2003 May 30 Friday
Quantum Dots Allow Detailed Capillary Imaging

Cornell University Professor of Engineering, Applied and Engineering Physics Walt W. Webb and his group have shown (click thru to the page to see cool pictures).

ITHACA, N.Y. -- Tiny blood vessels, viewed beneath a mouse's skin with a newly developed application of multiphoton microscopy, appear so bright and vivid in high-resolution images that researchers can see the vessel walls ripple with each heartbeat -- 640 times a minute.

The capillaries are illuminated in unprecedented detail using fluorescence imaging labels, which are molecule-size nanocrystals called quantum dots circulating through the bloodstream. Quantum dots are microscopic metal or semiconductor boxes (in this case cadmium selenide-zinc sulfide) that hold a certain number of electrons and, thus, have a wide number of potential applications in electronics and photonics.

Writing in the latest issue of the journal Science (May 30, 2003), researchers at Cornell University and a nanocrystal manufacturer, Quantum Dot Corp., report that the nanocrystals are particularly useful for producing high-resolution, three-dimensional images inside living tissue.

"We have demonstrated a new approach to using quantum dots for biological studies of living animals," says Watt W. Webb, Cornell's S.B. Eckert Professor of Engineering and professor of applied physics, co-inventor of multiphoton microscopy (with Winfried Denk) and leader of the experimental imaging team at Cornell.

"Of course, there are easier ways to take a mouse's pulse," says Webb's Cornell collaborator, senior research associate Warren R. Zipfel, "but this kind of resolution and high signal-to-noise illustrates how useful multiphoton microscopy with quantum dots can become, in a biological research context, for tracking cells and visualizing tissue structures deep inside living animals."

Zipfel cited the study of vascular changes in cancer tumors as one possible application, cautioning that the Cornell researchers are not ready to recommend human-medicine clinical applications for quantum dot imaging, in part because some of the best fluorescing nanocrystals have unknown toxicity. However, mice used in the Cornell study are still alive and apparently healthy, months later, and are being monitored for long-term effects of their treatments.The Cornell researchers used quantum dots for fluorescence imaging microscopy because when excited by light, they emit bright fluorescence in different colors, according to their size, reports biophysics graduate student Daniel Larson. The quantum dots were 6 to 10 nanometers in diameter. (A nanometer is one one-billionth of a meter. By comparison, a red blood cell, at 7 millionths of a meter, is a thousand times bigger). "Even with their water-soluble coating, which is something like being encased in a soap bubble, the quantum dots are only about 24 nanometers in diameter," Larson notes.

Webb explains that the laser scanning microscope used in multiphoton microscopy is particularly adept at producing high-resolution, three-dimensional images inside living tissue because it combines the energies of two photons, striking a molecule at the same time, with an additive effect. Under the conditions used, this only occurs at the focus of the laser, so only at that point is the molecule excited to a state that results in fluorescence emission. This excitation is the same as if it arose from the absorption of a single photon of higher energy, but it is three-dimensionally localized since it is only occurring at the beam focus. The scanning microscope moves the laser beam across the area being imaged at a precise depth. When repeated scans at different planes of focus are "stacked," the result is a brightly lit and vividly detailed three-dimensional image -- and video that takes a viewer inside a living organism..

Because of the special properties of the nanoparticles, multiphoton microscopy with quantum-dot imaging can be 1,000 times brighter in tissue than conventional organic fluorophores (the chemical labels that are temporarily added to samples), says Webb. "We looked to quantum dots for even brighter images at better resolution, and that's what we found."

Results presented in the Science report show highly detailed images of capillaries beneath the skin of a living mouse after quantum dots were injected through a vein in its tail, as well as capillaries through the adipose (fat) layer around the mouse's ovaries. The researchers were particularly surprised at the saw-toothed ripples in the walls of one capillary image -- until they made a calculation. Noting the time it took to scan that part of the tiny blood vessel and the animal's heart rate during the experiment, they determined that each ripple represented the undulation of the capillary wall from one heartbeat.

Besides demonstrating the feasibility of microscopic angiography with quantum-dot labeling through skin and adipose tissue -- two of the most challenging tissue types -- the researchers said they had resolved several fundamental questions, including the fact that sometimes as many as half the dots in a preparation are not fluorescent.

Other authors of the Science article are Marcel P. Bruchez, principal scientist at Quantum Dots; Rebecca M. Williams, a research associate with the National Institutes of Health (NIH)-funded Bioimaging Resource at Cornell; Frank Wise, professor of applied and engineering physics; and Stephen W. Clark, a graduate student in Wise's laboratory. Funding came from NIH, the Defense Advanced Research Projects Agency and the National Science Foundation.

Note that as part of their quantum dot compound they used cadmium which is a toxic metal. For human imaging the development of quantum dots that have less potential for toxicity is desireable. Another problem with this approach is that since it uses light it would require the use of endoscopes to image internal organs. Still, the increased level of detail would be valuable in many circumstances.

The ability to image capillaries is of particular interest because capillary growth is a crucial element of cancer tumor growth. The ability to study this process with quantum dots (e,g, to test anti-angiogenensis compounds) will be useful for cancer research.

It is possible that quantum dots could be used in tricky ways to detect where new capillaries are growing and hence where a tumor is growing. If quantum dots could be developed that would mark existing capillaries in a way that persisted for weeks then this could ability be used in such a way that new capillary growth and hence new tumor growth could be detected. It is possible to make different types of quantum dots that emit at different frequencies. What could be done is to mark existing capillaries with quantum dots that emit light at once frequency and then a few days, weeks, or months later come back and inject quantum dots that emitted at a different frequency. Then imaging of an organ in a way that looked for each frequency of light could be done to detect capillaries that have capillaries that only emit at the frequency that the quantum dots from the second injection emit. Those capillaries that emitted at only one frequecy would be new growth capillaries and probably an indication of new growth tumor cells.

Webb says the quantum dot imaging technique allows a great increase in imaging resolution as compared to previous imaging techniques.

The using of quantum dots, rather than conventional dyes, resulted in a thousand-fold increase in resolution, says Webb. Additional studies found that the technique works well in fat tissue as well as through skin. "And they both scatter light like mad," he notes.

Another possible use of quantum dot imaging would be as a more sensitive method for detecting circulatory problems.

By Randall Parker 2003 May 30 11:08 PM  Nanotech for Biotech
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Personal Aircars Inevitable?

NASA scientist Dennis Bushnell tells Technology Review that electronic technology advances in GPS, auto-pilot and other areas will allow unskilled people to pilot aircars.

The technology of personal VTOL transportation is "expanding and will soon be exploding," says Bushnell, with at least a dozen individuals and groups in the United States now competing to produce a safe, dependable aircar. The U.S. Army and Navy are developing aircar-type vehicles for military applications, and a NASA researcher has also been working on a design. Most of the action seems to be in the United States, though at least one foreign company—Urban Aeronautics in Israel—is also in the race.

The companies currently trying to design vertical take-off and landing vehicles for mass use may be premature in their efforts given the current state of materials technology. But materials advances using nanotechnology should eventually enable the construction of flying craft that are much lighter and stronger. Also, powerplants with higher thrust-to-weight ratios should also eventually be constructable due to coming materials advances.

The other key area of enabling technologies is in electronics and computing. The amount of decision-making load that would need to be off-loaded from the human operator would of course have to be far greater if people who are not trained pilots are to operate personal aircars. Certainly the capacity of computers will continue to advance quite rapidly. The challenge will be to develop software sophisticated enough to recognize a large range of operating conditions and dangers and to react appropriately.

Check out Moller International's Moller Skycar. Roadable Aircraft International (RAI) is at an earlier stage of development but their concept drawings look interesting.

By Randall Parker 2003 May 30 03:15 PM  Airplanes and Spacecraft
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2003 May 29 Thursday
Nanog Stem Cell Gene Enables Pluripotency

Teams led by Austin Smith of the University of Edinburgh in Scotland and by Shinya Yamanaka of the Nara Institute of Science and Technology in Japan have discovered a gene they named nanog which may be capable of turning any cell into an embryonic stem cell.

In one crucial experiment, Smith's team inserted copies of the human nanog gene into mouse embryonic stem cells, and subjected those cells to laboratory conditions that normally force such cells to mature and become one kind of tissue. The human nanog gene prevented that process.

The experiments suggest that as long as the nanog gene is turned on a cell will not differentiate into a specialized adult cell type. What would be interesting to know is whether non-embryonic stem cells also have nanog turned on.

The development of the means to control the expression of genes such as nanog which regulate the type of tissue that cells become will eventually open the door to the ability to grow replacement organs and stem cell therapies to rejuvenate aged stem cell reservoirs. In other words, this latest result is an important step toward the development of the means to reverse the aging process.

So why did they call the gene Nanog? Tir Nan Og is the land of the forever young in Celtic mythology. Tir means Land. Na Nog or Nan Og stands for "Of Youth" or "Of The Young". We in this age are living so close to the time when the breakthroughs that will make Engineered Negligible Senescence possible that we could fairly be said to be living in Tir Tairngire or "Land of Promise". Tir Na Nog is pronounced teer na no-'gue and many of us may live in it some day.

Tir Na Nog is also known as Mag Mell or "plain of joy". It bears some resemblance to Philip Jose Farmer's Riverworld since anyone who dies there reawakes the next day fully restored.

Tir Nan Og is the land to which the Irish faeries know as Tuatha de Danann (Too-ah day Thay-nan, or Tootha day danan) flead when their lands were taken by the Milesians. In Tir Nan Og they spend their days feasting, gaming, love-making and partaking of beautiful music. The faeries can even enjoy the thril of battle, for anyone slain is resurected the following day. It is the paradise that mortals can only dream of.

It is one big party.

No ploughing, no work is needed to make a living in Tir Nan Og: the faerie make love, have feasts, hunt and even play at war with one another--those that die one day are resurrected the next morning to join in the fun again. Occasionally, they grow curious about the humans who live on the other side of the Great Mist, or need to strengthen themselves with a fresh and vigorous human bloodline--and that is when they step out of their dark forests, through the silvery mist to be called into Legend...

Update: New Scientist coverage:

"Nanog seems to be a master gene that makes ESCs grow in the laboratory," says Ian Chambers, one of the team at the Institute for Stem Cell Research (ISCR), Edinburgh, Scotland. "In effect this makes stem cells immortal."

BBC coverage:

Their finding could ultimately enable scientists to transform stem cells from adults into cells that have all the characteristics of those taken from embryos.

By Randall Parker 2003 May 29 10:34 PM  Biotech Organ Replacement
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Bionic Man To Be Called Robo Sapiens?

Israeli scientist Amir Karniel discusses the human future as robo sapiens.

"In another 50 years, new creatures, a new species of humans will live among us. It is entirely possible that in the future they will make up the majority of humanity. They will be known as robo-sapiens." This declaration did not come from science fiction master Isaac Asimov, but rather from Dr. Amir Karniel, an expert in electrical engineering from the Technion, a researcher in the area of "motor control," which aims to discover how the brain controls the movement of the body, sends instructions and receives feedback from the nervous system.

One needn't replace an entire extremity with an electro-mechanical device to become, in effect, a robo sapiens. As Karniel points out, we've already started in that direction with such implanted devices as pacemakers. There are also lots of ways to enhance a human body with sensors what would leave all the extremities and muscles intact.

Picture youself having nanotech light sensors embedded into your retinas and even on the outer layers of your eyes that let you shift into infrared or perhaps to enhance your sight in low light conditions. Another useful enhancemenet would be a far more sophisticated replacement for hearing aids made by replacing the cilia in the ears with nanotubes and nanofibers that could hear much lower sound levels. The nanotube cilia could even be shifted into configurations which allow one to hear high frequency sounds that are outside of normal human hearing range.

Another appealing enhancement is Robert Freitas's proposal for respirocytes to replace red blood cells with a much greater capacity to store oxygen. These devices would have such a larger capacity to carry oxygen that they would reduce the risk of drowning or dying from smoke inhalation in a fire or dying from lack of oxygen in other ways. Of course they would enhance athletic performance as well.

By Randall Parker 2003 May 29 11:52 AM  Cyborg Tech
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Venter, Duke U Initiate Search For Genetic Causes Of Disease

Craig Venter says at his new Center for the Advancement of Genomics DNA sequencing will cost only 1 dollar per 800 base pairs.

At his new center, the cost of sequencing DNA will be as low as $1 for 800 DNA units, he said, a substantial saving on current costs.

That works out to about 0.125 cents per base pair. Let us put that in some recent historical perspective. In 1998 DBA sequencing cost 50 cents per base pair.

When we started the project in the late '80s, it cost about $5 to sequence a base pair; that has dropped to about 50 cents per base pair,

As of November 2002 the U.S. Human Genome Research Project of the US Department of Energy was quoting a cost of 9 cents per finished base pair. This makes comparisons a bit difficult. The effort to sequence the human genome involved repeated sequencing to look for errors. Is Venter quoting a verified sequencing cost of 0.125 cents per base pair or just a first pass cost that low? Either way his cost is at least an order of magnitude lower than the DNA sequencing costs of just a couple of years ago. However, his cost still puts the cost of sequencing a person's complete genome (about 2.9 billion base pairs) in the millions of dollars. Costs are still a few orders of magnitude too high for the sequencing of one's own genome to become commonplace.

There are research groups and venture capital start-up companies working on more radical advances in DNA sequencing. See here and here for example.

Venter's institute has signed an agreement with Duke University to collaborate to discover the genetic contributions to various diseases and to develop faster and cheaper tests for genetic variations that contribute to disease.

Part of their goal is to identify genetic hiccups found in major illnesses such as heart disease, cancer, infectious diseases, even sickle cell anemia. But it’s also to find accurate, inexpensive tests that will tell individuals what’s likely to make them ill long before they’re in danger, so they can opt for preventive measures — maybe even genetic "repair patches."

As the cost of DNA sequencing continues to drop the scale and number of efforts to discover the genetic causes of diseases will continue to rise. Most importantly, the rate at which the genetic causes of disease are discovered will steadily accelerate year after year until the vast bulk of the genetic variations that contribute to disease are identified.

By Randall Parker 2003 May 29 12:56 AM  Biotech Advance Rates
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2003 May 28 Wednesday
Attractive Men Have Healthier Sperm

A group of men had sperm samples taken and pictures taken of them. Their sperm was tested and separately they were rated for looks by a group of women. The men judged to be better looking had higher quality sperm on average.

Maria Sancho-Navarro, a researcher at the University of Valencia, said men were generally rated as being attractive if they had "symmetrical" faces.

"The women found that men with symmetrical faces were more attractive. These men had eyes, ears and nose that were more symmetrical than the other men," she told BBC News Online.

This is not too surprising. The ability of women to judge the healthiness of potential mates would have been of considerable selective value. Many problems that occur during fetal development cause asymmetry in the resulting organism. So for humans to find facial symmetry as an important component in judging attractiveness is not surprising.

It would be interesting to know is whether people with symmetrical faces have longer life expectancies.

Also, on a related note, another study found that men who were shown pictures of women to rate their attractiveness and separately heard the same women sing without seeing their faces tended to find the women with the more pleasing voices to have more attractive faces on average. Is the sound of a voice another measure of the quality of embryo development?

The New Scientist coverage of the sperm quality and physical attractiveness study is here.

By Randall Parker 2003 May 28 11:24 PM  Biotech Reproduction
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Nanofiber DNA Micro-Injection Technique Developed

Researchers at Oak Ridge National Laboratory and the University of Tennessee have developed a micro-injection technique to deliver DNA into a cell's nucleus using nanofibers.

ORNL researchers expect big things from nanostructures

OAK RIDGE, Tenn., May 19, 2003 -- Arrays of nanofibers able to deliver genetic material to cells quickly and efficiently have researchers at Oak Ridge National Laboratory excited about potential applications for drug delivery, gene therapy, crop engineering and environmental monitoring.

Tim McKnight of ORNL's Engineering Science and Technology Division and researchers from several other laboratory divisions and the University of Tennessee are working to advance the science of micro-injection. The work builds upon the group's success with fabricating carbon nanofibers, which are tiny needles that provide a new approach to genetic manipulation of cells and biological organisms.

"By using an array of millions of carbon nanofibers that can be grown on various platforms -- or substrates -- we can streamline a proven technique for altering the DNA content of a cell," McKnight said.

That proven technique, micro-injection, involves introducing genetic material, DNA, directly into a cell's nucleus. This allows researchers to genetically alter the attributes of a cell and to exploit the cell to perform desired functions such as to produce a pharmaceutically active compound to grow under adverse conditions or to detect environmental hazards.

The group's technique, which has grown from a project funded by ORNL seed money in the spring of 2002, allows for highly controlled rapid delivery of genetic material into large numbers of cells.

"While we have focused predominantly on mammalian cells, the parallel micro-injection-based technique should be quite transferable to a wide variety of cell types, including those with rugged cell walls such as plants and bacteria," McKnight said.

Of particular interest is the fact that the new method allows researchers to attach DNA to the nanofibers. When they insert these nanofibers into cells, the DNA can be used to program the cell to produce new proteins, but it is not free to move around within the cell. As such, it has a less likely chance of inserting into the cell's chromosomes or being segregated to daughter cells when the cell divides. Mike Simpson of the group has somewhat paradoxically called this a "non-inheritable genetic modification."

This non-inheritable tethered DNA method has exciting potential, McKnight said. For instance, it may address some of the concerns related to genetically modified organisms. Already, scientists are using these organisms for a variety of agricultural and environmental applications. A well-known example is golden rice, engineered for improved nutritional value to help feed the world's expanding population. Locally, the group's collaborators at the University of Tennessee's Center for Environmental Biotechnology use genetically engineered bacteria immobilized to a sensing platform to provide highly sensitive warning systems against environmental toxins.

In the areas of agricultural and environmental applications, some people are concerned about the potential of uncontrolled release of genetically modified organisms to the environment. However, the tethered DNA approach might significantly reduce the risk of such release. While the organisms might escape from the system, the nanofibers hold the modifying DNA captive.

"So when or if the organisms become detached from the nanofibers, they would no longer have access to the modifying DNA and therefore should revert to their normal genetic makeup," McKnight said.

