methods by which these surgical robots are controlled.

Robotics are being introduced to medicine because they allow for unprecedented control and precision of surgical instruments in minimally invasive procedures. So far, these machines have been used to position an endoscope, perform gallbladder surgery and correct gastroesophogeal reflux and heartburn. The ultimate goal of the robotic surgery field is to design a robot that can be used to perform closed-chest, beating-heart surgery. According to one manufacturer, robotic devices could be used in more than 3.5 million medical procedures per year in the United States alone. Here are three surgical robots that have been recently developed:

* da Vinci Surgical System
* ZEUS Robotic Surgical System
* AESOP Robotic System
More at Howstuffworks.

The Da Vinci surgical system has enjoyed a lot of publicity recently. Here is an excerpt from an article in Future Feeder:
. . . In robotic-assisted surgery, the da Vinci robot is an extension of the surgeon’s hands in a way not previously possible with minimally invasive surgery via laparoscopy, he said.

“And that’s the key to its success,” Boggess added. “The robot takes us a big step beyond traditional laparoscopy. It allows us to operate more naturally, the way we do in open surgeries, but still preserve a minimally invasive approach with small incisions.”

As in laparoscopy, robotic surgery involves small incisions of one-fourth to three-fourths of an inch, into which sleeves are inserted as ports for placement of specialized instruments and a video camera.

“Robotic surgery allows us to virtually place our hands inside the patient without the need for large incisions,” Boggess said.

After sleeve placement, the robot, much like a post with three arms, is wheeled over and its center arm docked to a port that holds the camera and the other arms docked to the instrument ports.

However, surgery with the da Vinci does not mean close proximity to the patient. Unlike with laparoscopy, the surgeon is seated across the room from the patient, with arms inserted into the nearby console, fingers on stirrup-like holders and eyes fixed on lenses for sharp magnified images of the surgical site. Focus is adjusted via foot pedals.

While laparoscopy allows manipulation of instruments up, down and side-to-side, surgery with the da Vinci allows more natural wrist movement.

The robot’s arms have wrists with eight degrees of freedom that allow the surgeon “to bend around corners and work in ways that are much more natural,” said Boggess. This allows full range of motion and the ability to rotate instruments 360 degrees through tiny incisions. Direct and natural hand-eye instrument alignment is similar to open surgery, with “all-around” vision and the ability to zoom in and out.

Another advantage with da Vinci is the elimination of tremor. Surgeons can scale, or ratio, their finger movement to that of the robotic instrument. A movement of inches at the console can be scaled down to centimeters in the patient.

So even a surgeon with a tremor can perform flawlessly with the Da Vinci surgical robot. The robot is actually an improvement in many ways, on the natural human surgeon--but it depends on the human surgeon. It is an augment, not a replacement.

These machines are quite expensive, and still experimental for many procedures. Nevertheless, in settings where medical provision is by private pay, these machines should gain in use. In settings of government provided medicine, the machines will take much longer to attain wide use, due to cost constraints.

Eventually, cardiothoracic surgeries and intracranial surgeries will be done routinely by robot, due to the delicate nature of those procedures.

Modern machines are capable of doing things that our grandfathers would not have imagined. Years in the future, our grandchildren will say much the same thing about their machines, referring to us and our own limited imaginations. This technological acceleration can be thought of as an intimation of the singularity.

Update: Here is a buy recommendation from Oneguysinvestments for ISRG, the company behind the da Vinci robot system.
Several new studies were released this year indicating continued improvements in cancer control, continence and sexual function for robotic prostatectomies -- 20% of prostatectomies are already performed with the da Vinci, and I think patient demand should continue to drive that much higher (their goal is hitting 25% this year, which I think is conservative). The only argument against da Vinci prostatectomies is now the high up front cost. It's definitely worth listening to the call (archived on their website) just for the clinical update.

My opinion on the cost issue: In most cases hospitals can't charge more for the robotic procedures than for open procedures, but in the future this might change with the clear benefits to insurers of much shorter hospital stays and better results.

Mitral valve repair, gastric bypass, and "da vinci hysterectomy" can all be significant drivers of procedure growth if the good results we've so far seen continue. The huge gynecological market is just beginning to be tapped and may show growth that compares to prostatectomies in the coming years (but for a much larger market). It took about two years of study before the prostate surgery took off for ISRG, so the gynecological growth may be a year or two from hitting its stride.

Read the whole thing and see what you think. I make no recommendations for investments on this blog.

Gene Therapy Poised for Widespread Use in Metal Implants

Metallic artery stents are routinely used to open clogged coronary arteries. One of the major problems with stents is the frequency of restenosis. Now, scientists have proven that genetic therapy can be administered by way of the stent, to cut down on restenosis.
This medical news today article describes research from the Children's Hospital of Philadelphia, where a team of cardiologists and scientists demonstrated the technique both in cell culture and in rodents.

Cardiologists frequently treat heart disease patients now by using stents to expand partially blocked blood vessels and improve blood flow. However, new obstructions may gradually form within the stents themselves and dangerously narrow the passageway. A newer generation of stents releases drugs to counteract this renarrowing process, called restenosis, but the polymer coatings that initially hold the drugs to the stents may stimulate inflammation. The inflammation in turn leads to restenosis.

Researchers at The Children's Hospital of Philadelphia have developed a novel technique to attach therapeutic genes to a stent's bare metal surface. This technique allows the genes to help heal the surrounding blood vessels, while avoiding the inflammation caused by polymer coatings.

The research team reported their proof-of-principle study, using cell culture and animal models, in the early edition of the Proceedings of the National Academy of Sciences, published online this week.

“This is the first study to demonstrate successful delivery of a gene vector from a bare metal surface,” said senior author Robert J. Levy, M.D., the William J. Rashkind Chair of Pediatric Cardiology at The Children's Hospital of Philadelphia. A gene vector is a biological substance, in this case an adenovirus, capable of delivering a therapeutic gene to target cells.

Dr. Levy's team created a unique water-soluble compound, polyallylamine biphosphonate, that binds to the stent's metal alloy surface in a layer with the thickness of only a single molecule. The biphosphonate holds and gradually releases adenovirus particles of the type used to deliver therapeutic genes.

In cell cultures, the adenovirus successfully delivered genes from alloy samples to animal arterial smooth muscle cells. In a second experiment using rodents, the researchers detected gene expression with significantly lower restenosis in the carotid arteries of animals with the experimental stents, compared to control animals with conventional, polymer-coated stents.

