Stress shortens chromosome telomeres and short telomeres are bad things to have.
Increasing scientific evidence suggests that prolonged psychological stress takes its toll on the body, but the exact mechanisms by which stress influences disease processes have remained elusive. Now, scientists report that psychological stress may exact its toll, at least in part, by affecting molecules believed to play a key role in cellular aging and, possibly, disease development.
In the study, published in the November 30 issue of Proceedings of the National Academy of Sciences, the UCSF-led team determined that chronic stress, and the perception of life stress, each had a significant impact on three biological factors -- the length of telomeres, the activity of telomerase, and levels of oxidative stress -- in immune system cells known as peripheral blood mononucleocytes, in healthy premenopausal women.
Telomeres are DNA-protein complexes that cap the ends of chromosomes and promote genetic stability. Each time a cell divides, a portion of telomeric DNA dwindles away, and after many rounds of cell division, so much telomeric DNA has diminished that the aged cell stops dividing. Thus, telomeres play a critical role in determining the number of times a cell divides, its health, and its life span. These factors, in turn, affect the health of the tissues that cells form. Telomerase is an enzyme that replenishes a portion of telomeres with each round of cell division, and protects telomeres. Oxidative stress, which causes DNA damage, has been shown to hasten the shortening of telomeres in cell culture.
The results of the study -- which involved 58 women, ages 20-50, all of whom were biological mothers either of a chronically ill child (39 women, so-called "caregivers") or a healthy child (19 women, or "controls") -- were dramatic.
As expected, most women who cared for a chronically ill child reported that they were more stressed than women in the control group, though, as a group, their biological markers were not different from those of the controls. However, in one of the study's key findings, the duration of caregiving -- after controlling for the age of the women -- proved critical: The more years of care giving, the shorter the length of the telomeres, the lower the telomerase activity, and the greater the oxidative stress.
Moreover, the perception of being stressed correlated in both the caregiver and control groups with the biological markers. In fact, in the most stunning result, the telomeres of women with the highest perceived psychological stress -- across both groups -- had undergone the equivalent of approximately 10 years of additional aging, compared with the women across both groups who had the lowest perception of being stressed. The highest-stress group also had significantly decreased telomerase activity and higher oxidative stress than the lowest-stress group.
"The results were striking," says co-author Elizabeth Blackburn, PhD, Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at UCSF. "This is the first evidence that chronic psychological stress -- and how a person perceives stress -- may damp down telomerase and have a significant impact on the length of telomeres, suggesting that stress may modulate the rate of cellular aging."
The link from mind to body
"Numerous studies have solidly demonstrated a link between chronic psychological stress and indices of impaired health, including cardiovascular disease and weakened immune function," says lead author Elissa Epel, PhD, UCSF assistant professor of psychiatry. "The new findings suggest a cellular mechanism for how chronic stress may cause premature onset of disease. Anecdotal evidence and scientific evidence has have suggested that chronic stress can take years off your life; the implications of this study are that this is true at the cellular level. Chronic stress appears to have the potential to shorten the life of cells, at least immune cells."
While it is not yet clear how psychological stress impacts telomeres, the team suspects stress hormones may play a role.
The next investigative steps
A next step in the research will be determining if prolonged psychological stress has an impact on telomeres in other types of cells, such as cells of the lining of the cardiovascular system.
The scientists also plan to further examine the impact of prolonged psychological stress on immune system cells, which mount the body's healing response to wounds, and defenses against illness. When the immune system needs to rev up, it produces more defense cells, which requires high levels of the telomerase enzyme, in order to maintain telomere length, thus allowing for additional rounds of cell division. The current study suggests that, for people under chronic stress, the telomerase activity of their immune cells might be impaired.
These scientists are now going to conduct a longitudinal study (following the same group of subject for years while repeatedly testing them) to prove that stress really does accelerate aging as measured by telomere length.
For those of you asking "What are telomeres and why are they important?" here is the short version: Telomeres are caps on the ends of chromosomes. They are made up of a very simple repeating sequence of DNA. Every time a cell divides its telomere gets shortened. Eventually the telomere gets so short that somehow as a result the cell can no longer divide or can divide only slowly and with increasing genetic damage.
So how to telomeres get long in the first place if they normally get shorter in all cells that divide? Way back at some step in the creation of an embryo (sorry, I don't know when, maybe when eggs and sperm are made? Or right after fertilization? anyone biologists reading this who know?) the telomerase enzyme gets turned on to lengthen telomeres. After that most (though perhaps not all) cell types do not have active telomerase and when they divide they get progressively shorter telomeres. The shortening of the telomeres serves as one limit on how many times cells can divide.
My guess on the study reported above is that the mechanism of telomere shortening the researchers are observing is that stress causes certain classes of cells to divide more rapidly. Keep in mind that not all cells divide. For example, most nerve and heart cells are what are called post-mitotic. They no longer go through mitotic cell division. But skin cells and the various types of adult stem cells divide. One major cause of aging is that adult stem cell reservoirs throughout the body go through so many divisions that their telomeres get too short and they can't divide very well to provide cells to do repair.
Evidence has previously been found linking telomere length to mortality risk. The length of telomeres in endothelial progenitor cells (a type of adult stem cell) is linked to increased risk of cardiovascular disease. So those cells would be logical candidates to check for telomere length in women who have been under sustained stress.
You might think that lengthening telomeres would be a great way to rejuvenate cells. Well, like so many things in life, it depends. In order for cancer cells to become cancerous one of the mutations that helps them divide better is to turn on telomerase (an enzyme that lengthens telomeres) so that telomere length won't be an obstacle to the cancer's growth. A blanket lengthening of all the telomeres of all the cells in your body (say by a gene therapy yet to be developed) would probably substantially increase your risk of cancer. Of course, for someone who is about to die from some non-cancer disease telomere lengthening might increase their lifespan by enabling adult stem cells and other cells to divide and repair damaged tissue.
Telomere lengthening techniques usable in cell culture have been developed. But the use such techniques on adult stem cells removed from your body would probably best be done in combination with genetic testing and selection processes (still to be developed) that would assure these stem cells do not already have genetic mutations that increase the risk of the cells going cancerous. Aubrey de Grey proposes reseeding adult stem cell reservoirs with cells that have lengthened telomeres. Aubrey goes so far as to argue that the replacement stem cells should have their telomerase enzymes removed entirely in order to provide a limit to cancer cell replication. Evidence from mice shows that bone marrow stem cell replenishment reduces the risk of atherosclerosis.
My advice: Avoid stress. Also, support scientific research into rejuvenation. Your telomeres are getting shorter every day and that is not good. We need safe rejuvenation therapies to give us young adult stem cells and other cell types.
A fairly new type of magnetic resonance imaging (MRI), called diffusion tensor imaging (DTI), has been used to examine the brains of children diagnosed with attention deficit hyperactivity disorder (ADHD) and ADHD children were found to have abnormal fiber pathways that connect the different parts of the brain.
CHICAGO – Children with attention deficit hyperactivity disorder (ADHD) display anatomical brain abnormalities beyond chemical imbalance, according to research presented at the annual meeting of the Radiological Society of North America (RSNA). Stimulant medications prescribed to balance brain chemistry appear to normalize some of these brain irregularities, a second study reported.
"We found abnormality of the fiber pathways in the frontal cortex, basal ganglia, brain stem and cerebellum," said lead author of both studies, Manzar Ashtari, PhD., associate professor of radiology and psychiatry at North Shore-Long Island Jewish Health System in New Hyde Park, N.Y.
"These areas are involved in the processes that regulate attention, impulsive behavior, motor activity, and inhibition--the key symptoms in ADHD children," Dr. Ashtari said. "They are also known to be part of a bigger circuit in the brain that establishes communication between the frontal lobe and cerebellum."
According to the National Institute of Mental Health (NIMH), ADHD affects 3 to 5 percent of children in the United States. Children with ADHD have difficulty controlling their behavior or focusing their attention.
Using diffusion tensor imaging (DTI) to compare 18 children with diagnosed ADHD with 15 control children to evaluate the brain's white-matter fiber development, Dr. Ashtari's team found differences in the brain fiber pathways that transmit and receive information among brain areas.
"Typically ADHD is described as a chemical imbalance, but our research has shown that there may also be subtle anatomical differences in areas of the brain that are important in this disorder," said co-principal investigator Sanjiv Kumra, M.D., a psychiatrist at the Zucker Hillside Hospital in Glen Oaks, N.Y.
If DTI brain scanning can be used to diagnose ADHD then that could lower the rate of misdiagnosis and kids wouldn't be given drugs unnecessarily. The treatment of ADHD with stimulant drugs appears to have a beneficial effect on brain development!
In the second study, the researchers found that children who had received stimulant treatment for ADHD had fewer white matter abnormalities than children who did not receive medication.
Patients consisted of two groups, each comprised of 10 children with ADHD. The first group had not taken medication or had been minimally exposed to medications. The second group was exposed to stimulants for an average of 2.5 years. Each of these groups was compared with 10 age- and gender-matched controls. The medicated ADHD children exhibited a normalization effect in fiber pathways of several brain areas.
"The findings from this small, cross-sectional study indicate that the therapeutic effect of stimulants may involve a brain normalization process," Dr. Kumra said.
Millions of American children are diagnosed with ADHD.
Between 3 percent and 5 percent of American children are diagnosed with ADHD.
The ability to use DTI to measure abnormalities of brains of children with ADHD will also allow comparison of different ADHD drug treatments to identify treatments that do a better job of reducing the size of the brain abnormalities.
DTI has also recently been used to identify abnormalities in brain fibers in schizophrenic patients.
WASHINGTON— Researchers at the Boston Veterans Affairs Health Care System – Brockton Division, Harvard Medical School, and the University of Massachusetts-Boston are using new imaging technology to gather valuable information about the brains of people with schizophrenia. This new variety of magnetic resonance imaging (MRI) is called diffusion tensor imaging (DTI). Using DTI on patients with schizophrenia, neuropsychologists have related smaller sizes in two distinct webs of brain fibers to two distinct types of cognitive malfunction.
The findings appear in the October issue of Neuropsychology, which is published by the American Psychological Association (APA).
Diffusion tensor imaging (DTI) uses a regular MRI machine to analyze the movement of water molecules in and around the fibers that connect different parts of the brain. Neuroscientists use DTI to track indicators of brain “connectivity” – factors such as the number, thickness, density and arrangement of axons (the hair-like extensions of neurons, which send messages to other neurons) and thickness of the insulating/conducting fatty myelin sheath in which they are embedded. If weaker structural integrity reduces connectivity, lead author Paul Nestor, PhD, says it may mean that, “different brain areas do not communicate as well – with less synchrony or harmony, akin to an orchestra or band playing out of synch.”
The researchers conducted neuropsychological tests on 41 patients with schizophrenia and 46 healthy controls, and used DTI scans on a 14-person subset of people with schizophrenia and healthy controls, a sample size typical of seminal studies of the human brain and comparable to early studies using functional MRI.
Brain images from the schizophrenic patients showed abnormalities in two functionally and anatomically different neural pathways – the uncinate fasciculus (UF) and the cingulate bundle (CB). Compared with age-matched controls, patients had smaller UF and CB. These bunches of axons are wrapped in myelin sheaths and bundled like electrical wire. The UF connects different parts of the frontal and temporal lobes and the CB connects parts of the prefrontal-cingulate regions. Each of these fiber tracts may help to define distinct neural networks. “We presume that the health of these fibers reflects the degree to which different parts of the brain are able to communicate,” says Nestor.
It seems reasonable to expect DTI will help to accelerate the development of drugs for schizophrenia as well. Comparison of patient brain scans before and after treatment will provide a way to compare the efficacy of different drugs in reducing brain abnormalities. To repeat a frequent FuturePundit refrain: advances in scientific and medical instrumentation enable the acceleration of advances in science and medical treatment.
Shigeru Omi of the World Health Organization says we are overdue for the next big flu pandemic.
"I believe we are closer now to a pandemic than at any time in recent years," said Shigeru Omi, regional director for the Western Region of the World Health Organization (WHO).
"No country will be spared once it becomes pandemic," he told a news conference on Friday.
"History has taught us that influenza pandemics occur on a regular cycle, with one appearing every 20 to 30 years. On this basis, the next one is overdue.
"We believe a pandemic is highly likely unless intensified international efforts are made to take control of the situation,"
Southeast Asian farming practices make mixing of influenza viruses across species much more likely.
Chickens, ducks and other animals are often allowed to roam freely on small Southeast Asian farms, and often come into close contact with wild animals and with family members.
Some animal health experts have been promoting so-called "closed-system farming," in which poultry are raised in a sealed environment where they face minimal exposure to outside infections. But the system is likely to be prohibitively expensive for many poor farmers.
One worrisome development is the spread of the H5N1 virus into more species in Southeast Asia. The thinking is that this spread gives the virus greater opportunity to coinfect a pig that also has a human-compatible flu infection so that the two viruses can exchange genetic code and produce a lethal virus that is human-compatible.
Klaus Stohr says the next pandemic is a matter of when, not if.
"There is no doubt there will be another pandemic," Klaus Stohr of the WHO Global Influenza Program said on the sidelines of a regional bird flu meeting in Bangkok, Thailand.
"Even with the best case scenario, the most optimistic scenario, the pandemic will cause a public health emergency with estimates which will put the number of deaths in the range of two and seven million," he said.
Note that the 7 million deaths figure assumes a less lethal virus. A more lethal virus with a potency similar to the 1918 outbreak could kill tens of millions.
Stohr says there is insufficient global vaccine production capacity.
The world's total capacity for flu vaccine now is only 300 million doses, and it would take at least six months to develop a new vaccine to fight a pandemic. The WHO wants to get "all issues on the table," monetary and scientific, that prevent getting more vaccine more quickly, he said.
...
The United States is the only nation that has commissioned work on potential pandemic bird flu vaccines, Stohr noted. The National Institutes of Health has given Aventis Pasteur and Chiron Corp. contracts to produce prototype bird flu vaccines that are expected to be ready for human tests late this year.
While strain H5N1 is the main fear strains H9N2 and H7N7 have also broken through to human populations and killed small numbers of people in recent years. So we can not be certain which strain to target.
A pandemic bird flu virus would require two vaccine shots for adequate protection.
A pandemic vaccine would need to protect against only one strain of flu virus -- the newly emerged one -- rather than three strains, as is the case with the annual flu shot. However, because nobody on Earth would have underlying immunity to the new strain, people would need to get two shots to be protected.
This means that there is only enough capacity to produce vaccine for about 150 million people. However, there is reason to hope that intradermal (rather than the standard intramuscular) delivery of standard flu vaccine would allow only one fifth of a normal dose to be used in place of the standard full dose. A new paper just out in the New England Journal of Medicine, "Dose Sparing with Intradermal Injection of Influenza Vaccine", found that intradermal injection allows vaccine doses to go 5 times as far in young adults.
Results Subjects who received an intradermal injection with one fifth the standard dose of influenza vaccine had increases in the geometric mean HAI titer by a factor of 15.2 for the H1N1 strain in the vaccine, 19.0 for the H3N2 strain, and 12.4 for the B strain on day 21, as compared with respective increases by a factor of 14.9, 7.1, and 15.3 for the intramuscular injection of the standard dose. Seroconversion and seroprotection rates were similar in the two groups on day 21, ranging from 66 to 82 percent and 84 to 100 percent, respectively. Local reactions were significantly more frequent among recipients of intradermal injections than among recipients of intramuscular injections, but such reactions were mild and transient.
One worrisome note on this study: If doctors start to routinely use fractional doses of flu vaccines then that will reduce the demand for flu vaccine production and that, in turn, will lead to a reduced capacity to make influenza vaccine. Then we will approach a pandemic with no more effective production capacity than we have now.
Not only is vaccine production capacity limited but also it takes 6 months to develop and manufacture a new strain of flu vaccine.
"It will take six to eight months before a company has all the paperwork done and the testing [to get the vaccine licensed]," he said.
"That can be shortened to perhaps two to three months if the paperwork and testing is done now.
The lag time for producing vaccine is a problem that needs to be solved by the development of a new method for producing vaccine. The use of fertile chicken eggs to grow vaccine is the biggest bottleneck. The development of a better method for producing vaccine would also likely result in a more rapidly scalable production technology as well. The development of the ability to grow vaccine in cell culture would allow faster scaling in part because cells can be grown much more rapidly than fertilized egg production can be scaled up.
The vaccine production problem is not going to get solved any time soon. This argues for the need to look at other ways to respond to a new flu strain which has pandemic potential. Methods to slow the rate of spread of a dangerous flu are needed. Far better methods could be developed to slow the speed of spread of an outbreak and many of these methods could be very low tech and cheap.
For example, children are major spreaders of influenza in schools. Well, how could schools be managed (short of shutting them down which would be very effective but a large burden to working parents) to reduce the spread of diseases? Here is one idea: Imagine transparent plastic dividers between aisles of chairs so that cough spray could not travel between rows and kids could not as easily touch each other. This could be extended to dividers between rows with some sort of ceiling contraption for raising the plastic dividers like blinds are raised. It is a cheap response. But this response requires lead time for buying and installing the dividers. So this would best be done before a pandemic flu strain emerged.
Another idea: conduct more studies on how influenza virus spreads. What percentage of flu spread happens through airbone droplets versus physical contact between people versus touching of contaminated surfaces? What locations (types of occupations, schools, etc) are where most flu cases are spread? The public should be supplied with excellent information at the start of an outbreak so that living patterns and daily routines can be adjusted to reduce risk of transmission.