In addition to investigating nanofiber platforms for DNA delivery, the group is involved in a $1.7 million three-year effort to apply nanofiber devices for high-resolution molecular imaging of cells and tissue. The sponsor, the National Institutes of Health, is specifically interested in molecular imaging because such information can provide insight into disease.

ORNL also is beginning a collaboration with the Institute of Paper Science and Technology. The project is aimed at using these techniques for genetic manipulation of loblolly pine, the most important wood pulp species in the United States. In addition, ORNL is pursuing the technique for transdermal drug or gene delivery, whereby a small nanofiber-based chip could be attached to the skin and would inject the drug or genes into the body.

The groups' research on nanostructures was published recently in the Institute of Physics Publishing's Nanotechnology (April 9). Co-authors are Anatoli Melechko of the University of Tennessee and Guy Griffin, Michael Guillorn, Vladimir Merkulov, Francisco Serna, Dale Hensley, Mitch Doktycz, Doug Lowndes and Mike Simpson of ORNL.

ORNL is a DOE multiprogram research facility managed by UT-Battelle.

The development of nanotechnological tools that operate on the scale of cells and biological macro-molecules is going to provide a level of control over cellular and organismal processes that will enable a much greater ability to fix and change cells. This, in turn, will lead to medical treatments that make the current methods of treating disease seem absolutely primitive. Advances in nanotechnology will help provide the means to eventually reverse the aging process and make old bodies young again.

By Randall Parker 2003 May 28 09:52 PM  Nanotech for Biotech
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CERN Physicists Plan To Make Mini Black Holes

Scientists at the European Center for Nuclear Research (CERN) want to use their atom smasher to make mini-black holes to study Hawking Radiation.

I mean, how can anyone resist the urge to imagine future headlines like "Artificial Black Hole Escapes Laboratory, Eats Chicago" or some such thing? In reality, there is no risk posed by creating artificial black holes, at least not in the manner planned with the LHC. The black holes produced at CERN will be millions of times smaller than the nucleus of an atom; too small to swallow much of anything. And they'll only live for a tiny fraction of a second, too short a time to swallow anything around them even if they wanted to.

I really really really hope they are right about the lack of danger involved in doing this. In James P. Hogan's science fiction novel Thrice Upon A Time his hero just happened to be working on a machine to send messages back thru time. Therefore his hero was able to save the planet Earth by sending a message back to warn a European physics research group that it would make a black hole if it conducted its planned experiment. But in reality we would have no such miraculous means to save us from a black hole eating away at the core of planet Earth.

By Randall Parker 2003 May 28 04:44 PM  Dangers Tech General
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Far-Infrared Radiation Bomb Detector Demonstrated

Terahertz far-infrared radiation can be used to detect bomb material in mailed letters and packages.

Novel NIST spectroscopic method can detect terrorist threats A novel technique that uses far-infrared (terahertz) radiation to rapidly identify bulk or airborne materials inside sealed paper or plastic containers has been demonstrated by scientists at the National Institute of Standards and Technology (NIST) and SPARTA Inc., of Rosslyn, Va. Described at a recent technical conference,* the technology has potential applications in homeland security such as detection of explosives in the mail or other non-metallic portable containers.

The method involves directing a far-infrared light source at a sample in a closed container, detecting the light transmitted through the materials, and then analyzing the light that was absorbed by the sample while making adjustments for the light absorbed by the container. Far-infrared radiation, which falls between visible light and radio waves on the electromagnetic spectrum, is partially transmitted through many materials. The pattern of light frequencies or spectra absorbed by a material depends specifically on the vibrations of the material's atoms and its crystalline structure.

This method can readily identify compounds made of molecules containing three to hundreds of atoms, the size of many threat materials. The two instruments employed, one using a pulsed laser and the other a glowing filament, are tabletop-sized and work at room temperature. Two years of experiments have demonstrated that the technique detects aerosols (such as those that might contain anthrax spores), pharmaceutical powders, most gases, several explosives and other common materials. The researchers have compiled a database of spectral characteristics for more than 100 materials and developed an automated software tool for rapidly identifying bulk materials based on their absorption spectra.

Further research aims to increase the sensitivity and throughput speed of the technology.

###

Campbell, M.B. and Heilweil, E.J., "Non-invasive detection of weapons of mass destruction using THz radiation," in Proceedings of SPIE Vol. 5070 Terahertz for Military and Security Applications, edited by R. Jennifer Hwu, Dwight Woolard, (SPIE, Bellingham, WA, 2003) in press.

Recall a recent post here about the use of shockwaves in photonic crystals to shift the frequency of a light source. That technique could be used to generate terahertz radiation which is otherwise difficult to generate. Nanotech MEMS devices to generate acoustic shockwaves in photonic crystals could be manufactured to make miniaturized terahertz radiation mail bomb detectors.

By Randall Parker 2003 May 28 04:02 PM  Dangers Tech General
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Possible March 16, 2880 Asteroid Impact Tsunami Modelled

The chances of asteroid 1950 DA hitting Earth in the year 2880 are only 0.3 percent. We really need to achieve Engineered Negligible Senescence so that we can still be around to worry about it when it gets here. If the human race still exists in 2880 (a big if) we should be able to deflect it from its path by then.

SANTA CRUZ, CA--If an asteroid crashes into the Earth, it is likely to splash down somewhere in the oceans that cover 70 percent of the planet's surface. Huge tsunami waves, spreading out from the impact site like the ripples from a rock tossed into a pond, would inundate heavily populated coastal areas. A computer simulation of an asteroid impact tsunami developed by scientists at the University of California, Santa Cruz, shows waves as high as 400 feet sweeping onto the Atlantic Coast of the United States.

The researchers based their simulation on a real asteroid known to be on course for a close encounter with Earth eight centuries from now. Steven Ward, a researcher at the Institute of Geophysics and Planetary Physics at UCSC, and Erik Asphaug, an associate professor of Earth sciences, report their findings in the June issue of the Geophysical Journal International.

March 16, 2880, is the day the asteroid known as 1950 DA, a huge rock two-thirds of a mile in diameter, is due to swing so close to Earth it could slam into the Atlantic Ocean at 38,000 miles per hour. The probability of a direct hit is pretty small, but over the long timescales of Earth's history, asteroids this size and larger have periodically hammered the planet, sometimes with calamitous effects. The so-called K/T impact, for example, ended the age of the dinosaurs 65 million years ago.

"From a geologic perspective, events like this have happened many times in the past. Asteroids the size of 1950 DA have probably struck the Earth about 600 times since the age of the dinosaurs," Ward said.

Ward and Asphaug's study is part of a general effort to conduct a rational assessment of asteroid impact hazards. Asphaug, who organized a NASA-sponsored scientific workshop on asteroids last year, noted that asteroid risks are interesting because the probabilities are so small while the potential consequences are enormous. Furthermore, the laws of orbital mechanics make it possible for scientists to predict an impact if they are able to detect the asteroid in advance.

"It's like knowing the exact time when Mount Shasta will erupt," Asphaug said. "The way to deal with any natural hazard is to improve our knowledge base, so we can turn the kind of human fear that gets played on in the movies into something that we have a handle on."

Although the probability of an impact from 1950 DA is only about 0.3 percent, it is the only asteroid yet detected that scientists cannot entirely dismiss as a threat. A team of scientists led by researchers at NASA's Jet Propulsion Laboratory reported on the probability of 1950 DA crossing paths with the Earth in the April 5, 2002, issue of the journal Science.

"It's a low threat, actually a bit lower than the threat of being hit by an as-yet-undiscovered asteroid in the same size range over the same period of time, but it provided a good representative scenario for us to analyze," Asphaug said.

For the simulation, the researchers chose an impact site consistent with the orientation of the Earth at the time of the predicted encounter: in the Atlantic Ocean about 360 miles from the U.S. coast. Ward summarized the results as follows:

The 60,000-megaton blast of the impact vaporizes the asteroid and blows a cavity in the ocean 11 miles across and all the way down to the seafloor, which is about 3 miles deep at that point. The blast even excavates some of the seafloor. Water then rushes back in to fill the cavity, and a ring of waves spreads out in all directions. The impact creates tsunami waves of all frequencies and wavelengths, with a peak wavelength about the same as the diameter of the cavity. Because lower-frequency waves travel faster than waves with higher frequencies, the initial impulse spreads out into a series of waves.

"In the movies they show one big wave, but you actually end up with dozens of waves. The first ones to arrive are pretty small, and they gradually increase in height, arriving at intervals of 3 or 4 minutes," Ward said.

The waves propagate all through the Atlantic Ocean and the Caribbean. The waves decay as they travel, so coastal areas closest to the impact get hit by the largest waves. Two hours after impact, 400-foot waves reach beaches from Cape Cod to Cape Hatteras, and by four hours after impact the entire East Coast has experienced waves at least 200 feet high, Ward said. It takes 8 hours for the waves to reach Europe, where they come ashore at heights of about 30 to 50 feet.

Computer simulations not only give scientists a better handle on the potential hazards of asteroid impacts, they can also help researchers interpret the geologic evidence of past events, Ward said. Geologists have found evidence of past asteroid impact tsunamis in the form of inland sediment deposits and disturbed sediment layers in the seafloor that correlate with craters, meteorite fragments, and other impact evidence. An important feature of Ward's simulation is that it enabled him to calculate the speed of the water flows created by the tsunami at the bottom of the ocean--more than 3 feet per second out to distances of several hundred miles from the impact.

"That's like a raging river, so as these waves cross the ocean they're going to stir up the seafloor, eroding sediments on the slopes of seamounts, and we may be able to identify more places where this has happened," Ward said.

He added that the waves may also destabilize undersea slopes, causing landslides that could trigger secondary tsunamis. Ward has also done computer simulations of tsunamis generated by submarine landslides. He showed, for example, that the collapse of an unstable volcanic slope in the Canary Islands could send a massive tsunami toward the U.S. East Coast.

A tsunami warning system has been established for the Pacific Ocean involving an international effort to evaluate earthquakes for their potential to generate tsunamis. Ward said that asteroid impact tsunamis could also be incorporated into such a system.

"Tsunamis travel fast, but the ocean is very big, so even if a small or moderate-sized asteroid comes out of nowhere you could still have several hours of advance warning before the tsunami reaches land," he said. "We have a pretty good handle on the size of the waves that would be generated if we can estimate the size of the asteroid."

Planetary scientists, meanwhile, are getting a better handle on the risks of asteroid impacts. A NASA-led campaign to detect large asteroids in near-Earth orbits is about half way toward its goal of detecting 90 percent of those larger than 1 kilometer in diameter (the size of 1950 DA) by 2008.

"Until we detect all the big ones and can predict their orbits, we could be struck without warning," said Asphaug. "With the ongoing search campaigns, we'll probably be able to sound the 'all clear' by 2030 for 90 percent of the impacts that could trigger a global catastrophe."

Rogue comets visiting the inner solar system for the first time, however, may never be detected very long in advance. Smaller asteroids that can still cause major tsunami damage may also go undetected.

"Those are risks we may just have to live with," Asphaug said.

See static images of the wave spread or see it as a movie.

A far better expenditure of the money currently going toward the Space Shuttle and International Space Station would be for the development of much better systems for identifying all asteroids that might strike the Earth. Such a system should be powerful enough to be able to identify comets that are going to enter the inner solar system for the first time. Both ground-based and satellite observatories should be funded at much higher levels to be able to identify well in advance every object that might hit Earth.

Objects such as comets whose orbital paths around the Sun that are highly elliptical and extend out beyond Jupiter are going to be harder to identify in advance. However, a very advanced tracking system ought to at least be capable of spotting such objects several months in advance. Fortunately such objects are far more rare than the asteroids that are in the asteroid belt and in closer orbits to the Sun.

By Randall Parker 2003 May 28 02:46 PM  Dangers Natural General
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2003 May 27 Tuesday
Shock Waves In Photonic Crystals Shift Light Frequency

John Joannopoulos and his photonic crystal research group at MIT have discovered that a shock wave travelling thru a crystal will cause light to reflect off the location of the wave and that this can be used to shift the frequency of light up or down as the light moves thru the crystal.

Because the shock wave is moving through the crystal, the light gets Doppler shifted each time it bounces off it. If the shock wave is travelling in the opposite direction to the light, the light¹s frequency will get higher with each bounce, while if it travelling in the same direction, the frequency drops.

After 10,000 or so reflections, taking a total of around 0.1 nanoseconds, the light can shift dramatically in frequency ­ from red up to blue, for example, or from visible light down to infrared.

It will eventually be possible to use non-destructive acoustic shockwaves in microelectromechanical systems (MEMS) devices to build crystals that will shift the frequency of light. It will also become possible to build devices that will take light that is spread over a wide range of frequencies and shift it to a narrower range.

One application of the ability to shift frequencies in this manner could be to increase the efficiency of photovoltaics. Many photovoltaic materials absorb only a narrow subset of the range of frequencies in natural light. If a photonic crystal could shift the natural light into a frequency band that the photovoltaics materials could convert to electricity then the same amount of photovoltaic material could generate more electricity.

A preprint of the article is available in PDF format. If you have Apple Quicktime installed an animation of the phenomenon is available for viewing.

By Randall Parker 2003 May 27 01:42 AM  Materials Advances
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2003 May 26 Monday
Euro Currency Notes May Get Embedded RFID Tags

The paper currency for the European Union may get RFID (Radio Frequency Identification) tags. (or see here)

"The main objective is to determine the authenticity of money and to stop counterfeits," said Prianka Chopra, an analyst with market research firm Frost and Sullivan in report published in March. "RFID (Radio Frequency Identification) tags also have the ability of recording information such as details of the transactions the paper note has been involved in. It would, therefore, also prevent money-laundering, make it possible to track illegal transactions and even prevent kidnappers demanding unmarked bills," Chopra said.

The Register has come up with a list of humourous applications for RFID currency.

Talking Euros for blind people and confused octogenarians: "No dear, I'm a fifty. Put me back in your purse and look for a five."

The curious thing about this particular item is that it is not so far from one real application of RFID currency: automatic currency counting in banks and other commercial establishments. In fact, a blind person could pass a hand-held device which has an embedded speaker over a note to have the note tell the person the denomination of the note.

Paper currency probably has a limited lifespan because counterfeiters will eventually figure out how to duplicate anything. It might well be the case that in 20 or 30 years physical unnetworked currency will be too easy to duplicate using nanotechnology for it to continue to be a safe store of financial value.

By Randall Parker 2003 May 26 11:18 AM  Surveillance Society
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Company To Sell Internet Web Cam Security Services

Priceline.com founder Jay Walker has founded a new company USHomeGuard whose purpose is to employ people to watch critical infrastructure sites over the internet using web cams to alert security officials of potentially dangerous intruders.

But if onsite cameras beamed photos to the World Wide Web, Americans could monitor these sites from home. If they spied a potential attacker - a masked man trying to scale a power plant fence, or a van parked next to a reservoir - they could alert security agents with a click of the mouse. Agents would call local authorities and help avert disaster.

This proposal is very much in keeping with ideas that science fiction writer David Brin has described in his non-fiction book The Transparent Society: Will Technology Force Us to Choose Between Privacy and Freedom? and in his fun fiction read Earth. There is a definite inevitability to Walker's business idea regardless of whether his company eventually succeeds in making it into a commercial success.

Government employees will amount to only a small fraction of the total number of people watching security cameras and other surveillance sensors. Far more people in private companies will conduct electronic surveillance. But the largest users of surveillance technologies will likely turn out to be private individuals watching their families, homes, romantic interests, celebrities, and anything else that interests them.

By Randall Parker 2003 May 26 01:34 AM  Surveillance Cameras
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Implantable RFID and GPS Devices

Applied Digital Solutions has brought out embeddable Radio Frequency Identification (RFID) chips capable of being implanted in a human body.

Imagine a tiny chip the size of a grain of rice that can be implanted under your skin to provide instant access to a range of potentially life- saving information. Or indeed, any information.

American company Applied Digital Solutions demonstrated just that at the IDTechEx Smart Tagging in Healthcare conference, held in London last month.

Paramedics could know instantly that a person they find passed out has a medical condition or an allergy to a particular drug. But the uses do not stop there. As storage device densities continually increase the amount of information storable by little chips embedded in a person's body will go up by many orders of magnitude.

Boston Globe reporter Angela Swafford has written a good article that surveys many of the possible uses for this technology. She even had a VeriChip inserted into her own body.

Theoretically, this VeriChip will allow doctors to call up my medical records even if I'm too badly hurt to answer questions. It is also supposed to allow me to get money from an automatic teller machine by flashing my arm instead of punching in my PIN number. Or reassure airport security that I am a journalist, not a terrorist.

Nokia and MasterCard are planning to put RFID chips into cell phones to make them into credit cards. There is not a whole lot of difference between an ATM card and a credit card and therefore it seems reasonable to expect that you could become your own credit card as well. But then how can someone who can't control their credit card spending cut their cards in half?

Applied Digital Solutions is also developing a subdermal GPS Personal Location Device.

PALM BEACH, FL– May 13, 2003 – Applied Digital Solutions, Inc. (Nasdaq: ADSX), an advanced technology development company, today announced that it has developed and successfully field tested a working prototype of what the company believes is the first-ever subdermal GPS “personal location device” (PLD). Field testing and follow-up laboratory testing of the disk-shaped prototype confirm that the specially designed antenna and the induction-based power-recharging method function properly.

The dimensions of this initial PLD prototype are 2.5 inches in diameter by 0.5 inches in depth, roughly the size of a pacemaker. As the process of miniaturization proceeds in the coming months, the Company expects to be able to shrink the size of the device to at least one-half and perhaps to as little as one-tenth the current size.

The induction-based power-recharging method is similar to that used to recharge implantable pacemakers. This recharging technique functions without requiring any physical connection between the power source and the implant.

Dr. Peter Zhou, Vice President and Chief Scientist of Applied Digital Solutions, said: “We’re very encouraged by the successful field testing and follow-up laboratory testing of this working PLD prototype. The specially designed antenna is working as planned. While reaching the working prototype stage represents a significant advancement in the development of PLD, we continue to pursue further enhancements, especially with regard to miniaturization and the power supply. We should be able to reduce the size of the device dramatically before the end of this year.”