This procedure utilizes adenovirus as a vector to introduce the genes for inducible Nitric Oxide Synthetase into the vascular cells. Adenovirus gene vector has caused problems in human use in the past, but a lot of progress has been made recently, making the procedure safer. Even so, non-viral vectors for gene therapy in stents will likely follow in short order.

Here is an abstract describing gene therapy using artificial heart valve leaflets. Potentially, any implanted device which is prone to inflammatory reactions or other reactions could be used for gene therapy. Given the increasing use of artificial implants in medicine, the widespread use of gene therapy cannot be far off.

Suspended Animation--Will it give Terminal Patients more Time?

Animal hibernation has long fascinated humans. Recently, scientists have begun to look into the possibility that humans might be able to use hibernation as a way to cheat death. Persons suffering from terminal illness such as cancer, might choose hibernation--to wait in suspended animation for a cure for their disease. Where is the science now?

From rxpgnews.com comes a story about hibernation, and a metabolic switch that triggers a state of torpor. Researchers at the UT Houston School of Medicine exposed mice to total darkness to look for the metabolic switch that mediates darkness-induced hibernation.

A series of experiments pinpointed 5-prime adenosine monophosphate (5'-AMP) as the key molecular mediator of the constant darkness effect, switching mice from a glucose-burning, fat-storing state to a fat-burning, glucose-conserving lethargy.

Active mammals – a bear foraging for food or a human running a marathon – also undergo a similar switch, burning glucose first to fuel their efforts, and as blood sugar is consumed, their bodies switch to burning fat.

"How does the body know when to switch? 5'-AMP is the signal. I believe it's the same metabolic system, whether we are talking about hibernation or not," said senior author Cheng Chi Lee, Ph.D., professor of biochemistry.

The team started with a basic question: What actually sets off hibernation? "These animals dig deep burrows," said Lee, an expert in circadian rhythms. "They are constantly in the dark. Why not darkness as a switch?"
This research was published in 19 Jan 2006 Nature.

Previous research used hydrogen sulfide and carbon monoxide as hibernation triggers in mice. Another known hibernation trigger in animals is an opioid like substance known as HIT, hibernation inducement trigger.

Cryonics is yet another approach to suspended animation. Freezing mature human cells produces irreparable damage. That may be a solvable problem. Human sperm, human ova, and human embryos are all frozen without damage. Why not adult humans?

What if people could choose suspended animation without any risk? How would society react to that choice? In welfare state societies, with cradle to grave social supports, the extra cost of supporting millions of people in hibernation might tip the economic balance. But if only the wealthy are able to go into a suspended state, to await a cure for terminal disease, how will the lower tiers react?

Biotechnology is not an ethereal, disconnected cognitive exercise. Every exciting discovery has long term repercussions. The future is not for the timid.

Update: Acceleratingtechnology.com points to this Sydney Morning Herald article about MGH Boston surgeon Hasan Alam, who continues to develop a method of inducing profound hypothermia, using pigs.

First he anaesthetises the animal, then cuts a major vein and artery in its abdomen to simulate multiple gunshots to a person's chest and abdomen.
As the pig rapidly loses about half its blood and enters a state of shock, Dr Alam drains its blood and stores it before pumping chilled organ preservation fluid into its system.

The animal's body temperature falls to about 10C until it is in a state of "profound hypothermia" and has no pulse and no electrical activity in its brain.

But after the blood stored earlier is warmed and pumped back into the pig's body its heart starts beating again and it comes back to life.

"It is still pretty awe-inspiring," Dr Alam said. "Once the heart starts beating and the blood starts pumping, voila, you've got another animal that's come back from the other side.

"Technically, I think we can do it in humans."

Dr. Alam is attempting to gain permission to use the technique in human patients who are so critically injured that they would certainly die without this type of heroic intervention. I would not want to be on the ethics committee of Mass General, dealing with this request. Most bioethicists who try to run such committees are not sufficiently seasoned in the real life and death world of trauma medicine, to understand such situations, where seconds can count. Read the entire article and think whether you would approve the procedure.

Featured Reference Site--MedBioWorld.com

I have a profound weakness for reference websites that contain a lot of links. Contained within the sidebar to the right, are many innocent appearing links which, when clicked, expose the unwary reader to thousands of new worlds--links to previously undiscovered websites.

Medbioworld.com is one of those seemingly innocent links.

Any reader that has the slightest interest in medical or biological topics should be warned not to visit the medbioworld site when they are pressed for time. Just bookmark the site, and go back to it later when you have more time.

Here is how the site describes itself:

MedBioWorld™ is the largest medical and bioscience resource directory on the Internet. The portal is currently ranked fourth for medical journals, third for medical directories, and first for bioscience directories by Google™, with:

8,200 journals within 80 medical specialties and 101 bioscience fields
7,000 medical and bioscience associations
32,000 Reuters Health and Industry news articles
3,100 medical and bioscience databases
2,000+ bioscience companies
Plus many other research and reference tools listed within the portals directory.

The internet represents a true revolution in knowledge access to the public. A person would be a fool to try to predict exactly where it will all end.

More Virus vs. Cancer News: From the UK

This older (2004) newscientist.com article describes a genetically modified adenovirus that can infect cancer cells and explode them from the inside. This is simply to show that this research has been ongoing with different viruses in different research labs around the world.

Deleting a key gene from the virus enabled it to infect and burst cancer cells while leaving normal tissues unharmed, reveals a study by researchers at Cancer Research UK and Queen Mary's School of Medicine and Dentistry, University of London.

Viruses spread by infiltrating the cells of their host. Normally, the detection of an intruder by a cell triggers a process called apoptosis, which causes the cell to commit suicide and prevents the virus spreading further. However, viruses can carry genes that allow them to slip past this cell death process in normal cells, causing infection.

The UK researchers deleted one such gene in an adenovirus. This meant that the virus was immediately detected by normal cells and was unable to spread. But in cancer cells, which grow uncontrollably and ignore the cell death process, the virus was able to thrive and spread rapidly. It then multiplied so vigorously that it killed the cancer cells by making them explode.

"The great thing about this strategy is that the cancer cell does all the hard work," says Nick Lemoine, director of the Cancer Research UK Clinical Centre at Bart's Medical School, who led the team. "It makes more and more virus to infect its neighbouring cancer cells. But if a normal cell is infected, it commits suicide before it can make new virus and spread of the virus is contained."

Go here to read the entire article.

