For years hydroelectric dams have shown up on lists of energy sources that are renewable and non-polluting. Environmental complaints about dams have been over more local considerations such as the fact that dams can disrupt fish spawning and that the dams contribution to water evaporation by increasing the surface area over which water can evaporate. Well, Philip Fearnside of Brazil's National Institute for Research in the Amazon says that dams increase the amount of plant matter that decompose in anaerobic condtions and produce methane which is 21 times more potent as a greenhouse gas than carbon dioxide.
In a study to be published in Mitigation and Adaptation Strategies for Global Change, Fearnside estimates that in 1990 the greenhouse effect of emissions from the Curuá-Una dam in Pará, Brazil, was more than three-and-a-half times what would have been produced by generating the same amount of electricity from oil.
This is because large amounts of carbon tied up in trees and other plants are released when the reservoir is initially flooded and the plants rot. Then after this first pulse of decay, plant matter settling on the reservoir's bottom decomposes without oxygen, resulting in a build-up of dissolved methane. This is released into the atmosphere when water passes through the dam's turbines.
Note that a dam in Brazil which is right on the equator is probably going to receive a lot more plant matter from a river that fills its reservoir than would a dam on a river further from the equator. Even if some hydroelectric dams turn out to be net producers of greenhouse gasses we can't assume that all hydroelectric dams cause more in warming effects from methane production than they prevent in avoided carbon dioxide release.
Methane is a valuable gas to capture in situations where it can be captured because methane can be burned for the energy. Also, the burning of methane turns the carbon in it into a compound (carbon dioxide) that is far less potent as a greenhouse gas.
Parenthetically, James Hansen of NASA has been arguing for several years that reduction in methane emissions would reduce global warming effects more cheaply than lowering carbon dioxide emissions (and see more on this here and here). I especially like his argument that lowering methane emissions would both increase air quality down at ground level where we live and decrease greenhouse warming effects. Hansen still thinks carbon dioxide emissions restrictions will be necessary. But why not first implement the far cheaper option of decreasing methane emissions and also get better ground level air quality in the bargain? Just the increase in ground level air quality alone would, in my opinion, justify the costs. Efforts to capture methane would be at least partially paid back because the captured methane could be burned for energy.
Update: Dave Schuler mentioned methane production from agriculture in the comments. I can't answer his question about the relative contribution agriculture makes to methane emissions. But this reminds me of recent research at the University of California at Davis which showed that most methane from cows comes from cow belching.
California dairy cows produce only half the amount of certain air pollutants as had been believed and, perhaps more important, most of a dairy cow's contribution to smog comes not from her fresh manure, but from her belching, according to preliminary findings by a UC Davis scientist.
Those unexpected results may affect the thinking and practices of California regulators and dairy operators trying to reduce air pollution.
"We have to re-think the idea that the only good solutions are engineering solutions, and consider biological avenues such as animal feeding and management to reduce emissions," said Frank Mitloehner, the UC Davis air quality specialist who is conducting the study.
For three months, Mitloehner and his co-workers have studied dairy cows in sealed environmental chambers to simulate emissions from one type of cow housing, known as freestall conditions. Under these controlled conditions -- the first study of its kind -- the researchers were able to collect precise measurements of the volatile organic compound (VOC) emissions that cows and their fresh waste produce.
"For the first time we can tell dairy farmers the source of VOCs from the cow-housing part of their dairy," Mitloehner said. "For the most tightly regulated pollutant, the 700 ozone-forming gases collectively called volatile organic compounds, that source is not the cows' fresh waste. It's the cows."
This result makes methane emissions reduction easier to do than was previously thought. Supplements of bacteria types or compounds that inhibit methane production could be placed in cow feed to reduce methane production. But the idea of changing feedstocks as a way to reduce methane emissions from cows is nothing new and I've come across mentions of research along these lines in Switzerland, France, Australia, and New Zealand. In NZ agricultural scientists are experimenting with different types of grasses to lower methane production in grazing animals. They found substantial differences in methane production depending on which grass was fed to animals. (and the CH4 mentioned below is methane)
Improving the quality of the diet of ruminants tends to result in higher feed intakes, which in turn tends to increase productivity and CH4 output per animal. However, if CH4 is expressed per unit of product, then using a smaller number of high-producing animals to produce a given amount of product emits less CH4 than using a larger number of lower producing animals. This is because a smaller proportion of the feed eaten is required to maintain the animal and because high feed intakes tend to reduce CH4 yield per unit of feed eaten. Concentrate diets produce less CH4 than forage diets but are too expensive for extensive use in New Zealand. Research undertaken by AgResearch and Dexcel indicates that certain forage species e.g. white clover, lotus and sulla, improve animal performance and produce less CH4 per unit of feed eaten. Experiments are currently underway to look at whether ryegrass cultivars selected for improved animal performance also result in lower CH4 yields per unit of product.
