Virus vs. Cancer: Reolysin Reovirus in Multiple Human Trials

Viruses are hardy pre-lifeforms, that have played a major role in the evolution of humans and other animals and plants. The articles featured in this posting deal with the reovirus labeled Reolysin, by Canadian company Oncolytics.

The novel anti-cancer therapy, REOLYSIN®, is a living virus, not a chemotherapy drug, that is toxic to cancer cells but not harmful to normal cells. This novel therapy, using a living virus, is the first of its kind available at CTRC.

...“This novel therapy has shown success because the reovirus replicates in and destroys the cancer cells within the patient’s body,” said Mita. “Cancer cells have several molecular and genetic abnormalities. In normal, healthy cells, the reovirus is unable to reproduce because of an enzyme named PKR. The enzyme is suppressed in cancer cells, and therefore the reovirus can replicate in the cancer cell and kill it.”

“REOLYSIN® typifies the true targeted therapy approach that seeks to use fundamental differences between cancer and normal cells as the basis for effective anti-cancer approaches and we are thus very excited about the this study,” said Francis Giles, MD, director of the CTRC Institute for Drug Development.

From article discussing human trials of Reolysin for metastatic sarcomas to the lung.

Another trial is ongoing in the UK:

The trial (REO 010) has two components. The first is an open-label, dose-escalating, non-randomized study of REOLYSIN(R) given intravenously with docetaxel every three weeks. A standard dosage of docetaxel will be delivered with escalating dosages of REOLYSIN(R) intravenously. A maximum of three cohorts will be enrolled in the REOLYSIN(R) dose escalation portion. The second component of the trial will immediately follow and will include the enrolment of a further 12 patients at the maximum dosage of REOLYSIN(R) in combination with a standard dosage of docetaxel.

Eligible patients include those who have been diagnosed with advanced or metastatic solid tumours such as bladder, prostate, lung or upper gastro-intestinal cancers that are refractory (have not responded) to standard therapy or for which no curative standard therapy exists. The primary objective of the trial is to determine the Maximum Tolerated Dose (MTD), Dose-Limiting Toxicity (DLT), recommended dose and dosing schedule and safety profile of REOLYSIN(R) when administered in combination with docetaxel. Secondary objectives include the evaluation of immune response to the drug combination, the body's response to the drug combination compared to chemotherapy alone and any evidence of anti-tumour activity. This is the third trial beginning in 2007 that is examining the role of REOLYSIN(R) in combination with standard chemotherapeutics.

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An animal model study using childhood sarcoma cell lines demonstrated significant activity of Reolysin against childhood sarcomas.

Particular viruses can be very useful for treating human disease, and eventually for augmenting normal human function and lifespan. That is because viruses have evolved to be excellent gene therapy vectors, and clever cell sneaks. Viruses can slip into cells and into cell nuclei, and have their way with the cell and its transcriptional apparatus--before the cell is even aware that anything has changed.

Viral therapies have the potential to be misused or misdirected, just like any other revolutionary approach to medicine and life extension. But it is important to understand that the tools that viruses bring to the table are significant, and are the result of billions of years of viral/cellular co-evolution.

More on Resveratrol

Scientists at Harvard and MIT have added to the "Resveratrol mystique." Their research adds weight to the Resveratrol::Sirt1 connection, and suggests that Resveratrol may be useful in preventing neurodegenerative diseases such as Alzheimer's.

The scientists have shown that a gene called SIRT1 and a plant compound found in red wine called resveratrol can protect against neuron degeneration in a mouse model of Alzheimer's disease and amyotrophic lateral sclerosis. The researchers demonstrated that activating SIRT1 and injecting resveratrol, which have both been previously associated with life-span extension in lower organisms, can also prevent cognitive problems in the mice.

The mice used in the study develop an approximation of human neurodegenerative disease over a period of weeks. As neurons in their brains die and lose connections, their spatial learning is impaired, and the mice develop difficulty associating cause and effect. Treatment with resveratrol reduced the death and degeneration of neurons in these mice and also restored their learning abilities to a level comparable to that of normal mice not suffering neurodegeneration. "Thus, resveratrol is not only neuroprotective, it also improves cognitive function after severe neurodegeneration," says Li-Huei Tsai, the professor of neuroscience at MIT who led the research with David Sinclair, a professor of pathology at Harvard. Tsai says this improvement in function suggests that resveratrol has potential for treating human neurodegenerative diseases.