Last year, the Company announced that it was accelerating development of PLD in response to demand from high-risk countries and other potential customers. The exact timing of commercial availability of PLD is unclear pending further technological refinements and achieving any required regulatory clearances. The PLD technology builds on United States Patent Number 5,629,678 for a "personal tracking and recovery system" which Applied Digital acquired in 1999.

In its PLD announcement last year, the Company said it is committed to providing customers with a full range of “personal safeguard technologies” that enhance personal safety, security and peace of mind. Other technologies in the Company’s line-up of life-enhancing technologies include VeriChip™, Digital Angel™, and Thermo Life™.

You might be wondering what this product is for. My added bolding of the statement about the "high-risk countries" points to one obvious use. They are probably referring to countries where kidnapping of wealthy people for ransoms occurs much more frequently than is the case in the most industrialized countries. Perhaps the device will be able to periodically broadcast a signal that reveals the location of a person once kidnapped.

A really cool health application would be to combine a heart monitor with GPS and cellular phone digital message broadcast to alert emergency workers when a person is having a heart attack. Other people with medical conditions such as epilepsy or diabetes that put them at risk of experiencing acute medical emergencies could also benefit from the ability of an embedded device to automatically make a cellular call for help. One could imagine people in high risk occupations such as forest fire fighters and search and rescue workers that have a risk of their being lost or injured in remote locations benefitting from having such a device in them.

A lot of other applications for this kind of technology can easily be imagined. For instance, parents could use it to keep track of the movement of their kids, either to find them at any moment in time or to download a record of their movements when they come home. This could be done surreptitiously so that a kid would never even know that a device had been implanted.

Law enforcement officials could require use of embedded RFID/GPS on parolees as a condition of parole. Stalkers who have court orders placed on them to avoid a celebrity or ex-girlfriend could similarly be tracked. Another really interesting application would be counter-terrorism. Imagine a suspected terrorist having a GPS tracking device secretly implanted. One way to do it would be to drug a suspected terrorist using food sent to his hotel room followed by insertion of a device while he slept. He might never suspect that he fell asleep because of drugs in his food if the drugging was done at a time late enough at night.

What would be even more clever would be to put components of a nanotech GPS device in food split up into a number of pieces too small to detect. The pieces could all be absorbed and then all migrate to the same destination in the body to hook up with each other and start functioning. A really sophisticated device could even record spoken conversations for later download. Then when the terrorist stayed in a hotel room or visited a restaurant that had embedded devices for triggering a radio download an encrypted transmission could be sent at his body to start the download.

Simpler RFID technology is on the verge of being used by clothing retailers to prevent theft and track inventory more accurately. Benetton announced a move to embed RFID tags in all Benetton clothing but after a furor was raised Benetton backed off from the proposal a month later. Another application is to combine RFID with a temperature sensor to allow perishible packages to indicate more accurately when shelf life has been expired.

Some day more advanced embeddable GPS tracking and radio transmitting devices will be interfaced to one's nervous system to allow one to instruct one's own embedded device to report that one believes one is either being kidnapped or otherwise in danger. Picture a mental keyboard where in one's mind one could type up a digital message or select from a list of prewritten messages and then order one embedded cell phone to send a brief digital message to a security agency, police, family, or employer.

By Randall Parker 2003 May 26 12:13 AM  Surveillance GPS
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2003 May 24 Saturday
Roche AmpliChip To Test Genes For Personalized Drug Selection

If you are under the impression that the use of individual DNA profiles for making personalized choices for medical treatments lay many years into the science fiction future then it is time to think again. The Roche CYP450 Amplichip will hit the market shortly and will be enhanced over the next 18 months to test for an increasing number of human genetic variations that relate to disease and disease treatment and even to detect viruses.

BASEL, Switzerland, May 7 (Reuters) - Roche Holding AG intends to roll out six "gene chip" tests over the next 18 months that can help diagnose how patients respond to certain drugs, detect viruses or expose a risk of developing cancer, the company said on Wednesday.

Roche is testing for a large variety of types of genetic variations in the genes coding for cytochrome P450 enzymes.

A microarray-based genotyping assay will be described that detects over two dozen allelic variants affecting CYP450 enzyme activity, including those caused by SNPs, frame shifts, multiple base repeats, and even complete gene deletion or duplication.

Individual variations in those enzymes will affect how quickly the liver breaks down drugs. Because of those individual variations there are enormous variation between individuals as to the best dose of a drug to take and even whether a particular drug will work. A person whose body breaks down a particular drug incredibly rapidly may not be able to derive any therapeutic benefit from taking it. Therefore they may benefit more from taking a different drug which they can not break down as easily.

The Roche product will be also be improved by automation so that it can be used in clinics and other point-of-care locations.

The product will include both a set of reagents and a microarray, and will be released in the second quarter of 2003. Initially, the technology will be restricted to use in reference laboratories, to which it will be marketed as an analyte-specific reagent (ASR) set. However, Roche expects that within the next 3–5 years, it will develop the technology into a fully automated system that can be marketed as a certified in vitro diagnostic. The company hopes to eventually bring the test closer to the patient for use in clinical laboratories or even at the point of care.

Jonathan Knowles, head of Roche research, promotes the use of the AmpliChip to reduce the guesswork involved in choosing which anti-depressant will treat an individual case of depression.

"There is a whole series of existing antidepressants," said Knowles. "The probability of anyone responding to any particular medicine is around 50% or even less. The only way to find out is to give someone a particular medicine for a couple of months and see if they feel better. If they don't feel better, then you try another one, and you keep going. There are all sorts of risks and emotional cost to the individual, an emotional cost to their family."

The test checks for genetic variations in genes that code for enzymes in the cytochrome P450 group of enzymes which are involved in breaking down toxic compounds and drugs in the liver and elsewhere in the body.

The new chip from Roche and Affymetrix will test for the most common variations in two genes, CYP2D6 and CYP2C19, which play roles in the way the body handles about 45 percent of the prescription drugs on the market,

This first generation AmpliChip surprisingly does not test the enzyme CYP3A which is the biggest metabolizer of drugs. But looked at from the standpoint of human genetic diversity it makes sense that Roche attached a greater importance to testing CYP2D6 because CYP2D6 is missing in 7% of caucasians and 2% of non-caucasians. CYP2D6 is also hyperactive in 30% of East Africans. Therefore what makes CYP2D6 testing more important than CYP3A testing is that CYP2D6 expression varies more from one person to the next.

This new test kit represents just the tip of the iceberg for the future use of knowledge of personal DNA sequence variations to choose medical treatments.

The testing of DNA sequence variations is not the only way to measure differences between people in gene function. Another way is to test methylation patterns on DNA that the cell uses to control gene expression.

Molecular Diagnostics’ in vitro diagnostics business grew by 14%. However, Molecular Diagnostics’ sales were down 1% overall and thus slightly below expectations as a result of the sharp downturn in sales to the biotech industry (-58%). By signing a licensing agreement at the beginning of the year with Affymetrix on the use of its GeneChip technology, Roche has laid the foundation for future growth in this newly created market. The AmpliChip P450, scheduled for launch in the second quarter of 2003, will be the first DNA chip-based diagnostic test that provides information on patients’ metabolic status. Roche also signed an agreement with the German-based company Epigenomics to codevelop a range of diagnostic tests for the early detection of cancers, their characterisation and prediction of treatment response.

Roche and Epigenomics are working on a three year collaboration to bring DNA methylation tests to market for use in making more personalized choices of best cancer treatments.

"We are very enthusiastic about this collaboration. Roche is already the world leader in cancer therapies and with this alliance we will complement our position in the diagnostics field. The products that are being developed as part of this collaboration address the urgent need for earlier detection of cancer in bodily fluids by more accurate screening tests, as well as identifying those patients who need chemotherapy and most likely respond to particular cancer therapies," says Heino von Prondzynski, Head of Roche Diagnostics and member of Roche's Corporate Executive Committee. "As the worldwide leader in in vitro Diagnostics we are committed to identify diseases early in order to improve treatment and enhance patients' quality of life. The alliance with Epigenomics will help us to remain at the forefront of the molecular diagnostics market and support our activities to pursue a market that could be greater than 3 billion Swiss francs ten years from now for our divisional cancer care program."

Alexander Olek, CEO of Epigenomics, adds: "This collaboration validates Epigenomics' DNA methylation technology and product development approach. By underlining the synergy between our in-house units, Diagnostics and Pharma Technology businesses, it allows us to pursue our vision of personalizing medicine. With the emerging trend of the pharmaceutical industry moving towards administering therapy only with a specific diagnostic test, we feel that the partnership with Roche Diagnostics solidifies Epigenomics' position as a leader in this field."

DNA testing is no longer just a research tool or a tool to test for rare inherited genetic diseases. It is moving very rapidly into widespread use to allow doctors to make more optimal decisions when choosing treatments for major diseases which have millions of sufferers.

The ability to conduct genetic tests in hospitals and clinics is going to become commonplace in the next few years. Therefore the biggest factor which will determine the rate at which genetic testing increases will be the rate at which the clinical significance is discovered for the hundreds of thousands of genetic variations that exist in the human population.

By Randall Parker 2003 May 24 05:47 PM  Biotech Assay Tools
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2003 May 23 Friday
Enzyme Makes HDL Cholesterol More Beneficial

A recent report about the benefits of the higher level of an enzyme provides a candidate for the use of gene therapy to reduce the risk of heart disease and of other illnesses associated with old age. Activity of an enzyme called paraoxonase can reduce the risk of heart attacks.

DALLAS, May 20 – An oxidation-fighting enzyme called paraoxonase (PON1) can significantly reduce the risk of heart attacks, according to research reported in today’s rapid access issue of Circulation: Journal of the American Heart Association. The enzyme attaches itself to high-density lipoprotein (HDL), which is known as “good” cholesterol. When PON1 is highly active, the risk for heart attack is cut by 43 percent, says study author Michael Mackness, Ph.D., of the University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom.

Postprandial peaks in plasma concentration of lipid hydroperoxides (in laymans terms: a boost in free radicals in fats in the blood after meals caused by the generation of fat free radicals in the gut during digestion) are theorized to contribute to the development of atherosclerosis and to the risks of heart disease and stroke. It is even possible that the boost in blood free radicals after each meal contributes to the general aging of the body. Peroxonase is probably working by breaking down lipid hydroperoxide free radicals into compounds that are less harmful to the body. More peroxonase attached to HDL cholesterol in blood serum probably causes the more rapid breakdown of lipid hydroperoxides after meals and therefore reduces the amount of cumulative damage that they cause.

The authors of this research paper state that if a dietary change or drug could boost PON1 activity then it is likely this would reduce the risk of heart disease and stroke. But a more permanent solution would be to do gene therapy to increase the blood levels of PON1. Researchers at University of Texas Southwestern Medical Center have already developed an experimental gene therapy for boosting paraoxonase levels.

Those veterans who have suffered brain damage from OP exposure during the war express significantly lower levels of PON, type Q, than those soldiers who remained well after the war. Other research has shown that these polymorphisms may also be involved in the development of Parkinson's Disease, amyotropic lateral sclerosis, and atherosclerosis. The inventors have developed gene therapy vectors that can be introduced into humans to boost their levels of PON and may lead to effective treatments to combat or prevent the aforementioned conditions.

There has been a lot of previous research into the role paraoxonase plays as an antioxidant in the blood.

The data are consistent with the hypothesis that lower expression of this anti-oxidant enzyme increases risk of coronary disease. Ageing has also been identified as an independent determinant of serum paraoxonase levels. Ageing is correlated with reduced serum paraoxonase levels, which may compromise the protective influence of enzyme. The results are consistent with the contention that the protective, anti-oxidant capacity of high density lipoproteins is at least in part genetically determined.

Gene therapy to raise paraoxonase might be useful for those younger people who have genetically low levels of paraoxonase. But note that since paraoxonase declines with age even people who have high levels of paraoxonase in their youth and middle age might benefit from gene therapy to boost paraoxonase as they age.

The reason for this post is to make a larger point: it may seem depressing to know that you probably have genetic variations that increase your risk for a variety of illnesses and that cause you to grow older faster. But a more optimistic way to see all the genetic risk factors that are being discovered is that future candidates for gene therapy are being identified. As more details are filled in about how different genetic variations contribute to development of diseases many potential benefits of future gene therapies are becoming better understood.

Is it realistic to expect that the effects of the deleterious genetic variations can be dealt with using gene therapies? Well, one reason to have that more optimistic view is that many genes are expressed only in a single organ or their role in the development of particular diseases is due to their effects in a single organ. Therefore gene therapy doesn't have to be able to reach every cell in the body (which would be incredibly hard to do) in order to be beneficial. In the case of paraoxonase the concentration of it in the blood is probably coming from synthesis in the liver followed by excretion into the blood. Therefore a gene therapy aimed at boosting blood paraoxonase only has to reach some cells in the liver. Another possibility would be to do gene therapy to stem cells that are capable of becoming liver cells. But the point is that gene therapy has to reach only a fairly small fraction of the body's cells in order to reverse the effects of an unfortunate inherited predisposition to disease. Your genetic inheritance does not have to dictate your health destiny.

By Randall Parker 2003 May 23 02:32 AM  Biotech Therapies
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2003 May 21 Wednesday
Europe Set For Prolonged Population Decline

Europe really is getting old.

It is estimated that by 2050, the number of people over 60 in Europe will have doubled to 40% of the total population, or 60% of the population of working age.

While this article is confused on this point the figures provided are for active (i.e. capable of working) population. The decline Europe's active population will be larger than the decline in the region's total population.

Its population declines from 331 million to 243, North America advances from 269 million to 355 million. Their big elephant is "Greater China" (including Taiwan) which sees its growth rate level out at 2.6 percent, ahead of North America's 2.3 percent, and far outpacing Europe's 1.1 percent.

Note that currently Europe has a larger total and active population than the United States and Canada. But at some point in the next 50 years Europe's working population will decline to a level below the current North American level while North America's working population will surpass Europe's current level.

For Ifri, Europe has two basic problems. The first is its dwindling population. From 2000 to 2050, the institute projects a decline in the EU's active population from 331 million to 243 million. Over the same period, the active populations of Greater China and South Asia move ahead, while the North American grouping rises from 269 million to 355 million.

A declining working population combined with rising working populations and more advancing populations elsewhere will shrink Europe's portion of the world economy to a little over half current levels.

By 2050, Europe's share of the world economy will only be 12 per cent against 22 per cent today.

Europe's population is going to shrink while the world as a whole grows.

Due to the dropping birth rate as well as the prolonged impact of the HIV/AIDS epidemic, the current Revision projects a lower population in 2050 than the 2000 Revision, namely, 8.9 billion instead of 9.3 billion. The European continent is the only region in the world whose population is set to decrease in the years to come, with a growth rate of -0.28 per cent.

Worldwide the elderly will grow as a percentage of total world population.

At the global level, the number of elderly people will grow from less than 1/2 a billion in 2000 to 1 1/2 billion in 2050 which as a share of the overall population is equal to an increase from 7% to 16%.

Of course these are all projections. Note that the world population project for 2050 was just cut by 400 million people which is about a 4 and a half percent decrease. That projection will no doubt be changed again. There are scientific and technological factors that could cause changes in population projections. Among those technological advances that could raise population growth:

  • Technological innovations that make it easier to raise children. Think technological advances that reduce housework, sophisticated tutor computers, more elaborate sensor systems for tracking the kids and warning of imminent dangers, and assorted other advances that unburden moms.
  • Biotech advances that will raise fertility rates for women in their 30s, 40s, 50s, and later.
  • The ability to genetically engineer offspring will reduce the uncertainty of the outcome and therefore reduce reluctance. If one can be guaranteed a very bright child with an innately happy and easy disposition then more will opt for children.
  • Dramatic breakthrus in life extension and youthful rejuvenation technologies.

Of course, global thermonuclear war, a bioengineered plague, or out-of-control nanoreplicators could all greatly reduce or perhaps even wipe out the human population. There are no guarantees in this life. But while fertility has been declining for some time due to the effects of technological advances on human society it is possible that some coming technologies will eventually begin to exert pro-fertility influences.

By Randall Parker 2003 May 21 02:14 PM  Trends Demographic
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New Pill Camera Can Be Maneuvered In Gut

Dr. Annette Fritscher-Ravens and colleagues at the University College London have successfully tested in humans a small swallowable gut camera that can be steered around in the gut.

Fritscher-Ravens and her colleagues say they have patented just such a method. Using technology very similar to that found in TV remotes or electronic car-keys, they attached tiny electrodes to the front and rear portions of the video capsule, along with a tiny antenna. Using a drive/reverse switch, they have been able to steer and propel the capsule through the gut, lingering wherever a lesion or other suspicious formation occurs

Passive camera pills known as capsule endoscopes are already available and in clinical and research use. But this new design allows doctors to tell the camera pill to move itself to areas of interest.

An existing passive capsule endoscope was recently used to discover greater side-effects from NSAIDs on the small intestine than had previously been reported.

The capsule endoscope, developed by Given Imaging, allows medical professionals to view the entire small intestine. The system uses a disposable miniature video camera contained in a capsule, which the patient swallows. The capsule passes through the digestive tract, transmitting color images, without interfering with the patient's normal activities. Capsule endoscopy diagnoses a range of diseases of the small intestine including Crohn's Disease, Celiac disease, benign and malignant tumors of the small intestine, vascular disorders, medication related small bowel injury and pediatric small bowel disorders.

The study enrolled 40 patients, with a mean age of 49.5, who had arthritis including osteoarthritis, rheumatoid arthritis and gout. Twenty patients took NSAIDS daily for three months. Twenty patients took acetaminophen alone or nothing at all. All patients fasted overnight and underwent capsule endoscopy. The pylorus, the sphincter muscle that controls the lower opening of the stomach where it empties into the upper part of the small intestine, was marked on each video. Two investigators who were not told which therapy the participants received, reviewed each video beginning after the pylorus, where the small intestine starts.

Severe injury to the small bowel was seen in 23 percent of NSAID users compared to no severe injury in the controls. Severe damage was associated with high doses of indomethacin, naproxen, oxyprozocin and ibuprofen.