Every tool that is developed for manipulating genes, opens more avenues for research into fighting the bio-killers of our day. From research into genes and DNA in the mid 20th century, to research on restriction enzymes and gene manipulation in the 1970s, to the rapid gene mapping of the 1990s, to the ever more advanced genetic manipulations of the 21st century. The breakthroughs from the biotechnology and genetic revolutions are coming. This genetically modified adenovirus will be just one of many to carry the heavy load for humanity.

Making an Ally of a Virus to fight Cancer

Thanks to medicineworld.org cancer blog for pointing out a fascinating study in the use of the Newcastle Disease Virus for treating cancer.

The study is reported at Isracast.com.
Professors Amos Panet and Zichria Zakay-Rones, from the Department of Virology at the Hebrew University Hadassah Medical School, have been involved during the past five years in research that could create a new and effective weapon in the fight against cancer, as well as change the way we look at viruses. As an obligatory parasitic entity with no independent life of its own, a virus must enter a living cell in order to multiply. The viral life-cycle begins when the virus inserts its genetic material into the host's cell, forcing it to replicate the virus' components, and eventually leading to the death of the cell. The NDV-HUJ virus, discovered by the Hebrew University in Jerusalem team, acts in a similar way, except for its outstanding preference for infecting cancerous cells. NDV-HUJ is a natural variant of NDV (Newcastle Disease Virus) which usually affects birds. Being an attenuated variant (e.g., weakened virus), it is innately preferentially targets and replicates in certain types of tumor cells, leaving normal cells almost unaffected.

....Viro-therapy is not a new idea. Its roots could be found in the mid 20th Century, when a number of physicians noticed an interesting phenomenon: some of their patients, who suffered from cancer and had an incidental viral infection, or subjected to vaccination, were now improving, experiencing a remission from their symptoms. In the 40's and 50's, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumors, and in 1956, one of the first human clinical trials with an oncolytic virus ("onco" meaning cancer, "lytic" meaning "killing") was conducted in patients with advanced-stage cervical cancer. Nevertheless, systematic research of this field was delayed for years, due to lack of more advanced technologies.

....Apoptosis or "programmed cell death" is the end stage in the life cycle of a cell. Every form of existing cancer treatment is aimed at causing selective apoptosis of cancer cells. The problem is that in cancer cells the apoptosis mechanism is damaged, thus allowing the cells to exist beyond their normal life span and multiply out of control. Existing cancer treatments use the apoptosis mechanism to destroy cancer cells, but due to the damage done to its apoptosis mechanism the cancer cell requires a stronger treatment in order to activate its "self destruct" mechanism. Stronger treatments mean more damage to normal cells in the body which is why Chemotherapy is considered such a harsh treatment.

....After receiving the NDV-HUJ virus treatment, one of the 14 patients exhibited a regression of the tumor, a surprising fact given the aggressive nature of the GBM cancer and the early phase of the clinical trials. These initial results are encouraging since no adverse side effects were noticed in the treated individuals.

The researchers will continue to study the mechanisms of viral infection of tumor cells, and ways in which this approach to therapy might strengthen the apoptosis mechanism in tumor cells. They will also work on maximizing the selectivity of the virus for the tumor cells. The virus used in the initial studies was an attenuated strain. Other forms of the virus might be more efficient, if the researchers can be sure the virus will not escape into the wild bird population.

There is much to learn about the nature of cancer, and the interaction of the human body's immune system with the malignancy. Introducing a viral infection into the total picture makes the study even more complex. It will take time to sort things out. The basic approach should be ultimately productive.

Update: Newhopeblog and Hyscience blog had previously posted on this story. I only discovered those blogs after posting this story, but the Newhopeblog in particular appears to have a lot of good medical resources. I plan to add them to my blogroll. Their source for the story was the ever capable Medical News Today.

Alzheimer Drug Appears Effective for Moderate Disease

Thanks to Neurology Watch News Blog for pointing to a progress report study on Memantine, a novel drug for Alzheimer's Disease. The study was done at NYU School of Medicine, and published in the January 2006 issue of Archives of Neurology. Memantine has been found to be useful for at least a year, for moderate to severe Alzheimer's Disease. That is excellent news for the sufferers from the disease, and particularly for their loved ones. The drug was inexplicably referred to as Namendaandreg at Neurology Watch, but hopefully they will correct the mistake.

"This study demonstrates that it is possible to alleviate some of the cognitive and functional losses associated with the later stages of Alzheimer's, providing a basis for greater optimism on the part of caregivers," says Barry Reisberg, M.D., Professor of Psychiatry at NYU School of Medicine, the lead investigator of the study, which is reported in the January 2006 issue of the Archives of Neurology.

According to this website, Memantine is:
a moderate affinity NMDA-receptor antagonist. Memantine has been developed by Merz Pharmaceuticals and is approved in Europe and the USA for the treatment of moderate to severe Alzheimer's disease. In addition memantine is available in Mexico and in several South American countries.

Efficacy of Memantine
Clinical data on memantine show

*
Benefit in cognitive and psychomotor functioning
*
Benefit in activities of daily living
*
Reduction of care dependence
*
Excellent tolerability

Memantine produces symptomatic improvements in learning under conditions of tonic NMDA receptor activation in Alzheimer’s disease. In contrast to first generation therapies, memantine is likely to show neuroprotective effects at concentrations used in the treatment of Alzheimer’s disease and to slow down disease progression.

Go here for more information.

Here is a brief abstract from a scientific article on memantine.

Memantine is also used in vascular dementia. There will likely be many more uses for the drug if it continues to be safe and effective in actual use. Any drug that can minimize Glutamate induced neurotoxicity will probably find much wider use in the future.

In addition, Memantine is related to the anti-Parkinson's and anti-influenza drug, Amantidine.

Genes are only 2% of Human DNA: What About the Rest?

Humans have a lot of "extra" DNA beyond what is contained in the 30,000 or so genes in the genome. Scientists expected humans to have 100,000 or more genes, given the complexity of the human organism. What is all that extra DNA doing? According to this report from news-medical.net, the worldwide race is on to locate the small DNA sequences that participate in the control of the "turning on" and "turning off" of genes.

Growing knowledge of how regulatory sequences control gene behavior has the potential to create new classes of treatment for nerve disorders and heart failure. Such sequences may also help to explain why humans are so complex, despite having one-fifth as much genetic material as wheat for instance. Medical center researchers are working on just one of more than 100 regulatory sequences identified so far, each the subject of intense study.

"Most people don't realize that genes make up a very small percentage of the human DNA code," said Joseph M. Miano, Ph.D., senior author of the journal paper and associate professor within the Cardiovascular Research Institute at the medical center. "Genes are relatively straightforward compared to what lies ahead. We believe that the real genetic gymnastics, the real intelligence of our system, is controlled by tiny bits of genetic material that tell genes what to do."