....The study is the first to suggest that resveratrol could actually improve cognitive function in patients with neurodegenerative diseases. "Generally, SIRT1 has been observed to be neuroprotective," says Leonard Guarente, the professor of biology at MIT who uncovered the connection between life span and the yeast equivalent to SIRT1 about 10 years ago. What's new about Tsai and Sinclair's work, he says, is its demonstration that activating SIRT1 prevents cognitive decline in mice with neurodegenerative disease. The study shows that "resveratrol can protect against memory loss and learning decline," says Guarente, who was not involved with the research.

Guarente says the study suggests that compounds that can activate SIRT1 could be used to treat neurodegenerative disease in humans as long as they can pass through the blood-brain barrier. This membrane surrounding and protecting the brain from chemicals in the blood presents a major challenge to any researcher developing drugs that target the brain. Mice in the study received injections of resveratrol directly into blood vessels in their brains, which would not be practical in human patients.

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This type of regenerative gene control via phyto-nutrients is particularly encouraging, given the most famous source of the nutrient is red wine.

Resveratrol and other phyto-nutrients have significant potential to benefit an aging population in the developed world--far beyond whatever in vivo anti-oxidant activity they may possess. The particular mechanisms of their beneficial potential is yet to be worked out.

Care for a Brand New Thymus?

Japanese scientists have built an artificial "lymph node" from thymus tissue, and transplanted it into immunodeficient mice.

The researchers, from RIKEN's Research Center for Allergy and Immunology in Yokohama, constructed their mouse aLNs by impregnating a two- to three-millimeter-diameter scaffold of the fibrous structural protein collagen with connective tissue extracted from the thymus of newborn mice and dendritic cells. Earlier work suggests that it is the connective tissue stromal cells which organize the structure of lymph nodes.

The aLNs were initially implanted into mice with a normal, healthy immune system, which had previously been injected with a harmless antigen compound to trigger an immune response. So the aLNs became populated with immune system T-cells and B-cells which specifically recognize and counter germs or cancer cells expressing the injected antigen.

These primed aLNs were then transplanted into two sets of mice--a group with a normal immune system which had never been exposed to the antigen, and a group in which the immune system did not function. When then exposed to the antigen both groups responded immediately by making appropriate protective antibodies--and the response to the antigen lasted for longer than four weeks, which means immune cells which retained 'memory' of the antigen had been generated.

Further investigation of the immunodeficient mice showed that T- and B-cells from the aLNs migrated to their spleens and bone marrows and were there generating large numbers of antigen-specific antibody-forming cells. The results also revealed some of the compounds involved in directing this migration process.

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This research has implications for the study of treatments for immune diseases, cancer, aging, and infectious disease such as AIDS. Thymosin is one of the several hormone levels that falls abruptly in the aging human. Growing an artificial thymus to boost thymosin levels appears within reach, if proven to be beneficial.

Also, here is a free collection of articles on Nanotechnology in Cancer.

And, here is more on an improved method for cervical cancer screening.

Better screening and better treatments. The two need to go hand in hand. Add better prevention to the mix and you are getting somewhere.

Google Tech Talk May 29 '07: Aubrey de Grey

Here is de Grey at Google, speaking for an hour about the technology of healthy extension of lifespan.

Hat tip Michael Anissimov and Brian Wang.

Ampakines Back in the News

Brain boosting drugs in the new Ampakine class are back in the news--this time in connection with the problem of respiratory depression from sedative/hypnotic drugs.

Researchers at the University of Alberta (Edmonton, AB) and Cortex Pharmaceuticals (Irvine, CA) believe that AMPAKINE drugs may provide protection from drug-induced respiratory depression, while simultaneously allowing the sedative or analgesic to continue working as it was intended.