Given the widespread long term use of NSAIDs this is an important result. A repeat of this study with a larger variety of NSAIDs and more test subjects could provide useful guidance in NSAID selection.

Update: this latest finding using a camera capsule to see the effects of NSAIDs on the intestines should not be surprising in retrospect. A 1999 study on mice found NSAIDs might be contributing to the development of inflammatory bowel disease.

A question raised by these experiments is the possible role of nonsteroidal anti-inflammatory drugs (NSAIDs) in promoting inflammatory bowel disease. In the researchers' mice, COX-2 inhibition by NSAIDs produced histologic changes reminiscent of human celiac disease. In view of the megaquantities of NSAIDs consumed worldwide, we'll need to delve more deeply into the full effects of COX-2 inhibition on immune homeostasis

By Randall Parker 2003 May 21 12:43 PM  Biomedical
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Will Human Race Cause Its Own Extinction?

Writing in Slate in response to Bill McKibben's book Enough, which is about the dangers of biotechnology, robotics, and nanotechnology, Jim Holt trots out a particularly lame argument about why we have little to worry about.

Accordingly, the Princeton physicist J. Richard Gott III has calculated that we can be 95 percent confident that the human species in its present form will be around for at least another 5,100 years but not more than 7.8 million years. (This, by the way, would give us a total longevity very similar to other mammal species, which on average go extinct 2 million years after they appear.)

To be meaningful a model has to be built on realistic assumptions. A model about species extinction has to consider environmental changes. The extinction of a species is far more likely to happen if the environment that the species evolved to live in suddenly goes thru radically changes. Well, news flash of the obvious: Humans are causing rapid changes in their own environment and will continue to do so.

Humans are major agents of changes in their own environment. Many of those human-caused changes have been beneficial for human survival. Human life expectancy for the world as a whole has risen dramatically over the last couple of centuries while the human population has reached levels never before seen in the history of the species. There are even technologies under development that promise to literally halt and reverse aging and this writer is a big supporter of the accelerated development of rejuvenation technologies. But the whole point of McKibben's argument is that humans are developing technologies that could be used to create threats to the continued existence of the human species.

An argument about historical longevity of mammalian species ought at the very least take into consideration that humans are causing the death of large numbers of other species (mammalian and otherwise). Many species now face much greater threats to their continued existence than they have in the past for the simple reason that humans have developed powerful abilities to change the environment and to cause the death of other species. Humans also have developed and continue to develop various abilities to cause the death of fellow members of their species. Of course humans have also demonstrated the willingness to use those abilities. Well, the features of human nature that are the source of that willingness are not going away (unless we do genetic engineering to change human nature - which probably will happen). At the same time, the ability of humans to cause the death of fellow humans looks set to increase quite dramatically as a wide array of technologies advance.

Let us take nanotechnology as an example. Nanotech assemblers are held out to eventually provide us with the ability to build anything cheaply and easily. Well, the ability to build anything includes the ability to build nuclear weapons. It may also include the ability to create new species that can out-compete existing species. There are recent historical precedents for how that could play out. Humans in the last couple of hundred years have moved species from various parts of the globe to other locales where they have never existed before. Introduced predator species in Australia, Hawaii, and other locales are killing existing species that have no evolved defenses for dealing with those predators. Some species are being completely wiped out by human-introduced species. It is not unreasonable to think there is a chance that some humans could manage to create a life form that has the potential to so change the environment of the globe as to cause the extinction of the human race as well.

The basic question that any debate about the future dangers of technology has to answer is whether the net effect of likely technological advances in the 21st century will favor the offensive or the defensive. Optimists assume that the kinds of dangers generated by technological advances be offset by even greater abilities to create systems to protect us from these dangers. But that assumption can not be proven and there are very plausible arguments against it.

Barring a natural disaster or total collapse of industrial civiliation humans are going to become so much more powerful in this century and will become so much more capable of changing their own environment that any argument about the risk of humanity's extinction that is built from historical data of average species longevity is hopelessly naive. Arguments from historical data have embedded in them the assumption of a low probability that in any time period there will be a huge change in the environment of a species. But that assumption does not hold for humans in the next 100 years. We will gain many new capabilities to affect our environment. We do not know whether we will use those abilities wisely enough to avoid our own extinction. It would be unwise hubris to assume that we will.

By Randall Parker 2003 May 21 10:37 AM  Dangers Tech General
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2003 May 20 Tuesday
Different Stem Cell Types Really The Same?

Researchers at Genzyme published some results last fall that suggesd that two different types of adult stem cells extracted from different parts of the body may not be different from each other.

Date: October 28, 2002

Genzyme Biosurgery (Nasdaq: GZBX), a division of Genzyme Corporation, today announced the publication of a research paper that casts new light on the nature of adult stem cells. In a paper published in the Oct. 28 issue of Tissue Engineering, scientists in Genzyme's Stem Cell Biology Research Laboratory demonstrate that many adult stem cells that have been claimed to be unique are actually "virtually indistinguishable" from one another in the laboratory, sharing many of the same physical and functional properties. The finding helps to clarify the many competing claims about the potential use of adult stem cells in a range of therapeutic applications.

In recent years, a growing number of researchers have reported that through a variety of proprietary methods they could generate cells with the potential to differentiate into a variety of specialized cell types, including nerve, cartilage, muscle, and endothelial cells. What has not been clear in these individual studies is whether the adult stem cells themselves are actually distinct, or whether they gained their distinction in the laboratory.

To help answer this question, Genzyme's study team systematically tested the approaches taken by various companies and laboratories. The Genzyme team isolated mesenchymal stem cells derived from the bone marrow of adults, and subjected them to a variety of the laboratories' research protocols used to develop cells capable of differentiating into nerve, cartilage, muscle, and endothelial cells. They found that regardless of the protocols used to isolate and propogate these cells, they were "virtually indistinguishable" from one another in several important ways. Each cell, for example, expressed the same or similar cell surface markers, or antigens. They also showed a common ability to undergo differentiation into nerve, cartilage, muscle, and endothelial cells based on culture conditions. The researchers concluded that although these stem cell populations were previously reported to be distinct from one another, on closer analysis they are not.

"We have shown that we can reproducibly isolate and propogate adult stem cells and demonstrate their potential to differentiate using a variety of methods," said Ross Tubo, PhD, director of Genzyme's Stem Cell Biology Research Laboratory. "These results give a strong indication that adult stem cells are robust and have great therapeutic potential for use in tissue regeneration. These findings help to clarify the complex and many times confusing literature surrounding adult stem cells."

Commenting on the findings of the Genzyme study, Dr. Diane Krause, associate professor of laboratory medicine at Yale University said: "The finding that these cells are very similar in their surface phenotype and their ability to differentiate into chondrocytes and neural-type cells helps us to make sense of the diverse literature in this field, paving the way for uniform isolation and propagation of mesenchymal stem cells for tissue engineering."

If adult cells from different reservoirs in the body that get used for different purposes are (at least in some cases) essentially the same as stem cells in other parts of the body then that would make it easier to get stem cells to use to develop various types of therapeutic treatments. It might turn out to be easier to, for instance, get some stem cells that would make good starters for growing replacement organs. This would be good.

The New Scientist has just picked up on this report and their story includes quotes from scientists who voice doubts about the conclusions which Genzyme researchers are drawing from their work. Some other stem cell researchers do not view the 12 chosen surface protein markers as definitive indicators of the type of a stem cell.

But not everyone agrees. Looking at 12 markers and two cell fates does not justify conclusions of such magnitude, says stem cell biologist Leonard Zon of Harvard University. "It's far from settled," he says. "I'd love for it to be simple, but it's not."

The other major point of contention has to do with how the cells were grown:

There is also debate over a seemingly small, but potentially important change in the method that Genzyme used to obtain MAPCs. A key step in obtaining MAPCs, according to Ohio-based Athersys, the company that has licensed the technology, is to grow bone marrow cells at a very low density. Yet Tubo's team obtained nothing this way and instead grew cells at a high concentration.

My guess is that it will be necessary to check a lot more markers (especially by measuring the expression of a large number of genes) to find out whether these stem cell types are really the same. If, for instance, growing stem cells at different densities changes what kinds of stem cells they are then what is really being demonstrated by these results might be just another way to change adult stem cell types into other adult stem cell types.

The bigger mystery continues to be just how difficult will it be to make stem cells into useful medical therapies? The potential payoffs include replacement organs, treatments for degenerative neurological disorders, and revitalization of aged stem cell reservoirs with youthful replacements. All of these uses of stem cells will eventualy help to reverse the aging process.

By Randall Parker 2003 May 20 08:45 PM  Biotech Organ Replacement
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Metal-Organic Frameworks May Solve Hydrogen Storage Problem

Metal-Organic Frameworks show promise as a way to solve the hydrogen storage problem for vehicles.

A new class of materials achieves that aim without the problems associated with other approaches, researchers report in the May 16 issue of the journal Science. Their work also points to ways of making the materials hold even more hydrogen.

"Hydrogen is an ideal fuel, because when burned it produces only water, which is quite harmless," said University of Michigan chemistry professor Omar Yaghi, whose work over the past 12 years led to the new materials. "But the problem has been, how do you store enough hydrogen for an automobile to run for 300 to 400 miles without refueling? You can't just put a huge tank of hydrogen on the back of an automobile; you have to concentrate the hydrogen into a small volume." That can be done by cooling hydrogen to an extremely low temperature or by compressing it under very high pressure, but neither option would be practical in a car or electronic gadget.

"Our idea was to create a material with pores that attract hydrogen," said Yaghi. "That makes it possible to 'stuff' more hydrogen molecules into a small area without resorting to high pressure or low temperature." The class of materials, called metal-organic frameworks (MOFs), can be made from low-cost ingredients, such as zinc oxide—a common component of sunscreen—and terephthalate, which is used in plastic soda bottles. Sometimes called crystal sponges, MOFs are essentially scaffolds made up of linked rods—a structure that makes for maximum surface area. Just one gram of a MOF, in fact, has the surface area of a football field.

The researchers found that they can increase the material's storage capacity by modifying the rods in various ways. "The material that we're reporting on takes up two percent of its weight in hydrogen," Yaghi said. "The U.S. Department of Energy (DOE) standard for use of hydrogen in automobile applications is about six percent. The exciting thing about this report is not only that we've discovered a new material that takes up hydrogen, but also that we've identified a clear path for how to get to six percent." In work published in Science last year, the researchers found that MOFs can also store large amounts of methane. "We now have materials that exceed the DOE requirements for methane, and we think we can apply the same sort of strategy for hydrogen storage."

MOFs should prove superior to metal hydride alloys, which also are being explored for hydrogen storage, said Yaghi. "One of the problems with metal hydride is that the stored hydrogen is chemically bound to the metal. That means that you have to pressurize the material to charge it with hydrogen, and you have to heat the material to high temperatures to discharge the hydrogen. The process of charging and discharging under these extreme conditions ends up contaminating the metal and breaking the whole process down, so these materials have a limited lifetime. With MOFs, the hydrogen is physically absorbed, not chemically absorbed, so it's easier to take the hydrogen out and put it back in without much energy cost."

A solution to the hydrogen storage problem would not by itself reduce the demand for fossil fuels. There would still be the need for alternative energy sources to use to generate the hydrogen in the first place. Still, the ability to easily and cheaply store and retrieve hydrogen with minimal energy loss would be a great enabling technology for the use of other energy sources.

The key point to keep in mind is that fossil fuels are both fuel sources and great forms of fuel storage (though natural gas is less easy to store). To move to a different source of energy (e.g. wind or solar or nuclear) for, say, transportation applications we need both that alternative source of energy and a way to put that energy into a form that is easy to put into vehicles. Many alternative sources of energy are made into electricity but existing types of batteries weigh too much and cost too much. However, existing methods for storing hydrogen are all quite unsatisfactory for transportation applications as well.

Whether a new battery technology or a new hydrogen storage technology will become the first viable non-fossil fuel energy storage technology for vehicles remains to be seen. A major commitment to shift to hydrogen as an energy storage form remains premature as long as there is not a great way to store it in vehicles.

Update: Yaghi explains why the MOFs do not need large temperature or pressure changes to store and retrieve the hydrogen.

"The hydrogen is physically attracted to the walls of the [material's] pores," he said. "This attraction makes it possible to stuff more hydrogen molecules into a small area without requiring either low temperatures or high pressures."

By Randall Parker 2003 May 20 06:50 PM  Energy Tech
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2003 May 19 Monday
Useful Home Robots For Lawn Mowing And Vacuuming

When my brother recently told me how much he likes the $200 Roomba home robot vacuum cleaner it served as a reminder that we are living in the era when, after decades of science fiction speculation, personal robot servants are finally starting to make an impact on everyday life. In another sign that robots are beginning to invade the home front the Toro iMow robotic mower is available for about $500.00.

Friendly Robotics of Israel makes a similar product for about $600 called the Robomower.

Robomower stays within the boundaries of a property using a thin wire perimeter placed on the edges of a lawn -- something akin to the invisible fence sensor technology used to contain pets.

The Robomower's brain records the lawns dimensions and obstacles, then operates on a computer-run navigation system until the job is done.

There do not appear to be (unless you dear reader can point to any others) any other major useful types of home robot products at this point in time.

While less useful from the standpoint of saving labor, Sony continues to come out with improvements for very popular the Aibo robot dog.

Also, in conjunction with AIBO's fourth anniversary, Sony will be releasing a sleek, new cobalt-blue colored AIBO Entertainment Robot [ERS-210A/LI] dubbed AIBO Cyber-Blue. Both AIBO EYES (suggested retail price $119.99) and AIBO Cyber-Blue (suggested retail price $1,299) can be purchased by visiting the Sony Style Stores (New York and San Francisco), Sony Gallery (Chicago), select retail outlets nationwide or by visiting http://www.us.aibo.com beginning May 20.

With AIBO EYES software, the four-legged robot can now be controlled remotely via e-mail commands. Users can send an e-mail message to the robot and receive a JPEG image with their computer or other mobile communication device, capturing a picture of what AIBO sees allowing them, for example, to view their home or children while away.

In addition, AIBO EYES software will allow family and friends to communicate through audio messages. For instance, AIBO owners can now send a message command from a remote device, such as a PC or mobile communication device, to AIBO and have the robot deliver a pre-recorded message aloud such as congratulations! Further, AIBO EYES will also enable owners to remotely e-mail message commands to AIBO and have the robot perform selected songs, such as When the Saints Come Marching In and Ode to Joy.

Speaking as someone who loves real biological dogs the idea of getting a robot dog strikes me as somehow disgusting. But Aibo has sold over 100,000 Aibos. Go figure.

One use of the Aibo robots is to compete in robot dog soccer leagues run by academic groups to test new software.

Rigged for soccer, the dogs communicate by radio and are fitted with tongue-depressor-shape "memory sticks" that slip inside the dogs' abdomens and contain all the team's codes. In Carnegie Mellon's software, dogs trade off being the leader depending on which one is closest to the ball. The leader goes for the ball, while teammates deploy themselves in support positions.

Robotics researchers find that competing to develop better soccer robots is accelerating the development of better robotic software.

Robotic soccer has been embraced by many researchers in the fields of artificial intelligence and robotics because it forces them to find ways for robots to learn how to work together and to do so at real-life speed.

There is even an International RoboCup competition that will be held in Padua Italy this summer.

Carnegie Mellon researcher Hans Moravec sees home servant robots with larger repertoires coming around 2020.

By 2020, "universal robots" will arrive. They can prepare an egg, put out the dishes and clean the table. At this stage, robots execute applications with "reptilian inflexibility," Moravec says, unable to deal with the unexpected.

My guess is that some of the tasks envisioned to be performed by home robots will no longer even need to be done by the time robots that can do them become available. Take the ironing of clothes for instance. It seems far more likely that nanotechnological developments of new textiles will result in clothes that do not need ironing and which can be cleaned far more easily. Imagine nanotech clothes that can be switched into a mode where they become repellant to dirt. You might pass clothes thru an electromagnetic field and as the clothes dropped thru the field the dirt would all come off. Other nanotechnological advances could lead to the development of self-cleaning shelves and carpets that transported the dirt to dirt collectors.

Moravec does not expect to see artifically intelligent robots that can engage in human-like abstract reasoning until 2050. Therefore, we have decades to live yet before we have to start worrying about robots taking over the world.

Joel Burdick, Professor of Mechanical Engineering at the California Institute of Technology and member of the Cal Tech Robotics Group, sees five technological obstacles to the greater use of robots.

According to Burdick, robots will become a part of every day life once five technological hurdles are cleared: computing power, sensor technology, power supply, motors, and smarts.

The first 4 obstacles that Burdick cites will all gradually fall because of technological trends that are being driven by much larger existing markets for other types of products such as laptop computers, cars, and consumer electronics devices. Microprocessor speeds will keep advancing because Moore's Law has at least several years to run yet. Even as current lithographic techniques for making semiconductor circuits reach their physical limits nanotechnological approaches to making electronic circuits will probably allow processors to keep getting faster. Newer and better generations of sensors will also continue to be made. A lot of work is going into better power supplies to satisfy the demands for a large assortment of consumer electronics and transportation applications. Motors similarly have many other existing uses.

In the long run software is the main class of problems that the robotics researchers will need to solve. Most of the other problems will be solved by scientists and engineers working to make better products for a wide range of applications. The biggest question in the long term is whether the development of better algorithms or the development of faster processors will be the rate-limiting factor for the development of artificial intelligence.

For more reading on robots the Robotics.com site has a nice page of links to sources of information about all aspects of robotics.

By Randall Parker 2003 May 19 08:09 PM  Robots Home
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2003 May 17 Saturday
Lab-On-A-Chip Designs Start To Become Useful

Small Times has a good article with interviews of researchers and industry leaders in the field of microfluidic chip development for biological science and biotechnology applications.

To illustrate the level of integration achieved with lab-on-a-chip, Knapp points to the Agilent 2100 Bioanalyzer. Using Caliper developed LabChip technology, the device measures out a specific quantity of protein sample, separates the protein mixture by size, stains the mixture with a fluorescent dye, and then de-stains the protein so that only the proteins are labeled. It then presents those results in a timed fashion to the optical detector. "You don't have to pour a gel. You don't have to load a gel. You don't have to stain or de-stain a gel. You don't have to scan the gel," he says. "All of those functions are integrated into the device."