....Researchers also concluded that genes, specific batches of code that direct protein construction, comprise just about 2 percent of all human DNA. A central question in genetics has become: what does the remaining 98 percent of human genetic material do?

Regulatory sequences are emerging as an important part of the non-gene majority of human genetic material, once thought of as "junk DNA." A new frontier in genetic research is the defining of the regulome, the complete set of DNA sequences that regulate the behavior of genes. DNA segments that code for proteins average 200 base pairs in length, whereas regulatory sequences typically include just six to 10 base pairs, making them hard to find.

....In Miano's study, the regulatory sequence under examination was the CArG box. The nucleotide building blocks of DNA chains may contain any one of four nucleobases: adenine (A), thymine (T), guanine (G) and cytosine (C). Any sequence of code starting with 2 Cs, followed by any combination of 6 As or Ts, and ending in 2 Gs is a CArG box.

According to Miano, there are 1,216 variations of CArG box that together occur approximately three million times throughout the human DNA blueprint.

....When a piece of genetic material, gene or regulatory segment, is conserved by evolution from mice to humans it suggests that the segment has a valuable function. Miano's screen required that CArG boxes shared by humans and mice be included in his expanded version of the CarGome. CArG boxes identified by the computer screen were then tested to see if they indeed interacted with SRF and changed the behavior of genes as predicted.

This approach resulted in the disclosure of more than 100 hypothetical CArG boxes and the same number of genes previously unknown to be targeted by CArG-SRF. Of those, 60 CArG boxes have been validated as exerting influence over a gene.

....In the larger picture, regulatory sequences may help to explain why humans have just 25,000 genes when, given the degree of human complexity, researchers had expected to find more than 100,000. Regulatory sequences may be part of the answer because they enable a single gene to produce the same protein at different times, places and concentrations with subtly different roles.

"Humans share about one quarter of their genes with fish," Miano said. "Something must be at work to explain why we are so many times more complex. Regulatory sequences offer one of several emerging explanations for how we do more with fewer genes."

Go here for the full story.

Mapping the genome was only the start of the solving of the puzzle. Now we have to learn how the whole Rube-Goldberg device really works.

Better Living Through . . . . Membranes?

Basically, membranes are a semi-permeable barrier. They're like a wall, except that gases, and even liquids, can seep through them. But--here's the key point--different molecules move through membranes at different rates. Membranes can therefore be used to sort things out, separating one type of molecule from another. Membranes have many uses on Earth, not only on Mars.

Here is an innovations-report about the discovery of a rubber-like membrane (by scientists at U of Texas, Austin), that retains hydrogen gas while allowing carbon dioxide gas to escape.

This member of a new family of membrane materials with superior gas-separating ability could lower the costs of purifying hydrogen for hydrogen-fueled vehicles. Hydrogen fuel cells are considered a leading alternative energy for running cars and other devices in the future. The membrane material could also replace an expensive step in current petrochemical processing, or reduce how much energy the step requires. The membrane was tested under conditions that mimic those routinely used by the petrochemical industry to refine petroleum components (crude oil and natural gas) for use.

"A significant amount of the hydrogen in use today goes into the refining industry to refine crude oil to produce gasoline or other products, so this membrane could lower refining costs," said Freeman, the Kenneth A. Kobe Professor in Chemical Engineering.

The membrane differs structurally and functionally from previous options, with a key advantage being its ability to permit hydrogen to remain compressed at high pressure. A compressed form of the light-weight gas is needed to process fossil fuels and for it to serve as a readily replaceable fuel for fuel cells.

Biological membranes perform an incredible number of vital functions for cells and sub-cellular components. Synthetic membranes are used in industrial and chemical processes for separation of liquids and gases.

The synthetic membrane recently discovered at UT Austin, will find a large number of important uses eventually. Reducing the costs of petroleum refining, and making hydrogen fuel cells more practical, are only two high impact uses for this membrane. It is easy to speculate that such membranes will be used for air recycling for anesthesia, undersea breathing uses, and possibly for air recycling in space. Those and many other uses will come when the membranes go into higher level production, and costs are lowered.

Nanotechnological membrane development is the next stage beyond mere chemical synthesis of membranes. With nanotech membranes, we may be able to approach the incredibly fine selectivity of biological membranes, while retaining the hardiness of non-living materials.

Telomeres and Telomerase -- Masters of Destiny?

This bio.com newsfeature discusses fascinating research by scientists from Brown University.
Human cells replicate anywhere from 60 to 90 times before senescence sets in, a phenomenon scientists believe is a safeguard against disease. While senescent cells still function, they don't behave the way young cells do - and are associated with skin wrinkles, delayed wound healing, weakened immune system response and age-related diseases such as cancer.

... Veterinarians took small skin samples from the monkeys' forearms. Scientists in the Sedivy lab tested the connective tissue for the presence of six biomarkers, or biological "red flags," that signal cellular aging. For replicative senescence, the most important biomarker is telomere dysfunction-induced foci, or TIFs. Presence of these structures signals that the protective chromosome caps called telomeres have dwindled enough to halt cell division.

Scientists painstakingly counted the cells with aging biomarkers. What they found: The number of senescent cells increased exponentially with age. TIF-positive cells made up about 4 percent of the connective tissue cell population in 5-year-olds. In 30-year-olds, that number rose as high as 20 percent.

..."This research confirms that telomeres are important in aging," he said. "But we've only scratched the surface. Now that we've come up with the tools and methods for further TIF research, I am eager to see if the same patterns play out in other tissue."

Brown post-doctoral research fellow Utz Herbig is the lead author of the article. Brown undergraduate Mark Ferreira rounds out the Brown research team. Laura Condel and Dee Carey from the Southwest Foundation for Biomedical Research also contributed.

The National Institute on Aging funded the work.

Source: Brown University

Another report from Bio.com is this industry analysis of telomerase activators from Geron Corp. Geron's telomerase activators should find good use in treatment of HIV disease, and of malignancies.
During the progression of HIV disease, certain immune cells called CD8+ cytotoxic T-cells undergo accelerated replicative senescence (cellular aging), and lose their ability to proliferate and kill HIV-infected CD4+ T-cells. Previous work by Dr. Effros and colleagues demonstrated that introducing the telomerase gene into CD8+ cells from HIV/AIDS donors increased their proliferative capacity, their ability to produce IFN(gamma), and their ability to inhibit viral replication and kill HIV-infected T-cells. Dr. Effros demonstrated that the small molecule telomerase activators TAT0001 (GRN951) and TAT0002 (GRN665) improved the proliferative response of T-cells and increased IFN(gamma) production. The new data presented at the Gordon Conference showed that HIV-specific CD8+ cells pre-treated with either TAT0001 or TAT0002 had enhanced ability to inhibit viral replication when co-cultured with HIV-infected CD4+ cells.