One can easily imagine a great reduction in agricultural methane production by seeding pastures and farm fields with grasses that are found to reduce methane production of cows. Countries willing to genetically engineer grasses to add factors that reduce methane production will be able to achieve the greatest reduction in agricultural methane emissions. This will probably turn out be a fairly cheap and easy way to reduce methane emissions.
Agricultural scientists Garry Waghorn and Michael Tavendale of AgResearch Grasslands in New Zealand have found that higher levels of condensed tannins in grasses reduce methane production.
Methane is either burped or expelled out in breath, and is a by-product of the fermentation of feed in the rumen. Dr Waghorn and Dr Tavendale say about 90 percent of all methane emissions come from ruminants. Greenhouse gases affect everyone, because the Government is committed to ratifying the Kyoto Protocol. Once the agreement is signed, New Zealand will face financial penalties if it exceeds the emissions it recorded in 1990. But, and this is the dilemma for the country, if agricultural production expands, so will gas emissions. Condensed tannins are a naturally occurring compound found in red wine, apple skins and cocoa, as well as some pasture grasses, including lotus and sulla. They can also be found in docks, white clover flowers and some seeds. Besides reducing methane emissions, condensed tannins have other animal-related benefits, including improved milk yields, increased liveweight gain, decreased internal parasite burden and reduced bloat, dags and fly strike. Dr Waghorn said tannins had in the past been considered "evil" because some plants, especially tropical ones, contained them in high concentrations, which were bad for animals. But in a temperate climate such as New Zealand's, condensed tannins werefound in "weedy species", or less common plants, he said. "It's unusual to find it in grasses, which is a problem because animals eat grass," Dr Waghorn said.
But in some reports I came across condensed tannins reduced methane emissions by only 15%. Tannins alone might not be a panacea.
Whereas reportedly only 2 percent of greenhouse gas effects in the United States come from agriculture New Zealand has only 4 million people but 10 million cattle and 45 million sheep. Therefore most of New Zealand's greenhouse gas emissions come from agriculture.
"New Zealand is unique in that over 50 percent of its greenhouse gas emissions arise from methane released by enteric fermentation," said Katharine Hayhoe, an atmospheric scientist at the University of Illinois, Urbana-Champaign, Illinois.
Therefore it is not surprising that New Zealand agricultural scientists are especially interested in reducing methane emissions from cows and sheep.
Purdue University researchers are reporting demonstration of a prototype chip that allows thousands of chemical compounds to be tested simultaneously for their ability to change the operation of cell membrane pumps.
Researchers at Purdue University have built and demonstrated a prototype for a new class of miniature devices to study synthetic cell membranes in an effort to speed the discovery of new drugs for a variety of diseases, including cancer.
The researchers created a chip about one centimeter square that holds thousands of tiny vessels sitting on top of a material that contains numerous pores. This "nanoporous" material makes it possible to carry out reactions inside the vessels.
The goal is to produce "laboratories-on-a-chip" less than a half-inch square that might contain up to a million test chambers, or "reactors," each capable of screening an individual drug, said Gil Lee, the project's leader and an associate professor of chemical engineering.
"What we are reporting now is a proof of concept," said Lee, one of three researchers who wrote a paper that details new findings in the current issue (Feb. 15) of the journal Langmuir. The two other researchers are Zhigang Wang, a postdoctoral fellow at Purdue; and Richard Haasch, a research scientist at the University of Illinois at Urbana-Champaign.
The work is part of overall research being carried out by an interdisciplinary team of scientists and engineers who are members of a Center for Membrane Protein Biotechnology. The center was created at Purdue in 2003 through a grant from the Indiana 21st Century Research and Technology Fund, established by the state of Indiana to promote high-tech research and to help commercialize innovations.