Some adjustments to reduce transmission risk are pretty obvious. People could go shopping later at night to reduce the number people in a store at any one time. Businesses could allow more people to work at home or to work at off hours. Better filtration systems could be installed in buildings to remove airborne particles from the air more rapidly. Public places could require covering of mouths and noses to reduce the discharge of cough particles into the air.
On the Gene Expression blog Canton points to an Australian firm, Genetics Technologies, that is offering a genetic test for potential athletic performance.
The test examines a gene known as ACTN3, which produces a structural protein found in fast-twitch muscle fibres. Research involving elite-level athletes from the Australian Institute of Sport has shown that the different forms (“variations”) of the ACTN3 gene may be associated with an improved ability to excel in either sprint/power events, or in endurance events. So whether you’re an athlete, or young athlete-to-be, the ACTN3 Sports Performance Test will help direct you toward achieving your maximum natural potential.
This test does not discriminate good athletes from bad athletes. ACTN3 Sports Performance Testing is designed to assist athletes with identifying the type of events, distances or sports in which success is more likely. The association of different genetic variants with power / sprint versus endurance events appears to apply in a wide range of sports, including track and field, swimming, cycling, rowing, judo, etc. Testing may also assist athletes in tailoring their training for optimal performance within their sport of choice.
The cost for this test is $110 Australian which is about $87 US. This test does not measure all the factors that go into determining potential for all types of athletic performance. Most of the genetic contributors to athletic performance still await discover. Rather, this test measures just one gene that affects the performance of fast-twitch muscle fibers. It will take the identification of probably thousands of more genetic alleles that influence athletic performance before genetic testing will achieve its full potential to predict individual athletic performance limits.
But what, exactly, are they offering you that can't be determined without this miracle of modern technology? A fundamental part of living life is figuring out your aptitudes. Being guided by statistics towards one sport or another doesn't save you time -- it just robs you of the opportunity to beat the statistics and be a marathon runner who has an abundance of fast-twitch muscle fibers.
But step back a bit and look at it from the perspective of those who have the ideal genetic variations for, say, sprinting. As a result of widespread genetic testing someone with less than optimal genetic variations for sprinting is going to have a harder time competing successfully even if that person never gets tested and has no idea what their genetic potential is. Why? Genetic testing is going to make it easier to find more people who have great genetic potential for a sport so that they can be steered toward that sport. As a result genetic testing will make it difficult for those with less than ideal genetic variants for a sport to compete in that sport.
I realize many people love to see someone prevail over daunting obstacles and tough odds. But the identification of all the genetic variations that contribute to athletic performance in combination with mass genetic testing is going to lead the identification and encouragement of large numbers of people who now are never trying seriously to perform in sports. Therefore people best suited for a sport will enter it in far greater numbers and those who now face tough but occasionally surmountable odds will face impossible odds.
What I said doesn't just hold for sports. Surely there are genetic variations that influence ability to excel in opera singing, ballet dancing, musical composition, musical performance, writing, engineering, and a great many other pursuits. It even seems very probable that there are genetic variations for the ideal special forces soldiers not only for athletic performance but also for handling extreme physical and mental stress. The identification of those genetic variations that contribute to many types of human performance will lead to genetic aptitude tests that will be used in combination with biotechnological instruments (e.g. scanning devices such as MRIs and CAT scanners) of how a person physically developed to provide a much more accurate picture of that person's performance potential. These tests will constituent what will be, in effect, biological aptitude tests. in combination with existing conventional aptitude tests these tests will steer people with specific types of greater potential more accurately toward the fields of human endeavour for which they have natural gifts.
Of course the identification of genetic variations that affect athletic performance will provide starting points for the development of drugs, gene therapies, cell therapies, and other treatments that will boost athletic performance and raise the potential for individual humans to achieve in a large range of areas. So just as we become more able to predict our potential we will be able to raise our potential as well. These biotechnogically raised levels of performance will also be to known limits, albeit higher limits. So there will be less mystery about our individual potential regardless of whether we decide to enhance ourselves.
Arryx has developed a device that can move movement of microscopic objects using lasers.
Chicago, IL. November 8, 2004. Arryx, Inc. announced today that it has added an infrared (IR) product to its line of BioRyx(R) 200 optical trapping systems. The BioRyx(R) 200 IR system extends Arryx’ proprietary, three-dimensional holographic laser tweezer technology into the infrared portion of the spectrum. Arryx’ easy-to-use real-time trapping software allows users to create a variety of infrared traps and simultaneously monitor and record fluorescence from a broad range of dyes. This gives researchers in biology and nanotechnology the unique ability to manipulate hundreds of microscopic objects, from blood and cancer cells to DNA and nanotubes, independently and simultaneously in three dimensions.
One of the initial applications of their technology is going to be the sorting of bull sperm to select cow gender in order to reduce the number of less valuable male cows (only females can make milk).
Arryx’ next product is its cell-sorting equipment, the CelRyx(TM) system. The initial applications of CelRyx(TM) system are designed to increase productivity and profitability in the cattle and dairy industries, by sorting cattle sperm for viability and gender selection, and the blood-bank equipment industry, by processing blood components.
Cow semen sorting by sex chromosome will be available in 2005.
"We have a partnership with a company involved in artificial insemination for cattle. With this system [expected to be out in 2005], you put cattle semen in one end of the machine and sorted cells (come) out the other," he said.
A physicist who was at the University of Chicago made scientific advances that made the laser tweezer technology feasible.
But it took David Grier, then a University of Chicago physicist and now director of the Center for Soft Matter Research at New York University, to develop the method to control multiple items at one time with a single beam. His technique involves splitting laser beams into multiple "beamlets," which operate on the nano level to control as many objects as desired.
Background information on Grier's laser tweezer work is available on his web site.
For information and background on the scientific and technical work that led to the implementation of laser tweezers, feel free to browse Dr. David G. Grier's Web site: http://physics.nyu.edu/grierlab/.
It is not clear whether Arryx's technology will ever be offered for sex selection of human offspring. Another company, Microsort, already offers human baby sex selection services using a different technology. Microsort's approach is not 100% accurate and requires in vitro fertilization (IVF). So it has some downsides. Note that Arryx is going to offer sex selection for cows. My guess is their approach is cheaper since it would have to be for animal husbandry. If Arryx's technology could sort a larger number of sperm then it opens up the potential for initiating pregnancies with artificial insemination without IVF and without the need to harvest eggs to use in IVF.
Eventually much easier and lower cost pre-conception sex selection technologies will be available for human use. As it stands now cheap ultrasound technology and selective abortion are already causing large excesses in male births in Taiwan, China, and India. Imagine what will happen worldwide as costs and risks of sex selection drop.
Arryx has also made a deal with a company called Haemonetics to developed their technology for blood processing. Their technology looks promising for all sorts of manipulations of large numbers of small things simultaneously.
A comparison of the sexual histories of 1600 identical and non-identical twins found that genetic variations play a large role in influencing the tendency to infidelity among women.
"We found that around 40 percent of the influence on the number of sexual partners and infidelity were due to genetic factors," Professor Tim Spector, director of the Twin Research Unit at St Thomas' Hospital in London, told a news conference.
Identical twins whose twin has strayed have twice the normal chance of straying.
The findings mean that someone with a philandering twin is far more likely to philander themselves. The average risk of female infidelity is about 22%, says Spector, but those with an unfaithful identical twin have a risk of 44%.
Women tend to stray to hook up with higher status men.
The study, which was published in the journal Twin Research, suggests that a genetic predisposition towards female infidelity may have evolved because it was important in allowing women married to "low status" men surreptitiously to become pregnant by "high status" men.
"If female infidelity and number of sexual partners are under considerable genetic influence, as this study demonstrates, the logical conclusion is that these behaviours persist because they have been evolutionary advantageous for women," the researchers write in their scientific paper.
From an evolutionary perspective, a woman’s best short-term strategy would be to clandestinely pursue men with better genes.
Prof Spector points out that women tend to have affairs with men of higher status than their husbands. However, the system would break down, he said, if "everyone was unfaithful, because there would be no pair-bonding".
It lends strong support to theories advanced by evolutionary psychologists such as Steven Pinker, of Harvard University, who argue that human sexual behaviour is at least partly determined by natural selection and our genes.
...
Professor Spector’s team did not identify any particular gene that contributes to a tendency to infidelity, though they did pinpoint three regions on chromosomes 3, 7 and 20 that might harbour such genes. He believes that there are between 50 and 100 genes that contribute to a tendency to infidelity.
I predict with high confidence that once DNA testing becomes cheap then before entering into more committed relationships many men and women will surreptitiously take DNA samples from each other and have the DNA tested for genetic variations that contribute to infidelity and to other behavioral tendencies as well. If your man likely to be a hard worker in the long term but is too young have a long work track record? Test him for alleles that contribute to a work ethic. Are you afraid he might have a tendency toward violence? Test for violence-promoting genetic variations. Afraid she is going to cheat? Check hundreds of genes for polymorphisms that cause cheating other undesired behaviors and decide whether the odds of undesired future behaviors are higher than you find acceptable.
Once it becomes possible to alter the brains of adults to increase or decrease the appeal of promiscuity will some men and women come under pressure from their mates to go get a treatment to remove their urge to stray? It seems plausible.
Also, once the genetic variations for monogamy and promiscuity all become identified and it becomes possible to control which genetic variations one will pass on to one's offspring will people tend to choose genetic variations that increase or decrease the incidence of infidelity in relationships? My guess is that people will tend to choose genetic variations that increase the appeal of monogamy. One reason is that people who are going to have many children will tend to favor having children who will want to stick around to take care of their own kids. But I'm not certain on that point. What do you think?
Update: One point needs to be made about hereditability of behaviors: Just because twins are, on average 44% likely to engage in infidelity of their twin has done so does not mean that those are the real odds for each twin whose twin has engaged in infidelity. Suppose, for example, that there are 100 genes that influence whether, say, married people will engage in extra-marital affairs. Well, one pair of twins might have half those genes in variations that predispose toward infidelity. Yet another pair of twins might have 75 of those 100 genes all in versions that predispose for infidelity and still another pair of twins might have all 100 of those genes in versions that predispose for infidelity.
The problem with studies of the behavior of groups twins is that such studies probably understate the extent to which genes can cause particular behaviors. There are people who have a set of genetic genes that pull them in opposing directions. But then there are people who have sets of genetic variations that very strongly pull them in particular directions. Take the twins in this study of infidelity. The twins where each twin engaged of infideilty probably, on average, have more genetic variations that predispose them for infidelity than do the twins where only one of the two twins in a pair engaged in infidelity.
You will see a lot of news reports claiming that the more sophisticated view is to see genes and environment as interacting to cause behaviors. That is true. But that argument is typically made to assure everyone that we really still each have ultiimate control over what we do and that we all have free will. But twins studies understate the extent to which genetic variations influence behavior because those studies deal with groups averaged together. Once DNA sequencing becomes cheap and each person in studies of human behavior can have their complete genome sequenced I expect to see many combinations of genetic variations found that exert extremely strong and even uncontrollably strong influences on human behavior.
Women’s fidelity has come under fire at the University of Chicago. Some claim that women are naturally endowed with cheating hearts, and they are pointing to the size of men’s testicles as proof.
A Chicago research team, led by Dr. Bruce Lahn, found that the intensity of sexual competition in a variety of primate species is directly related to the size of males’ testicles. After obtaining DNA sequences from the SEM2 gene from 12 species of primates, including humans, the team examined the evolution of these primates’ sperm.
“We found that the rate of evolution is much higher—that is, the gene has undergone much more dynamic changes—in primate species with promiscuous females than in primate species with monogamous females,” Lahn said. “In other words, when males have to compete more in the game of fertilization, their semen protein has to make more innovations along the way.”
...
Human testicles fall somewhere in the middle of chimp and gorilla testicles in size. This suggests that women’s fidelity patterns likewise fall somewhere in between these two species, so that women are neither as faithful as gorillas nor as naughty as chimps.
Lahn's group studied semenogelin, a major protein in the seminal fluid that controls the viscosity of semen immediately following ejaculation. In some species of primates, it allows semen to remain quite liquid after ejaculation, but in others, semenogelin molecules chemically crosslink with one another, increasing the viscosity of semen. In some extreme cases, semenogelin's effects on viscosity are so strong that the semen becomes a solid plug in the vagina. According to Lahn, such plugs might serve as a sort of molecular “chastity belt” to prevent fertilization by the sperm of subsequent suitors, though they might also prevent semen backflow to increase the likelihood of fertilization.
Lahn and his colleagues compared the SEMG2 gene, which contains the blueprint for semenogelin, from a variety of primates. They began by sequencing the SEMG2 gene in humans, chimpanzees, pygmy chimpanzees, gorillas, orangutans, gibbons, macaques, colobus monkeys, and spider monkeys. These species were chosen because they represent all the major mating systems. These include those in which one female copulates with one male in a fertile period (such as gorillas and gibbons); those in which females copulate highly promiscuously (such as chimpanzees and macaques); and those in which mating practices fall somewhere in between (such as orangutans where a female will copulate with the dominant male, but may also copulate with other males opportunistically).
Update III: Over on the Gene Expression blog Godless Capitalist reports on Jared Diamond accepting the existence of variations in testes size as a function of racial and ethnic group. This is a sign that selective pressures caused by infidelity have not been uniform across the entire human race down through history since humans spread out across the planet. It seems quite possible that some or all of the genetic variations mentioned at the top of this post that influence infidelity vary their distribution along with the genetic variations that cause large testis size.
First off, chronic back pain causes brain shrinkage that is equivalent to 10 to 20 years of brain aging.
CHICAGO --- Chronic back pain, a condition afflicting many Americans, shrinks the brain by as much as 11 percent — equivalent to the amount of gray matter lost in 10 to 20 years of normal aging, a Northwestern University research study found.
Loss in brain density is related to pain duration, indicating that 1.3 cubic centimeters of gray matter (the part of the brain that processes information and memory) are lost for every year of chronic pain, said lead researcher A. Vania Apkarian, associate professor of physiology at Northwestern University Feinberg School of Medicine and a researcher at the Northwestern University Institute of Neuroscience.
The study, the first to examine brain changes in chronic pain conditions, was published in the Nov. 23 issue of The Journal of Neuroscience.
About 6 percent of the American population is probably suffering from brain shrinkage from chronic back pain. On top of that there are people suffering from chronic stomach pain and other forms of chronic pain. So it is likely that more than 20 million Americans are suffering cognitive losses due to chronic pain.
At least 25 percent of Americans suffer from back pain; in one fourth of these individuals, back pain is chronic and unremitting.
Although chronic pain greatly diminishes quality of life and increases anxiety and depression, it previously had been assumed that the brain reverts to its normal state after chronic pain stops.
Apkarian and co-researchers used structural magnetic resonance imaging brain scan data and two automated analysis techniques to contrast brain images from 26 participants with chronic back pain with those from matched normal subjects.
All participants with chronic back pain had unrelenting pain for more than a year, primarily localized to the lumbosacral region, including buttocks and thighs, with or without pain radiating to the leg.
The participants were divided into neuropathic — exhibiting pain because of sciatic nerve damage — and non-neuropathic. Brain scans showing gray matter volume were compared.
In earlier research, Apkarian and colleagues found that back pain sustained for six months or longer is accompanied by abnormal brain chemistry, indicated by chemical changes in the area of the brain known to be important in making emotional assessments, including decision-making and for controlling social behavior. Based on these results, Apkarian’s laboratory group embarked on the brain atrophy study.
It is possible that some of the observed decreased gray matter shown in this study reflects tissue shrinkage without substantial neuronal loss, suggesting that proper treatment would reverse this portion of the decreased brain gray matter, Apkarian said.
The atrophy also may be attributable to more irreversible processes, such as neurodegeneration. Other research has shown that spinal cord neurons undergo apoptosis — cell death — in rats with neuropathic pain.
“Given that, by definition, chronic pain is a state of continuous persistent perception with associated negative affect and stress, one mechanistic explanation for the decreased gray matter is overuse atrophy caused by excitotoxic and inflammatory mechanisms,” Apkarian said.
The researchers hypothesize that atrophy of brain circuitry involved in pain perception may dictate the properties of the pain state, such that as atrophy of elements of the circuitry progresses, the pain condition becomes more irreversible and less responsive to therapy.
Other researchers on the study were Yamaya Sosa, physiology; Sreepadma Sonty, neurology; Robert M. Levy, M.D., neurosurgery; R. Norman Harden, M.D., physical medicine and rehabilitation; Todd B. Parrish, radiology; and Darren R. Gitelman, M.D., neurology, radiology and the Cognitive Neurology and Alzheimer’s Disease Center, at Feinberg.
Obesity also causes brain losses.
St. Paul, Minn. – Women who are obese throughout life are more likely to lose brain tissue, according to a study published in the November 23 issue of Neurology, the scientific journal of the American Academy of Neurology. Loss of brain tissue has been linked to cognitive decline.
Researchers in Sweden studied the relationship between body mass index and brain atrophy (loss of brain tissue) in 290 women. The women were born between 1908 and 1922 and had four follow-up examinations between 1968 and 1992. During the final exam, they had a computed tomography (CT) scan to measure for any loss of brain tissue. Body mass index (BMI) is a measure of body fat that shows weight adjusted for height. Overweight is a BMI of 25 to 30 kg/m2. Obesity is a BMI of 30 kg/m2 and above.
An overweight or obese BMI was linked to a loss of tissue specifically in the temporal lobe. Nearly 50 percent (144) of the women had temporal atrophy. At the time of CT scan, their body mass index was an average of 27 kg/m2, which was 1.1 to 1.5 kg/m2 higher than the women without brain atrophy. Overall the women’s BMI increased over the 24-year period, but the increase was greater for those who lost tissue in the temporal lobe. The risk of atrophy increased 13 to 16 percent per 1.0 kg/m2 increase in BMI.