The drug tested in this study belongs to a novel class of molecules known as AMPAKINE compounds being developed by Cortex Pharmaceuticals, Inc. located in Irvine, California. AMPAKINE compounds act on the most common excitatory receptor in the brain, the AMPA "Glutamate type receptor," which has been shown in rodent models to boost the brain's own protein for improving age-related deficits in memory mechanisms. In primate models AMPAKINE compounds have replicated the studies in rodents and in adults patients suffering from Attention Deficit Hyperactivity Disorder, significant clinical and statistical improvement in increase attention and decrease hyperactivity have been observed. The U. Alberta research provide evidence that another important AMPAKINE indication is to stimulate primitive areas of the brain called the pre-Botzinger Complex responsible for breathing, without causing side effects. The pre-Botzinger Complex generated respiratory-related oscillations similar to those generated by the whole brainstem in vitro, and neurons with voltage-dependent pacemaker-like properties that have been identified in this brain region.

In a study published in 2006, Dr. John J. Greer of U. Alberta demonstrated that certain AMPAKINE compounds enhance the respiratory drive and breathing rhythm at the brain-stem level containing the pre-Botzinger Complex in laboratory rats whose respiration rates were purposely suppressed by administration of central nervous system depressants.

Dr. Greer found that respiratory depression induced by these agents can be reversed or prevented in test animals with an experimental AMPAKINE drug, without a reduction of pain relief or sedation.

Greer and coworkers treated rats with the opioids analgesic fentanyl or the barbiturate sedative Phenobarbital, both commonly prescribed in the United States. Greer used a technique known as plethysmography, which measures blood flow throughout the body, to determine the level of respiratory distressed caused by the drugs. When drugged rats were treated with the AMPAKINE , the respiratory distress quickly resolved. The drug worked in both newborn and adult rats. Interestingly, the drug on its own did not affect blood flow in animals not treated with the sedative drugs, nor did administration of the drug cause noticeable arousal in the animals.

Greer concluded, in a study published in the September 20, 2006 issue of the American Journal of Respiratory Critical Care Medicine, that CX546, "effectively reverses opioid- and barbiturate-induced respiratory depression without reversing the analgesic response."

"These results open up the real possibility of combining an ampakine compound with commonly prescribed barbiturates or opiates to reduce the likelihood that life-threatening respiratory depression will occur," noted explained Roger G. Stoll, Ph.D., Chairman, President, and CEO of Cortex.

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Ampakines hold out a promise for effective palliative treatments for Alzheimer's and other neurodegenerative disease. Currently, the Cortex drug CX717 is being held up by the FDA over toxicity concerns. Consequently the stock price of Cortex is currently quite low--trading below US $3 a share for over a year.

It is easy to see that should Cortex navigate through the labyrinthine bureaucracy of the FDA and reach approval for any of its Ampakines in development, that the stock price could rise rapidly.

Frankly, it is the potential for cognitive enhancement in normal people that fascinates me the most about the Ampakines. But the potential to make a substantial profit on a fairly small investment is also attractive. But do your own research before investing.

The Current Reality of Aging

This New Yorker article describes the current state of the aging process in North America. The reality is particularly stark for those without close family and friends, and with few assets.

By the age of sixty, Americans have lost, on average, a third of their teeth. After eighty-five, almost forty per cent have no teeth at all.

Even as our bones and teeth soften, the rest of our body hardens. Blood vessels, joints, the muscle and valves of the heart, and even the lungs pick up substantial deposits of calcium and turn stiff. Under a microscope, the vessels and soft tissues display the same form of calcium that you find in bone. When you reach inside an elderly patient during surgery, the aorta and other major vessels often feel crunchy under your fingers. A recent study has found that loss of bone density may be an even better predictor of death from atherosclerotic disease than cholesterol levels. As we age, it’s as if the calcium flows out of our skeletons and into our tissues.

To maintain the same volume of blood flow through narrowed and stiffened blood vessels, the heart has to generate increased pressure. As a result, more than half of us develop hypertension by the age of sixty-five. The heart becomes thicker-walled from having to pump against the pressure, and less able to respond to the demands of exertion. The peak output of the heart decreases steadily from the age of thirty. People become gradually less able to run as far or as fast as they used to, or to climb a flight of stairs without becoming short of breath.

Why we age is the subject of vigorous debate. The classical view is that aging happens because of random wear and tear. A newer view holds that aging is more orderly and genetically driven. Proponents of this view point out that animals of similar species and exposure to wear and tear have markedly different life spans. The Canada goose has a longevity of 23.5 years; the emperor goose only 6.3 years. Perhaps animals are like plants, with lives that are, to a large extent, internally governed. Certain species of bamboo, for instance, form a dense stand that grows and flourishes for a hundred years, flowers all at once, and then dies.