"The new work conducted by Dr. Effros confirms and extends her earlier studies with TAT0001 and TAT0002, showing that our drug candidates enhance multiple functions of the cytotoxic T-cells that keep HIV in check," stated Calvin B. Harley, Ph.D., Geron's chief scientific officer. "These data, our ongoing safety studies and other product development activities are leading us to a novel pharmacologic approach for the treatment of HIV/AIDS."

Geron is active in all phasis of telomerase and telomerase inhibitor research. The company also is doing much work in stem cell research.

Telomeres are nucleic acid sequences at the end of chromosomes. Telomeres shorten with each cell division, up to the "Hayflick limit" of cell divisions.
At that point, cells resist the stimuli to divide.

Here is a research report from bio.com discussing possible use of telomere treatments for cancer.

Some scientist speculate that telomeres may be at the root of many species extinctions.


This is very dangerous territory, and must be covered with all meticulous thoroughness. Geron has been following a productive trail for many years now. It is a good company to follow, as well as its competitors.

Update: Here is a link to a story from medicineworld.org
Chromosome ends, or telomeres, are repetitive stretches of DNA that protect chromosomes in much the same way as plastic tips on shoelaces prevent the fabric from fraying. Each time a cell divides, its chromosome ends get a little shorter, and eventually the cell can no longer divide because its critical genetic information is exposed. In stem cells, however, a protein called telomerase normally maintains the telomeres' length, allowing the cells to divide indefinitely.

Now, the Hopkins scientists report that mice engineered to have just half the normal amount of telomerase can't maintain their stem cells' chromosome ends, showing that a little telomerase isn't enough. In these "half-telomerase" mice, their telomeres shortened over time, bringing an early demise to stem cells that replenish the blood supply, immune system and intestine, the scientists report. Moreover, offspring of these mice bred to have normal levels of telomerase still exhibited early loss of stem cells, the scientists report in the Dec. 16 issue of Cell.

...Because sperm and egg arise from stem cells, too, their telomeres gradually shorten, and each successive generation starts out with chromosomes whose telomeres are even shorter than their parents, the scientists report. The failure of telomerase to lengthen these telomeres explains why successive generations develop the physical symptoms of the disease at younger ages than their parents or grandparents, say the researchers.

...
"Normal levels of telomerase didn't lengthen short telomeres in our mice, so the longer the telomeres are to start with, the longer transplanted stem cells will be able to divide and the more likely the transplant is to succeed," explains Greider.

To engineer the half-telomerase mice, Ling-Yang Hao, then a graduate student, knocked out one copy of the telomerase gene in non-laboratory mice, whose telomere length is similar to humans'. (Typical laboratory mice have very long telomeres.).

He then bred these half-telomerase mice to one another and the team studied offspring that also carried just one telomerase copy. (Because one copy of each gene is inherited from each parent, only 50 percent of the offspring would be expected to end up with only one telomerase copy; 25 percent would have no telomerase gene, and 25 percent would have two copies of the telomerase gene.).

By the fifth generation, mice had severely shortened telomeres and exhibited failure of organs that have high turnover of their cells -- the bone marrow and intestine among them.

"We thought there might be some relationship between telomerase, telomere length and the survival of stem cells, but it was really exciting to see it," says Greider.

...The scientists are now mating these short-telomere mice with mice with regular-length telomeres to see whether telomere length goes back up. They're also studying the affected stem cells to find out exactly how critically short telomeres are affecting their survival.
The scientists were funded by the National Institutes of Health and the Johns Hopkins Institute for Cell Engineering. Authors on the paper are Hao, Armanios, Greider, Margaret Strong, Baktiar Karim, David Felser and David Huso, all of Johns Hopkins School of Medicine. Karim and Huso are with the Department of Comparative Medicine.

Three Bridges to Tomorrow

JW Bats of Tech Future Blog has provided an intriguing story about the quest for nano-factories. The full story is available at this link, or you can read the abbreviated version here.


Snowcrash at Biosingularity presents a study from UC Irvine that examines how single memories are processed in multiple regions of the brain simultaneously. Different aspects of the same "memory" were processed in the hippocampus, the amygdyla, and the anterior cingulate cortex. Snowcrash also earlier discussed a research study on a related topic from Johns Hopkins.

Bio.com presents the observation of evolution in action.
While biologists have understood the basic machinery underlying polyphenisms, the mystery remained how such complex traits, which involve mutations in multiple genes, could evolve and persist.

"It's long been known that polyphenisms are controlled by hormones, with the brain sensing environmental signals and altering the pattern of hormonal secretions," said Nijhout. "In turn, these hormonal patterns turn sets of genes on or off to produce different traits. However, we understood only the developmental mechanism, and how it is possible with a single genome in an animal to produce two very different phenotypes," he said.

"There had been theoretical models to explain the evolutionary mechanism -- how selective pressures can maintain polyphenisms in a population, and why they don't converge gradually into one form or another," said Nijhout. "But nobody had ever started with a species that didn't have a polyphenism and generated a brand-new polyphenism. Such a demonstration could offer important insights into the evolutionary mechanism underlying such traits."

There you have three stories indicating progress in the understanding of nanotechnology, evolutionary genetics, and the science of memory formation. All three relate to the singularity and have the potential to bring about great changes in human society when they are better understood.

Learning the language of mind and memory, gaining the ability to master nano-level creation and manipulation, and understanding the complexities of the evolutionary mechanism--these are three important bridges to another level of understanding the world that we are all a part of.

Ethanol from Cellulose: More than anyone dreamed?

The Energy Blog reports on an important new study on biofuels from UC Berkeley.
The Berkeley study shows that while ethanol from corn only gives you 20% more energy than you put into the process, ethanol from cellulose (switchgrass) provides almost 800% of the energy used to produce it.
First of all I hope this report, by an independent organization, will once and for all put to rest the controversy as to whether the net energy value is positive or negative. My support of ethanol for fuel is reinforced by this report. I see some disruptive times in switching from corn ethanol to cellulosic ethanol which is required to both conserve energy and to produce enough ethanol without compromising our food supplies. It is also true that it is more efficient to burn the feedstock in a CHP (combined heat and power) generator and use the electricity to power EV's and plug-ins. This possibly presents another difficult transition in that, at the present time and for the next 15-25 years, our vehicle fleet will be primarily dependent on liquid fuels and we will need all the ethanol we can produce in order to help keep the price of fuels under control. Our ethanol production capacity is rapidly ramping up to help meet this need and possibly could supply 20% of our liquid fuels by 2020. Thanks to The Energy Blog.