“This study indicates that a high BMI is a risk factor for dementia in women. Other studies have reported similar findings,” said Deborah Gustafson, PhD, of Sahlgrenska University Hospital in Göteborg, Sweden and also the Medical College of Wisconsin in Milwaukee. “Obesity is another factor that should be actively intervened upon to reduce diseases of advanced aging.”
The researchers didn’t pinpoint a reason why obesity leads to brain atrophy. They said there are several possible mechanisms.
“Obesity is related to ischemia, hypertension, and cerebrovascular and cardiovascular diseases. These conditions contribute to an unhealthy vascular system, and therefore, to a higher dementia risk,” said Gustafson. “Obesity may also increase the secretion of cortisol, which could lead to atrophy.”
The temporal lobe appears to be highly susceptible to the effects of ischemia and other vascular diseases in the brain, and is evidence of cerebral degeneration and neuronal death, Gustafson said.
These two reports effectively raise the stakes for two major health problems. Losses in cognitive ability have huge macroeconomic and personal costs. Overweight people with chronic pain suffer a cognitive double whammy. We need both better treatments for chronic pain and better therapies to prevent obesity.
By eating phytoplankton sardines may prevent the process where when phytoplankton die they settle on the bottom of the ocean and then get broken down (presumably by bacteria) to release methane. Over-fishing sardines may increase methane release into the atmosphere.
Milky, turquoise-colored “dead zones,” sometimes as large as New Jersey, of rotting fish and caustic stench floating off the coast of southwest Africa, may be a sign of things to come for other areas along the coastlines of the eastern Atlantic and Pacific oceans. Toxic gas eruptions—bubbling up from the ocean floor to kill sea life, annoy human seaside residents, and may even intensify global warming—cause the dead zones. But the humble sardine may help to save the day, according to a study from the Pew Institute for Ocean Science.
In an article published in the November issue of Ecology Letters, authors Andrew Bakun and Scarla Weeks compare several areas around the world where strong offshore winds cause an upwelling of nutrients in the ocean and thus a population explosion of phytoplankton, the microscopic plant life that drifts through the ocean. Studying the waters off the coast of Namibia, the scientists report how the resulting overproduction of phytoplankton dies and sinks to the bottom, and how the decaying organic matter releases copious amounts of methane and poisonous “rotten egg” smelling hydrogen sulfide gas.
As methane is 21 times more effective than carbon dioxide at trapping heat in the atmosphere, the resulting climate change may intensify this upwelling process and open the possibility of even larger and more plentiful eruptions.
One action to help keep this situation from worsening, the authors say, is to avoid the overfishing of sardines, which can devour large quantities of phytoplankton.
“The region in question formerly hosted a large population of sardines that have been overfished,” says Bakun, a member of the Pew Institute and professor of marine biology and fisheries at the University of Miami Rosenstiel School of Marine and Atmospheric Science. “It is at least encouraging that a minor resurgence of sardine abundance coincided with a noticeable temporary hiatus in eruption frequency off Namibia in 2002.”
Bakun and Weeks, from the University of Cape Town in South Africa, also warn that areas near Cape Mendocino, California, and Cape Sim, Morocco, may be dangerously close to the “tipping point,” possibly ripe for phytoplankton population explosions followed by their gaseous demise.
“This study demonstrates that overfishing one species of fish, such as sardines, can profoundly alter an entire marine ecosystem in ways that may be difficult or impossible to reverse,” says Ellen Pikitch, executive director of the Pew Institute for Ocean Sciences and an expert on fishery science and management.
Pew’s Chief Scientist Elizabeth Babcock adds, “The California sardine population has recovered somewhat since it peaked in the 1940s and was depleted by the early 1960s. We hope that the population can continue to recover as a hedge against development of such a regrettable situation on our own coast.”
Healthy sardine populations for a healthier atmosphere. Who would have thought?
For at least the last 5 years James Hansen of NASA has been arguing that reduction in methane gas emissions is a cheap way to delay global warming while providing more immediate health benefits (see the middle and end parts of that post).
Here is a story of a significant advance for treating a chronic debilitating disease. While this latest treatment is a good thing that will benefit many sufferers of Multiple Sclerosis a comparison of the financial figures for drug costs, treatment costs, and other costs of MS versus the amount of money spent on MS research illustrates a larger problem in medicine today: too little money is spend on research into diseases that are costly to treat and costly to live with.
We start out first with the happy news. The US Food and Drug Administration has approved Tysabri for sale as a treament for MS.
Cambridge, MA; San Diego, CA; Dublin, Ireland – November 23, 2004 – Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc (NYSE: ELN) announced today that the U.S. Food and Drug Administration (FDA) has approved TYSABRI (natalizumab), formerly referred to as ANTEGREN®, as treatment for relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical relapses. FDA granted Accelerated Approval for TYSABRI following Priority Review based on one-year data from two Phase III studies, the AFFIRM monotherapy trial and the SENTINEL add-on trial with AVONEX®(Interferon beta-1a).
TYSABRI, the first humanized monoclonal antibody approved for the treatment of MS, inhibits adhesion molecules on the surface of immune cells. Research suggests TYSABRI works by preventing immune cells from migrating from the bloodstream into the brain where they can cause inflammation and potentially damage nerve fibers and their insulation.
Tysabri by itself greatly reduced the MS relapse rate.
AFFIRM is a two-year, randomized, multi-center, placebo-controlled, double-blind study of 942 patients conducted in 99 sites worldwide, in which patients were randomized to receive either a fixed 300 mg IV infusion dose of TYSABRI (n=627) or placebo (n=315) every four weeks. TYSABRI reduced the rate of clinical relapses by 66 percent relative to placebo (p<0.001), the primary endpoint at one-year. The annualized relapse rate was 0.25 for TYSABRI-treated patients versus 0.74 for placebo-treated patients.
AFFIRM also met all one-year secondary endpoints, including MRI measures. In the TYSABRI-treated group, 60 percent of patients developed no new or newly enlarging T2 hyperintense lesions compared to 22 percent of placebo-treated patients (p<0.001). On the one-year MRI scan, 96 percent of TYSABRI-treated patients had no gadolinium enhancing lesions compared to 68 percent of placebo-treated patients (p<0.001). The proportion of patients who remained relapse free was 76 percent in the TYSABRI-treated group compared to 53 percent in the placebo-treated group (p<0.001).
When combined with the existing Avonex drug (which is the protein hormone Interferon beta-1a) the result was a lower relapse rate than when used with Avonex alone.
Approval was also based on the results of another Phase III clinical trial, SENTINEL. SENTINEL is a two-year, randomized, multi-center, placebo-controlled, double-blind study of 1,171 AVONEX-treated patients in 123 clinical trial sites worldwide.
In the SENTINEL trial, AVONEX-treated patients who continued to experience disease activity were randomized to add TYSABRI (n=589) or placebo (n=582) to their standard regimen.
SENTINEL achieved its one-year primary endpoint. The addition of TYSABRI to AVONEX resulted in a 54 percent reduction in the rate of clinical relapses over the effect of AVONEX alone (p<0.001). The annualized relapse rate was 0.36 for patients receiving TYSABRI when added to AVONEX versus 0.78 with AVONEX plus placebo.
Note that the annualized relapse rate from the first trial that used only Tysabri was lower than the annualized relapse rate from the second trial of Tysabri and Avonex in combination. Though it is not clear that the sample sizes and the characteristics of the two sets of experimental subjects were comparable. Still, Tysabri looks like it is a more effective treatment of MS.
Some people can't handle existing anti-MS drugs due to the severity of side effects. Expect many of those patients to shift to Tysabri. Also, some may add Tysabri to existing treatments to reduce the odds of relapse.
Guesstimates have ranged from $20,000/year to as much as $30,000/year. By comparison, Avonex, Betaseron and Copaxone cost about $13,000 per year, Rebif $16,500 per year.
My guess is that Tysabri will put some downward pricing pressure on the other competiting drug treatments for MS. Also, its high price serves as an incentive for other pharmaceutical companies to develop better MS drugs. Estimates for Tysabri yearly peak sales range from $1 to $2 billion to $3 billion.. Estimates of the number of patients who can no longer use existing MS drugs in the US range from 40,000 to 50,000 all the way up to 175,000. Estimates for the number of MS sufferers in the US range from 350,000 to 400,000. Well, at a price of $30,000 year it would take 100,000 patients using Tysabri to reach $3 billion yearly sales. Currently the total market for MS sales split across all existing products is $4 billion. Total dollar volume of MS drug sales will likely grow as a result of Tysabri's introduction. In the longer run more MS drugs will be introduced to try to get a percentage of MS drug sales.
Much more money is spent on MS treatment than is spent on MS research.
In the United States, the annual cost of MS is approximately $20 billion; this amount pales in comparison with the level of investment in MS research at NIH*. For FY'04 and FY'05, it is estimated NIH will spend $101.3 million and $102.8 million on MS research, respectively. Two NIH institutes primarily conduct or fund research on MS: NINDS that funds 75%, and NIAID that funds about 20%.
My guess (and this is a high confidence guess) is that the US government spends easily 20 or 30 times more money (through Medicare, Medicaid, and other government medical programs) to treat MS patients and to take care of MS patients than it does on research. This strikes me as very foolish. Auto-immune diseases (which MS is suspected of being along with rheumatoid arthritis and type I diabetes) will not be as hard to completely cure as, say, cancer or heart disease. There are many more research grant applicants than money to fund them. There is no shortage of qualified researchers who can be funded to speed up the rate of progress.
Let me put it another way: There are about 400,000 MS sufferers in the United States. The NIH is spending about $200 million per year on research. Well, that is about $500 in research per sufferer. Think about this in terms of lost tax revenue. Many MS sufferers can no longer work and therefore pay thousands of dollars less in taxes per year than they would if they were working. So MS is a net loss to the government even before getting to the cost of government-funded treatments. Throw on top of that the money that the US government pays to treat MS sufferers and the size of the effort to find a cure for MS seems penny wise but pound foolish. Of course the same argument probably holds for many other national governments as well. The Western nations ought to agree to large coordinated increases in research into a variety of diseases as a way to avoid huge future health care costs.
Consider the future pay-off. At some point in the future drugs that permanently halt MS will be introduced and the total dollar volume of MS drug treatments and other medical testing and treatments for MS will plummet. We are still on the uphill slope of MS drug sales though since all the existing treatments try to restrain the behavior of the immune system rather than retrain it to permanently deactivate or kill off immune cells that want to attack nerve cells. But once the knowledge becomes available to allow therapies to be developed that can fix the immune system MS treatment costs and all related medical care costs for MS sufferers (which are multiples of the few billion spent on these drugs) will plummet by orders of magnitude.
Update: Note that the introduction of this new MS drug is expected to cause MS drug sales to go up by $2 billion per year. That increase alone is about ten times more than the US government spends on MS research. The amount spent on research strikes me as far too low when we compare research expenditures with the amount of money spent on treatments that do not even work well. Look at this drug. Imagine you had MS. If the drug works on you like it does on the average patient it means you will get an MS relapse and deteriorate further about once every 4 years. Granted that is much better than what happens if you do not take the drug. But it is far from an optimal solution, either for your health, your ability to go on working and earning income comparable to what you make now, or in terms of costs.
The amount of money spent on medical research is incredibly small when compared to the amount spent on treatments. Worse yet, the gap between the amount spent on research and the amount spent on treatment is widening.
Under the compromise legislation, NIH will receive about $28.4 billion, a 2% increase of $563 million over last year. This will give most institutes and centers increases of 1.6% to 2.4%, failing to keep pace with the biomedical research and development price index, projected at 3.5%
Businesses will pay 7.8 percent more, on average, for employee health plans in 2005, even though many firms have shifted some premium costs to their workers, a new study projects.
Think about it: Medical spending costs are increasing while the total effort going into government funded medical research is decreasing. This seems like a huge mistake to me.
Health-benefits costs rose 7.5 percent this year, down from a 10.1 percent increase in 2003, according to a survey from Mercer Human Resource Consulting. Consumer-price inflation is running about 3 percent.
...
For 2005, employers forecast an overall cost increase of 6.6 percent, assuming they change plan designs, drop a plan or change vendors, the survey said. However, companies predicted a 10 percent increase if they were to stay with their current health plan and vendor.
Total medical costs are going up 10% while NIH funding is going up by 2%. Yet as I've previously argued: Scientific Advances Are The Solution To High Medical Costs.
The Methuselah Foundation has awarded its first prize to a scientist for extending life-spans of middle aged mice. (same article here and here)
Dr. Aubrey de Grey, Chairman of The Methuselah Foundation (www.Mprize.org), awarded the first ever Methuselah Mouse Rejuvenation Prize to Dr. Stephen Spindler, who lead the first experiment to achieve rejuvenation in middle-aged mice, making them biologically younger while extending their lifespans.
The award was presented on November 21st during the 2004 Gerontological Society of America Conference in Washington, D.C.
Dr. Spindler's research was astounding because it began with mice that were in middle age. This research, first reported in Proceedings of the National Academy of Science achieved decisive increases of 15% average and maximum lifespan, AND was accompanied by significant early reductions of deaths from cancer. The fact that mice actually became younger was verified by genetic microarray analysis. Video showing that mice were more active and vibrant than their years can be found at http://www.biomarkerinc.com/html/video1-hi.htm
The Methuselah Foundation has attracted a number of notable donors and sponsors.
The Methuselah Foundation is supported by individuals who are no longer willing to stand by and do nothing while the diseases of aging disable and then take their irreplaceable loved ones away. They are taking matters into their own hands and inviting others to join with them to cure and reverse aging. Among the over 100 donors and sponsors, including the X PRIZE Foundation, Foresight Institute, the Life Extension Foundation, Dr. William Haseltine -- Founder of Human Genome Sciences and Dr. Raymond Kurzweil -- noted futurist and entrepreneur.
In addition to extending the lives of middle aged miced another one of Spindler's notable and useful achievements was showing that most of the gene expression changes caused by long term and life extending calorie restriction diets occur in mice which are first put on calorie restriction when they are elderly.
Finally, we investigated the effects of CR in mouse heart. Eight weeks of CR reproduced many of the long-term effects of CR on gene expression and physiology. CR rapidly decreased natriuretic peptide B and collagen I and III expression. CR reduced perivascular collagen accumulation and cardiomyocyte size in the left ventricle. These results suggest that hearts of LT-CR mice are physiologically younger than those of control mice. Switching CR mice to control feeding rapidly returned 91% of the CR responsive genes to control expression levels. Thus, CR rapidly and reversibly induced genomic changes associated with reduced cardiovascular pathology.
Importantly, these results suggest that it should be possible to use rapid treatments with pharmaceuticals and other compounds to identify agents that mimic the rapid changes in gene expression caused by caloric restriction. The gene expression biomarkers of caloric restriction can also be used to develop pharmaceuticals targeted to its genomic effects.
The usefulness of this result is that it can be used to more rapidly scan for drugs that act as calorie restriction (CR) mimetics which are capable of putting an organism's metabolism in the same state that is seen in animals or humans on calorie restricted diets. The calorie restriction extends average life expectancy. But consistently eating a small amount of calories every day is beyond the will power of most people and most people do not want the gaunt appearance seen in many CR practitioners. A drug that could induce the same metabolic state without requiring a constant fight against eating would appeal to a lot of people as a far easier way to extend their lives.
Recently, studies have shown that three dwarf mice mutations are capable of extending life span by approximately 40% through a molecular mechanism that may be different from that found in CR animals. These mutations also delay and ameliorate the effects of age-related diseases. BioMarker scientists--in collaboration with other scientists--are identifying the gene expression biomarkers associated with this model of life span extension.
Dr Stephen R. Spindler, scientific co-founder of BioMarker, studied longevity-related expression in 12,000 genes in mice using cDNA microarray chips. Gene expression data from these experiments indicate that even a brief period of caloric restriction produces about 70% of the changes associated with life span extension. These gene changes are correlated with a number of significant cellular changes including destruction of pre-cancerous cells (apoptosis), protection of cells from toxins and carcinogens, reduction in inflammation and improvements in cardiovascular health.
The bit about CR inducing pre-cancerous cells to die holds out the possibility that one could reduce one's risk of cancer by periodically going to a low calorie diet. Imagine doing a CR diet one month a year. One might kill off some pre-cancerous cells that otherwise would develop into a fatal cancer. It would be interesting to see whether periodic CR could increase average life expectancy of mouse strains by reducing the incidence of cancer. A CR mimetic drug holds out the possibility of doing the same thing.
Also see the Better Humans coverage of this story.
As the inaugural Rejuvenation Prize, Spindler's award sets the bar for other teams competing to reverse aging in mice, including the six teams already enrolled. To win, these teams must beat Spindler's record using groups of at least 20 mice that show rejuvenation in at least five different markers of aging.
Alex Tabarrok of Marginal Revolution argues in a Tech Central Station article that commercial spacecraft safe enough to enable a large commercial space tourism industry are still a very distant prospect.
Since 1980 the United States has launched some 440 orbital launch rockets (not including the Space Shuttle). Nearly five percent of those rockets have experienced total failure, either blowing up or wandering so far from course as to be useless. The space shuttle has a slightly better record of safety -- it was destroyed in two of 113 flights. There are lots of millionaires willing to spend one or two million dollars for a flight into space but how many will risk a two to five percent chance of death?
It is true that we have been "learning by doing" or in this case by learning by exploding. In the 1960s the risk of failure was a stunning 12%. As in other industries, learning by doing reduced the failure rate dramatically over the first units but more slowly thereafter. In the 1970s the failure rate dropped to 5.2% but nearly thirty years later the failure rate for rockets still hovers between four and five percent. We can expect similar slow and steady improvements in the future but there is little reason to expect dramatic improvements in rocket technology.