The idea that living things shut down and not just wear down has received substantial support in the past decade. Researchers working with the now famous worm C. elegans (two of the last five Nobel Prizes in medicine went to scientists doing work on the little nematode) were able to produce worms that live more than twice as long and age more slowly by altering a single gene. Scientists have since come up with single-gene alterations that increase the life spans of Drosophila fruit flies, mice, and yeast.

The full article is well worth reading, if for no other reason, to understand what gerontologists are trying to fight, and to motivate you to support anti-aging research.

Everyone wants to live forever, but no one wants to grow old. It is a conundrum which only very clear and creative thinking can solve.

Edmonton Aging Symposium--Aubrey de Grey Moderates

Here is the first video from the Edmonton Aging Symposium, provided by The Methuselah Foundation.

Biological Flavonoids--Don't Throw them Away Just Yet

A recent study from the Linus Pauling Institute at OSU Corvallis concludes that bioflavonoids have little if any use as antioxidants.

The study, published in Free Radical Biology and Medicine, found flavonoids are highly metabolized, which alters their chemical structure and diminishes their ability to function as an antioxidant. Although the compounds appear to have three to five times more antioxidant capacity than vitamins C or E, the body sees them as foreign compounds and modifies them for rapid excretion in the urine and bile

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The authors further stated that biological flavonoids may induce the body to excrete more carcinogens, and possibly reduce the risks of cancer and heart disease through other mechanisms than antioxidant activity.

Another study, from Denmark, purports to show that consumption of anti-oxidant supplements such as Vitamin C, Vitamin A, Vitamin E, and Beta Carotene--among others--are of no use in prolonging life and may actually increase morbidity and mortality.

Both of these studies have been used in an attempt to prove that the consumption of vitamins and phytonutrients are of limited if any benefit in the quest to prolong life and reduce risk of illness.

Unfortunately, the Danish study appears to confuse association with causation--a common error among researchers poorly trained in epistemology--and the Linus Pauling Institute study failed to follow the physiology of ingested flavonoids far enough.

It is abundantly clear that many researchers, in their eagerness to publish, fail to think their subject through clearly enough to present a coherent and valid conclusion to either the public, or to fellow scientists. This is more the fault of the competitive environment of modern science than a sign of intellectual or character deficits in the researchers. It is a publish or perish world for academics and researchers.

Quercetin, Resveratrol, Curcumin, Green Tea, Ginger, proanthocyanidins, and other plant-derived nutrients have demonstrated significant potential for reduction of morbidity of many types.

Many flavonoids have demonstrated clear anti-inflammatory effect in various biological models and syndromes. A serious researcher would look further for the source of the physiologic effects of flavonoids, rather than issuing a blanket statement of "no effect" with respect to the narrow issue of particular ways of measuring anti-oxidant activity in vivo. Much more was left undone and unsaid that is of far more importance, than what was demonstrated.

Particularly disappointing is the response of "science blogs" reporting on these and similar studies. Unfortunately, a false image of the underlying facts has been projected to the lay public, which may have unfortunate long term results for some.

Regenerative Medicine--A New Approach to Embryonic Stem Cell Replacement Tissue

Imagine if you will, being able to grow embryonic stem cells to regenerate your failing cells, tissues, and organs--just from your own sperm or eggs. No need to create a fertilised zygote or mated embryo, so there should be no ethical objections from anti-abortion politicians and their constituents.

In the February 15th issue of G&D, Dr. K. John McLaughlin and colleagues report on their success in using uniparental embryonic stem cells to replace blood stem cells in mice. Uniparental embryonic stem cells are an appealing alternative source of patient-derived embryonic stem cells, as they have several advantages over embryonic stem cell lines generated by somatic cell nuclear transfer (also known as therapeutic cloning).

....This study shows for the first time that parthenogenetic blood cells can replace those of an immunocompromised adult mouse. McLaughlin and colleagues also show that this is also possible using embryonic stem cells where both genomes are solely derived from sperm of one male (androgenetic), adding fertile males to the potential patient pool.