The Microfluidic chip industry is going to produce successive generations of designs that are going to be progressively more complex, smaller, cheaper, and longer lasting. Just as microprocessors became useful for an increasingly large number of applications as they went thru this cycle so it shall be with microfluidics.

The microfluidics industry has developed more slowly than analysts had forecast.

Perhaps most unfortunate of all, microfluidics companies never were able to convince customers of the merits of the technology. What Frost & Sullivan predicted would be a $3.4 billion market by 2004 is just $175 million in 2003, according to the market research firm's analyst Nate Cosper.

But novel applications of microfluidics technology are being developed. For instance, a new prototype device will sort out the most viable sperm for use in in vitro fertilization.

University of Michigan researchers have developed prototype microfluidic devices that can automatically and rapidly sort sperm and isolate the most viable swimmers for injection into an egg. The Microscale Integrated Sperm Sorter does it all on one disposable device.

Many top university labs are working on microfluidics and more generally on what is called BioMEMs (where MEMS stands for MicroElectroMechanical Systems). For instance the Quake group at CalTech is working on "a DNA sequencing technology based on microfabricated flow channels and single molecule fluorescence detection". The promise of this technology is to allow faster and cheaper DNA sequencing using much smaller sample sizes.

By Randall Parker 2003 May 17 08:21 PM  Biotech Advance Rates
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Neutrino Weapon Could Neutralize Nuclear Weapons

A neutrino emitting weapon could neutralize nuclear bombs anywhere on the planet.

But the "muon storage ring" generator needed to propose the neutrino beam would need to be 1000 kilometres wide. It would also require 50 gigaWatts of power to operate - the same as used by the entire UK - and would cost an estimated $100 billion to construct.

The development of such a device would take many years.

However, the researchers stress that the method is well beyond the capabilities of current particle accelerators and would require substantial R&D and financial investment by many nations

Such a weapon as a defense against nukes runs up against some major problems. It has to be aimed at within a few meters of a nuke to disable it. So it is useless against a well hidden nuke. The biggest nuclear threat the United States faces in the future is probably from nukes smuggled in by terrorists. Therefore the value of this as a defense against the primary threat is questionable. Also, it would cause serious and probably fatal damage to any human hit by the beam.

Some comments in the full text of the paper draw attention to other problems with this approach: the nuke will still explode at a lower level and it will take a few minutes to make that happen.

We have shown that it is possible to eliminate the nuclear bombs from the surface of the earth utilizing the extremely high energy neutrino beam. When the neutrino beam hits a bomb, it will cause the fizzle explosion with 3% of the full strength. It seems that it is not possible to decrease the magnitude of the explosion smaller than this number at this stage. It is important to decrease this number to destroy bombs safely. We are not sure what this means when the plutonium or uranium is used to ignite the hydrogen bomb. We may just break the bomb or may lead to a full explosion. The whole process takes a matter of a few minutes in the case considered in this paper although, of course, it depends on the intensity of the neutrino beam. When the bombs are stored in the form of plutonium ball separated from the explosives, what we can do is to melt them down or vapor them away. It takes substantially longer time for this process to occur.

If it takes a few minutes to knock out a nuke then the beam device can not knock out a large number of nukes rapidly. If it can do one nuke in 3 minutes then at most it can knock out 20 nukes in an hour. Therefore it could not stop a large scale attack of ICBMs even if the beam could somehow be directed accurately to fast moving targets. Also, the nukes will still emit a small fraction of the amount of energy they would emit if they exploded normally. A particle beam designed to simply make an ICBM malfunction and explode during boost stage seems a more reasonable approach than to attempt to knock out a nuke on a travelling ICBM.

Because of the large surface area needed for the device the Moon becomes a candidate worth considering for the site of construction. Though the costs of hauling materials to the Moon to construct it would be very high it could be reduced if most of the needed materials could be mined and processed on the Moon.

By Randall Parker 2003 May 17 10:42 AM  Dangers Tech General
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2003 May 16 Friday
Cancer Researchers Discover Way To Grow Hair

It is very gratifying when some researchers working on something less important like cancer research accidentally hit upon a discovery for how to deal with a far more important medical problem: male pattern baldness.

“Other researchers have shown that beta-catenin and other genes in the Wnt (“wint”) pathway are important for normal development of hair follicles in embryos and after birth,” says Dlugosz, an associate professor of dermatology in the U-M Comprehensive Cancer Center. “What’s new about our study is the finding that a brief activation of beta-catenin in resting hair follicles could be enough to trigger the complex series of changes it takes to produce a normal hair.”

The original purpose of the research study was to learn how the Wnt signaling pathway and beta-catenin are connected to cancer development, according to Fearon, the Emanual N. Maisel Professor of Oncology in the U-M Cancer Center. “Beta-catenin carries signals from growth factors called Wnts to the cell’s nucleus,” Fearon says. “If beta-catenin expression in the cell isn’t adequately controlled and regulated, it changes normal patterns of gene expression. This can lead to several types of cancer, especially colon cancer.”

The study used genetically altered mice developed in the U-M Transgenic Animal Model Core. By adding a packaged set of genes called a construct to fertilized mouse eggs, U-M researchers created a new strain of transgenic mice with an inducible form of beta-catenin in their skin cells and hair follicles.

Van Mater induced beta-catenin signaling activity by applying a chemical called 4-OHT to shaved areas on the backs of the transgenic mice and matched control mice with normal beta-catenin genes. This chemical turned on the beta-catenin in the skin and follicles of the transgenic mice. The plan was to use 4-OHT to turn on beta-catenin activity in the transgenic mice until skin tumors developed, and then turn off beta-catenin activity to see if the tumors disappeared.

“But we never saw tumors -- just massive hyperplastic growth of hair follicle cells,” Van Mater says. The scientists also noticed other skin changes that suggested an exaggerated growth phase of the hair cycle. Dlugosz suggested applying 4-OHT just once, instead of every day, and to do it during the hair follicles’ resting phase or telogen.

“Hair follicles are like a mini-organ in the body,” explains Van Mater, a graduate student in the U-M Medical School’s Medical Scientist Training Program. “Unlike most organs in the adult body, hair follicles go through regular cycles of growth, regression and rest. They are able to regenerate completely during each growth phase. Previous studies had suggested that a Wnt signal might be the switch that drives resting hair follicles into the active growth phase. By treating the transgenic mice with a single application of 4-OHT, we hoped to mimic the effect of a short pulse of Wnt expression in normal mice.”

So Van Mater started over -- applying 4-OHT just once to the shaved backs of transgenic mice and normal mice during the telogen phase of the hair cycle. Fifteen days later, the transgenic mice needed another shave, but there were no signs of new hair growth on the control mice.

“Our findings suggest some potential strategies for inducing hair growth, but it is premature to think these results will lead to new approaches for treating common male-pattern baldness,” Dlugosz cautioned. “Many hair follicles in bald and balding men are greatly reduced in size, so merely reactivating hair growth would not produce a normal hair. Also, activation of beta-catenin in the body would need to be tightly regulated, since uncontrolled beta-catenin activity can lead to tumors of hair follicle cells or tumors in other sites, such as the colon, liver or ovary.”

These cautious researchers are reluctant to see their discovery used to reverse hair loss because the treatment might cause cancer. Of course this just makes it more important to discover a cure for cancer. If safe and reliable treatments to quickly kill cancer cells were available then any side-effects of curing baldness could be dealt with.

By Randall Parker 2003 May 16 02:38 PM  Biotech Therapies
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Bone Marrow Stem Cells Shown To Migrate To Damaged Livers

Human adult bone marrow stem cells transplanted into immune-deficient mice migrated to the livers of the mice and showed signs of differentiating into functional liver cells.

"There is a huge demand for liver transplants but there are never enough organs, and the procedure is not always successful," says study leader Jan A. Nolta, Ph.D., associate professor of medicine. "We're hoping that in the future we can use bone marrow or umbilical cord blood stem cells from matched donors to help treat liver disease and reduce the need for liver transplants."

Nolta and her colleagues isolated highly purified human stem cells from bone marrow and umbilical cord blood and transplanted them into immune-deficient mice. The purified stem cells normally give rise to cells that mature into red blood cells and white blood cells.

A month later, after the human stem cells had established themselves in the animal's bone marrow, the investigators induced liver damage. Some mice also were given human hepatocyte growth factor to increase the number of stem cells that developed, or differentiated, into liver cells (also known as hepatocytes).

A month after inducing the liver damage, the investigators compared the damaged organs to healthy ones from control mice that also had been transplanted with human stem cells. They tested the livers for the presence of human albumin, a protein produced only by liver cells. Any human albumin found in these mice would have to have come from transplanted human stem cells that had developed into liver-like cells.

Nolta and her colleagues found the greatest number of human-albumin-producing cells in the damaged livers of mice that had been treated with human hepatocyte growth factor. In some cases, albumin began showing up as early as five days after treatment. The number of stem cells that had differentiated into liver-like cells was low, however, making up less than 1 percent of all liver cells. Human albumin was not detected in mice with healthy livers.

The investigators believe that the stem cells moved from the bone marrow into the circulating blood, then left the blood to reside in the damaged liver, where they became liver-like cells that produced human albumin.

"These results show that human stem cells from bone marrow and umbilical cord blood are a potential source of liver cells," says Nolta, who also is a member of the Hematopoietic Development and Malignancy Research Program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

The study also represents the first successful animal model for studying how stem cells from human bone marrow and umbilical cord blood might be used to treat liver disease.

Nolta and her colleagues now are working to increase the number of human stem cells that differentiate into liver cells in this model by studying the signals that draw the cells into the liver and control their transformation, a feature known as stem-cell plasticity. In addition, they are investigating the use of blood-forming stem cells for the repair of heart and skeletal muscle.

Cell therapies will become incredibly useful very quickly once scientists develop better ways to control how stem cells migrate and turn into target tissue cell types (the process of cellular differentiation). Gene therapies will be developed that have the effect of ordering stem cells to become particular types or go to particular organs. Also, additional growth factors will be identified and worked into therapeutic regimes performed on stem cells to instruct them to multiply and become desired cell types.

We are coming ever closer to the era when repair and replacement of the most diseased and damaged tissue will become routine and easy to do. It is difficult to say when that era will arrive in full force. However, there are enough early stage successes being reported that it seems unlikely that we will have to wait longer than 20 years before it becomes common to basically order large numbers of stem cells to go hither or thither to meet some urgent need.

Fifty years from now youth will find it hard to believe that people used to die because of organ failure. The techniques used for the production of human replacement parts will become so well understood and cheap to employ that the idea of dying for lack of a healthy liver or kidney will seem as absurd as dying of scarlet fever seems today in industrialized countries (where most people no longer even know what scarlet fever is).

The future will be marked by the end of long-believed inevitabilities. The biggest shock to come will happen when people realize that aging is going to cease to be inevitable. There are already hundreds of millions of people alive who will live to see that day.

By Randall Parker 2003 May 16 01:45 AM  Biotech Organ Replacement
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2003 May 14 Wednesday
Will The Death Of Genetic Privacy Hasten The End Of Freedom?

Writing in The New Atlantis Christine Rosen has written a very useful survey of some of the current and potential future uses of individual human genetic information entitled Liberty, Privacy, and DNA Databases.

And yet, step-by-step and often for defensible reasons, we are paving the way for the universal, compulsory, DNA sampling of citizens. These are not simply the musings of science fiction; they are the logical conclusion of the technological infrastructure of DNA identification—such as Britain’s Biobank—that we are eagerly building. In the beginning, the reasons for such databases will be familiar, modern, liberal, and compelling: to cure disease, to catch criminals, to ensure that children have a healthy beginning to their lives. But the end in sight is a drastically different society and way of life. We may come to know too much about ourselves to truly live in freedom; and our public and private institutions may know so much about us that equal treatment and personal liberty may become impossible.

My biggest problem with her essay comes at the end (partially excerpted above) where she argues that the loss of genetic privacy will contribute to a loss of liberty. Certainly the more we know about each other's abilities, weaknesses, and predispositions the more we will judge each other differently. But we already do that using countless other means of knowing about each other. Harvard graduates are routinely assumed to be much brighter and more together than high school drop-outs. Someone driving an expensive car will be treated with more respect by police when pulled over than someone driving a junker. Good-looking people are treated better than less attractive people. People routinely hire other people based on advice they hear thru grapevines of social and business connections. Countless other examples can be cited.

Christine Rosen does not flesh our the motivations for her conclusion in sufficient detail for the reader to know why she views the loss of genetic privacy as a threat to liberty. Possibly she'll do so in a future essay (hint, hint). However, her mention of equal treatment in conjunction with personal liberty provides a clue. Is meaning here equal treatment before the law? Or is it equal treatment in the workplace? Is being treated equally the same as being treated fairly? Do people have to know less about us in order to treat us fairly?

Let us look at some of the ways that genetic information can now or will in the future be able to be used:

  • To know that a person is who they say they are.
  • To know who is a person's genetic parent or child.
  • To identify who was in a particular place carrying out a particular criminal act.
  • To idenfity who was in a partcular place carrying out some non-crimnal act that is of interest (e.g. who left dirty dishes in the sink).
  • To more accurately predict a person's risk for various diseases.
  • To more accurately predict a person's intelligence.
  • To more accurately predict a person's probability of engaging in various criminal behaviors.
  • To more accurately predict a person's desires.
  • To more accurately predict a person's level of motivation or some personality characteristic.

How helpful will genetic sequence information be for the purpose of prediction of characteristics or behaviors of a person will depend on just how big an influence genetics has on various aspects of personality and intelligence. Certainly physical environmental factors, chance accidents during embryonic development, and experiences all have impacts that limit the value genetic sequence information by itself. In order for genetic sequence information to have a significant impact on how people treat each other the sequence information has to have some predictive value or it will have more in common with horoscope information as a means to judge people.

Suppose genetic information does have some predictive value for each of the above listed purposes. Is it wrong for people to use it to help make guesses about the potentials and likely behaviors of others? If so, why? As a practical matter we need to judge each other and do so daily. If we can do it more accurately will that make us treat each other more or less fairly overall? Keep in mind that our judgements are frequently wrong and sometimes unfair. But they are also frequently necessary.

Put yourself in the position of a job interviewer. You have one position and twenty applicants. Suppose the availability of DNA sequencing information would cause you to choose a different person to hire. Is it wrong to use that information? After all, the person who you would not hire if you did not have the DNA sequencing information would not have been hired because of some other reasons that the DNA sequencing information effectively weighs against. Is it fair for you to have access to that other information but not the DNA sequencing information? Judgements are always less than perfectly accurate. DNA sequencing information may make judgements more accurate on average. Is this a bad thing? If so, why?

Must the death of privacy translate into the death of freedom? Science fiction writer David Brin argues in his non-fiction book The Transparent Society: Will Technology Force Us to Choose Between Privacy and Freedom? that we really don't have a choice about the future loss of privacy. Technological advances will make it too easy for individuals and governments to do various forms of survelliance. But if we allow not just governments but also individuals to use the survellance technologies then we do not have to wind up living under an authoritarian or totalitarian state.

There are technological trends in biotechnology that will make personal DNA privacy impossible to maintain as well. The development of nanopore DNA sequencers combined with microfluidics will eventually allow the construction of very cheap, small, portable, and easy to operate DNA sequencing devices. Such devices will be impossible to effectively ban. They will be able to be made to look like other devices and will be easily smuggled. Also, surreptitious acquisition of cell samples will be too easy to be prevented. For example, a woman will be able to get a cell sample from a date by just giving him a full mouth kiss at the end of the evening and then spitting her mouth's saliva into a cup when she closes her front door. Or she can do it by running her hand thru the guy's hair to get some loose hairs that have a bit of cells at their ends. Or if a person has dandruff on their jacket and leaves the jacket on their chair to temporarily leave the room of a business meeting then someone else will be able to quickly get a bit of the dandruff off the jacket.

I'd really like to see more specific explanations of how increased information availability will make a society less just and less free overall. We face a future where the quantity of available information of all kinds looks set to increase enormously. If there will be harmful effects then the mechanisms by which these harms will be done ought to be articulated in greater detail.

By Randall Parker 2003 May 14 06:42 PM  Biotech Privacy
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2003 May 13 Tuesday
Personality Changes With Age And So Do Crime Rates

Personality changes as people age.

WASHINGTON — Do peoples’ personalities change after 30? They can, according to researchers who examined 132,515 adults age 21-60 on the personality traits known as the “Big Five”: conscientiousness, agreeableness, neuroticism, openness and extraversion. These findings are reported in the May issue of the Journal of Personality and Social Psychology, published by the American Psychological Association (APA).

From this large sample of volunteers recruited and examined over the Internet, lead researchers Sanjay Srivastava, Ph.D., and Oliver P. John, Ph.D., working at the University of California at Berkeley, found that certain changes do occur in middle adulthood. Conscientiousness increased throughout the age range studied, with the biggest increases in a person’s 20s; this trait is defined as being organized, planful, and disciplined, and past research has linked it to work performance and work commitments. Agreeableness increased the most during a person’s 30s; this trait is defined as being warm, generous, and helpful, and has been linked to relationships and to prosocial behavior. Neuroticism declined with age for women but did not decline for men; this trait is defined in people who worry and are emotionally unstable. It has been linked to depression and other mental health problems. Openness showed small declines with age for both men and women. Finally, extraversion declined for women but did not show changes in men.

Both neuroticism and extraversion scores were higher for younger women than for younger men. But for both of these traits – and most strikingly for neuroticism – the apparent sex differences diminished with age.

Of the 132,515 participants, 54 percent were female, all lived in the U.S. or Canada, 86% were White and 14% were Asian, Black, Latino or Middle Eastern. A subset of the sample – 42,578 – were asked about their socioeconomic status. Of these participants, 405 (1%) said they were poor, 7,614 (18%) said they were working class, 23,024 (54%) said they were middle class and 10,718 (25%) said they were upper-middle class.