...
If progress continues at the same rate as it has over the past 30 years how long will it take to achieve a level of safety of say a 1 in 10,000 chance of failure? Note that in comparison to other means of travel this is very, very dangerous. Commercial airlines, for example, have a fatality rate of .2 fatalities per 1,000,000 departures or a 1 in 5 million chance.
Projecting from the historical rate of progress in improving rocket launch safety Alex shows that if that rate of improvement continues then even in the 22nd century space launch will not become as safe as air flight is today.
Some space enthusiasts argue that space flight safety improvements are retracing the same pattern that aviation safety improvements followed,. However, I've done my comparison of aircraft and spacecraft safety records. By my estimation airplanes in 1938 were orders of magnitude safer than spacecraft today.
But let's go back even further to look at aircraft safety in 1938. That's when some US government agency was created that started tracking aircraft safety. It is not clear from the table what kind of fatal accident rate measure they were using. But compare the 1938 rate of 11.9 to the 1950 rate of 5.0 and the year 2000 rate of 1.1. The 1938 rate of fatal accidents was about an order of magnitude higher than it is now. But its still more than two orders of magnitude lower than the fatal accident rate of the Space Shuttle.
1938 was 35 years after the first aircraft flight of Orville and Wilbur Wright on December 17, 1903 at Kitty Hawk North Carolina. Manned space travel began on April 12, 1961 when a Soviet air force pilot, Major Yuri A. Gagarin, made an orbit of the Earth. So manned space travel is over 40 years old. Space travel into Earth's orbit is orders of magnitude more dangerous after 40 years than aircraft travel was when it was only 35 years old.
Note that comparisons between airplanes and spacecraft using the data I cited are difficult becuase a lot of airplace safety statistics are in accident rates per million miles flown. This is not useful for spacecraft that get up into orbit and then go around the Earth many times without and ending up where they started each time. Also, Alex's use of fatalities per departures is a more useful measure. However, even there it is not clear to me whether the 1,000,000 departures are departures of humans or departures of aircraft. So I'm not sure if he is doing an apples to apples comparison with rocket and space shuttle launches.
Cronaca blogger David Nishimura points out that the death rate for climbing Mount Everest is comparable to the death rate from rocket launches. Rand Simberg responds that SpaceShipOne supposedly changed the rate of rocket launch technology advance. Alex is having none of this argument. Alex says that refinements in existing approaches using existing state of the art in materials and design just can not begin to close the gap in space flight safety as compared to aircraft safety.
I admire Rutan and I have little doubt that he has made significant advances in rocket design but what I showed in my article was that safety could have improved by a factor of ten or even 100 and rockets would still be too unsafe to support a large tourism industry.
What's so great about space tourism anyway? Even though an increase in rocket safety of a factor of ten is not much when considering the safety of large numbers of people it is very significant when thinking about satellite launches or temporary low-orbit launches. A reduction of risk of this amount means much lower insurance costs that will open up space to new private development.
I am with Alex on this point. Newer rockets have been designed in recent years and have unexpectedly blown up on launch. Rutan's accomplishment is not as radical as some media reprots present it for a number of reasons. First of all, whether he has designed a safer spaceship is will not be proven unless and until it has flown hundreds and even thousands of times without mishap. Also, and very importantly, SpaceShipOne does not do that much. It can not achieve orbital velocity or decelerate from orbital velocity. In my view the Scaled Composites SpaceShipOne flight was important because it demonstrated the potential for prizes to spur innovation. It also opens up the possibility that dangerous orbital spacecraft can be designed and built for much lower costs than NASA and big aerospace companies typically spend.
So then will there be little space tourism in the 21st century? Will you never be a space tourist? Nanotechnological advances may provide new materials that will allow very safe spacecraft or an even safer space elevator to be built. However, even if the answer to the first question remains "No" for most or all of the 21st century and even if you decide you do not want to risk travelling to space in spacecraft that are less safe than today's jumbo jets that does not mean you will never travel into space. If you want to live long enough to travel into space your best bet is to support the development of Strategies for Engineered Negligible Senescence. Donations to the Methuselah Mouse Prize will increase your odds of living long enough to still be around when space flight becomes cheap and very safe. If you want to be able to do more in your life support rejuvenation for life extension. My guess is that life extension will become possible long before space flight becomes as safe as commercial aviation is today.
Here is some news you can use. First off, Torbjörn Åkerstedt, a sleep researcher at the Karolinska Institute in Sweden, has found that stress without a disruption of sleep patterns is not enough to cause work burn-out.
While stress is clearly involved, the precise causes of the symptoms have been unclear. A high level of the stress hormone cortisol has been blamed, for instance. But based on his team’s recent work, Åkerstedt says: “We think that people can function quite well on high levels of stress - it’s only when their sleep is disrupted that you get burnout.”
The team took regular sleep EEG readings of 35 patients who had been off work for a minimum of three months. The tests consistently showed extreme sleep fragmentation and disruption. These patients were living on as little as four or five hours of sleep each night, with a 40% reduction in slow-wave sleep compared with healthy people.
One weakness of this study is that a person who doesn't have to get up and go to work every day lacks that motivation to get up in the morning and go to sleep at night. It might be that the lack of participation in work activities causing the disruption in sleep cycle.
If you are going to work heavily it can be counterproductive to let the work interfere too much with your sleep cycle. It would be interesting to know whether people who burn out and who are not sleeping regularly would benefit from melatonin supplements or some other treatment or therapy to get the sleep cycle restored to a healthy pattern.
Burn-out is not the only risk that comes from poor sleep habits while under stress. James Gangwisch and colleagues at Columbia University found that getting fewer hours of sleep per night puts one at substantial risk for obesity.
(Las Vegas, NV) - November 16, 2004 - The less you sleep, the more likely you are to become obese, according to a study being presented at the North American Association for the Study of Obesity (NAASO)'s Annual Scientific Meeting held November 14-18.
The study, by researchers at Columbia University's Mailman School of Public Health and the Obesity Research Center, demonstrated a clear link between the risk of being obese and the number of hours of sleep each night, even after controlling for depression, physical activity, alcohol consumption, ethnicity, level of education, age, and gender. The study was an analysis of data taken from the National Health and Nutrition Examination Survey I (NHANES I).
Specifically, the study found that subjects between the ages of 32 and 59 who slept four hours or less per night were 73 percent more likely to be obese than those who slept between seven and nine hours each night. People who got only five hours of sleep had a 50 percent higher risk than those who were getting a full night's rest. Those who got six hours of sleep were just 23 percent more likely to be substantially overweight.
"The results are somewhat counterintuitive, since people who sleep less are naturally burning more calories," said lead researcher James Gangwisch, a post-doctoral fellow in psychiatric epidemiology at Columbia University. "But we think it has more to do with what happens to your body when you deprive it of sleep as opposed to the amount of physical activity that you get. Other studies have shown that leptin levels decrease and grehlin levels increase in people who are sleep-deprived, leading to increased appetite and consumption."
Why would that happen? According to Gangwisch, one possible answer can be found in looking back at our early forebears. "The metabolic regulatory system may have evolved to motivate humans to store fat during summer months when the nights are shorter and food is plentiful, which was a survival mechanism for the body to prepare for the dark winter months when food would not be as plentiful," said Gangwisch. "As a result, sleeping less could serve as a trigger to the body to increase food intake and store fat."
"Sleep deprivation activates a small part of the hypothalamus (region of the brain) that is also involved in appetite regulation," says Eve Van Cauter of the University of Chicago, one of the nation's leading sleep researchers.
If the rise in obesity is caused, at least in part, by poorer sleep habits why is this the case? One explanation is that electric light allows us to more easily continue do things when it gets dark rather than go to sleep. Another possibility is that electric light causes a stimulation of cells in the eye that are involved in telling the brain whether it is day or night. Biological clocks may be getting thrown off by artificial light sources. Increased viewing of TV and computer web surfing may each be contributing to the obesity epidemic.
It might be easier to prevent undesired weight gain if we turned down the brightness levels of our TV sets and computer monitors and if we turned down internal lighting to the bare minimum. Or the use of melatonin to make one tired might help keep or take the weight off.
A number of web sites claim that it would take 40 bananas to get 1 mg of melatonin. But in my experience a few bananas can help to make one drowsy. A number of foods contain melatonin.
Pineapples, apples, oranges, bananas, strawberries, kiwi fruits, peppers, spinach, nuts and tomatoes contain melatonin. The highest melatonin concentration has been found in oats, rice and sweet corn.
Are Wheaties the way to go? Why eat melatonin-containing corn, oats, or rice cereals for breakfast with a banana sliced onto them when you are trying to wake up?
Of all the plant-based foods, oats, sweet corn and rice are richest in melatonin, containing between 1,000 and 1,800 picograms (1,000,000 picograms = 1 milligram) of melatonin per gram. Ginger, tomatoes, bananas and barley have about 500 picograms per gram. However, very large amounts of food would be necessary to equal the amount of melatonin available in a supplement pill. For example, 20 bowls of oats would yield just one milligram of melatonin
One web site claims that Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) depress melatonin levels and evening exercise depresses melatonin for up to 3 hours afterward. So are people who exercise at gyms in the evening interfering with their ability to get to sleep at night? If they treat their aches and pains from a work-out by taking aspirin or ibuprofen are they increasing their likelihood of insomnia and weight gain? Could be.
Also, if you are trying to fall asleep at night it might make more sense to listen to a book-tape in the dark than to read a book using a light.
Update: There are a couple of additional reasons why getting more sleep may make weight control easier. First of all, the more hours you are awake the more hours you have to eat. Go to bed a couple of hours earlier and you might avoid one last snack before bedtime. Also, a well rested mind is more capable of judging the consequences of decisions to eat and has a stronger will to resist.
It also hurts ''executive function'' -- the ability to make clear decisions, said Dr. Philip Eichling, sleep and weight-loss specialist at Arizona. ''One of my treatments is to tell them they should move from six hours to seven hours of sleep -- less sleepy, less hungry,'' he said.
“One reason the genes for disruptive sleep may have persisted is that poor sleep patterns make people gain weight and retain fat,” said Professor Tim Spector, director of the Twin Research Unit at London’s St Thomas’ Hospital, which carried out the research.
He added: “These genes may have helped our ancestors through periods of famine and the Ice Age.”
One problem with this argument is that there are genes that can be mutated to cause people to put on more weight that would not have had the effect of disrupting sleep. Wouldn't mutations in those other genes been more heavily selected for since the sleep disrupting mutations would tend to decrease efficiency while awake? On the other hand, some people do have sleep-disrupting genetic variations. So perhaps there is something to Spector's theory.
During the study, the researchers examined the sleep patterns of 1,024 volunteers from the Wisconsin Sleep Cohort Study, a population-based longitudinal study of sleep disorders that began in 1989. Participants between the ages of 30 and 60 underwent nocturnal polysomnography (a test during which a number of physiologic variables are measured and recorded during sleep) and blood sampling once every four years. They also reported on their sleep habits every five years through questionnaires and six-day sleep diaries.
The researchers' data showed a 14.9 percent increase in ghrelin and a 15.5 percent decrease in leptin in people who consistently slept for five hours compared with those who slept for eight. Mignot said the results were consistent regardless of participants' gender, BMI or eating and exercise habits. "The effect must be very strong to appear in [this entire] population," he said.
"It was quite amazing that a hormone can track a person's self-reported amount of sleep so well," he added. "To my knowledge, this is the first time that a peripheral marker in the blood is shown to correlate with habitual sleep amounts in a general, normally behaving population."
The researchers also found that in people sleeping less than eight hours (74.4 percent of the sample), increased BMI was proportional to decreased sleep. They reported that a 3.6 percent increase in BMI corresponded to an average nightly sleep duration decrease from eight hours to five hours.
Patricia Prinz reviews the latest results in PLoS Medicine. (PDF format) Also in PDF format is the full text of the paper in PLoS Medicine.
In another study Eve Van Cauter, Esra Tasalim, Plamen Penev at the University of Chicago and colleagues found that reducing sleep in health male volunteers upped the ratio of ghrelin to leptin.
Van Cauter and colleagues studied 12 healthy male volunteers in their early 20s to see how sleep loss affected the hormones that control appetite. Theses hormones -- ghrelin and leptin, both discovered in the last ten years -- represent the 'yin-yang' of appetite regulation. Ghrelin, made by the stomach, connotes hunger. Leptin, produced by fat cells, connotes satiety, telling the brain when we have eaten enough.
Van Cauter's team measured circulating levels of leptin and ghrelin before the study, after two nights of only four hours in bed (average sleep time 3 hours and 53 minutes) and after two nights of ten hours in bed (sleep time 9 hours and 8 minutes). They used questionnaires to assess hunger and the desire for different food types.
"We were particularly interested in the ratio of the two hormones," said Van Cauter, "the balance between ghrelin and leptin."
After a night with four hours of sleep, the ration of ghrelin to leptin increased by 71 percent compared to a night with ten hours in bed.
Get lots of sleep!
Artificial magnetic fields may some day protect humans travelling to the Moon or even further away.
Astronauts could one day be protected from harmful cosmic rays during a long haul spaceflight by a powerful magnetic bubble generated by their own craft.
A new project to investigate the possibility of fitting spacecraft with a “magnetosphere” of their own, underway at the Massachusetts Institute of Technology, US, recently received a cash boost from the NASA-funded Institute for Advanced Concepts.
This is a greater problem on the Moon and Mars and on a trip to Mars. In Earth's orbit the planet's magnetic field (a.k.a. magnetosphere which creates the Van Allen radiation belts of mostly proton particles captured around the Earth) provides some protection from cosmic and solar radiation. The atmosphere provides an even greater level of protection.
Humans can not live on the surface of the moon or Mars in structures that are only thick enough to contain atmosphere. A solar flare or burst in cosmic radiation would eventually kill humans unless a greater level of protection can be provided.
The amount of any radiation increase depends strongly on where one is located. If you are in a spacecraft outside the Earth's magnetic field, the radiation doses can be quite large (as much as tens of Gray—1 Gy = 100 rad), depending on how much spacecraft shielding there is around you. If you are in a spacecraft, such as the Space Shuttle or International Space Station, in Low-Earth Orbit, the doses are lower (up to tens of milligray)—specific values depending upon the altitude and inclination of the orbit and the amount of shielding provided by the spacecraft.
The creation of an artificial magnetic magnetic field powered by a mini-nuclear reactor or even by solar panels might allow humans to spend much longer periods of time on the surface of Earth's moon or Mars. Here is another reason to develop space nuclear reactors. More power is almost always useful.
Last night Charlie Rose conducted a group interview of Robert Klein, campaign chair for the Calfornian Proposition 71 embryonic stem cell funding initiative, Brook Byers, partner at venture capital firm Kleiner Perkins Caufield Byers, and Susan Desmond-Hellman, president of product development for Genentech. The general area of discussion was about biotechnology and medicine. These three interviewees all agreed on one very important point: only innovation can solve the problems caused by high and rising health care costs. It was gratifying to see these figures make an argument that is familar to readers of my blogs. Scientific and technological advances will be the ultimate solutions to the rapidly rising costs of medical care.
The view that innovation is the solution to our health care cost problems is not a new one. The late Lewis Thomas M.D., who was director of the Memorial Sloan-Kettering Cancer Center and the author of many essays on biology, was making that argument decades ago. Later in his life in 1992 Thomas repeated the argument that only scientific advances can produce the treatments that will make the major diseases of our time cheap to treat.
To be sure, we do have some spectacular surgical achievements in the headlines--the transplantation of hearts, kidneys, livers, and the like--but these are what I have called halfway technologies, brought in to shore things up after the still- unexplained diseases of these organs have run their course. And these measures, plus the new advances in diagnostic precision, account for a large part of the escalating costs of health care today. It seems obvious, to me anyway, that the only practical policy for bringing down those costs will be by more and more basic research in biomedical science, in the hope and expectation that we can then begin to understand, at a deep level, the underlying events in human disease. Sooner or later I am confident that this will be accomplished, and I hope for the sooner.
In one of his Lives Of A Cell books (this is an old memory, forget which one, probably Lives Of A Cell: Notes Of A Biology Watcher) published some time in the 1970s Thomas noted that before the advent of effective treatments of tuberculosis the many tuberculosis sanitariums were very expensive to operate. But he pointed out that once effective drugs against TB were developed the vast bulk of the sanitariums were quickly shut down as their patients were quickly and cheaply cured of TB. Thomas contended that expensive treatments are expensive because they fail to fix the underlying causes of diseases and that just about any really effective treatment is going to be pretty cheap. I agreed with him then and decades later I've grown only more confident that he correctly saw the fundamental problem (far more important than tort law, regulations, tax law, government entitlements programs, or market failures) that is the root of high medical costs.
"In my own early professional life when I was an intern on the wards of Boston City Hospital the major threats to human life were tuberculosis, tetanus, syphilis, rheumatic fever, pneumonia, meningitis, polio, septicemia of all sorts. These things worried us then the way cancer, heart disease, and stroke worry us today. The big problems of the 1930s and 1940s have literally vanished."
A few of those diseases have made a come-back of sorts. But all are still problems of much lower orders of magnitude than they were a century ago. But what is most important to note is that when effective treatments were found for them the costs of preventing and treating them became a small fraction of the costs that those diseases previously inflicted on their victims, families of victims, and the rest of society.
Aside: One surprise in the Charlie Rose show discussion came from the venture capitalist Brook Byers. Byers says there are multiple groups in the United States and England that are working on nanoscale-level devices for very rapidly and cheaply sequence whole human genomes. Byers expects this problem to be solved in a few years.