The Berkeley study can be found here.

Randall Parker at Futurepundit is famous for his condemnation of biofuels as a waste of land and fuel. He is not alone. Many energy commentators have long maintained that biofuels, including ethanol, will never be economically viable. This study appears to suggest that cellulosic ethanol has the potential to supply much more of the transportation energy supply than most experts ever imagined.

Update:Here is a very informative article about fuel ethanol from CNNMoney. Hat tip to Deep Wealth Blog, a very interesting blog on investing strategies.

Transhumanism hits the Mainstream

In a grudging acknowledgement to the inevitable, the Guardian newspaper printed an article about cognitive enhancing technologies.

The pace of development in four distinct disciplines - neuroscience, biotechnology such as genetics, computing and nanoscience - is such that many envisage dramatic breakthroughs in how we can modify ourselves, our physical and mental capabilities. We could live much longer and be much stronger and cleverer - even be much happier. A whole new meaning to "Be all you can be".

The Washington Post journalist and author of Radical Evolution, Joel Garreau, argues that we are at a pivotal point in human development. Having directed our technological ingenuity on the world around us, human beings are now turning it on to their own bodies and minds. From here on in, we will have the tools to engineer our own evolution.

... So we're not talking about radical new steps, only an acceleration of existing trends. For example, if you can have Viagra for an enhanced sexual life, why not a Viagra for the mind? Is there a meaningful difference? If we show such enthusiasm for "improving" our noses and breasts with cosmetic surgery, why not also improve our brains? As computers continue to increase in power and shrink in size, why shouldn't we come to use them as prostheses, a kind of artificial limb for the brain? If we have successfully lengthened life expectancy with good sanitation and diet, why can't we lengthen it with new drugs? Ritalin is already being traded in the classroom by US students to help improve their concentration.

There's no stop button available. Much of the research that could be ultimately used for human enhancement is urgently needed to counter such neuro-degenerative diseases as Alzheimer's.

There is more at the original link, with the typical Guardian spin. They may be Luddites, but they try to be trendy Luddites.

Hat tip Mindhack.

The general public will never get a grasp of what is happening as long as the mainstream information sources are studiously looking the other way. If thousands of high school students are taking ritalin so as to score higher on their SAT, there is no doubt that many of them will carry this approach to self enhancement with them into adulthood. As I mentioned in "Smart Drugs", the pharmacology is only getting better.

Regenerating Tissue: Two Approaches

Snowcrash has an excellent posting on stem cells and how stem cells are turned into tissues. This is an incredibly important field of research which is a critical part of the SENS approach to rejuvenative therapies. Go check out the article, the good link, and the great graphic.

Singularity News points to an interesting article from Wired News dealing with regenerative therapies that do not rely upon stem cells.
When a worm is chopped in two, the missing part often re-grows. Researchers at several biotech companies are challenging the assumption that humans can't perform a similar feat by developing drugs that encourage self-regeneration.

Hydra Biosciences is working a regeneration drug that stimulates heart muscle-cell regrowth, and could lead to better recoveries for heart attack sufferers. The protein-based drug induces mature cells to become a little bit like stem cells.

It causes heart cells to "dedifferentiate" partially, reverting them to an earlier stage of development and activating their ability to generate more muscle cells. Stem cells, by contrast, are fully undifferentiated, meaning they're a clean slate and have the ability to turn into any type of tissue. But replacing damaged or diseased tissue by regenerating a patient's own tissue, advocates say, has a leg up on stem cell-based procedures because it eliminates many potential medical problems, like immune rejection.

"Stem cell therapy involves using cells from outside the body, so there's the potential for incompatibility," says Mark Keating, head of the human genetics division at the Novartis Institutes for Biomedical Research and an advisor to Hydra. "The cells can also divide too fast and become cancerous." He cautions, however, that it is too early to tell which of the two types of procedures will work best when tested in humans.


Of course autologous stem cells taken from the person himself are perfectly compatible, but those are generally adult stem cells (unless frozen stem cells from cord blood or embryonic clones are available). In general, what Mark Keating says is true.

The de-differentiation of mature cells is an interesting approach to creating quasi stem cells. Some of you may have read The Body Electric by Robert Becker. He is an orthopedist who pioneered the use of electromagnetic stimulation for healing difficult to heal bone fractures, and also pioneered the use of silver electrodes for healing chronic osteomyelitis infections that did not seem to heal with any other treatment. Anyway, Becker postulated that his electric stimulation was actually de-differentiating cells (either wbcs or fibrocytes) to form immature cells that then differentiated to osteoblasts, which then formed new bone to heal the fracture.

I doubt that is what actually happened, rather he was probably stimulating adult stem cells to become osteoblasts/osteocytes, but the concept of de-differentiation has always intrigued me, even after stem cell therapies became more practical.

Cancer is a form of de-differentiation that goes wildly out of control. Any modern therapies designed to regrow body parts will have to be carefully designed to avoid increased incidence of malignancies.

New Reports on Synthetic Biology

Biosingularity Blog links to an exciting suite of articles in The Scientist. These articles discuss different aspects of the revolutionary new quest to build artificial living cells. Go here for the starting point, then follow the links to the other stories.

Craig Ventner (pictured above), is a prominent part of the The Scientist discussions. He is famous for accelerating the project to map the human genome, and now wants to be the first to synthesize a living, reproducing cell. Different researchers are working on various approaches to synthetic cells.

Thanks to Snowcrash at Biosingularity for the link.

Creating living, reproducing cells, is one way to learn about the necessary mechanisms of life that have evolved over billions of years. It may be the best way to learn to improve on those mechanisms, in the long run. The hit or miss methods often used in biological research have worked well in discovering the various pieces of the puzzle. We know that the puzzle has more pieces than we have in the box. We also know that the pieces, once we know we have them all, will have to be put together in certain ways, or the puzzle will not "work."

Fortunately there are many tricks that have been learned over the years in science, engineering, information science, etc. that should come in handy in the many variations of the assembly process.

Remarkable Study Links Mechanisms behind Alzheimer's and Down's

Thanks to Bio.com for a report on research findings that may suggest treatments for Alzheimer's Disease, as well as for Down's Syndrome and other forms of mental retardation.