....The researchers took a two-step approach: First they injected uniparental ES cells into wild-type blastocyts to generate chimeric animals; then they harvested these chimeric fetal livers for transplant into lethally irradiated hosts. The scientists found that uniparental ES cells, regardless of parent-of-origin, were able to functionally reconstitute the entire hematopoietic system of adult mice. Furthermore, the scientists were also able to grow progenitor blood cells in culture from uniparental ES cells, and upon transplant into irradiated adult mice, show that these cells contribute, long-term, to the function of their hematopoietic system.

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In other words, using either only eggs for a female or only sperm from a male, researchers were able to grow embryonic stem cells as replacement blood cell progenitors. These replacement cells functioned and kept the mice alive.

There are still issues of "imprinting" to be worked out when attempting to regenerate different body tissues from asexually produced ESC's. But at least the cells from this approach would be immunologically compatible with the donor. Immunological compatibility is something that sexually produced ESC's cannot guarantee, for purposes of organ regeneration.

Either way, it will be several years before humans can take advantage of this new opening in regenerative medicine.Some feminists had hoped that only females would be able to produce viable ESCs by the asexual method. They had hoped to use that leverage to force males in the US Congress to vote for unlimited funding for nuclear transfer and cloning technologies to produce new stem cell lines.

My question is--why not do both? I am constantly disgusted by the leftists who try to minimize the importance of non-embryonal approaches to creating stem cells, just as I am disgusted by the religious rightists who try to make every technology that deals with haploid cells into an abortion issue.

Unfortunately both groups of closed minded individuals have their own areas of power--where they work to limit our choices. Too bad.

Mitochondrial Paradigm for ... Aging and Cancer

In looking at aging, it is not enough to look at the nuclear genome. One must also look at the mitochondrial genome, and how the mitochondria interact with the nuclear genome.

Dr. Wallace looks at the ancient history of mitochondria as a free-living organism, and the subsequent symbiosis of mitochondria living inside eucharyotic cells. Then he looks at the mitochondrial genome and how it might affect a person's prospects for a long healthy life. 58 minutes.

Kombucha and Probiotics--Symbiotic Foods

Scientists have recently theorized that the necessary chemical and hormonal treatments for extending human lifespan, could be produced by "artificial cells" created to be implantable chemical/pharmaceutical factories. By programming the artificial cells to produce just the right bio-modifying agents at just the right time for a particular individual's needs--most people could avoid doctor's offices and hospitals for long periods of time. Particularly if biosensors that could be queried over wireless networks by the the person's physicians, were also implanted.

But that type of thing is at least a decade in the future. Why not take advantage of tiny chemical factories that are already available, and that could be more easily genetically modified? I am referring of course to "pro-biotics". The lactobacilli found in yoghurt, and similar bacteria prevalent in the mammalian gut, have been very helpful to humans over the decamillenia.

Kombucha is a particularly interesting form of probiotic tea.

The tea contains a symbiosis of yeast species and acetic acid bacteria, mostly Bacterium xylinum. Species of yeast found in the tea can vary, and may include: Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii and Zygosaccharomyces bailii. The culture itself looks somewhat like a large pancake, and is often mistakenly referred to as a mushroom.

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I was recently introduced to Kombucha by a colleage. Go here for more interesting articles on kombucha.

Bacteria can be made to produce a lot of useful proteins and enzymes, fairly easily. The same is true for yeast. Many of our necessary vitamins are produced in our guts by bacteria. It is time we humans learned to teach our guests how to serve us even better. At this time, the horizons of symbiosis appear to reach a very long way.

Given that these gut bacteria live in the small intestine, beyond gastric acid and gastric proteolytic enzymes, it seems likely that administering peptides via probiotic organisms could be a useful alternative to parenteral administration.

Hormone Replacement: Some People Think It Works

A recent meta-analysis of Human Growth Hormone (HGH) effect on mortality and morbidity painted a pessimistic picture. Certainly a lot of "science" blogs jumped on the story and instantly turned "thumbs down" on HGH replacement. Personally, I say "not so fast." Meta-analysis studies such as this cannot provide a definitive answer to a question. They can only suggest new approaches to experimental study.