The solution to the problem of cheap DNA testing will lead to much lower costs for drug development. How? Well, one way is that during clinical trials it will be possible to use smaller sets of trial participants to check out which genetic patterns each drug works best and worst with. Also, many drugs are held off of the market because they are too harmful to some subsets of society who have particular genetic sequences. Clinical trial participants who have adverse reactions to new drugs will be able to have their DNA sequences checked to see if genetic causes for the adverse reactions can be identified. Then drugs that would otherwise never be sold to the public can be approved for use with subsets of the population who are genetically compatible with those drugs. We will each have drugs that we can't use due to some genetic variations we each have. But more drugs will be able to make it onto the market than can be approved today.
The ability to quickly identify which genetic sequences make some people have adverse reactions to a given drug or to have much higher responsiveness to a drug (e.g. because their liver doesn't break it down as quickly) will also allow drug developers to more quickly and easily puzzle out the mechanisms by which the drugs vary in how they interact with different people. The knowledge of the genetic variations involved in drug response differences will allow drug developers to build animal models of genetic variations that cause different reactions to drugs and to design drugs that eitehr work with a larger set of genetic variations or to design different drugs for different genetic variations.
Using ultrasound in combination with the drug t-PA can improve response to an ischemic stroke, according to a study involving 126 patients. This first-of-its-kind human trial compared the safety and efficacy of ultrasound and t-PA versus use of t-PA alone. The trial was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health (NIH). The finding appears in the November 18, 2004, issue of the New England Journal of Medicine.
Since 1996, the clot-busting drug t-PA (tissue plasminogen activator) has been the only FDA-approved therapy for acute ischemic stroke. Previous studies have shown that t-PA, when administered within 3 hours of onset of ischemic stroke, can greatly improve a patient's chance for a full recovery. t-PA cannot be used to treat the less common hemorrhagic stroke.
Researchers wanted to test the effectiveness of using transcranial Doppler ultrasound (TCD) in combination with t-PA, and to ensure that ultrasound did not cause bleeding into the brain. Utrasound is a safe, non-invasive, FDA-approved diagnostic test that uses sound waves to measure blood flow velocity in large arteries. An international team led by Andrei Alexandrov, M.D., associate professor of neurology at the University of Texas-Houston School of Medicine, examined 126 patients who suffered an ischemic stroke. All patients received intravenous t-PA within 3 hours of stroke onset. The 63 patients in the control group received t-PA alone, while the other 63 patients received t-PA in combination with continuous TCD monitoring that started shortly before the patients received the drug. A small device attached to a head frame was used to deliver the ultrasound.
Results showed that 49 percent of patients who received continuous ultrasound and t-PA showed dramatic clinical improvement and little or no blockage within 2 hours after therapy began compared to 30 percent who received t-PA alone. Notably, 38 percent of the patients who received continuous ultrasound and t-PA showed no blockage within two hours, compared to 13 percent who received t-PA alone. In all, 73 percent of patients who received the combined therapy showed complete or partial clearance of the clot, compared to 50 percent in the control group. Bleeding into the brain was experienced by 4.8 percent of patients in both groups. This early improvement of blood flow to the brain resulted in a trend that 13.5 percent more patients who received continuous ultrasound and t-PA had recovered completely by 3 months after stroke.
The team also found that patients who experienced complete clearance of their clot within 2 hours following treatment had the greatest likelihood of regaining body strength, speech, and other functions affected by stroke. Researchers named the trial CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia Using transcranial ultrasound and Systemic t-PA).
It will be cheap and easy to implement the lessons learned from this discovery and the benefits will be enormous.
This discovery was made by accident by an observant nurse. Emergency room nurse Patti Bratina observed that the stroke patients which were being monitored by Dr. Alexandrov using ultrasound recovered much better than typical stroke patients.
It happened at the University of Texas-Houston Medical School about five years ago, when Dr. Andrei V. Alexandrov, newly arrived from the University of Toronto, was using ultrasound technology to monitor the progress of stroke patients treated with tissue plasminogen inhibitor (tPA), a clot-dissolving drug that had just been given approval by the U. S. Food and Drug Administration for use against strokes (it had been approved for use in heart attacks more than a decade earlier). The nurse, Patti Bratina, noticed that many of the patients being monitored by Alexandrov were making remarkable recoveries, regaining use of their limbs and other faculties much faster than could be expected. Perhaps, she suggested, ultrasound had something to do with that.
Dr. Alexandrov wisely followed up on her suggestion. The result is a NEJM paper entitled Ultrasound-Enhanced Systemic Thrombolysis for Acute Ischemic Stroke.
Stroke is the third leading cause of death in the United States. It is the leading cause of long-term disability in the United States. Each year, more than 600,000 people suffer a stroke in the United States, resulting in approximately 150,000 deaths. The yearly cost of stroke in the United States is more than 40 billion dollars. Yet, one cannot fully measure the cost of stroke in dollars. The effects of stroke are felt not only by the patient, but also by the patient's family and friends, and by society in general.
There are about 4.4 million stroke survivors in the United States today and likely tens of millions more in the rest of the world. Imagine higher rates of recovery for the future millions of stroke sufferers. Costs in physical therapy, nursing services, and other costs will be reduced by a cheap and easy improvement in how stroke is initially treated in emergency wards.
Of course, the ideal solution to stroke will be therapies that prevent it from happening in the first place. My guess is we will need gene therapies or cell therapies to repair the cardiovascular system perhaps along with gene therapies to change blood chemistry in such a way that prevents cholesterol build-up. My guess is the liver would be the target for the latter category of gene therapies but the blood vessels would be the target of gene therapies designed to repair them.
NASA's X-43A research vehicle screamed into the record books again Tuesday, demonstrating an air-breathing engine can fly at nearly 10 times the speed of sound. Preliminary data from the scramjet-powered research vehicle show its revolutionary engine worked successfully at nearly Mach 9.8, or 7,000 mph, as it flew at about 110,000 feet.
The high-risk, high-payoff flight, originally scheduled for Nov. 15, took place in restricted airspace over the Pacific Ocean northwest of Los Angeles. The flight was the last and fastest of three unpiloted flight tests in NASA's Hyper-X Program. The program's purpose is to explore an alternative to rocket power for space access vehicles.
"This flight is a key milestone and a major step toward the future possibilities for producing boosters for sending large and critical payloads into space in a reliable, safe, inexpensive manner," said NASA Administrator Sean O'Keefe. "These developments will also help us advance the Vision for Space Exploration, while helping to advance commercial aviation technology," Administrator O'Keefe said.
Supersonic combustion ramjets (scramjets) promise more airplane-like operations for increased affordability, flexibility and safety in ultra high-speed flights within the atmosphere and for the first stage to Earth orbit. The scramjet advantage is once it is accelerated to about Mach 4 by a conventional jet engine or booster rocket, it can fly at hypersonic speeds, possibly as fast as Mach 15, without carrying heavy oxygen tanks, as rockets must.
The design of the engine, which has no moving parts, compresses the air passing through it, so combustion can occur. Another advantage is scramjets can be throttled back and flown more like an airplane, unlike rockets, which tend to produce full thrust all the time.
Before the flight NASA was predicting an 11 second burn. The 10 second burn might be the reason they didn't break Mach 10.
The scramjet burned fuel for about 10 seconds off the southern California coast, US, to reach a speed of about Mach 9.6 (11,500 km per hour). It then glided for 10 minutes before diving into the Pacific Ocean.
NASA has cancelled the follow-on X-43C vehicle and switched the money toward a return to the Moon.
A Nasa programme to build a larger scramjet vehicle, the X-43C, has been cancelled amid the drive to produce a vehicle capable of returning to the Moon and journeying to Mars in order to fulfil President Bush's vision for space exploration.
Human stunt trips are not as important for spaceflight as technological advances in spacecraft design. But stunt trips make for better politics apparently.
For all the details on this aircraft see my previous post on the X-43A. Also, go here for links to QuickTime movies of the launch.
To reiterate my attitude toward this kind of flight: This is what NASA ought to be doing but with orders of magnitude greater efforts. NASA ought cancel the Space Shuttle, stop manned flight for several years, and spend all that money pushing the envelope to develop radically more advanced technologies for space launch and space flight.
One other thing NASA ought to be doing much more of: Develop defenses against the danger posed by large asteroids.
The gene for Sonic hedgehog proves it can stimulate old adult neural stem cells to grow more rapidly.(same article here)
Now, a UC Berkeley bioengineer has devised a way to enhance the utility of adult stem cells that could steal some of the spotlight away from embryonic stem cells and eventually lead to treatments or cures for diseases such as Alzheimer's and Parkinson's.
...
Schaffer's team took DNA from a rat and isolated the gene that produces the Sonic hedgehog protein. They then cloned that gene, inserted it into a harmless virus which they then injected into the rat's brain. The virus delivered the Sonic hedgehog genes to the brain stem cells, stimulating them to divide three times faster than normal, which in turn tripled the production of new neurons.
Researchers discovered a couple of years ago that Sonic Hedgehog is a major regulator of neuron cells. The body uses the Sonic protein in multiple tissues for development, such as the skin, hair, intestine, pancreas and brain, from the embryo stage to the adult stage. Schaffer’s investigation focuses on Sonic’s role in the brain.
“To regenerate tissue, or replace a lot of neurons, you need to mass-produce the cell, and then you need to take those mass-produced cells and induce them to differentiate them into neurons. So we’re very interested in Sonic Hedgehog because we found it’s a powerful way to mass produce the cells initially,” Schaffer said.
Parkinson's Disease and other brain diseases will some day be treated with stem cell therapies. Since neural stem cell growth appears to slow in people suffering from depression it is even possible that stimulation of neural stem cell growth could become a treatment for depression.
Neural stem cell growth appears to slow with age as well. Techniques to stimulate of neural stem cell growth may well become standard therapies to prevent the age-related decline in the ability to form new memories.
A couple of cautions however: First off, stem cells programmed to grow much more rapidly might grow too much and turn into neurons in locations they are not needed and even potentially harmful. Scientists will need to develop methods to not only stimulate cell growth but also to turn off the source of stimulation once the needed cells have been produced.
Also, stimulating old stem cells to grow more rapidly might not be wise if the old cells have accumulated a lot of DNA mutations. Old cells are at greater risk of becoming cancer cells because of the damage they have accumulated. So considerable care will be needed to in selecting older cells that can safely be stimulated into acting young again. One way to try to reduce the threat of cancer on old cells will be to do gene therapies to old stem cells to fix growth regulation genes that may have gotten dangerously mutated over a period of years.
"It used to be on the fringes completely, but now it's seeping into the mainstream," says Steven Roy Goodman, a college and graduate-school admissions consultant in Washington. "If you're one of hundreds of kids fighting for one of 10 spots, you'll do everything you can to get the extra edge."
William Pollack, a psychologist and director of the Centers for Men and Young Men at Harvard University's McLean Hospital, says he has spoken with more than 50 students who say they've used stimulants to raise their test scores. "I've seen it become a trend," Dr. Pollack says.
Adderall is used for long study jaunts.
More than 6.4 million prescriptions for Adderall were filled last year. Some of these prescriptions are being used by students seeking a quick fix for studying.
A Yale University junior said Adderall helped him read the 576-page novel "Crime and Punishment" and write a 15-page paper — all in 30 hours.
"In earlier generations, people would take NoDoz and get themselves high on caffeine and that sort of thing," said the student, who asked not to be identified. "This is more efficient than that."
Ritalin is used to avoid being distracted by anything aside from the problem at hand.
Twenty-four-year-old Chul Yim is among those considering Ritalin as a stimulant to help him focus before his important law school admission test.
"What was described to me is it gives you tunnel vision. You focus on the question. Once you're done with that question, you move on to the next question and you still have that energy," said Yim.
I'm not arguing for using these drugs. But if you are considering a drug like Ritalin note that the benefits are likely to be greater for someone who is easily distracted. If you think your mind stays focused while taking a test Ritalin is less likely to provide a benefit.
Also, lots of brain enhancers really present you with a trade-off. See, for example, my post Caffeine Alertness Comes At Cost Of Word Recall. A stimulant amphetamine-based drug like Adderall can make a mind race too quickly or make a person jittery. There is no guarantee it will provide a net benefit. Though I can easily imagine someone taking the SAT twice, once normal and once on Adderall. Even there, it might make more sense to try practice tests with and without your preferred drug to find out if it really will help you.
I personally would be reluctant to start using an amphetamine. There is the real danger of permanent neuronal damage. If you are not scared by the idea of using stimulant drugs you really ought to be. See my previous posts Methamphetamine Addict Brain Scans Show Extensive Losses and Partial Recovery From Methamphetamine-Induced Brain Damage. You only get one brain. Do not abuse it.
For some alternatives also see my previous posts Scientists Demonstrate Best Way To Use Caffeine and Modafinil Boosts Human Mental Abilities. Modafinal may be safer than amphetamines when the need is simply to avoid sleepiness and time sleeping. But I'm not convinced that modafinil doesn't exact some cost in the form of some permanent damage. Use any of these compounds sparingly.
The resounding victory of California's $3 billion ballot initiative for embryonic stem cell studies may have the unintended consequence of slowing research on the national level and creating a backlash from religious conservatives who feel emboldened by President Bush's reelection, say activists on both sides of the issue.
...
Under Proposition 71, California researchers are eligible for $295 million a year in grants to work on cell colonies -- or lines -- taken from five-day-old human embryos.
...
In August 2001, Bush struck a compromise, announcing he would allow federal funding for research on the limited number of cell lines that existed then. Researchers and patient groups have been frustrated by those restrictions, saying the 20-plus available lines and $24 million in federal grants have not been sufficient.
...
Brownback's cloning ban would make it a crime for patients treated outside the United States with therapies derived from embryonic stem cells to reenter.
Think about that last part. Some day Americans may go abroad for embryonic stem cell therapy and in the process turn themselves into permanent expatriates. If the choice is between permanent exile and death quite a few people will choose exile - at least if they can find a country that will accept them as residents.
Look at it from a purely financial standpoint: Prop. 71 will increase total money available in the United States for embryonic stem cell research even if all federal funding of embryonic stem cell research is ended. The amount California will start spending is far in excess of what the US federal government is currently spending. Also, if the federal goverment stops spending on embryonic stem cell research it will probably shift the money toward adult stem cell research. So with the California money the total amount going to stem cell research of all kinds will go up. That will speed progress overall.
Of course if Congress outlaws embryonic stem cell research entirely then embryonic stem cell research in California would be stopped regardless of what money is available. Is such an outcome possible? I would expect the more center-of-the-road Republican Senators and Congressmen from the Northeast and perhaps some from the Midwest and Northwest (e.g. Mormons from Utah) to band together with the Democrats to block such a move. But that is speculation on my part.
Whatever the United States federal and state governments do about embryonic stem cell research will affect the rate of advance of embryonic stem cell research. But it is inevitable that therapies based on embryonic stem cells will be developed in East Asian countries regardless of what the United States does.
Also, if human embryonic stem cell research is banned in the United States adult stem cell research will still produce lots of therapies. In the longer run methods will be developed to turn adult stem cells and even adult differentiated cells into any cell type that will be needed for therapy. The big advantage of embryonic stem cells is that they are pluripotent. That means they have the capability to become all other cell types. Well, eventually techniques will be discovered to turn adult cells into pluripotent cells.
Once it becomes possible to turn adult cells into pluripotent cells will most of the religious opponents of embryonic stem cell research take the position that the creation of such pluripotent cells is immoral because such cells will have the ability to develop into fetuses? Or will the religious folks decide that since the pluripotent cells were not created from an egg or an embryo that those cells do not have a soul and hence are acceptable for use in creating treatments?
Even if the embryonic stem cell research opponents remain opposed to the use of all pluripotent stem cells for research and therapy one way around restrictions against pluripotent stem cells would be to find ways to create very multipotent (capable of becoming many but not all cell types) stem cells. Basically dedifferentiate or despecialize cells almost all the way back to early embryo state but stop just short of that most flexible state. Some promising research on chemical compounds that dedifferentiate cells has been published. The search for compounds to differentiate and dedifferentiate (specialize and despecialize) stem cells is accelerating due to advances in biotechnology for growing and screening cells. So more compounds will come along that will allow scientists to basically program around restrictions on the use of embryonic stem cells. Also, it may be possible to extract highly multipotent or even fully pluripotent stem cells from the blood of pregnant women.
Be careful what you choose to learn first.
Nov. 11, 2004 — No matter how hard we try to change our behaviors, it's the old ways that tend to win out over time, especially in situations where we're rushed, stressed or overworked, suggests a new study of human memory from Washington University in St. Louis.
"Our study confirms that the responses we learn first are those that remain strongest over time," says Larry Jacoby, Ph.D., a professor of psychology in Arts & Sciences at Washington University and co-author of the study.
The study, titled "Which Route to Recovery? Controlled Retrieval and Accessibility Bias in Retroactive Interference," appears in the November issue of Psychological Science, a journal of the American Psychological Society. The research was conducted at Washington University by Jacoby and two other psychologists: Cindy Lustig, now at the University of Michigan, and Alex Konkel, now at the University of Illinois.
...
Participants in the study first learned one way of responding to a cue word (e.g., "Say 'cup' when you see 'coffee' "), and then later learned another way (e.g., "Now say 'mug' when you see 'coffee' "). They were given memory tests both immediately after learning the words, and the day after. Some people were told to control their memory and give only the first response ('cup'). Others were told to just give whichever response came automatically to mind.