A new UCLA/Veterans Affairs study implicates defects in the machinery that creates connections between brain cells as responsible for the onset of Alzheimer disease.

The defect in PAK enzyme signaling pathways -- vital to creation of these connections, or synapses -- is related to loss of a synapse protein in certain forms of mental retardation, such as Down syndrome. The new finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.

...This new study implicates the PAK enzyme-signaling pathway, which is known to play a role in synapse formation and developmental cognitive deficits, or mental retardation.


The PAK enzymes form a family that includes two members known to localize to synapses (PAK1 and PAK3). Both are known to play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. Both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients to an extent sufficient to contribute to cognitive decline.

The research team finds that blocking these PAKs in middle-aged mice causes memory loss together with deficits in a protein involved in making neuronal connections. In humans, the same protein shows large losses in Alzheimer as well as in Down syndrome, the most common cause of mental retardation.

It is interesting to think of Down's syndrome as an ongoing process like Alzheimer's, rather than a "set in stone" condition. In other words, in spite of the chromosomal defect (trisomy21) of Down's syndrome, effective treatments might still be developed for the cognitive aspects of the disease by treating the underlying mechanism of the cognitive problems. Can you imagine millions of "Flowers for Algernon" scenarios playing out in families around the world? At both ends of the age spectrum? It is amazing to contemplate.

This study even ties into the theory of Abeta 42 (sticky protein) causation of Alzheimer's, since it was found that oligomers of Abeta42 caused similar types of defects in PAK as those found in Alzheimer's.

Smart Drugs: What are the Prospects?

We begin with an article from Sciam Mind, by Michael Gazzaniga.
Enhancing intelligence is not science fiction. Many "smart" drugs are in clinical trials and could be on the market in less than five years. Some medications currently available to patients with memory disorders may also increase intelligence in the healthy population. Likewise, few people would lament the use of such aids to ameliorate the forgetfulness that aging brings. Drugs that counter these deficits would be adopted gratefully by millions of people.

Drugs designed for psychotherapy can also be used to enhance certain regular mental functions. Just as Ritalin can improve the academic performance of hyperactive children, it can do the same for normal children. It is commonly thought to boost SAT scores by more than 100 points, for both the hyperactive and the normal user. Many healthy young people now use it that way for that purpose, and quite frankly, there is no stopping this abuse.

... consider the following. In July 2002 Jerome Yesavage and his colleagues at Stanford University discovered that donepezil, a drug approved by the FDA to slow the memory loss of Alzheimer's patients, improves the memory of the normal population. The researchers trained pilots in a flight simulator to perform specific maneuvers and to respond to emergencies that developed during their mock flight, after giving half the pilots donepezil and half a placebo. One month later they retested the pilots and found that those who had taken the donepezil remembered their training better, as shown by improved performance. The possibility exists that donepezil could become a Ritalin for college students. I believe nothing can stop this trend, either.

...Recently geneticists have discovered that even such abstract qualities as personality and intelligence are coded for in our genetic blueprint. Studies of the genetic basis of g are just beginning, and because g most likely arises from the influence of many genes, the hunt will be a long one. Yet one study has already found that a gene on chromosome 6 is linked to intelligence.

So-called genetic brain mapping could help the search. Scientists are looking at the structural features (size, volume, and so on) of the brains of many individuals, including twins, familial relatives and unrelated individuals. By scanning all these brains in magnetic resonance imaging machines and looking at the differences, researchers have been able to determine which areas of the brain are most under the control of genes. These studies have emerged only in the past three to four years. Geneticists hope that once they know which brain areas are most affected by heredity, they can figure out which genes are responsible for those regions. With this kind of reverse mapping, the experts should be able to learn more about the genetics of intelligence.

...Whatever happens, we can be sure that cognitive enhancement drugs will be developed and that they will be used and misused. But just as most people do not choose to alter their mood with Prozac and just as we all reorient our lives in the face of unending opportunities to change our sense of normal, our society will absorb new memory drugs according to each individual's underlying philosophy and sense of self. Self-regulation will occur. The few people who desire altered states will find the means, and those who do not want to alter their sense of who they are will ignore the drug potions. The government should stay out of it, letting our own ethical and moral sense guide us through the new enhancement landscape. by Michael Gazzaniga

Next we go to Nootropics.com, a Hedweb site. This review of "Smart Drugs 2" by John Morgenthaler and Steven Fowkes, links to discussions of several potential smart drugs, as well as discussions about the underlying neuroscience and pharmacology involved. Here, we are introduced to modafinil, an increasingly prescribed drug that seems to do what it is supposed to do, with few serious side effects.

Modafinil, or Provigil, is a new stimulant with several different indications, and many more off label uses. Modafinil.org lists 45 uses of modafinil, cognitive enhancement being number 45. Modafinil.com is another Hedweb site, full of links to other pages describing the neuropharmacology of provigil, and the underlying neuroscience involved. Modafinil is becoming very popular with young professionals who never seem to have enough time to get everything done. Militaries use it for special ops troops, helicopter pilots, and pilots on long bombing missions. It works for ADD/ADHD, as an adjunct for depression, for cerebral palsy, and many more dysfunctions. Cephalon is coming out with a single isomer formulation of modafinil called "Nuvigil."

Both donazepil and modafinil are available from physicians, and over the internet. The ethics of internet prescribing are a bit shaky, but expect these drugs to become more available, rather than less, with time.

The last stop on today's smart drug train is the Ampakine station. Ampakines have the potential to not only help normal people think more clearly, as Donazepil and Modafinil seem to do, but to also make them "smarter." Ampakines directly affect the basic learning system of the brain.

New Scientist presented an article last May titled "11 Steps to a Better Brain." Gary Lynch, the inventor of ampakines, was cautious but optimistic:
The drug acts only in the brain, claims Lynch. It has a short half-life of hours. Ampakines have been shown to restore function to severely sleep-deprived monkeys that would otherwise perform poorly. Preliminary studies in humans are just as exciting. You could make an elderly person perform like a much younger person, he says.

While donazepil works on the acetylcholine system, and modafinil works on dopamine receptors, ampakines in contrast affect the glutamate receptors, specifically AMPA receptors. From neurotrasmitter.net, here are a few dozen scientific abstracts dealing with potential ampakines and mechanisms of ampakines--if the wikipedia article did not give you enough information.

That is a lot of information to digest, although if you take these drugs it may not be as difficult as you might think. Perhaps a joke, perhaps not? In time, people who choose not to boost their cognition may be less common than those who choose to do so.