While anecdotal evidence is not proof of any scientific principle, some may find it interesting to see examples of "successful" treatment with hormone replacement. These two videos are promotional videos by a hormone replacement clinic in Palm Springs, California. This clinic has been in business for over a decade now.
Total Hormone Therapy Vid. 1
Total Hormone Therapy Vid. 2

The concept of hormone replacement therapy is simple. HGH, DHEA, Thymosin, male and female sex hormones, and often Thyroxin will fall in concentration with age. To better approximate the physical condition of a younger person, you would theoretically want to replace hormones that tend to drop off in concentration dramatically with age. You would also want to see a drop in the pro-inflammatory and other harmful hormone levels that rise with age, at the same time.

It is not proven to work, other than anecdotally. But the idea deserves better experimental analysis than it has received so far, at least in the US.

Michio Kaku: BBC Special Report on Immortality

"This girl may live to be a thousand years old."

So begins Theoretical Physicist Michio Kaku,who is featured in this report on how time perception varies with age, and how that relates to the winding down of the human organism with time.

A fascinating inquiry into long life in nature, and the prospects for human longevity.

Alcor Cryonics Video

This 28 minute video from Alcor looks at the history of life extension technology--specifically the cryonic approach to making "death" reversible indefinitely.

Immortality Institute conference presentation: Brian Wowk

Low temperature suspended animation without freezing is referred to as vitrification. This is a fascinating 26 minute video detailing a method of cryopreservation that prevents cellular damage from expanding ice crystals. This process will be first utilised for preserving organs for long-term storage before transplantation, once early problems are worked out. Eventually animals will be successfully vitrified using this technique. When such animal vitrification and de-vitrification is routinely successful, humans will be next. Related websites: http://www.Mprize.org http://www.ImmInst.org http://www.alcor.org

Exploring Life Extension--A Film by the Immortality Institute

This one hour and 45 minute film explores cryonics (cryogenics), caloric restriction, transhumanism, and other scientific pursuits of extreme life extension. Related websites: http://www.Mprize.org http://www.ImmInst.org http://www.sens.org

TED 2006 Conference Presentation: Aubrey de Grey

Here is a presentation by Aubrey de Grey at the TED 2006 Conference. De Grey's SENS organisation recently received a grant of $3.5 million from Paypal cofounder Peter Thiel. De Grey is certainly not a conventional tie and labcoat type of scientist. But he may be exactly what is needed to shake longevity research out of its doldrums. Presentation by Aubrey de Grey at the Technology Entertainment Design (TED) Conference 2006. http://www.ted.com/conference/flashpage.cfm?conferenceKey=2006 Related websites: http://www.Mprize.org http://www.ImmInst.org http://www.Sens.org

Ray Kurzweil Predicts

Kurzweil predicts human immortality by way of nanomedicine. "Nanobots" in our bloodstreams will repair cellular and tissue damage as fast as it occurs. Affordable computers will be a thousand times more powerful than a human brain . . . Kurzweil clearly believes in "singularity now!"

According to Kurzweil, here's what we can expect in the not-so-distant future:

—Doctors will be doing a backup of our memories by the late 2030s;

—By the late 2020s, doctors will be sending intelligent bots, or nanobots, into our bloodstreams to keep us healthy, and into our brains to keep us young;

—In 15 years, human longevity will be greatly extended. By the 2020s, we'll be adding a year of longevity or more for every year that passes;

—In the same timeframe, we'll routinely be in virtual reality environments. Instead of making a cell call, we could "meet" someone in a virtual world and take a walk on a virtual beach and chat. Business meetings and conference calls will be held in calming or inspiring virtual locations;

—When you're walking down the street and see someone you've met before, background information about that person will pop up on your glasses or in the periphery of your vision;

—Instead of spending hours in front of a desktop machine, computers will be more ingrained in our environment. For instance, computer monitors could be replaced by projections onto our retinas or on a virtual screen hovering in the air;

—Scientists will be able to rejuvenate all of someone's body tissues and organs by transforming their skin cells into youthful versions of other cell types;

—Need a little boost? Kurzweil says scientists will be able to regrow our own cells, tissues, and even whole organs, and then introduce them into our bodies, all without surgery. As part of what he calls the "emerging field of rejuvenation medicine," new tissue and organs will be built out of cells that have been made younger;

—Got heart trouble? No problem, says Kurzweil. "We'll be able to create new heart cells from your skin cells and introduce them into your system through the bloodstream. Over time, your heart cells get replaced with these new cells, and the result is a rejuvenated, young heart with your own DNA";

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Kurzweil as author, is an example of an uber-synthesist. He sifts through mountains of information to find technology trends. He predicts the future, without bothering to have tongue in cheek.