Those controlling their responses did a good job of giving only the first response on both days. The interesting results were for the people who responded automatically, giving whichever response came to mind. On the first day, their answers were split evenly between the two possibilities. However, on the second day, they gave the first response ('cup') much more often than the second response ('mug'). The second response seemed to fade from memory, while the first response grew even stronger than it had been on the first day.
In their study, the researchers sought to take a new look at why old habits seem to prevail over our attempts to change our behavior. Their findings suggest that even though the strength of an old habit may fade over time, our memory for it will be stronger then any new good intentions that succeed it.
This helps to explan why people too often revert to practicing old bad habits when they are trying to follow newer and better habits. One practical suggestion comes from this report: If you are going to learn two behaviors that you will use to respond to some situation and you think you'll be better off doing one of the two behaviors more often then learn that behavior first.
NASA is going to try for a new rocket jet speed record with the final unmanned X43A test flight.
The final flight of NASA's X-43A hypersonic research aircraft is still on schedule for Monday afternoon, Nov. 15, weather permitting. The mission is intended to flight-validate the operation of the X-43A's supersonic-combustion ramjet - or scramjet - engine at a record airspeed of almost Mach 10, or 10 times the speed of sound. The X-43A and its modified Pegasus booster rocket was mated to NASA's B-52B launch aircraft on Thursday, Nov. 11. Pre-flight checks of the X-43A and the booster are occurring Friday and Saturday, with final closeouts and fueling slated for Sunday, Nov. 14th. Takeoff on Nov. 15 is tentatively scheduled for about 1 p.m. Pacific time, with launch about an hour later over the Pacific test range off the coast of Southern California.
The flight will begin at Edwards Air Force Base.
As with the first two flights, the third X-43A will be carried aloft by NASA's B-52B launch aircraft from NASA's Dryden Flight Research Center on Edwards Air Force Base. The B-52B "mothership" will release the combined X-43A and Pegasus booster stack at 40,000 feet altitude off the coast of Southern California. The booster will then accelerate the experimental vehicle to nearly Mach 10, or almost 7,000 mph, at approximately 110,000 feet altitude. At booster burnout, the 2,800-pound, wedge-shaped X-43A will separate, and fly briefly on a preprogrammed path, performing a set of tasks and maneuvers before splashdown in the ocean.
In theory scramjets ought to be able to operate up to at least Mach 15.
The last X-43A vehicle has additional thermal protection for the Mach 10 flight, since it will experience heating roughly twice that of the Mach 7 vehicle. Reinforced carbon-carbon composite material has been added to the leading edges of the vehicle's vertical fins to handle the higher temperatures.
For the Mach 10 flight, which equates to approximately 7,000 mph, the booster rocket will launch the X-43A to 110,000 feet before it separates and the X-43A operates its scramjet. The research vehicle will travel about 850 miles before splashing into the ocean. As with the previous X-43A vehicles, it will not be recovered.
...
A scramjet (supersonic-combustion ramjet) is a ramjet engine in which the airflow through the whole engine remains supersonic. It is thought that a scramjet can operate from Mach 5-6 up to at least Mach 15.
The air passes through so quickly that the time available to burn fuel is extremely short.
The scramjet concept is simple: Accelerate the vehicle to about Mach 4 by a conventional jet engine, then start the scramjet engine (which has few or no moving parts) by introducing fuel and mixing it with oxygen obtained from the air and compressed for combustion. The air is naturally compressed by the forward speed of the vehicle and the shape of the inlet, similar to what turbines or pistons do in slower-moving airplanes and cars.
While the concept is simple, proving the concept has not been simple. At operational speeds, flow through the scramjet engine is supersonic - or faster than the speed of sound. At that speed, ignition and combustion take place in a matter of milliseconds. This is one reason it has taken researchers decades to demonstrate scramjet technologies, first in wind tunnels and computer simulations, and only recently in experimental flight tests.
The previous X-43A flight set a record at Mach 7.
In the process of demonstrating a scramjet-powered airplane in flight for the first time, the March 2004 flight set a world speed record for an "air breathing" (jet-powered) vehicle. It flew at nearly Mach 7, or 5,000 mph. It easily surpassed the previous record set by the military's now-retired SR-71 Blackbird high-altitude reconnaissance aircraft, which flew at about Mach 3.2.
The higher speed encountered during the 11 second burn brings hotter temperatures.
To prepare for the Mach 10 flight, the third scramjet was upgraded slightly. A thicker layer of thermal insulation was added to the engine, wing edges, tail and nose. The nose is expected to reach about 2000°C - roughly 600 degrees hotter than the previous Mach 7 flight.
Reasons not to get too excited: The aircraft is unmanned. It is a throw-away that will not be recovered when it crashes into the Pacific Ocean. NASA has no follow-on money allocated to build on this design with a better hypersonic scramjet aircraft design. The whole Hyper-X project that produced three X-43A vehicles (this is the third and final) cost $230 million. But orders of magnitude larger sums must be spent operating the obsolete Space Shuttle to go visit the white elephant International Space Station to accomplish very little real science or technological advance.
Still, useful lessons will be learned from the X-43A. Some day a new effort that pushes the envelope of scramjet operation even further may build upon what was learned in this effort.
Malnutrition in the first few years of life leads to antisocial and aggressive behavior throughout childhood and late adolescence, according to a new University of Southern California study.
"These are the first findings to show that malnutrition in the early postnatal years is associated with behavior problems through age 17," said Jianghong Liu, a postdoctoral fellow with USC's Social Science Research Institute and the lead author of the study published in the American Journal of Psychiatry's November issue.
"Identifying the early risk factors for this behavior in childhood and adolescence is an important first step for developing successful prevention programs for adult violence," she said.
For 14 years, researchers followed the nutritional, behavioral and cognitive development of more than 1,000 children who lived on Mauritius, an island in the Indian Ocean off the coast of Africa.
The sample of boys and girls included children with Indian, Creole, Chinese, English and French ethnicities.
Researchers assessed their nutrition at age 3, looking for four indicators in particular:
- angular stomatitis, or cracking in the lips and corners of the mouth that is caused by a deficiency of the B vitamin riboflavin;
- hair dyspigmentation, a condition – found primarily in tropical regions – where children's hair takes on a reddish-orange color due to protein deficiency;
- sparse, thin hair created by a deficiency in protein, zinc and iron; and
- anemia, which reflects iron deficiency.
The children's intelligence level and cognitive ability were also tested, and social workers visited their homes to come up with a so-called adversity score that summarized factors such as the income, occupation, health, age and education levels of their parents and their overall living conditions.
At ages 8, 11 and 17 years, the researchers looked at how the children were behaving in school and at home.
At age 8, teachers gave feedback about whether the subjects were acting out in school with behavior ranging from irritability to picking fights with other children.
At age 11, the feedback came from parents who told researchers about whether their children lied, cheated, got into fights, bullied others, destroyed property or used obscene language.
At age 17, both parents and teachers reported on antisocial behavior such as stealing, drug use, destroying property or being deliberately cruel to others.
Over time, a link became evident between malnourishment and antisocial or aggressive behavior, said Adrian Raine, a co-author of the study and holder of the Robert Grandford Wright Professorship in Psychology in USC's College of Letters, Arts and Sciences.
Compared to those in the control group – the group that did not suffer from nutritional deficiencies – malnourished children showed a 41 percent increase in aggression at age 8, a 10 percent increase in aggression and delinquency at age 11 and a 51 percent increase in violent and antisocial behavior at age 17.
While social class did not play a significant factor in behavior, intelligence level did, Raine said.
"Poor nutrition, characterized by zinc, iron, vitamin B and protein deficiencies, leads to low IQ, which leads to later antisocial behavior," he said. "These are all nutrients linked to brain development."
Researchers also found that the more indicators of malnutrition there were, the greater the antisocial behavior.
The findings have implications for the United States, Raine said, where 7 percent of toddlers suffer from iron deficiency, a number that jumps to between 9 percent and 16 percent in adolescent and female groups.
Iron deficiency is between 19 percent and 22 percent in black and Mexican American females, he said.
"This is a problem in America. It's not just a problem in the far-away Indian Ocean," Raine said. "If it's causal, there's an intervention implication there. At a societal level, should parents be thinking more about what kids are eating?"
Of course to make use of this information in America we'd have to at least implicitly acknowledge that there are group differences in behavior that have biological causes rather than social causes. Whether biological origins or genetic or nutritional or some other factor (e.g. pathogens, pollutants) that sort of thinking is taboo among most academics, reporters, and political activists.
Raine has previously reported that protein and omega 3 fatty acid supplementation of diets of poor children in Mauritius decreased their level of criminal activity when they got older.
Raine has done a lot of other interesting work on the biological mind and the biological roots of behavior. For example, see my post Brain Scans Show Abnormalities In Psychopaths.
Is low-lying coastal property a bad investment? Will the polar bears be driven to extinction by the total melting of the Arctic Ice Cap? Will the climate of Alaska and Canada become more congenial for those who prefer warmer weather? Should we panic? Is disaster looming? Why these grand questions? It is time for yet another prestigious and apocalyptic climate trends research report.
The newly released Arctic Climate Impact Assessment report predicts major Arctic snow and ice melting over the next 100 years.
WASHINGTON—The Arctic is warming much more rapidly than previously known, at nearly twice the rate of the rest of the globe, and increasing greenhouse gases from human activities are projected to make it warmer still, according to an unprecedented four-year scientific study of the region conducted by an international team of 300 scientists.
At least half of the summer sea ice in the Arctic is projected to melt by the end of this century, along with a significant portion of the Greenland Ice Sheet, as the region is projected to warm an additional 7 to 13°F (4-7°C) by 2100. These changes will have major global impacts, such as contributing to global sea-level rise and intensifying global warming, according to the final report of the Arctic Climate Impact Assessment (ACIA).
The assessment was commissioned by the Arctic Council (a ministerial intergovernmental forum comprised of eight nations, including the United States, and six Indigenous Peoples organizations) and the International Arctic Science Committee (an international scientific organization appointed by 18 national academies of science).
• In Alaska, Western Canada, and Eastern Russia average winter temperatures have increased as much as 4 to 7°F (3-4°C) in the past 50 years, and are projected to rise 7-13°F (4-7°C) over the next 100 years.
• Arctic sea ice during the summer is projected to decline by at least 50 percent by the end of this century with some models showing near-complete disappearance of summer sea ice. This is very likely to have devastating consequences for some arctic animal species such as ice-living seals and for local people for whom these animals are a primary food source. At the same time, reduced sea ice extent is likely to increase marine access to some of the region’s resources.
• Warming over Greenland will lead to substantial melting of the Greenland Ice Sheet, contributing to global sea-level rise at increasing rates. Over the long term, Greenland contains enough melt water to eventually raise sea level by about 23 feet (about 7 meters).
• In the United States, low-lying coastal states like Florida and Louisiana are particularly susceptible to rising sea levels.
• Should the Arctic Ocean become ice-free in summer, it is likely that polar bears and some seal species would be driven toward extinction.
I'm not particularly worried about the flooding of Florida retirement communities. The retirees can all move onto cruise ships. The Love Boat TV show could be resurrected with spin-offs that are hybrids with Law And Order TV shows set on different ships. Instead CSI: Miami and CSI: Las Vegas there could be CSI: Norwegian Valkyrie and CSI: Princess Casino.
One aspect on which researchers are keeping their eye: the release of methane and carbon dioxide as permafrost thaws and tundra decomposes. Even if the advance of forests to higher latitudes soaks up some of this released CO2, this still leaves methane - a much more potent greenhouse gas - free to enter the atmosphere.
Ron Bailey, science writer for the libertarian Reason magazine says not so fast. Ron points to lots of contrary facts that argue for a less apocalyptic view of future climate history.
But University of Alabama at Huntsville climatologist John Christy, a climate expert on whom I have relied for years, makes some interesting observations about the Arctic Council's report. "If you look at the long term records, the Arctic has been as warm or warmer than it is today," says Christy. He cites temperature data from the Hadley Centre in the UK showing that from 70 degrees north latitude to the pole, the warmest years on record in the Arctic were 1937 and 1938. This area is just slightly above the Arctic Circle.
Furthermore, those same records show that the Arctic warmed twice as fast between 1917 and 1937 as it has in the past 20 years. After 1940, the Arctic saw a big cool-down and climatologists noted sea ice expanding in the northern Atlantic. Christy argues that what he calls the Great Climate Shift occurred in the late 1970s and caused another sudden warming in the Arctic. Since the late 1970s there has not been much additional warming in the region at all. In fact, on page 23, the Arctic Council Assessment offers very similar data for Arctic temperature trends from 60 degrees north latitude—the area that includes most of Alaska and essentially all of Greenland, most of Norway and Sweden, and the bulk of Russia.
Ron's article has lots more fun facts about what is going on with the climate. Check it out.
So should we be alarmed? Should we wait for the science to become more certain? What is the prudent position to take? Keep in mind that even if the more apocalyptic projections are closer to the truth any choice that uses resources to reduce CO2 emissions with current technology or technology that will be available in the short-to-medium term ends up incurring opportunity costs. Money spent to comply with a massive international regulatory scheme to reduce CO2 emissions would be money not spent on other activities that would cause economic growth. Economic growth gives us more wealth with which to solve problems more easily in the future.
An argument can be made that we should wait a couple of decades to respond to the green house gas build up in order to wait for a scientific understanding of the problem and also because better cheaper technologies for reducing carbon dioxide (CO2) emissions will be available then. Money spent to use today's technologies will buy us less emissions reduction than money spent 20 or 30 years from now using the technologies available then. Also, slower economic growth would condemn large chunks of the populaitons of less developed countries to prolonged poverty. Given that most of the projected damage from green house warming comes in the last part of the 21st century waiting two or three decades does not cause that much harm (assuming of course that it even causes any harm at all).
However, there is yet another argument worth considering from climate scientist James Hansen of NASA. Hansen has put forward the rather persuasive argument that reduction in non-CO2 green house emission such as soot and methane would provide immediate human health benefits while simultaenously providing a greater cooling effect than the same number of dollars spent on reduction of CO2 emissions would provide. Hansen does not argue against reducing CO2 emssions (see Hansen's clarification of his position on CO2 emissions for more details). However, his basic insights are that not all emissions are equally costly to reduce and that some emissions reductions provide guaranteed improvement in ground air quality and hence benefits for human health. So why not go for reducing those types of emissions first? Makes sense to me.
There is another argument that I hear less often though my regular readers hear it often enough from me: Why not spend more money on research to develop less polluting technologies rather than spend far larger sums on a massive international CO2 emissions enforcement regime for the Kyoto Accords? Kyoto and other proposed regimes for CO2 emissions reduction have cost estimates that range from the tens of trillions of dollars to the hundreds of trillions of dollars . I mean, we are talking about mind-booglingly huge sums of money.
Isn't there an easier and less painful way to deal with a potential problem whose exact costs and benefits may not even be as bleak as the doom-sayers claim? Is it that international bureaucrats and left-liberal lovers of regulations like to make people suffer? Do they think that living in a modern industrial economy amounts to a form of original sin that has to be punished in order to save our ecological souls from damnation by the world Gaia spirit?
Well, instead of a regulatory regime with costs that range into the hundreds of trillions of dollars imagine research efforts that are aimed at developing energy technologies that are simultaneously cheaper and cleaner. Then market mechanisms would do the work of displacing polluting technologies with cleaner technologies.
A research approach would cost a few orders of magnitude less than the regulatory approach. A few orders of magnitude lower cost approach would translate into rather hefty numbers of dollars with a range of tens of billions or hundreds of billions of dollars. That would be plenty of money to fund a lot of research into photovoltaic materials, lighter weight lithium polymer batteries, fuel cells, superconducting materials, nuclear pebble bed modular reactors, and other energy technologies that hold out the possibility of energy sources that are cleaner and cheaper.
Update:Over at Marginal Revolution Fabio Rojas sums up a Daniel Ben-Ami essay about environmentalists and points out that a lot of environmentalists favor solutions to environmental problems that mandate a reduction in production.
He notes that since the Enlightenment people have thought that human progress comes from mastery over nature and from being more productive, but many environmentalists think that human well being is harmed by being more productive. It's an important point that leads to some real policy differences. If you think that we have too many green house gases, then you have two choices: stop manufacturing or learn to manufacture without as much pollution. Too many environmentalists opt for the first choice, which is bad because so much of the world's poor look to gain from industry.
Since so many environmentalists think this way they tend to have an outsized influence on framing how environmental issues get debated. The range of policy options that get debated too often tends to be short on more innovative solutions that avoid the need for decreases in economic products.
Is the influence of Enlightenment thinking on the decline? It seems to me that the Enlightenment view of nature is similar to the Christian view in that humans are held as being above nature and hence have a right to master it use it. Are we moving toward a more pagan age with a reduced embrace of both the Enlightenment view and the Christian views of nature?
Also see Daniel Ben-Ami's essay.
The discussion of global warming provides a striking example of how this works. Almost everyone accepts that climate change means that the world needs to cut back on emissions of greenhouse gases. Yet this would almost certainly mean holding back economic growth, meaning that a large part of the global population will remain poor. There is hardly any discussion of how to deal with global warming while generating substantial economic growth at the same time. Indeed it will be argued that economic growth, far from being the problem, is central to humanity's capacity to handle climate change.
There are two recurring themes running through the environmentalist approach to economics. First, an obsession with the need for limits. The environmentalist debate, in numerous different ways, assumes that strict limits must be put on economic activity. Such premises ignore or at least downplay the power of human creativity. Economic activity does indeed often throw up problems - such as pollution - but it also, it will be argued, provides the means to overcome them.
...