This study contradicts an often cited view that personality traits are genetically programmed to stop changing by early adulthood. There is considerable evidence against it, say the authors. In the study, “average levels of personality traits changed gradually but systematically throughout the lifespan, sometimes even more after age 30 than before. Increasing conscientiousness and agreeableness and decreasing neuroticism in adulthood may indicate increasing maturity – people becoming on the average better adapted as they get older, well into middle age.”

The full paper is available online in PDF format (i.e. you will need Acrobat Reader or an equivalent PDF viewer to read it). Page 7 of the PDF has a nice set of graphs that plot the measured personality characteristics as a function of age.

The really interesting question that this paper does not answer is what causes the personality changes as people age? Does experience with life cause most of the changes? That sounds plausible. But it also seems plausible that physical aging processes cause some parts of the mind to slow down or change in function in ways that change personality.

It is important to discover the causes of personality changes with age because eventually it will become possible to reverse the aging process. Will doing so make people less agreeable? Will it make them more prone to commit violent crimes? Will the reversal of the declining levels of hormones that happens with age make some people more inclined to start fights and do physical damage to others? That sounds only too plausible.

One problem with this study is that it was not longitudinal. The paper provides good arguments for why the researchers believe that there was not sampling bias of types of internet users as a function of age. They probably are reporting a real phenomenon.

What is needed are studies that try to get at the question of how much physical aging processes cause personality changes and which specific physical age-related changes cause which specific changes in personality and behavior.

There are ways this question can be approached. First off, people do not all age at the same rate. Physical measures of aging could be done along with personality measures for people of the same age. Personality changes might be found to happen more rapidly in people whose aging biomarkers are more advanced than those same biomarkers are for others of the same age who have personalities which are more like younger personalities. Blood hormone levels, insulin resistance, different cognitive abilities (since they do not all decline at the same rate), oxidative stress indicators, bone density, and many other biomarkers could be used. But unfortunately such a study would be orders of magnitude more expensive than an internet personality test study.

When it becomes possible to reverse the aging process then people will feel more energetic and will experience higher levels of hormones and more active minds. Their sexual drives will increase and their physical strength will increase. It seems likely that some of these changes will cause an increase in the rate at which people commit crimes. Murder, rape, and other violent crimes will likely rise and it seems likely that even non-violent white collar crime rates will rise as well.

To get a sense of just how much higher crime rates are for youths and early adults see this excerpt from the US FBI 1995 Uniform Crime Report.

Offenses involving only offenders under 18 years of age accounted for 22 percent of the overall Crime Index clearances, 14 percent of the violent crime clearances, and 25 percent of the property crime clearances.

Keep in mind that while that represents a fairly large age bracket the pre-teens are committing very few of those crimes. To get a sense of just how important age is as a factor in violent crime check out this chart of age-specific murder arrest rates. After peaking around the age of 19 murder arrests per 100,000 population drop by more than an order of magnitude by the late 40s and continue to drop by another factor of 3 by the early 60s.

We face a basic question about when it becomes possible to reverse the aging process: how much will the rates of various types of crime rise?

I won't go into it here but the story about crime and age is considerably more complicated for other types of crime. Some criminologists think that criminal personalities just shift their criminal activities toward less physically strenuous activities as they get older. Also, they learn skills that let them carry out other forms of criminal activity.

Still, an aged person made youthful by future biotechnology will have a greater general level of energy, greater strength, greater sexual drive, and stronger desires and appetites. The stronger drives and desires will be more likely to overpower inhibitions. The inability to resist impulses is a quality which many theorists think characterize the criminal mind. Well, a person who experiences an increase in the frequency and size of the impulses and of the ability to act upon them will act on them more often.

By Randall Parker 2003 May 13 09:29 PM  Biotech Society
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2003 May 12 Monday
Scott Gottlieb On The Real Future of Medicine

Writing in The New Atlantis Scott Gottlieb has written a survey of how computer technology, gene arrays, and other advances are transforming how drugs are developed, diseases are detected, and treatments are delivered. His essay is entitled The Future of Medical Technology.

This new ability to diagnose and treat certain diseases early, from infectious agents like hepatitis C to degenerative ailments such as Alzheimer’s and Parkinson’s, may obviate the need for the types of tissue, organ, or stem cell therapies that often attract the most public attention. Moving from wet lab to computer, from random to rational drug design, from species biology to the individual unique DNA profile, companies adopting the in silico paradigm are unlocking the long-hyped promise of genomic medicine, making targeted drugs and diagnosis a reality and drug development faster, cheaper, and better.

While the ability to detect diseases earlier is helpful the real problem with a disease like Parkinson's or Alzheimer's is that there is currently no way to halt disease progression regardless of when it is discovered. Early detection of a neurodegenerative disease at this point pretty much just allows you to start worrying about it sooner.

Of course, some day there probably will be treatments that will halt disease progression for some diseases and early intervention with, say, gene therapy may allow later cell therapy or growth of replacement organs to be avoided. But early detection is not going to eliminate most of the demand for stem cell therapies and replacement organs. Organs grow old. Adult stem cell pools become senescent. Also, accidents in the form of everything from physical trauma to toxic chemical exposures happen. There are going to be plenty of uses for stem cells and replacement organs no matter how many advances are made in drug developement and in gene therapy.

The only thing that is going to reduce the reduce the demand for embryonic stem cells is the development of techniques that allow adult cell types (and not just adult stem cell types) to be transformed into other cell types including other stem cell types. This will come with time. The ways that cell diffentiation state is controlled will be elucidated. An increasing number of techniques for manipulating cell differentiation state (e.g. gene therapies, hormones, drugs developed for that purpose) will be found.

Gottlieb is on firmer ground when he describes the future potential of computers to speed drug development and generally to speed the rate at which biological systems are figured out.

In the future, a supercomputer sitting in an air-conditioned room will work day and night, crunching billions of bits of information to design new drugs. Multiplying at the speed of Moore’s Law, which predicts that computer processing power doubles every three years, this drug discovery machine will never need to rest or ask for higher pension payments. It will shape how we use the abundance of genomic information that we are uncovering and will be the deciding factor for the success of medicine in an age of digitally driven research.

The big challenge of biological systems is that they are complex and small. They are hard to watch. We do not know most of what there is to know about what goes on in cells. We can not predict how molecules we might introduce will interact with the existing systems in cells. Our problem is that we need tools that are commensurate to the systems we are trying to understand. We need the ability to sense more things at the same time continuously and cheaply. We need faster DNA sequencing. We need better tools for manipulating biological molecules very precisely on their own scale. After decades of chasing cancer, neurodegenerative diseases, and other disease what is changing is that we can begin to see the day coming when we will have those tools which operate at the scale of biological systems and that will make it fairly easy to take apart, manipulate, and predict the behavior of biological systems.

Computers are great general enablers for the development of instrumentation. They collect data, control actuators, and process the data. But semiconductors are being used in ways that go beyond just connecting to sensors and collecting dat from them. Semiconductor technology is being used to scale sensing and manipulating systems down to the level of biological systems. Silicon chips are being used to sense and interact with biological systems. Silicon chips are even being made into mini-chemistry labs. Tools are being developed that operate on the same level as the systems under study.

The other way that computers are contributing is in simulations. But the "rational drug design" process that Gottlieb reports on in his article is still an ideal to strive toward that lies in the future. There have been a few success stories. But computers are not yet fast enough and we do not have enough information on all the proteins in cells to be able to simulate how a drug will interact with a real biological system. For a sense of how drug development is done currently read Derek Lowe. When he writes about drug development he gives a real sense of where drug development is at when he describes the inability to get drugs to where they are desired and only where they are desired.

We have enough trouble just getting our compounds out of the intestines and into the blood; subtleties past that are often out of our range. As far as targeting things to specific spots inside the cell, that's generally not even attempted. What we shoot for is selectivity against the enzyme or receptor we're targeting (as much as we can assay for it, which sometimes isn't much.) Then we just try to get the compound into the cells and hope for the best.

Numerous unforeseeable problems come up. Cell outer surfaces and internals have enormous numbers of different surfaces. They have many different proteins that are constantly changing in shape and presenting new surfaces for possible drug binding. A drug which is developed to be aimed at a particular receptor might also end up having affinity for other types of receptors whose existence are not even suspected. Truly rational drug design will happen when it becomes possible to predict in advance whether a drug will reach the desired target receptor and that it will bind only on that receptor. We are a long way away from being able to do that. All these unforeseeable problems mean that in drug development there is still a very large element of luck at every stage of development.

Derek also has a great recent post on the same theme that I've struck above: we need tools that get down inside a cell to watch and manipulate it on the scale that a cell operates.

But I think the general trend is unstoppable. If we're going to understand the cell, we're going to have to get inside it and mess with it on its level. There are doubtless plenty of great ideas out there that haven't been hatched yet (or have been and are being kept quiet until they've been checked out.) For example, I'd be surprised if someone isn't trying to mate nanotechnology with RNA interference in some way. (There's a hybrid of two hot fields; I'll bet that grant application gets funded!) It all bears watching - or participating in, if you're up for it.

Here is the most important point I'd like to make about the future of medicine: the most powerful future treatments will not be classical drugs. Cell therapies will be incredibly powerful and of course they will be cells, not drugs. Granted, cells will be manipulated by drugs as part of the preparation to make them suitable for delivery. But the cells, properly programmed in their DNA, will be the main agents of therapy when they are used. Also, replacement organs are going to become incredibly important. Another major type of treatment will be gene therapy. The gene therapy will be more akin to a computer program than a classical chemical drug.

The biggest change coming in medicine is coming as a consequence of a fundamental limitation of classical drug compounds: they do not carry enough information. Cells, organs, and complete bodies are very complex information processing systems. The genome is akin to an extremely complex computer program. It seems unreasonable to expect that when a very complex information processing system goes seriously awry that the most serious problems that arise can be dealt with using molecules which have such low information content. By contrast, gene therapy and cell therapy should both be thought of as therapeutic agents that have much higher information content.

By Randall Parker 2003 May 12 12:48 AM  Biotech Advance Rates
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2003 May 11 Sunday
Leon Kass On Ageless Bodies And Happy Souls

Writing in the brand new and promising magazine The New Atlantis Leon Kass, chairman of George W. Bush's President’s Council on Bioethics, worries about biotech's ability to cause a greater amount of conformity in human societies. (bold emphasis added)

As with cosmetic surgery, Botox, and breast implants, the enhancement technologies of the future will likely be used in slavish adherence to certain socially defined and merely fashionable notions of “excellence” or improvement, very likely shallow, almost certainly conformist.

This special kind of restriction of freedom—let’s call it the problem of conformity or homogenization—is in fact quite serious. We are right to worry that the self-selected non-therapeutic uses of the new powers, especially where they become widespread, will be put in the service of the most common human desires, moving us toward still greater homogenization of human society—perhaps raising the floor but greatly lowering the ceiling of human possibility, and reducing the likelihood of genuine freedom, individuality, and greatness. (This is Tocqueville’s concern about the leveling effects of democracy, now augmented by the technological power to make them ingrained and perhaps irreversible.) Indeed, such homogenization may be the most important society-wide concern, if we consider the aggregated effects of the likely individual choices for biotechnical “self-improvement,” each of which might be defended or at least not objected to on a case-by-case basis.

Note that his fear of conformity is not chiefly of a Brave New World type where everyone is genetically engineered to be the same. He thinks that even in a society with a great deal of personal freedom people will use biotechnology to make themselves more like each other. Imagine every woman getting the same breast job to have identical sized breasts or every person getting a perfect set of teeth that look just like everyone else's perfect set of teeth. Or imagine every guy getting treatments to turn their biceps into exactly the same buff size.

Incompatible Personality Types Are A Greater Threat Than Conformity

The odd thing about Leon Kass's writings on biotechnology and bioethics is that on one hand he has plenty of fears about biotech and yet on the other hand he seems to bring such a classical humanities mindset to his analysis that he does not have a good sense of where the big dangers lie. Conformity as the biggest problem from widespread enhancement of self and offspring? This seems implausible. There will be too many ways to enhance self and offspring, too many differences in tastes, and too much competition to try to make oneself look unique for that to happen. The whole purpose of haute coutere is to allow the cutting edge to look different than the rest of the populace and there is a vigorous competition to stay ahead and to look different. This competition combined with the considerable variation in tastes, values, and interests that exist in human populations could well interact with the capabilities that biotechnology will provide to create a future where the human race will split into different factions and groups that have increasingly less in common.

People will inevitably try to give their children genetic enhancements for specific purposes. Some will attach greater importance to musical ability or language skills or mechanical and mathematical reasoning skills. A competitive person will want to create a child with a very competitive personality. A committed pacifist will want to produce a child who has an aversion to violence and conflict. Sprinter track athletes will, on average, make different choices for their offspring than distance runners. But they both make different choices than tennis players who in turn will make different choices than golfers. One reason has to do with the physical demands of these sports. But they also have very different mental demands. Team sports demand different personality characteristics than solitary sports. Sports that involve facing a competitor in a direct struggle place different demands on a person than sports that require solitary concentration.

Look at professional occupations. Surgeons will make different choices than primary care physicians. For instance, the surgeons may place greater emphasis on hand-eye coordination potential where the primary care physician will see greater value in verbal skills and empathetic personality. A trial attorney will bring different priorities to a judgement about personality characteristics than will an attorney who practices corporate law that requires much time working on documents to create carefully crafted financial contracts. A patent attorney will bring yet another mindset to the same question of what personality characteristics to choose for offspring. A CPA working closely with any of those attorneys will bring yet another set of life experiences, patterns of thinking, and values to the question.

The point here is that people will tend to favor giving their children abilities that match their own strengths, interests, and aspirations. Since different people have different strengths and interests and since there is some trade-off between different kinds of abilities (e.g. clearly the case in muscle fiber types for sprinters and distance runners) the existing differences in occupations and abilities in the human population will tend to cause a divergence in the kinds of genetic endowment choices that people make for their offspring.

Kass has a stronger case for conformity on the question of outward appearances. In terms of appearance parents will tend to opt to choose genetic combinations that produce more pleasing appearances. In some sense that will cause a convergence as fewer children are born with physically less appealing appearances. But even here humans will not converge on a single ideal form. There is no single most preferred ideal appearance. For instance, there is considerable variation in opinions on ideal breast size in women and ideal butt size and shape in both men and women. If women are choosing the genes for their children then different decisions will be made than if men are doing it. If a couple makes the choices thru a process of negotiating a compromise then yet another different average set of choices will be made and the kind of dialog that will happen between a man and a woman to make offspring genetic endowment decision will not simply produce an average outcome that represents combined averages of only men or only women making the decisions. Since all these cases will happen (e.g. men will have a bigger say in Muslim countries while women will have a bigger say in the West) this will be yet another source of variation in the choices that will be made for the genes that future generations of progeny will be given.

Another source of differences in offspring genetic endowment choices will be pop culture fads. Let a woman with a particular appearance be the star of a hit movie or singer of a hit song and then some people will choose to make their offspring patterned after her. This could even go as far as copying her DNA. As I've previously argued, genetic privacy will be impossible to protect. A superstar will be at risk of having a skin or saliva sample stolen from them to be sequenced in cheap compact DNA sequencing machines. But the following year a different fad will take off. Also, the large number of cable and satellite channels and their trends are causing a fracturing of pop culture into more subcultures. Different groups will follow different fads. While one group of women will be trying to have daughters that look like Selena another group will be trying to have daughters that look like Madonna or Pink or Murphy Brown or Jennifer Lopez. Meanwhile the guys will be pushing for Jeri Ryan or Jolene Blalock look-alikes.

A Distinction Between Biotechnology And Medicine?

Kass tries to draw what I see is a false distinction between biotechnology and medicine.

Although this is not the time and place to develop this point further, it is worth noting that attempts to alter our nature through biotechnology are different from both medicine and education or child-rearing. It seems to me that we can more-or-less distinguish the pursuit of bodily and psychic perfection from the regular practice of medicine. To do so, we need to see that it is not true, as some allege, that medicine itself is a form of mastery of nature. When it functions to restore from deviation or deficiency some natural wholeness of the patient, medicine acts as servant and aid to nature’s own powers of self-healing.

What is natural wholeness? Picture a healthy liver. Picture a liver that is diseased. Well, imagine some future drug that binds to every diseased liver cell and causes it to commit cell suicide (apoptosis) so that healthy liver cells can replicate and replace the sick cells. To treat the same disease condition instead imagine a future gene therapy sent in to reprogram the sick liver cells to become healthy again. The same outcome is achieved: all healthy liver cells. Imagine a third case where a new liver is grown and then transplanted into the body to replace the diseased liver. Imagine a fourth case where a hormone is discovered that will encourage adult stem cells in the body to mobilize and move to the liver to replace diseased cells. The "deviation or deficiency" from "some natural wholeness" is restored in all cases. Are any of these approaches not properly called medicine? If so, why?

It is difficult to understand what point Kass is trying to make. Does one step outside of the bounds of nature or of the intended natural order if one manipulates human flesh at too low of a level and with too fine a level of control? Or is the problem that the risk of abuse is too great if our powers to do manipulation become too great?

Choosing The Essential Qualities Of Humanity

Kass is worried that biotechnology will allow the alteration of essential qualities of what it means to be human. We may eventually be able to change ourselves or our offspring to no longer be human.

In short, only if there is a human givenness, or a given humanness, that is also good and worth respecting, either as we find it or as it could be perfected without ceasing to be itself, does the “given” serve as a positive guide for choosing what to alter and what to leave alone. Only if there is something precious in the given—beyond the mere fact of its giftedness—does what is given serve as a source of restraint against efforts that would degrade it.