His biological predictions may even be timid, but Kurzweil's predictions of nanotech healers and machine super-cognition may be more than a little optimistic--from his point of view.

Humans are certainly not ready for super-intelligence, and computers have no point of reference. Human intelligence is based on emotions, which are based on biological drives. Computers have nothing similar to build on, other than a need for electricity, more memory, and faster processors. As soon as computers begin to understand the need for speed and power, we may all be in trouble. Computers are not bound by billions of years of kludgy evolution--they can evolve exponentially.

So it comes down to: how soon can engineers/scientists build emotions and drives into computers--computers with actuators and power to act in the physical world? Because that is when Kurzweilian things start happening. Only computers can program massively parallel computers. They simply need a good reason to do so.

Zeroing In on Genetic Mechanisms of Ageing

The genes are largely responsible for how we look, how intelligent we are, and how long we will live. Finding genes that help determine our lifespan is important in the quest to scientifically extend the human lifespan. Now, scientists have zeroed in on one likely gene candidate, p16INK4a, that when over-expressed leads to cellular senescence in pancreatic islet cells, brain, and blood stem cells.

Teams from the medical schools at the University of North Carolina at Chapel Hill, University of Michigan and Harvard University observed similar results in pancreatic islet cells and brain and blood stem cells.

The results show disparate cell types share a common aging mechanism and suggest that aging-related diseases such as diabetes result from a failure of cell growth, said Dr. Norman E. Sharpless, co-author on the three studies and an assistant professor of medicine and genetics at the UNC School of Medicine. "The studies indicate that certain stem cells lose their ability to divide and replace themselves with age as the expression of p16INK4a increases," said Sharpless, a member of the UNC Lineberger Comprehensive Cancer Center.

The trio of reports are published online Sept. 6 in the journal Nature. The three research teams are from the medical schools at UNC, the University of Michigan and Harvard University.

The UNC study focused on p16INK4a effects on the function of pancreatic islet cells. Islet cells are responsible for insulin production and secretion. Because p16INK4a stops cancer cells from dividing and demonstrates increased expression with age, the scientists suspected the gene played a similar role in aging. The researchers developed strains of mice that were either deficient in p16INK4a (the gene was deleted, or 'knocked out") or genetically altered to have an excess of the protein to a degree seen in aging.

According to Sharpless, islet proliferation persisted in p16INK4a -deficient animals as they aged, "almost as if they were younger animals." In mice with an excess of p16INK4a, "islet cells aged prematurely; they stopped dividing early."

"This suggests that if we could attenuate p16INK4a expression in some way in humans, it could lead to enhanced islet re-growth in adults and a possible new treatment for diabetes," Sharpless said.

Similar results were found in the other studies, which focused on brain stem cells and blood stem cells.

The Michigan researchers, led by Dr. Sean Morrison, examined the role played by p16INK4a in neural stem cells, progenitor cells that can form new neurons and other brain cells. The team showed that p16INK4a increases markedly in those cells with aging. Moreover, p16INK4a -deficient neural stem cells work better and don't age to the same extent that wild-type (normal) stem cells do, Sharpless said.

Dr. Janakiraman Krishnamurthy, lead author of the UNC study and a postdoctoral scientist in the Sharpless lab, was a co-author of the Michigan report. The Harvard team, led by Dr. David Scadden, studied the role of p16INK4a in hematopoietic stem cells, which proliferate continuously during the adult lifespan and produce massive amounts of new blood cells on an hourly basis. Their results suggest that p16INK4a is the molecular basis for an old-age "signal" previously observed in blood stem cells. The Harvard study also showed that blood stem cells from old mice lacking p16INK4a functioned better than old cells from wild-type mice, suggesting p16INK4a causes aging of these cells as well.