A particular hate figure for environmentalists is Francis Bacon (1561-1626), the earliest advocate of the notion that man should attempt to take control over nature. For Vandana Shiva, one of India's leading environmentalists, his views are akin to rape and torture. She argues that: 'His was not a "neutral", "objective", "scientific" method. Rather it was a peculiarly masculine mode of aggression and domination over women and non-Western cultures. The severe testing of hypotheses through controlled manipulations of nature, and the necessity of such manipulations if experiments are to be repeatable, were formulated by Bacon in clearly sexist metaphors. Both nature and the process of scientific enquiry appear conceptualized in ways modelled on rape and torture - on man's most violent and misogynous relationship with women.' (35)
Shiva isn't on the fringes of environmentalist thinking - in 2000 she gave a prestigious BBC Reith lecture as part of a series on 'respect for the earth' (36). Neither is she alone in castigating Bacon in such extreme terms. For instance, a collection edited by Herman Daly includes a 1947 essay in which the author CS Lewis compares Bacon to Marlowe's Faustus - selling his soul to the devil (37).
For environmentalists, there is no difference between control over nature and the destruction of the Earth. Mastery of nature is, in this view, synonymous with its obliteration. But for the supporters of the Enlightenment there is a fundamental difference between conquest and destruction. Human mastery of nature means controlling disease, averting natural disasters and above all overcoming scarcity. Conquest of nature is fundamental to human progress, and at the centre of the development of civilisation.
I'm all for mastering nature. Lets build giant reflectors in orbit in the year 2030 or 2040 (using a nanotech bean pole to bring up the construction materials into orbit) and reflect light toward or away from Earth as needed.
The Earth Institute at Columbia University, NYC--Researchers suggest that reductions of trace gases may allow stabilization of climate so that additional global warming would be less than 1° C, a level needed to maintain global coastlines. Although carbon dioxide emissions, an inherent product of fossil fuel use, must also be slowed, the required carbon dioxide reduction is much more feasible if trace gases decrease.
In the current edition of Proceedings of the National Academy of Sciences, Drs. James Hansen and Makiko Sato of NASA's Goddard Institute for Space Studies (GISS) at the Earth Institute at Columbia University suggest that avoidance of large climate change requires the global community to consider aggressive reductions in the emissions of both carbon dioxide and non-carbon dioxide gases called trace gases. Humans have already increased the amount of carbon dioxide in the air from 280 parts per million (ppm) to 380 ppm. If the world continues on its current trajectory of increasing carbon dioxide, methane and ozone, the likely result will be large climate change, with sea level rise of a few meters or more.
Hansen and Sato point out that if methane and other trace gases are reduced, climate could be stabilized, with warming less than 1°C, at carbon dioxide levels of 520 ppm. However, if the trace gases continue to increase, carbon dioxide would have to be kept beneath 440 ppm. A cap of 440 ppm seems practically impossible to stay under due to existing energy infrastructure. However, Hansen and Sato suggest that, with the possibility of new technologies by mid-century, it is feasible to keep carbon dioxide levels from exceeding approximately 520 ppm.
The co-authors suggest that the non-CO2 gases could be addressed via a Montreal Protocol-like process, or by adding additional gases to the Montreal Protocol itself. The Montreal Protocol has been very effective in reducing emissions of gases that destroy stratospheric ozone. Developed and developing countries have worked together harmoniously in this process, with the World Bank providing support for participation of developing countries.
Cutting back on methane emissions would be pretty cheap to do and would provide health benefits for reasons unrelated to global warming.
Sophisticated brain imaging techniques show that when storing and accessing memories, individuals who carry a genetic variant linked to a heightened risk of Alzheimer Disease "activate" brain functions differently than do non-carriers, even when no outward signs of disease are present, according to a study reported in the November-December issue of the American Journal of Geriatric Psychiatry (AJGP).
The study by investigators at Columbia University is one of two in the current issue of the journal offering new evidence that brain imaging technology known as positron-emission tomography or PET scans has the potential to play an increasingly prominent role in the study and treatment of Alzheimer Disease (AD).
The second report, from researchers at Baycrest Centre for Geriatric Care, the Centre for Addiction and Mental Health PET Center and the University of Toronto, describes an advance in using PET scans to detect the presence of brain deposits known as beta-amyloid plaques, which are believed to be a telltale sign of the disease.
While it is interesting to know that there is a difference in brain function of elderly people who have a genetic variant for Alzheimer's it is the second report that is especially interesting. The ability to detect beta amyloid plaque build-up before Alzheimer's Disease symptoms become noticeable has a couple of uses. First of all, the ability to study the progression of plaque build-up will make it easier to measure the effectiveness of intervention therapies aimed at removing or stopping the build-up of plaque.
Scarmeas said the above conundrum could be solved if the PET scans could be paired with tests that would offer some biological evidence of the disease. That's why he's intrigued by another study in this same AJGP issue in which a team headed by Nicolaas Verhoeff, M.D., Ph.D., from the Kunin-Lunenfeld Applied Research Unit at Baycrest Centre for Geriatric Care, the PET Centre at the Centre for Addiction and Mental health, and the University of Toronto, reports that it successfully used a novel PET scan technique to detect beta-amyloid plaques, one of the brain lesions linked to AD. Thus, now we may be able to explore which are the earliest changes that could be detected in AD: changed brain functions during "active" memory processing or deposition of brain chemicals linked to AD.
As it now stands, doctors have no laboratory tests they can use for confirming the existence of AD or for monitoring its progression. Diagnosis is confirmed only after a relatively clear set of symptoms appears. However, autopsies of AD victims have revealed abnormally high levels of what are known as beta-amyloid plaques. Some scientists believe beta-amyloid plays a central role in AD-related brain damage. They also suspect that abnormally high levels of the substance begin accumulating in the brains of AD patients long before symptoms appear. But they have lacked a reliable test for detecting amyloid build-up.
Verhoeff and his colleagues recruited five AD patients and six healthy volunteers. All were injected with a new compound designed to cross from the bloodstream into the brain, attach itself to amyloid deposits and then send out harmless radioactive signals that can be detected with a PET scan. This new compound, which had been originally developed at the University of Pennsylvania in collaboration with the Centre for Addiction and Mental Health PET Centre in Toronto, was compared to another compound that had been developed independently at the University of Pittsburgh. What the study found is preliminary evidence that the new compound or "tracer" may also be effective at allowing the researchers to use PET scans to discriminate between amyloid levels one would expect to see in AD versus non-AD patients.
Currently if a doctor could tell you that you have beta amyloid plaque build-up there is probably not much you could do in response except perhaps to follow any dietary advice gleaned from population studies of Alzheimer's Disease risk. However, eventually effective treatments will be developed to reverse beta amyloid plaque build-up. If the treatments have no side-effects and are easy to deliver then everyone may decide to get treated periodically as they get older. However, if the treatments are difficult to administer (e.g. injection of antibodies into the brain) or carry some risk (e.g, a vaccine that occasionally causes brain inflammation) it would be better to get a PET scan to test for the presence of plaque build-up. Then only those with plaque build-up could get treated.
In the short to medium term a PET scan technique that can detect beta amyloid plaque build-up is going accelerate scientific research. For scientists trying to understand AD progression and testing methods of intervention against it the ability to measure plaque levels will be quite valuable. Every advance in the ability to watch internal biological processes whether normal processes or disease processes, makes it easier to understand and manipulate those processes.
Normally in each cell of a female body one of the two X chromosomes has been deactivated by the placement of methyl groups (a carbon and 3 hydrogens) along the backbone of the DNA double helix. That deactivation is random. Suppose there are two X chromosomes in a woman called A and B where the A chromosome came from her mother and the B chromosome came from her father. In approximately half of the cells the A's will be deactivated and in the other half of the cells the B's will be deactivated. Well, in women who have gay sons the deactivation of the X chromosomes is skewed with one of the X's more often deactivated than the other.
But when Sven Bocklandt of the University of California, Los Angeles, compared blood and saliva samples from 97 mothers of gay men with samples from 103 mothers without gay children he found this process was extremely skewed in the mothers with gay sons, with one X chromosome being far more likely to be inactivated than the other. Only 4% of the mothers without gay sons showed this skewing, compared with 14% of mothers with at least one gay son. Among mothers with two or more gay sons, the figure was 23%.
This result suggests that eventually any woman will be able to have a genetic test done what will predict the odds that one of her sons will be born homosexual.
One can easily imagine all sorts of responses to this. It is safe to say that most women and most men do not want to have homosexual children. The degree of that preference varies and some people do not have a strong preference against their own children being homosexual. There is no doubt even a minority of people who would prefer their children to be homosexual.
So will women who are at greater risk of having homosexual sons become more reticent to have children? Or will they use reproductive technologies such as MicroSort to tip their odds toward having a daughter instead?
One question unanswered by this study is whether the skewing of X chromosome shut-down also increases the odds of lesbianism. The mechanism for producing lesbian female children may be (and I'm guessing is) entirely unrelated to the mechanism for producing homosexual sons. But a follow-up study could easily answer this question by repeating the same analysis with the mothers of lesbian daughters.
Of course, understanding of a genetic mechanism for the development of homosexuality will eventually lead to the development of treatments to alternatively prevent or cause a homosexual outcome. One question I do not have a guess about is whether control over sexual orientation of offspring will produce more or fewer homosexuals. You might argue that since most people either prefer heterosexual children or have no preference (or are at least so politically correct that they won't publically admit to a preference) it is hard to see how control over sexual orientation could increase the number of homosexuals. But there is one big point to consider: It takes only a small fraction of the population to choose having a homosexual child to increase the number that are born. Suppose that only 3% of male births are homosexual. It would take only 1 in 20 women (or gay men who hire a surrogate woman to carry a baby) deciding they'd rather have homosexual son to increase the number born.
My guess is that there is a greater chance that control of reproduction could increase the number of lesbians. After all, it is women who carry the babies, not men. Will most lesbian women want to have heterosexual or homosexual daughters? Anyone have a reason to think they know the answer?
This question of preferences for offspring sexual orientation is part of what I consider to be a huge coming issue: when people can control more characteristics of their offspring what choices will they make? Some choices are not hard to guess. People will want their kids to be smarter and better looking. But what will be the chosen frequency of, say, blondness or introversion versus extroversion? Or height? Tall overall is my guess. But how much taller? Will the distribution of heights become narrower since people won't want to burden their kids with excessive height? (that is my guess). Will personality choices for offspring become problematic for society as a whole? See my posts Altruistic Punishment And Genetic Engineering Of The Mind and Brain Rewards For Carrying Out Altruistic Punishment for more on that question.
A new study finds surgery to transplant an ovary to the upper arm is feasible and preserves hormonal function in women undergoing treatment for cervical cancer. The report details the technical procedure and outcome of only the second successful human ovarian autotransplantation in the world. The study will be published in the December 15, 2004 issue of CANCER, a peer-reviewed journal of the American Cancer Society. A free abstract of this study will be available via the CANCER News Room upon online publication.
While treatment for cervical cancer, including systemic chemotherapy and regional administration of ionizing radiation, improves survival and cure rates, it can also cause permanent ovarian failure. Since cervical cancer is diagnosed during reproductive years, ovarian failure can be a severe blow to a patient's quality of life. While protecting a patient's fertility has often been studied, there have been no effective options.
Hormonal regulators, such as gonadotropin-releasing hormone, have demonstrated ovarian protection in rats but conflicting data in nonhuman primates. Cryopreservation of embryos has been successful, but there have been no reported successful cryopreservation and transplantation of oocytes or primordial follicles, which are necessary for future fertility. Attempts at ovarian tissue autograft or xenograft without blood vessel anastamoses in animal models and human cases have been promising but hampered by large follicle loss due to ischemia. However, animal models with anastamoses have demonstrated success, but there has been only one prior successful human autotransplant.
In this second successful human trial, C. Hilders, M.D., Ph.D., and a gynecologic surgical team of the Leiden University Hospital, The Netherlands developed a new method of ovarian autotransplantation to preserve ovarian function in a woman treated for cervical cancer. This method does not require developing a donor site with an implant over several months and utilizes a donor site that is easily accessible to noninvasive monitoring and has suitable vasculature.
Autotransplantation of a healthy ovary into the upper arm using brachial vessels to establish blood supply resulted in a functional ovary. Blood flow to and from the ovary was adequate to maintain cyclical follicular growth as verified by ultrasound and clinical examination. Moreover, the surgery did not result in additional operating time.
The authors conclude, "it seems likely that ovarian autotransplantation will be a realistic goal to achieve for women facing cancer, treated by high dose pelvic radiation, to preserve reproductive and hormonal function, thereby substantially improving the quality of life post-treatment."
Note that this is a case of autotransplantation, meaning transplantation between locations in the same body. However, the approach taken here opens up the possibility of temporary transplantation of ovaries between people as well. One can imagine a woman with cervical cancer asking all her friends to volunteer for tissue type compatibility testing so that one of them can keep an ovary alive for her during some more severe form of cancer treatment where the use of chemotherapy would pose a hazard to the ovary even if the organ was placed on the woman's own arm.
But ovary transplants onto arms is still mighty inconvenient and obviously a temporary measure. Another future possibility is that cryopreservation techniques might be improved enough to make cryopreservation a viable option. Cryopreservation would be useful as a way to allow a woman to more reliably reproduce in her late 30s, 40s, and even later ages. Take just one ovary out of a woman when she is, say, 20 years old, cryopreseve it for 20 years, and then transplant it back into the woman to serve as a much younger ovary. This might not only raise the fertility of middle aged women but might also reduce the rate of birth defects for women who reproduce later in life since a cryopreserved ovary would presumably produce a younger egg that would be less likely to contain genetic mutational damage.
Since growth of replacement ovaries will most likely become feasible in two or three decades the long term cryopreservation of ovaries is likely at most to be a transitional technique. Better to just grow a new pair of ovaries for a woman in her late 30s and throw in some genetic engineering to remove a few harmful genetic variations that she doesn't want to pass on to her kids along with adding a few genetic variations that she does want to pass along (e.g. I predict natural blondness will be incredibly popular).
However, there is another potential use of organ cryopreservation: provide a supply of key organs in event of traumatic injury. Combine the ability to grow replacement organs with the ability to freeze them. Anyone with enough money and fear of death from injury could have organs grown from their own starter cells to ensure immunocompatibility Then in event of an injury an organ could be thawed and transplanted to supply a heart, liver, or other needed replacement part.
Even cryopreservation for emergency replacement organs is likely to be a transitional technology at most. If immuno-suppressive techniques improve enough then it will not be necessary to store emergency replacement organs for each individual. If each replacement organ can be made compatible with a large range of people then a much smaller stock of recently grown organs could be constantly replenished to provide replacements to the small subset of the population that needs them. In that scenario organs there would still be a place for organs that are grown for individuals since people will want to replace organs as they age as part of a regular maintenance regime of rejuvenation therapies.
My guess is that by the time tissue engineering techniques have advanced far enough to make routine growth of replacement organs possible immunosuppression techniques will allow a fairly small stocks of organs to serve as the sources of emergency replacement organs. If there is a cost in terms of general suppressed immune response for such an approach then the emergency organs will be used to keep a patient alive until a custom and fully immune compatible organ can be grown up to provide a more compatible replacement for the temporary and less compatible organ.
There is of course one other option worth mentioning: artificial organs. Artificial heart technology is maturing with a number of promising products under development. The CardioWest Temporary Total Artificial Heart won US FDA approval in October 2004.
The CardioWest Temporary Total Artificial Heart (TAH) on Monday became the only device of its kind to be approved by the U.S. Food and Drug Administration.
"This takes the CardioWest TAH off of the Medicare 'experimental list,'" said University of Arizona cardiothoracic surgeon Dr. Jack G. Copeland, who led the study of the device. "It's a huge relief to know that 19 years of work with the device has been officially recognized and that a technology that we believed in has now been released for use by others."
The CardioWest TAH is not being pitched as a permanent solution but rather a tool to use to strengthen a body so that eventual donor heart transplantation has better odds of success.
Then there are cyborg-like bioartificial organs that blend artificial parts with human cells. A bioartificial kidney has recently been tested successfully at the University of Michigan.
ANN ARBOR, Mich. -- The first test in humans of a bioartificial kidney offers hope of the device's potential to save the lives of people with acute renal failure, researchers at the University of Michigan Health System report.
While the phase I/II study was designed primarily to look at the safety of using this device on humans, the results also suggest improvement in kidney function. The patients enrolled in the trial faced an average 86 percent likelihood of dying at the hospital. Six of those 10 patients survived more than 30 days after treatment with the bioartificial kidney. The study appears in the October issue of the journal Kidney International.
"These results showed this type of human adult progenitor/stem cell is well-tolerated by patients with acute renal failure, and resulted in some improvement of the patients' clinical conditions. It's a small study but it was compelling enough for us and the FDA to go forward with a full phase II study," says lead study author H. David Humes, M.D., professor of Internal Medicine at the U-M Medical School. Humes developed the renal tubule assist device, or RAD, the cell cartridge that is key to the bioartificial kidney.
The RAD is being developed for future commercial applications under license to Nephros Therapeutics Inc.
...
The bioartificial kidney includes a cartridge that filters the blood as in traditional kidney dialysis. That cartridge is connected to a renal tubule assist device, which is made of hollow fibers lined with a type of kidney cell called renal proximal tubule cells. These cells are intended to reclaim vital electrolytes, salt, glucose and water, as well as control production of immune system molecules called cytokines, which the body needs to fight infection.
Conventional kidney dialysis machines remove these important components of blood plasma, along with toxic waste products, and cannot provide the cytokine regulation function of living cells. Traditional therapy for patients with acute or chronic renal failure involves dialysis or kidney transplant, both of which have limitations.