The long term goal is to adjust the genes themselves, to do a better job of improving cognition than any one drug, or symphony of drugs, could possibly do. In the meantime, expect smart drugs to be delivered by pill, injection, skin patch, long term implant, and even injector pumps. The intelligence of a population is serious business, more serious than most people understand. For now.

What is Happening to the IQ of the UK?

A big hat tip to Kevin at Intelligence Testing. He points to a recent article in Gene Expression Blog that discusses a possible decline in intelligence among schoolchildren in the UK.

Kevin also kindly provides a link to the original article in timesonline.

Many of you are aware of the "Flynn Effect" which claims that there is an ongoing increase in intelligence "g" with each new generation. The findings in the UK may stand in contradiction to the Flynn Effect. Since no one understands the Flynn effect, you can be sure no one understands this more recent finding either.

Nevertheless it is very important for what it may say about trends in the developed world. Having a mean population IQ of 100, as the UK does, provides the UK with a predictable supply of men and women with IQs of 110, 120, 130, and 140. These higher IQs are where much of the work of advanced civilisation are done. Without a reliable supply of higher IQ humans, an advanced civilisation would grind to a standstill.

If the mean IQ of the UK were to fall to, say, 90 or below, what would that do to the supply of the higher IQ people who run the complex functions of society? The supply would slowly dry up, from the top of the tail down. At that point, if the UK wants to continue doing advanced research, it will have to import its scientific and engineering talent from abroad.

The mean population IQ of the UK is still around 100, and will stay there, not least because it is set by definition. But you understand the concept, assuming there were a Platonic ideal IQ of "100", defined as the mean population IQ of the UK as measured in the year 2000, the mean IQ of the UK could certainly drop in comparison.

Naturally, I am using the UK as an example, because the study linked to above was done in the UK. But I am actually taking the UK as a metaphor for the western nations. Previous postings here demonstrated the relationship between IQ and national wealth. So. If western cultures have the stomach for it, they need to find out if this "contra-Flynn" effect is real, and what caused it.

More Genetic Discoveries Related to Aging

Biosingularity presents a most intriguing story about mice growing old before their time because researchers at Howard Hughes Medical Institute knocked out the gene Sirt6. Sirt6 helps repair DNA nicks. Snowcrash elaborates:
Knocking out a gene that helps repair nicks in DNA causes young mice to develop many of the degenerative characteristics of their wizened elders. Mice lacking the gene develop hunchback, thinning skin, decreasing bone density, and a declining immune system — all in the span of a month.

The researchers do not know whether the accelerated aging-like effects of losing the gene, called SIRT6, relate to its role in DNA repair. Nor do they know whether the degenerative effects are relevant to the natural aging process. However, they said, the discovery offers an intriguing new model for studying DNA repair, as well as its possible role in aging-related degeneration.

The researchers were put onto the trail of the Sirt genes because of a discovery over twenty years ago that the counterpart gene in yeast, sir2, regulates aging in yeast and preserves genomic stability.

The research on SIRT6 is part of a broad effort in the Alt laboratory to study the role of a family of seven known mammalian sirtuin genes. These studies were prompted by findings some two decades ago that a yeast counterpart called Sir2 maintains genomic stability and regulates aging in yeast cells. Researchers had also found that enhancing the activity of Sir2’s counterparts in the roundworm and fruit fly extended their life span.

Alt and his colleagues were particularly interested in the sirtuin genes because of the yeast Sir2’s role in maintaining chromatin — the complex of DNA and protein that makes up chromosomes.

“While we’ve been exploring the effects of knocking out each of the sirtuin genes, we’ve found that the SIRT6 knockout produces the most dramatic effects,” he said. In their experiments, Alt and his colleagues explored the effects of knocking out SIRT6 at both the cellular and whole-animal levels.

Biosingularity is an excellent source of information about new biological discoveries, because snowcrash filters out the nonsense reports and concentrates on discoveries of potential importance. Read the entire story at Biosingularity.

Most of you will understand immediately how important this type of research is. Proceeding from discoveries in yeast to discoveries in mice, then to discoveries in larger mammals and humans--that is the inevitable progression as the mysteries of the gene are solved, catalogued, and made ready for use.

Reminding us that we are only a few breakthroughs away from a true revolution in energy production and distribution, Energy blog returns to the topic of ultracapacitors. The new product discussed appears to blur the boundaries between ultracapacitors and storage batteries. See this posting for more details. Also see this previous Energy Blog posting on supercapacitors.

The hydrogen economy becomes unnecessary if electricity itself can be stored efficiently in a medium that can charge and discharge through an indefinite number of cycles, and store electricity with almost no leakage. If a renewable energy source of electricity charges the automobiles electric storage directly, without intervening hydrogen and fuel cells, the process is more efficient and less unwieldy.

Society Decides Against Boys

Hat tip to Intelligence Testing for the link to Professor Werner Wittman's presentation on gender differences at the 12th biennial meeting of the ISSID in Adelaide.

The pdf file of the presentation is here. Professor Wittman presents data on measured sex differences, and discusses the significance of current popular educational approaches to dealing with these differences (ignoring them). He concludes that educational systems are skewed toward girls' superior reading and language skills, particularly in the early and middle years. As a result many boys may end up being discarded and cast aside by the system.

Christina Hoff Sommers, in her excellent The War Against Boys, goes in much more detail to explain how assumedly well intentioned reforms in educational training and implementation have resulted in the trashing of a substantial proportion of boy students.

Colleges are approaching a graduation ratio of 60% female to 40% male. Schools of education are pretending there is no problem, even while Microsoft, NASA, Boeing, and most large corporations in north america are bemoaning the coming dearth of qualified engineering graduates. Males are statistically superior to females in spatial skills which are utilised in math, physics, engineering, computer science, architecture, and several other occupations. The higher the level of skill in math, the greater the discrepancy in qualification between males and females.

Anthropologist Lionel Tiger described this process as it was occurring. There can no longer be any doubt of the fallout from these misguided policies in Colleges of Education. Only rigidly mindless political correctness prevents professors of education from admitting their mistake and trying to make amends.

The Quest for More Energy--here and on the moon

JW Bats at Tech Future Blog, has a great post about a new nano-photoelectric technology. Here is the original story and the source for the graphic.

The Speculist has a great story about the heating fusion race. China, Russia, and the US are in a neck and neck race to the moon, to retrieve the fusion fuel, Helium3. Who will be the first to harness the energy of the future, and possibly control the cis-lunar environment?

Peak oil debunked also has a good two part series on the race to mine the moon, and to industrialise outer space.