Before medicine advanced far enough to make abortion a fairly low risk procedure we did not have to worry much about where human life began. Before life support equipment become so sophisticated that it could keep alive brain dead people we similarly did not have to worry much about where human life ended. But advances in technology require that we define human life more carefully. One can react to these advances in a few ways:

  • Outlaw the use of technologies and procedures that can create situations where the humanness of a life form is hard to discern.
  • Take a laissez faire attitude and simply do not worry about it.
  • Try to break down what it means to be a human in far greater detail and justify the value of various qualities of some humans and identify and defend which qualities must be included or excluded in future offspring

People who are properly fearful of the dangers of biotechnology who do not want to face hard questions of what it means to be a human tend to opt for the first choice. Don't want to decide whether the human brain grafted onto a lion's body should be accorded full human rights? Ban it. Don't want to decide whether various genetic enginering modifications of offspring change a human into something else and, importantly, something that threatens humanity then just ban it. But recognize this reaction for what it is: it represents a desire to avoid a reductionist approach to breaking down humanity into its component parts to define it unsentimentally and without religious awe. Basically, the discoveries of biological science and their exploitation by biotechnology (which makes human nature infinitely mutable) force us to give up a certain form of religious belief about human nature as an indivisible whole.

The most radical libertarians tend toward the second view. Individual humans, endowed with basic unalienable rights, will, as free agents, make the best decisions and use biotechnology to engineer better future generations. There is an element of technological utopianism to this view where humans really are perfectible if only the unfettered market is allowed to work with infinite wisdom.

The third view is in some ways harder to hold because it requires one to feel the least amount of sentimentality or religious awe about human nature. It is not inherently optimistic. We are what we are and until we figure out all the myriad consequences of what we are and what biotechnology and other technology will enable us to become we can not predict with any assurance whether we will create a utopia, a dystopia, a splintering of the human race, or extinction of our species. It requires a very reductionist approach to trying to understand human nature as a product of evolution and with considerable variation in personality types and intellectual abilities across the human population as a result of different selective pressures and mutational events in various locales down thru history.

One of the biggest problems with the third view is that biological science is inevitably going to discover a variety of genotypic variations which produce personality and behavior phenotypes which cause varying degrees of problems for the rest of us. Some genotypes will be discovered that dramatically increase the odds that someone will commit violent crimes such as murder and rape and armed robbery. In other cases the genotypes will be discovered to code for more narcissistic and less fair and less considerate personailties.

The Components Of Human Nature Must Be Defined Scientifically

The ability to do personality engineering poses a basic challenge to certain religious views of human nature by making it seem to be less a manifestation of a supernatural spirit or soul. This might explain why a lot of religious conservatives who are opposed to germ line genetic engineering have not been able to articulate a better argument against it. The greatest danger that we face in maintaining human society is that individual people and governments could choose to place genes into offspring that make them incompatible with a free and open society. The possibilities range far beyond the ability to make people happy and resistant to depression and anxiety. It will become possible to genetically engineer extremely dangerous predatory psychopaths, cunningly manipulative narcissists devoid of consciences, or extreme compliant workers of a totalitarian state. Personality genetic engineering could be enormously beneficial and yet at the same time it has the potential to destroy the human race. But to appreciate the full potential of personality genetic engineering we must approach human nature as made up of a number of separately manipulable components.

While the debate about bioethics and biotechnology is far more vigorous on the political Right than on the political Left (leaving aside the European fears about biotech in agriculture - fears which are not based on scientific understandings for the most part) the Right's debate has not been terribly productive so far. The reason for this is simple: to have a productive debate about the effects of biotechnology on human nature and human society requires that we adopt a far more scientific view of human nature. To the extent that participants in the debate on the political Right are unwilling to do that they run the risk of making themselves irrelevant to efforts to address the real problems posed by advances in biotechnology.

By Randall Parker 2003 May 11 05:34 PM  Biotech Society
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400,000 Human Embryos In Storage In US Fertility Clinics

A new survey discovered 400,000 frozen human embryos in storage in a survey of over 400 US fertility clinics

The freezers of U.S. fertility clinics are bulging with about 400,000 frozen human embryos, a number several times larger than previous estimates, according to the first national count ever done, released today.

Some of the embryos are being retained in storage because the parent owners feel moral qualms about having them destroyed. In other cases the embryos are for future attempts to start pregnancies.

Since an attempt to start a pregnancy with in vitro fertilization (IVF) involves use of drugs to produce 5 to 15 eggs from the ovaries at a time for fertilization and then 3 to 4 embryos are placed in a woman per attempt the number of women involved is only a fraction (a third? a fifth?) of the reported 400,000 embryos.

The article puts the fees charged for embryo storage at $1500 per year. That price places upper bounds on the future popularity of both egg and embryo storage. Still, if a larger and more automated facility could lower those costs by an order of magnitude and if eggs could be stored rather than embryos then it would not be surprising to see affluent young women begin to arrange to have some of their eggs placed in storage so that the eggs would be available for starting pregnancies when they older and less fertile. The biggest argument against doing that is that it seems likely with the current pace of advance in working with stem cells that it will become possible within a couple of decades to create egg cells from stem cells. As new techniques are developed for controlling adult stem cells it seems likely that even they will be able to be converted into eggs. Therefore older women will be freed from the constraint of declining ovarian egg releases.

By Randall Parker 2003 May 11 11:18 AM  Biotech Reproduction
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2003 May 09 Friday
Rising Carbon Dioxide Causing Forests To Expand Into Deserts

Atmospheric carbon dioxide is rising due to the large scale burning of coal, oil, natural gas, and other fossil fuels. This is creating fears of global warming. However, if a new report from Israel is correct high atmospheric CO2 will cause forests to expand into arid deserts.

Rehovot, Israel — May 8, 2003 — Missing: around 7 billion tons of carbon dioxide (CO2), the main greenhouse gas charged with global warming. Every year, industry releases about 22 billion tons of carbon dioxide into the atmosphere. And every year, when scientists measure the rise of carbon dioxide in the atmosphere, it doesn’t add up – about half goes missing. Figuring in the amount that could be soaked up by oceans, some 7 billion tons still remain unaccounted for. Now, a study conducted at the edge of Israel’s Negev Desert has come up with what might be a piece of the puzzle.

A group of scientists headed by Prof. Dan Yakir of the Weizmann Institute’s Environmental Sciences and Energy Department found that the Yatir forest, planted at the edge of the Negev Desert 35 years ago, is expanding at an unexpected rate. The findings, published in the current issue of Global Change Biology, suggest that forests in other parts of the globe could also be expanding into arid lands, absorbing carbon dioxide in the process.

The Negev research station is the most arid site in a worldwide network (FluxNet) established by scientists to investigate carbon dioxide absorption by plants.

The Weizmann team found, to its surprise, that the Yatir forest is a substantial “sink” (CO2-absorbing site): its absorbing efficiency is similar to that of many of its counterparts in more fertile lands. These results were unexpected since forests in dry regions are considered to develop very slowly, if at all, and thus are not expected to soak up much carbon dioxide (the more rapidly the forest develops the more carbon dioxide it needs, since carbon dioxide drives the production of sugars). However, the Yatir forest is growing at a relatively quick pace, and is even expanding further into the desert.

Why would a forest grow so well on arid land, countering all expectations (“It wouldn’t have even been planted there had scientists been consulted,” says Yakir)? The answer, the team suggests, might be found in the way plants address one of their eternal dilemmas. Plants need carbon dioxide for photosynthesis, which leads to the production of sugars. But to obtain it, they must open pores in their leaves and consequently lose large quantities of water to evaporation. The plant must decide which it needs more: water or carbon dioxide. Yakir suggests that the 30 percent increase of atmospheric carbon dioxide since the start of the industrial revolution eases the plant’s dilemma. Under such conditions, the plant doesn’t have to fully open the pores for carbon dioxide to seep in – a relatively small opening is sufficient. Consequently, less water escapes the plant’s pores. This efficient water preservation technique keeps moisture in the ground, allowing forests to grow in areas that previously were too dry.

The scientists hope the study will help identify new arable lands and counter desertification trends in vulnerable regions.

The findings could provide insights into the “missing carbon dioxide” riddle, uncovering an unexpected type of sink. Deciphering the atmospheric carbon dioxide riddle is critical since the rise in the concentrations of this greenhouse gas is suspected of driving global warming and its resulting climate changes. Tracking down carbon dioxide sinks could help scientists better assess how long such absorption might continue and lead to the development of efficient methods to take up carbon dioxide.

I am of the view that the fears of global warming are overblown because within a few decades technological advances in many fields will make photovoltaics and other renewable energy sources much cheaper than they are now. Once nanotechnological manufacturing methods become cheap then all houses and other structures will have photovoltaic siding and roofs and many other structures. Computers will be so many orders of magnitude faster 20, 30, and 40 years from now that they will be able to speed up the rate of scientific experimentation and engineering design by orders of magnitude by doing simulation experiments to find better designs. This will greatly speed the discovery of processes for making cheap renewable replacements for fossil fuels. Therefore projections about CO2 levels 50 or 100 years hence based on current fossil fuel demand trends are hopelessly naive.

This latest report suggests that the rising CO2 levels of the next few decades will provide some benefits to humanity. When renewable replacements for fossil fuels become cost competitive there may well be a debate at that point as to whether we should continue burning fossil fuels at a rate fast enough to maintain CO2 at a level that will support the continued spread of forests into deserts.

Also, it will become possible to genetically engineer crop plants to grow faster and with less irrigation in a high CO2 environment. It seems reasonable to expect that crop plants will be genetically engineered to be optimized for higher CO2 environments. Among the benefits of such optimization would be a reduced need for irrigation and more rapid plant growth. As a consequence of this it would not be at all surprising if 30 or 40 years from now the agricultural industry becomes a major source of political support for the continued burning of fossil fuels.

By Randall Parker 2003 May 09 11:39 AM  Engineering Environmental
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Why Human Life Extension Will Help The Environment

Biogerontologist Aubrey de Grey argues that if people had longer life expectancies they'd be far more supportive of measures that would improve the environment of the planet Earth 100 years and longer from now. After all, if people are going to be around to deal with the long term consequences of what happens now they are going to be far more likely to care about the environmental consequences of what happens.

Writing in the Usenet group sci.life-extension Aubrey sees life extension as beneficial to the environment.

If you *expect* to live another century or two, you probably *will* act (at least somewhat) to make sure this planet does too.

...

If you want to make sure this planet lives another century or two, your best bet is probably to make people alive today do so too.

I try to make a habit of pointing this out to environmentalists, and especially to environmentalists who focus on overpopulation as a reason to eschew life extension. My mileage varies...

Aubrey also thinks that the public would be far more supportive of the development of life extending therapies if scientists were more willing to discuss just how soon they believe significant life extension therapies could be developed.

I'm saying that even though a healthy proportion of educated/thinking people think as you (and me) about the long-term future of the planet, the same cannot be said for the public at large. Really this is no more than a generalisation of the reason there is such widespread apathy about life extension research: scientists' perpetual refusal to discuss timescales just reinforces the view that no serious breakthrough is likely within the lifetime of anyone presently alive, and with that mindset it is no surprise that the public don't agitate for such research to be expedited.

I am firmly in Aubrey's camp in terms of believing that dramatic extensions of human life are achievable in a time frame that would benefit most of those living today in industrialized countries. The only reason most of us may not end up living long enough to benefit from these therapies is that scientists are not currently asking for the money to make a serious push to develop them.

While many fear that extended life will simply mean extended old age the most promising ways for extended life involve a return of an organism's body to a much more youthful state using "Strategies for Engineered Negligible Senescence" (SENS).

On August 12th 2001, a small roundtable meeting was held at UCLA, Los Angeles, to discuss a wide range of issues surrounding the possibility that, within a few decades, biotechnology might be developed that would enable us to reverse all the key lifespan-limiting components of human aging. The meeting was a sequel to one held in Oakland in October 2000 entitled "Strategies for Engineered Negligible Senescence" (SENS), so the UCLA meeting was entitled "SENS 2". Full funding was generously provided by the Maximum Life Foundation (see http://www.maxlife.org/).

The October meeting, SENS 1, gave rise to a highly controversial and provocative article, "Time to Talk SENS: Critiquing the Immutability of Human Aging", which is to be published in the Annals of the New York Academy of Sciences as part of the Proceedings of the 9th Congress of the International Association of Biomedical Gerontology [1]. (More details of that meeting, including a transcript, are online at http://research.mednet.ucla.edu/pmts/sens/index.htm .) The central conclusion of that article was that there is a substantial possibility that, within about ten years, we could take a mouse aged about two years (i.e., with a remaining life expectancy of six months or so) and restore it to sufficiently youthful physiology that it would live a year longer than otherwise.

Part of the problem is that many of the scientists who have skills needed to develop the Methuselah Mouse (mice would effectively serve as testbeds to try out prospective therapies) have a bigger focus on figuring out how things work. What is needed is more of an engineering mindset. With an engineering mindset the focus would not be to wait until every mechanism of aging is figured out in detail. Engineers ask if they have the tools needed to do a job and if they do they start working on a solution. Well, we have the tools needed to start now to develop therapies to reverse aging. What we need is the proper mindset and for money to be allocated to the attempt.

In spite of the lack of an ambitious engineering effort to reverse aging some pieces of the puzzle are being worked on. All the work to develop stem cell therapies is applicable. The same is true for tissue engineering efforts and attempts to grow replacement organs. But there are many other pieces that are not getting a lot of effort devoted to them. For instance, a lot of work needs to be done to develop the means to clear the junk out of cells - particularly post-mitotic cells - that accumulates as cells age. But the effort in this area is still pretty minimal. Also, work should be done to create a mouse that has all its mitochondrial DNA moved to the nucleus. Such a mouse line could be used to check whether putting mitochondrial DNA in a safer location will prevent or delay either a decline in energy output or conversion of some cells into major sources of free radicals or both.

The public needs to begin demanding major research efforts to develop therapies to reverse aging. Absent those demands the development of anti-aging and rejuvenation therapies will take many years longer than is necessary.

By Randall Parker 2003 May 09 01:09 AM  Aging Reversal
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2003 May 08 Thursday
Key Gene For Life Extension By Calorie Restriction Identified

A new study provides evidence that a form of a common vitamin plays a key role in regulating the response of cells to calorie restriction. Calorie restriction is the only reliable way to extend maximal lifespace of a large range of species and a great deal of work is going in to trying to figure out how calorie restriction does that.

Keep in mind while reading this article that nicotinamide is another name for niacinamide and nicotinic acid is another name for niacin. Niacin is the form of vitamin B3 that causes the flushing effect of hot red skin because it causes the release of histamine from mast cells into the bloodstream. Niacin also has a cholesterol lowering effect. Niacinamide is the form of vitamin B3 that people take if they want to avoid the flushing effect but niacinamide does not lower cholesterol.

Also, the NAD mentioned in the article is an acronym for Nicotinamide Adenine Dinucleotide. NAD (sometimes called NADH) is involved in mitochondrial metabolism for breaking down sugars and serves as an energy-carrying molecule. There has been a lot of speculation that calorie restriction may lengthen lifespan in part by causing changes in the regulation of mitochondrial operation that reduce the amount of free radical species generated and therefore reduces the rate of accumulation of damage that leads to old age. However, there has also been speculation that calorie restriction turns on repair systems. In the latter hypothesis calorie restriction makes cells respond as if they are under environmental stress and to take better care of themselves perhaps at the expense of performing at a lower level.

One of the take-home lessons from this article is that large doses of niacinamide taken regularly might either reduce lifespan in general or at least it might block the lfespan-extending effects of calorie restriction.

BOSTON, MA-- Researchers at Harvard Medical School (HMS) have discovered that a gene in yeast is a key regulator of lifespan. The gene, PNC1, is the first that has been shown to respond specifically to environmental factors known to affect lifespan in many organisms. A team led by David Sinclair, assistant professor of pathology at HMS, found that PNC1 is required for the lifespan extension that yeast experience under calorie restriction. A yeast strain with five copies of PNC1 lives 70 percent longer than the wild type strain, the longest lifespan extension yet reported in that organism. Their findings are reported in the May 8 Nature.

The PNC1 protein regulates nicotinamide, a form of vitamin B3. Sinclair's group previously found that nicotinamide acts as an inhibitor of Sir2, the founding member of a family of proteins that control cell survival and lifespan. Sir2 extends lifespan in yeast by keeping ribosomal DNA stable. PNC1 converts nicotinamide into nicotinic acid, a molecule that does not affect lifespan. In doing so, it keeps nicotinamide from inhibiting Sir2, allowing the yeast to live longer.

The finding implies that lifespan is not simply dependent on accumulated wear and tear or metabolism, as some researchers have suggested, but is at least partly controlled by an active genetic program in cells--one that could theoretically be boosted. "In contrast to the current model, we show that the lifespan extension from calorie restriction is the result of an active cellular defense involving the upregulation of a specific gene," Sinclair said.

For decades researchers have known that severe calorie restriction extends the lives of many organisms like yeast, fruit flies, worms, and rats, and it also slows the aging process and prevents cancer in rats. But why less food seems to help organisms live longer has been puzzling. While Sir2 is a necessary part of the equation, calorie restriction does not affect Sir2 levels, indicating that Sir2 must be regulated by another protein that does respond to calorie restriction.

Some researchers have speculated that NAD, a cofactor of Sir2 and a common metabolite in the cell, acts as a regulatory mechanism. Because NAD levels vary with rates of metabolism in yeast, this model suggests that calorie restriction might lengthen lifespan by lowering metabolism. However, Sinclair's group showed that the effect of PNC1 was independent of NAD availability. They believe that the real regulator of Sir2 is nicotinamide, which is one of the products of the reaction between Sir2 and NAD.

PNC1 levels are highly sensitive to environmental cues like calorie restriction, low salt, and heat that are known to make yeast live longer. Sinclair's team believes that the PNC1/nicotinamide pathway provides a genetic link between the environment of an organism and its lifespan, allowing an organism to actively change its survival strategies according to the level of environmental stress it senses.

In humans, the picture is undoubtedly more complicated; for one, humans have seven Sir genes, not just Sir2. The nicotinamide pathway is also different in humans, but Sinclair's group has shown that nicotinamide inhibits human SIRT1, a homologue of Sir2. His group is now investigating human genes that may play the same role as PNC1.

One of the immediate implications of the work is that it emphasizes the functional difference between nicotinamide and nicotinic acid. Nicotinic acid (niacin) is a known anticholesterol treatment, while nicotinamide (or niacinimide) is sometimes touted for anti-aging abilities and is in clinical trials as a therapy for diabetes and cancer. However, the two substances are sometimes sold interchangeably as supplements under the name vitamin B3. "Our study raises the concern of taking high doses of nicotinamide," Sinclair said, because nicotinamide puts a damper on Sir2's actions in the cell.