While this device operates outside of the body its developers hope to eventually miniaturize it to allow implantation in the body for long term use.
There is a general thread running through all these reports and speculations: organs are going to become as manipulable and replaceable as auto car parts. The sooner this happens the better.
A team at the US National Institues of Health working with researchers in Norway has found that babies who cry for a long time turned out at age 5 to have much lower IQs than the control group.
BACKGROUND: Long term studies of cognitive development and colic have not differentiated between typical colic and prolonged crying. OBJECTIVE: To evaluate whether colic and excessive crying that persists beyond 3 months is associated with adverse cognitive development. DESIGN: Prospective cohort study. A sample of 561 women was enrolled in the second trimester of pregnancy. Colic and prolonged crying were based on crying behaviour assessed at 6 and 13 weeks. Children's intelligence, motor abilities, and behaviour were measured at 5 years (n = 327). Known risk factors for cognitive impairment were ascertained prenatally, after birth, at 6 and 13 weeks, at 6, 9, and 13 months, and at 5 years of age. RESULTS: Children with prolonged crying (but not those with colic only) had an adjusted mean IQ that was 9 points lower than the control group. Their performance and verbal IQ scores were 9.2 and 6.7 points lower than the control group, respectively. The prolonged crying group also had significantly poorer fine motor abilities compared with the control group. Colic had no effect on cognitive development. CONCLUSIONS: Excessive, uncontrolled crying that persists beyond 3 months of age in infants without other signs of neurological damage may be a marker for cognitive deficits during childhood. Such infants need to be examined and followed up more intensively.
In 2002, a team of UK researchers, led by Professor Dieter Wolke at Bristol University, found children who had cried excessively as babies, beyond three months, were 14 times more likely to develop attention deficit hyperactivity disorder (ADHD) and do worse at school as eight year olds.
Professor Wolke said: "This confirms what we found.
"Now there really is more certainty there is really something going on."
He believes the core of the problem is one of under-regulation.
"With ADHD you can't regulate your attention. You can't concentrate, for example. The same thing is happening with crying.
Such persistent, uncontrollable crying "seems to be a very good indicator of potential risk," Dr. Malla Rao of the National Institutes of Health in Bethesda, Maryland, told Reuters Health.
As such, Rao said, parents should not simply "dismiss" their child's crying as being due to gastrointestinal problems such as heartburn or colic, but should notify their child's pediatrician.
But it is unlikely the pediatricians will be able to deliver any sort of treatment that will prevent the eventual cognitive deficits. However, researchers probably ought to deliver a wide range of tests to a group of persistently crying babies to see if any toxin or pathogen might be causing neurological damage. If that was the case then an effective treatment could probably be devised. But if the cause of the neurological deficits is genetic or some event that happened at an earlier point in development then all the pediatrician is going to be able to say to parents is to plan on eventually giving you kid Ritalin when ADHD becomes a problem.
In the longer run this sort of discovery points to why biotech therapies for altering brain development will become acceptable. Imagine politicians trying to explain to young mothers that gene therapy or cell therapy for their continuously crying babies would constitute too much of an unnatural intervention. Mom is going to be thinking the crying means her baby is in pain and the fact that it will grow up dumb and hyperactive. She's going to demand that her Congressman votes to allow treatments that will make her kid happier, smarter, and calmer.
Matthew Newman and colleagues at UT Austin found that bullying leaves more lasting effects if it is first encountered in late adolescence.
People who were bullied all revealed slightly higher levels of stress. But while those bullied earlier in life seemed to respond normally to provocation, people bullied for the first time late in puberty are more withdrawn and sensitive to violence.
There are also sex differences between those bullied for the first time during puberty, with females more likely to react aggressively when provoked and males are much more likely to turn to alcohol to escape bad situations.
Newman admits that the results may seem counterintuitive, as older children might be expected to cope better with being bullied. But he points out that previous studies in animals and humans have shown that the reaction to bullying becomes more pronounced as puberty progresses. He suggests that children who are bullied earlier in puberty may be better prepared to cope with the more stressful experience of later victimization and so suffer fewer consequences in adulthood.
What is this an argument for? Vaccination from a lifetime of avoidance of conflict by use of early puberty bullying. Yes, you heard me. Kids need to get bullied early and often so that their first experiences with bullying will not come in late puberty. They need to build up emotional defenses that can only come from early bullying.
This result is consistent with the idea that people who grow up in tough neighborhoods are tougher emotionally. But the comparison here is between people who are bullied early versus people who are first bulled in late adolescence. Neither article linked to above mentions reactions of a control group of adults who were never bullied. Surely such people exist. Some kids grow up in really rural areas with few peers to bully them and some grow up so big for their age that their peers are afraid to bully them. So do bully-free kids grow up to handle stress well? Or do they lash out or slink away when provoked?
There is also the genetic angle to consider. The New Zealand Longitudinal Dunedin Multidisciplinary Health and Development Study found that a variation in the gene monoamine oxidase-A (MAOA or MAO-A) strongly predisposes abused children to become violent and criminal. It is possible that early childhood abuse is such a different experience for children than bullying during adolescence that abuse a different response than early or late adolescent bullying. Children may move through a series of stages where violence has different effects on their longer term development.
That there are children who carry an MAO-A variant that predisposes to greater violence in response to abuse argues for a reduction in the total amount of abuse children receive. But it becomes possible to genetically test each child for genetic variations that impact how children response to various types of mistreatment and rough treatment we may even find that it is beneficial for some children to get some bullying done to them at some stages whereas other children may be at risk of a worse outcome regardless of when they are abused or bullied.
Researchers at the University of Illinois at Chicago have had preliminary success with a method of immunization intended to dissolve the plaques in brain tissue that are associated with Alzheimer's disease.
When injected directly into the brain of mice, antibodies against a plaque protein retarded growth of the plaques by up to two months. No adverse side effects were found.
"By injecting the antibodies directly into the brain, we were able to circumvent the problems others have encountered in developing a vaccine for this terrible disease," said Neelima Chauhan, research assistant professor in the UIC College of Medicine.
Results of the study appear in the current issue of the Journal of Neuroscience Research.
Two methods of immunization have been tried in Alzheimer's disease. In the first, called active immunization, researchers inject the antigen itself -- pieces of the sticky beta amyloid protein that constitutes the plaques -- into patients to spur the production of antibodies that should neutralize the protein and prevent it from accumulating in brain cells.
But after success in animals, clinical trials of active immunization failed when 6 to 8 percent of the patients in the study developed meningocephalitis, an inflammation of the tissue surrounding the brain.
Passive immunization did not even succeed in animal studies. In this method, researchers inject ready-made antibodies, rather than the antigen, into the animal. But high concentrations of the antibodies are required to be effective, and the large doses were found to cause hemorrhaging and inflammation.
Aware of such problems, Chauhan tried a modified passive immunization method in laboratory mice that are used as a model for the disease. In a single injection, she delivered the antibody directly into the third ventricle, a narrow cavity located between the two hemispheres of the brain, and then examined the animals' brain tissue at one, four and eight weeks.
Since the antibody did not have to circulate throughout the mouse's body where it might be absorbed, Chauhan was able to use a smaller dose than in other passive immunization studies.
Note the plaques came back more slowly in young mice. The ability to clear the plaques by itself would not fully restore brains to a more youthful condition in which plaques would not form in the first place. We still need many other rejuvenation therapies for the brain.
At one and four weeks, the density of amyloid protein was 67 percent less than in control animals. But by eight weeks, with no further antibody injections, the protein had again accumulated. The younger the animals were, the slower the plaques regrew.
No side effects, such as hemorrhaging or inflammation, were evident.
"The results suggest that periodic administration of antibodies directly into the brain might offer a safer method for treating Alzheimer's," Chauhan said. "The vaccine reduces the accumulation of amyloid proteins for at least four weeks, providing a window during which other treatments could be used to prevent the formation of new plaques."
Alzheimer's is an age-associated degenerative neurological disease and the leading cause of dementia in older people. An estimated 10 percent of Americans over the age of 65 and half of those over age 85 have Alzheimer's.
Imagine the cost of Alzheimer's ballooning up to $300 billion per year or more in the United States in a few decades. Makes the cost of research to cure it seem very cheap by comparison. Keep in mind that the money spent finding a way to prevent Alzheimer's is a fixed cost. Once the cure is found the research on that topic doesn't have to continue. Whereas if we do not get a cure for decades to come them the high yearly cost of treatment keeps rising and it goes on continually. Biomedical research spending can produce cures that basically pay from the day the cure is found until humans no longer exist in this universe (I'm assuming that we won't be able to transfer our knowledge to humans who may exist in parallel universes but that assumption may some day prove to be incorrect).
Currently, more than 4 million Americans suffer from the disease and the number is projected to balloon to 10 to 15 million over the next several decades. Alzheimer's is now the third most expensive disease to treat in the United States, costing close to $100 billion annually.
You can read the abstract of the paper here: Effect of age on the duration and extent of amyloid plaque reduction and microglial activation after injection of anti-A[Beta] antibody into the third ventricle of TgCRND8 mice.
While the Elan Pharmaceuticals experimental vaccine AN-1792 against Alzheimer's amyloid plaques caused brain inflammmation in a small subset of people treated I still think a better vaccine may be able to eventually work well against amyloid plaques. In fact, a new oral vaccine has just been tested in mice and shows promise.
Alzheimer's disease is characterized by progressive loss of cognitive function due to amyloid-beta (Aß) deposits in the central nervous system. If these deposits could be stopped or slowed, Alzheimer's disease might become more manageable. In the current issue of the Journal of Alzheimer's Disease, a novel paper from researchers from the National Institute for Longevity Sciences, NCGG, Japan and Center for Neurological Diseases, Brigham & Women's Hospital, Harvard Institute of Medicine shows that a new oral vaccine treatment is effective in reducing Alzheimer's disease pathology.
Immunization results from the production of antibodies which attack the harmful agent, using the body's own defenses to remove the threat. In an earlier immunization study, 6 percent of the subjects developed acute meningoencephalitis, most likely caused by autoimmune T-cell activation. This caused the trial to be stopped. By developing vaccines that can minimize this T-cell activation while retaining the production of Aß-antibodies, a safer treatment might result.
The researchers attached Aß DNA to an adeno-associated virus vector and administered this vaccine to mice orally. Not only were the Aß levels decreased, but the T-cell immune response was significantly reduced. A single dose of this vaccine enhanced the production of Aß-antibodies for more than 6 months. Immunohistochemistry of the mouse brain tissue showed that the extra-cellular amyloid deposits were clearly decreased compared to the non-treated mouse.
Hideo Hara, M.D, writes "This new oral vaccine does not induce strong T cell immune reactions, and hence it could reduce the side effect of such meningoencephalitis…This new therapy seems to be effective for prevention and treatment of Alzheimer's disease."
The article is "Development of a safe oral Aß vaccine using recombinant adeno-associated virus vector for Alzheimer's disease" by Hideo Hara, Alon Monsonego, Katsutoshi Yuasa, Kayo Adachi, Xiao Xiao, Shin'ichi Takeda, Keikichi Takahashi, Howard L. Weiner and Takeshi Tabira. It appears in the Journal of Alzheimer's Disease, Vol.6, Number 5, published by IOS Press
You can view the abstract here.
Kids are out of control because their medial temporal lobes have little say in what they do.
SAN DIEGO, Oct. 27 – A person's ability to have voluntary control over behavior improves with age because with development, additional brain processes are used, according to scientists at the University of Pittsburgh School of Medicine.
The research, presented today at the Annual Meeting of the Society for Neuroscience, helps to resolve questions about how working memory – a function that allows people to perform tasks as diverse as making toast to solving complex math problems – develops and changes from childhood to adulthood.
"This study gives us a good picture of how our ability to have voluntary control over our behavior using working memory changes and improves with maturity," said Beatriz Luna, Ph.D., associate professor of psychiatry at the University of Pittsburgh School of Medicine.
"Anyone with kids or teenagers knows that they can make irrational decisions when they are under stress," said Dr. Luna. "That is not just because they are trying to be difficult – kids simply are not yet able to access the brain regions that allow adults to react in a more controlled way. What this may mean is that adolescents may be able to act like adults under normal conditions, but under stress they may go back to a more instinctual, less thought-out response."
Note that stress increases memory recall but decreases problem-solving ability. Do middle-aged adults retain more problem-solving ability under stressful conditions than do young adults, adolescents, and children? Also, do criminals lose more problem-solving ability under stress than do non-criminal members of populations? Anyone know of there is any research literature on this question? It would be interesting to see whether the degree of decay of problem-solving ability under stressful conditions in adolescence correlates with future criminal behavior.
Working memory is where the brain stores information used to make immediate calculations, similar to the random access memory (RAM) in a computer. Like RAM, the information stored in working memory is dumped when it is no longer needed. Working memory allows the brain to take in information and create planned responses using abstract thought. Without it, human behavior would consist mostly of reflexive actions, and humans would not have been able to develop higher mental abilities.
In a group of 20 healthy 8- to 30-year-olds, Dr. Luna and her colleagues used a test called an oculomotor delayed response task to track memory-guided saccades (eye movements) while imaging their brains using functional magnetic resonance imaging (fMRI). Study participants briefly were shown a pinpoint of light and asked to remember where the light appeared. Ten seconds later, they were asked to look at the location where the light had been using just their memory. The 10-second time lapse was chosen because it would force the subjects to use their working memory – and not short- or long-term memory.
Results of the imaging study showed that pre-adolescent children relied most heavily on the prefrontal and parietal regions of the brain during the task; adolescents used those regions plus the anterior cingulate; and in adults, a third area of the brain, the medial temporal lobe, was brought in to support the functions of the other areas.
Adults did best with the saccade test probably because the medial temporal lobe helps refine encoding of information into working memory. In practical situations, introduction of the medial temporal lobe into the working memory process likely provides the kick needed to keep information around long enough and clearly enough for the brain to mull it over and make a rational, informed decision rather than an impulsive, reflexive action.
"Understanding working memory will inform us about how thinking occurs and how it is linked to other brain processes – and because working memory also is one of the major brain systems impaired in many psychiatric illnesses, understanding these links could inform the development of new treatments," said Dr. Luna.
This brings up an obvious question for those of us who expect medical treatments will be devised to change the speed and direction of brain development: Will it become possible to accelerate the growth of neurons and the development of connections in the brain to allow the medial temporal lobe to gain more influence on behavior at younger ages of child development? Will parents take their juvenile delinquents to get hormonal or gene therapies to enhance the connections the medial temporal lobe and the rest of the brain? Or will parole boards make the development such connections (verified by fMRI scans) as requirements for granting of parole to convicts?
This report is reason to be optimistic about one potential problem that may result from future rejuvenation therapies. A population made more youthful by rejuvenation may become more violent and criminal. While that is certainly going to happen to some extent this report suggests that when middle aged and old aged people can some day regain the use of fully rejuvenated and youthful bodies their rates of crime probably will not increase back up to the average level of criminal activity that their population cohorts engaged in when they were young. If the brain develops lasting neural wiring patterns into adulthood that give the rational brain a stronger ability to restrain impulses then my guess is that rejuvenation therapies will not reduce the strength of those neural connections.
The activity of the Sun over the last 11,400 years, i.e., back to the end of the last ice age on Earth, has now for the first time been reconstructed quantitatively by an international group of researchers led by Sami K. Solanki from the Max Planck Institute for Solar System Research (Katlenburg-Lindau, Germany). The scientists have analyzed the radioactive isotopes in trees that lived thousands of years ago. As the scientists from Germany, Finland, and Switzerland report in the current issue of the science journal "Nature" from October 28, one needs to go back over 8,000 years in order to find a time when the Sun was, on average, as active as in the last 60 years. Based on a statistical study of earlier periods of increased solar activity, the researchers predict that the current level of high solar activity will probably continue only for a few more decades.
The research team had already in 2003 found evidence that the Sun is more active now than in the previous 1000 years. A new data set has allowed them to extend the length of the studied period of time to 11,400 years, so that the whole length of time since the last ice age could be covered. This study showed that the current episode of high solar activity since about the year 1940 is unique within the last 8000 years. This means that the Sun has produced more sunspots, but also more flares and eruptions, which eject huge gas clouds into space, than in the past. The origin and energy source of all these phenomena is the Sun's magnetic field.
Since increased sunspot activity is correlated with higher solar energy output it is possible that Earth climate temperatures in recent decades have been higher due to increased solar radiation hitting the Earth.
Because the brightness of the Sun varies slightly with solar activity, the new reconstruction indicates also that the Sun shines somewhat brighter today than in the 8,000 years before. Whether this effect could have provided a significant contribution to the global warming of the Earth during the last century is an open question. The researchers around Sami K. Solanki stress the fact that solar activity has remained on a roughly constant (high) level since about 1980 - apart from the variations due to the 11-year cycle - while the global temperature has experienced a strong further increase during that time. On the other hand, the rather similar trends of solar activity and terrestrial temperature during the last centuries (with the notable exception of the last 20 years) indicates that the relation between the Sun and climate remains a challenge for further research.
We are in an unusually long period of increased Solar activity. So an eventual decline seems highly likely. What we do not know is what will happen to Earth's climate when the Sun's output finally does decline. Depending on how far it declines cooling could become a bigger risk than warming. But we can't predict whether that will be the case. But human technology will advance so far in the next few decades that large scale climate engineering to cancel out either a warming or a cooling will become feasible. So either way I do not think we need to be deeply concerned in the short run.
This latest report builds on a previous research paper produced by Sami K. Solanki and colleagues several months ago which took a look at sunspot activity going back only 1000 years. See my previous post Sun Energy Output At Over 1,000 Year Peak for more information. Also see