Sharpless cautions that any promise of a potential new aging treatment based on p16INK4a should include two important caveats. "First, even though old mice lacking p16INK4a show enhanced stem cell function, they do not live longer. This is because p16INK4a is an important cancer-suppressor gene, and mice lacking p16INK4a develop more cancers than old, normal mice," he said.

"Secondly, in all three studies, p16INK4a loss was associated with an improvement in some but not all of the consequences of aging. There are clearly things in addition to p16INK4a that contribute to aging. We don't yet know what they are."

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Now it would be helpful to find a drug or genetic therapy that would block the anti-senescence effect of p16INK4a, but leave the tumour suppressor effect of the gene intact. I suspect that such a treatment would show significant pro-longevity effects.

There are many more pieces of this puzzle to find, but finding this particular piece will lead to the quicker finding of subsequent pieces.

Proteomic Mass Spectrometry--Advanced Tools for Bio-Research

The average cell is flooded with an ever-changing population of proteins. To understand what a cell is doing, it helps to be able to take a "snapshot" of all the proteins, examining them carefully for signs of dangerous mutations.

Brian Druker of the Oregon Health and Science University in Portland and Roberto Polakiewicz, chief scientific officer of Cell Signaling Technology in Danvers, MA, have extended the role of proteomic mass spectrometry in order to detect cell signalling protein mutations that may lead to cancer.

"There are potentially hundreds of mutations in a given patient," says Jeffrey Tyner, a postdoc in Druker's lab. Only some of those mutations actually contribute to the cancer -- and evaluating all of them is time-consuming.

In essence, DNA sequencing reveals only what the cell could do. Protein mass spectrometry, in contrast, provides a clearer picture of what the cell is doing. That's why Cell Signaling Technology believes its approach is more efficient. "Proteomic [mass spectrometry] gives you the true readout of what's going on in the cell," says Mark Cobbold, a clinician scientist at the University of Birmingham, U.K.

Druker's mass spectrometry study focused on acute myeloid leukemia, the most common form of the disease. And, while three common gene mutations are often to blame for it, in 30 to 50 percent of cases, the cause is unknown, says Tyner.

Druker hopes to duplicate his success in previous work on another form of leukemia, which led to the first successful molecularly targeted cancer drug, Gleevec (Imatinib). Approved for clinical use in 2001, the drug works by specifically binding to an abnormal tyrosine kinase protein and inhibiting it. The drug has worked wonders for some patients. "Druker is taking molecular medicine forward. Now he's looking for other [leukemia targets] using a proteomics approach," Cobbold says.

Looking at a cell's actual molecular activity using mass spectrometry lets Druker avoid much of the guesswork in searching for cancer mechanisms. Instead of years, it took his lab just weeks to uncover a mutation in a gene for a kinase called JAK3 that causes the signaling molecule to be abnormally active. They found the mutation in a cell line, then verified the result in patients.

In proteomic mass spectrometry the researchers first break up cancer cells, purify their proteins, and cut them up. They then further purify stretches of protein characteristic of active tyrosine kinases. This mixture is put into the mass spectrometry machine, which sequences the proteins. With this information, researchers know which proteins are abnormally active and why -- because of a mutation, for example -- and can search for a drug that acts against them.

Tyner hopes their work can be translated into clinical tests for determining the molecular cause of a patient's tumor. Protein mass spectrometry profiles of cells from a tumor biopsy could identify which protein is running amok and what drug would work best on it. "It's very attractive, the idea of looking at signaling in tumors and from that uncovering [genetic] profiles," says Cobbold.

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Proteomics research is expanding almost exponentially, as its importance is sinking in. The Wikipedia link above provides several links to proteomics resources. Here is an animation that illustrates the use of mass spectrometry in protein sequencing. Here is a blog that specializes in mass spectrometry, and deals with proteomics occasionally.

This type of technology will become commonplace in the modern anti-aging clinical laboratory. Clients will be scheduled routinely for analysis of cell-signalling networks, both to formulate initial treatments, and to monitor ongoing treatment results. It is likely that many clients will learn initially about their cancers, or other serious diseases, from their anti-aging screening.

Because medical insurance companies are not likely to pay for these procedures for decades yet, early comprehensive anti-aging diagnosis and treatment will be quite expensive.