An obvious follow-up to this study would be to try giving large doses of nicotinamide to mice on calorie restriction to see if the nicotinamide prevents the metabolic changes that calorie restriction causes. In particular, it would be interesting to look at gene expression changes as measured by gene arrays. Stephen Spindler and his group have already argued for using gene arrays to test for calorie mimetic drugs But they'd also work for testing compounds that blocked the beneficial effects of calorie restriction.

By Randall Parker 2003 May 08 04:24 PM  Aging Reversal
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GPS Tracking Devices On Cars To Track Activity Of Others

In a comment section of a previous post someone has just posted claiming that a police force secretly put a GPS tracking device on his car. This leads to the obvious question of whether doing that is legal. Here's an article that reports routine installation of GPS devices by private investigators to track individuals who are not even married.

Virginia Beach Private Investigator Lee Oakes uses GPS everyday. He secretly installs magnetized units - it can take as little as 10 seconds - under the cars of individuals his clients pay him to follow.

I could see how a private investigator would have less legal problem doing it for one half of a married couple since the car that would be tracked would typically be jointly owned by the couple. But an example cited in the article involved tracking a fiance who had a cheating heart. Well, the article claims this is perfectly legal:

Again, using a GPS tracking device on a vehicle is not illegal...as long as you don't commit a crime (breaking into the car, tapping into the car's power supply, altering the car's driving characteristics, etc.) installing the device.

This might vary by state. Does anyone know? This article is reporting on Hampton Roads and Virginia Beach and so it is dealing with Virginia state law.

Also, are there fewer restrictions on monitoring and surveillance by private individuals than by police forces and other government agencies?

If current law remains in effect how ubiquitous will monitoring of others become? Because of continuing technical advances the devices will only become cheaper, smaller, and easier to use.

By Randall Parker 2003 May 08 01:14 PM  Surveillance GPS
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Use Of Plastic Surgery Will Become The Norm In Future

The weight of societal norms about the alteration of physical appearance will shift in the direction where most people will have looks which have been medically altered in some way.

"By the year 2020, no one will ask you whether you've had aesthetic surgery, they will ask you why you didn't have aesthetic surgery," predicts Sander Gilman, a University of Chicago professor who has studied the history of plastic surgery.

Today, he says, it's acceptable to live in a world where you can change your looks but choose not to. But in 20 years or so, he says, "in certain societies - Brazil, Argentina, more and more the UK, South Korea, Japan - the [question will be], 'Why didn't you take advantage? Why are you walking around bald?' " he says.

As a precedent the article cites the example of the increasingly widespread use of orthodontics work to improve the appear of teeth.

It seems reasonable to expect advances in biotechnology to lower the cost, pain, and inconvenience associated with plastic surgery and other medical alterations in appearance. To take just one example, currently the only way to replace hair lost by hair pattern baldness with real hair is to have plugs of hair moved to the front surgically. But eventually it seems reasonable to expect gene therapies to be developed which can be injected or delivered via a surface cream or paste.

Also, collagen injections will eventually be replaced by gene therapy injections that instruct cells in an area to make more collagen. A procedure that has to be repeated periodically will be replaced by a procedure that has to be done only once.

The biggest area of cost lowering innovation will be in the development of techniques to use gene therapies to mold a face or other surface feature without performing surgery. Once such therapies become available the pain, risk, time, and cost of appearance modification will all drop so far that appearance modification will become very commonplace.

As for what everyone will look like: the big mystery is whether all people will converge on some universal look. My guess is that there will not be a single ideal appearance but rather several of them since there is some variation in personal ideals for the appearance of others. Think of it as analogous to different tastes in cars, music, and clothes.

By Randall Parker 2003 May 08 10:41 AM  Biotech Society
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2003 May 06 Tuesday
SARS Death Rate And Incubation Period Estimates Raised

The latest estimates for the SARS mortality rate is even higher than the last revision upwards.

The mortality rate for those younger than 60 is between 6.8 percent and 13.2 percent, but jumps to between 43.3 percent and 55 percent for those 60 and older, the study found.

This work is being published in The Lancet.

The research, led by Dr. Roy M. Anderson and Dr. Christl A. Donnelly, both of Imperial College in London, is to be reported in Saturday's issue of The Lancet, the British-based medical journal.

The current 10 day quarantine period used for those suspected of exposure to SARS may not be long enough.

The Lancet study, based on 1,425 SARS cases in Hong Kong up to April 28, also found that the maximum incubation period -- the time it takes between getting infected and becoming ill -- may be as long as 14 days.

Here is my advice for the day: Do Not Get SARS! Also, stay the heck away from China.

By Randall Parker 2003 May 06 11:10 PM  Dangers Natural Bio
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US House Bill On Blue Collar Worker Life Expectancy Unrealistic

Some Congresscritters in the US House of Representatives are trying to be clever.

A bill pending in the House of Representatives would allow businesses with union workers to reduce their company pension obligations by billions of dollars, because statistics show that most blue-collar workers do not live as long as other Americans.

US corporations spent the better part of the 1990s raising their estimates for long term expected rates of return on their pension fund investments. When they got up to 9 and 10 percent as long term expected rates of return they entered the lunacy zone. Many have lowered their estimates somewhat but are still excessively optimistic. Markets do not grow in earnings over the long term faster than the economy grows as a whole. In fact, John Maudlin argues that public stock returns actually underperform the overall economy by about 1 percent. The US economy is not going to grow at 6 or 7 percent over the long term let alone 9 or 10 percent. Therefore actuarial assumptions about future earnings for many corporate pension funds are already unrealistic. We don't need the US Congress stepping in to provide companies another way to make their pension fund actuarial assumptions even worse.

One critic of this proposal quoted by The New York Times says that the bill does not require companies with lots of white collar workers to raise their assumptions of retiree life expectancy to adjust for the fact that white collar workers live longer. Therefore the net effect of this bill for corporations would be to lower the average assumed life expectancy they use for workers overall. If the bill really has that effect it is foolish.

There is an even more serious problem with the actuarial assumptions made by pension funds about life expectancy: the rate of advance of biomedical science is accelerating. As a consequence of the acceleration of the advance of biological science and technology the gradual rise in life expectancy which has characterized the last century will not be repeated in the 21st century. In the next few decades big killer diseases such as cancer which for decades medical science has made only slow progress against will be defeated entirely. Also, and more importantly, cell and gene therapies will be developed which have rejuvenating effects and successful techniques for growing replacements for most types of organs will be developed as well.

Simply put, the historical model of slow steady rise in life expectancy is going to be shattered by the development of revolutionary biotechnologies which will cause large rapid increases in human life expectancy. Linear actuarial extrapolations of past trends will not provide a useful guide to future trends in human life expectancy. Biogerontologists, equipped with the increasingly powerful tools of molecular biology such as DNA sequencing machines, microfluidics chips, gene array chips, and other tools and techniques will increasingly turn toward the pursuit of Strategies for Engineered Negligible Senescence to end human aging entirely. The tools at the disposal of biological engineers are already powerful enough to start working in earnest toward such an ambitious goal. Using the current armament of laboratory tools and techniques biologists now have the ability to start to develop and test some of the major types of rejuvenating therapies in mouse models. Within 20 years and perhaps even sooner many of those therapies could be ready for human trials. Therefore it seems unreasonable to expect a continuation of past trends of slowly rising human life expectancy.

By Randall Parker 2003 May 06 01:27 AM  Aging Reversal
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2003 May 05 Monday
China Continues To Be SARS Threat To Rest Of World

Experts fear that SARS will become endemic in China and that the need to contain SARS in China will become a long term problem for the world.

If China becomes a reservoir for Sars, other countries, particularly its neighbours, will have to maintain constant vigilance for cases arriving from the Far East.

Professor Tedder said it was possible that stringent surveillance precautions would be in place in the UK and Europe for the foreseeble future - and perhaps for years to come.

He said: "What it may prove to be is a very effective dry run - one wonders what will happen next time."

Given its mortality rate we really are lucky that SARS is not more easily transmittable. If the latest crossover of a virus from another species into humans had been an influenza with a lower mortality rate than SARS but still fairly high (say 2% like the 1918 Spanish Flu) it would not have been controlled in Western countries as easily. SARS ought to serve as a wake-up call for a future lethal virus that is more easily transmittable.

Then there is the continuing problem posed by SARS. It may become permanently established in China. If that is what is happening then it seems inevitable that sooner or later it will become established in the Indian subcontinent and Africa as well.

The World Health Organization has recently published a summary table of results of tests on how long the SARS virus can survive outside the body. The ability of the SARS virus to survive on a plastic surface at room temperature for at least 2 days provides key evidence for how SARS has been able to spread thru apartment buildings and hospitals.

Another experiment in Germany suggests that killing the SARS virus on surfaces is not a trivial matter.

German scientists found a common detergent failed to kill the virus, indicating that some efforts to sterilize contaminated areas may be ineffective. An experiment conducted in Japan concluded that the virus could live for extended periods in the cold, suggesting it could survive the winter.

On the bright side, the vast bulk of new SARS cases are happening in China and Hong Kong. But given the primitiveness of the health care system in much of China and the attempts of some probable SARS sufferers in China to avoid contact with authorities (poor Chinese people do not trust the government to care for them) it is likely that even if the Chinese government is honestly reporting all known SARS cases (by no means a certainty) there are probably cases in China that are going undetected. One should really take the WHO case numbers with a grain of salt for other reasons as well. The WHO's definition of what constititues a SARS case is narrower than the definition used by some national health authorities (notably the US CDC). India is reporting 20 SARS cases which India claims are confirmed by lab tests and yet WHO has no SARS cases listed for India. The number of SARS cases reported by WHO for the United States includes only the cases that the CDC lists as probable (and perhaps not even all of those? Or is WHO slow about updating counts?). The problem is that most people who have had a milder case of SARS do get listed as probable. Until reliable lab tests are widely used and accepted as definitive I expect WHO SARS case figures will continue to represent only a subset of all people infected by the virus.

On another brighter note, reports of relapsed SARS cases turn out to be unfounded.

HONG KONG -- A dozen former SARS patients here who were initially thought to have suffered relapses actually had other medical problems, health officials said Sunday, as the rate of new SARS cases being reported around the world slowed somewhat.

It is very unlikely that SARS will become established in Western industrial countries. Quarantines other public health measures can contain any new outbreaks that occur in large part because SARS is not too easily transmissible. However, as long as SARS is being passed around in China it threatens to make it into other less developed parts of the world.

By Randall Parker 2003 May 05 04:41 PM  Dangers Natural Bio
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2003 May 04 Sunday
The Future Of Nutritional Genomics

Writing in the New York Times Bruce Grierson explores the potential use of individual genetic profiles to choose the ideal personalized diet.

A trip to the diet doc, circa 2013. You prick your finger, draw a little blood and send it, along with a $100 fee, to a consumer genomics lab in California. There, it's passed through a mass spectrometer, where its proteins are analyzed. It is cross-referenced with your DNA profile. A few days later, you get an e-mail message with your recommended diet for the next four weeks. It doesn't look too bad: lots of salmon, spinach, selenium supplements, bread with olive oil.

Once DNA sequencing costs fall far enough and more DNA sequence variations are tied to health risks and to interactions with dietary and other health habits personal dietary advisories will become possible to create. However, the most powerful use of personal genetic profiles will likely to develop therapies that reduce individual genetic risks and problems.

Suppose someone has a greater risk of getting heart disease on a high saturated fat diet. Well, people still want to eat fat. When the genetic variations that increase heart disease risk are all identified and the mechanisms by which they increase risk become better understood it is very likely that therapies will be developed to change the expression of the genes of high risk people. In the extreme one can imagine genetic therapies to fix the causes of genetic risks.

Gene therapy will even be utilized to make food consumption easier to do. For instance, one can easily imagine those with lactose intolerance getting a gene therapy via a swallowed pill to program intestinal cells to make more lactase enzyme to break down lactose.

By the time that nutritional genomics becomes possible it is likely that complete genetic variation mapping for each person will become possible. Therefore a person won't send a DNA sample off to be tested just for nutritional advice. Rather, someone will submit their genetic map to an advice service and the advice service will then respond with specific dietary and lifestyle recommendations. Also, the service will probably include a suggested list of preventative treatments including drugs to take regularly and preemptive gene therapies to undergo.

By Randall Parker 2003 May 04 03:58 PM  Biomedical
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2003 May 02 Friday
GABA Neurotransmitter Rejuvenated Aged Monkey Brains

Visual pattern recognition was enhanced in elderly Rhesus monkeys by injection of GABA onto their neurons.

Scientists may have discovered why the brain’s higher information-processing center slows down in old age, affecting everything from language, to vision, to motor skills. The findings may also point toward drugs for reversing the process.

A brain chemical called GABA helps neurons stay finicky about which signals they respond to – a must for the brain to function at its peak. Certain neurons in very old macaque monkeys lose their pickiness, researchers have found, seemingly because they don’t get enough GABA. These results appear in the journal Science, published by the American Association for the Advancement of Science (AAAS).

If a lack of GABA is indeed responsible for the old neurons’ indiscriminate firing, this problem may be simple enough to treat. Existing drugs, such as Xanax, increase GABA production, according to author Audie Leventhal of the University of Utah School of Medicine. These drugs haven’t been carefully tested on the elderly, though.

"The good news is there are a lot of drugs around that can facilitate GABA-ergic function and maybe some of them will help," said Leventhal.

Leventhal and his colleagues studied visual function in monkeys he believes are the oldest in the world. The monkeys live in a colony in Kunming, China, established as part of a Chinese and Russian experimental program in the 1950s. At 30 years old (around 90 in people years), these animals have lived around twice as long as they do in the wild.

“They really do sort of look like grandpa. They have thinning hair and wrinkles,” Leventhal said.

In monkeys, as well as humans, visual function declines with age. While the eye itself does degenerate, this decline also involves the vision-related section of the cerebral cortex, which is responsible for many “higher-order” brain functions.

What the researchers discovered about the visual system likely applies to age-related declines in other parts of the cerebral cortex, according to Leventhal,

"If it's going on in the visual cortex, it's probably going on in other parts of the cortex," he said.

In the visual cortex, each so-called “V1 neuron” responds only to the sight of objects at a specific orientation or moving in a certain direction. GABA probably restricts the V1 neurons from responding to any other types of stimuli. This process helps the brain make sense out of the vast quantities of visual information coming in through the eyes.

"It’s like New York City or Boston during a blackout,” Leventhal said, describing what would happen if neurons weren’t restricted to specific responses. “With all the gating mechanisms like the stoplights out, you’d think traffic would move faster. But it doesn’t."

The researchers recorded the activity of individual neurons in the visual cortex of old and young macaque monkeys, while showing the monkeys various images on a computer screen. The devices that monitored the neurons also held small glass tubes of substances that could be released directly onto the neurons. The substances were GABA, a GABA-enhancing compound called muscimol, and a GABA-blocking compound called bicuculline.

The GABA blocker made the neurons less selective in the young monkeys, but had no significant effect in old monkeys. Presumably, that’s because the older neurons had already lost much of their selectivity, according to the researchers.

GABA and the GABA-enhancer had a relatively small effect in the young monkeys, moderately increasing the percentage of cells that were selective for particular orientations and directions. In the old monkeys, however, GABA and the GABA-enhancer had a much stronger effect, significantly increasing the percentage of highly selective cells.

Thus, the visual cortex of the older monkeys seemed to function less effectively, because GABA wasn’t limiting the neurons to specific responses. Exactly how this change occurred isn’t completely clear. In their Science paper, the researchers speculate that perhaps GABA production decreases in older brains.

Leventhal is hoping that more researchers will begin study aging in monkeys.

“It’s absolutely remarkable to me that my lab is the only lab in the world studying higher brain function in old monkeys. Old monkeys are rare, but the world is full of old human primates,” Leventhal said. “Hopefully we can drum up a little interest, and encourage other people who are trying to figure out how come their kids are smarter than they are now.”

The effect of the injected GABA was of short duration.

The effect lasted only as long as GABA levels were maintained. When the chemical was removed, the brains of the old monkeys reverted to their aged confusion within a few minutes, Leventhal said. Added GABA appeared to have no effect on the young.

Benzodiazepines such as Librium, Valium, and Xanax may reverse some of the mental decline caused by aging.

"It may be that already approved GABA (boosting drugs) have a positive effect on mental decline in the brains of older adults, but nobody has ever looked," he told Reuters Health.

The next logical step is to test the effects of known GABA-increasing drugs on older brains.

Dr Richard Harvey of the UK's Alzheimer's Society says new drugs with fewer side-effects may need to be developed to make best use of this discovery.

"The benzodiazepines, which include Xanax (alprazolam) and Valium (diazepam) affect the GABA system in the brain. "However they are highly addictive, and any benefits you might get from enhancing GABA are mitigated by the significant problems of physical and psychological dependence.

All of our brains are getting older.

"Brain function gets worse as we get older, pure and simple. It's not whether it will get worse, it's a matter of how much worse it will get," Leventhal said. "The ramifications of this are to correct brain degradation in the elderly. That is significant to every human being."

What will be interesting to discover is why GABA levels decline with age. Do GABA-producing cells die off? Or are there signals that inhibit the production or release of GABA in aged brains? Or do old cells have insufficient energy output from their mitochondria to support the production of GABA?

Leventhal believes the aging phenomenon that causes these results is happening throughout the brain.

Leventhal believes a lack of GABA as people age will not just affect vision but all higher brain functions.

The boosting of GABA with drugs will not be as safe and effective as the natural production of GABA by young healthy nerve cells. Still, this discovery points the way for drug development and further research into how the brain ages. This research brings closer the day when we know how to slow and even reverse brain aging.

Update: Leventhal learned about the Rhesus Macaque monkeys in China during a sabbatical in China.

He also is an honorary professor at the University of Science and Technology in Anhui, China, a connection that came about because a number of his graduate students have been Chinese and he did a sabbatical there.

By Randall Parker 2003 May 02 06:15 PM  Aging Reversal
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