The vessels discussed in the research paper are cylindrical cavities that are open at the top and sealed at the bottom with a material called alumina, which contains numerous pores measured in nanometers, or billionths of a meter.
Researchers are working to duplicate how cell membranes function on chips in order to test the potential effectiveness of new drugs to treat diseases. Membranes, which surround cells and regulate the movement of molecules into and out of the cells, contain a variety of proteins, some of which are directly responsible for cancer's ability to resist anti-tumor chemotherapy drugs. These proteins act as tiny pumps that quickly remove chemotherapy drugs from tumor cells, making the treatment less effective. Cancer cells exposed to chemotherapy drugs produce a disproportionately large number of the pumps, causing the cells to become progressively more resistant to anticancer drugs.
Engineers and scientists in the Purdue center are trying to find drugs that deactivate the pumps, which would make the chemotherapy drugs more effective. The researchers are developing synthetic cell membranes to mimic the real thing and then plan to use those membranes to create chips containing up to 1 million test chambers. Each chamber would be covered with a membrane containing the proteins, and the chambers could then be used to search for drugs that deactivate the pumps, Lee said.
Such an advanced technology could be used to quickly screen millions of untested drug compounds that exist in large pharmaceutical "libraries." The chips could dramatically increase the number of experiments that are possible with a small amount of protein.
"It's been very hard to study these proteins because they are difficult to produce in large quantities," Lee said. "The devices we have created offer the promise of making chips capable of running thousands of reactions with the same amount of protein now needed to run only about 10 reactions."
Findings being reported in the paper detail how researchers created the device with the same "microfabrication" techniques used to make computer chips. The reactors range in diameter from about 400 to 60 microns, or millionths of a meter. Human hairs are about 100 microns wide.
Note that there are two advantages to this chip. First off, more tests can be run at once in parallel. But also note that the protein used in the test is difficult to isolate or produce. The small size of each cell on the chip allows much smaller amounts of the protein to be used per test. So the protein can be used to run orders of magnitude more tests.
The ability to run orders of magnitude more tests in parallel will speed up many types of experiments. Notably, it will speed up screening for drugs to use against cancer as noted above. Cancer cells develop many mutations that give them resistance to anti-cancer chemotherapies and other anti-cancer agents. Once the tools area developed to very rapidly test resistant cancers against drugs that might block their mechanisms of resistance the possibility opens up that anti-cancer drugs might be able to be developed so quickly that once drug-resistant cancer cells emerge drugs that block the mechanisms of resistance could be found before patients would otherwise be expected to die.
In a recent report on how lung cancer becomes resistant to the anti-cancer drug gefitinib (Iressa) scientists guessed that the mechanism of resistance had to do with a mutation in epidermal growth factor protein (EGFR) which is where gefitinib binds to stop cancer growth. These scientists at Harvard's Beth Israel Deaconess Medical Center (BIDMC) sequenced the EGFR gene in a patient with gefitinib-resistant cancer and sure enough their hunch was right. Well, people are dying from their gefitinib-resistant cancers and other cancer drug resistant cancers. What we need are DNA sequencing technologies and other technologies for testing cancer cells and screening drug candidates that are extremely fast. then once a drug-resistant mutation shows up in a patient the identification of the mechanism of drug resistance and the search for a new drug will be able to be done before the patient dies.
Once we have biochips and nanotechnology that are fast enough to adapt to the cancers faster than the cancers can adapt to each new round of drug treatment then it will be possible to cure cancer. The shift toward the use of technologies from the semiconductor industry to do testing and manipulation of biological systems is going to lead to orders of magnitude faster and cheaper ways to develop drugs and other disease treatments.
Researchers working with human embryonic stem cells are forming collaborative relationships with doctors at fertility clinics because the two groups are pursuing answers to some of the same questions. The development of techniques to better grow stem cells in laboratories will lead to better techniques to grow an embryo before it is implanted in a would-be mother's womb. Researchers in the field expect embryonic stem cell research to produce knowledge helpful in improving assisted reproduction technologies before the same research leads to development of stem cell therapies and growth of replacement organs.
Stem cell laboratories often use many of the same methods as those used to help couples conceive.
"These are technical advances," Snyder said, citing examples such as finding the best ways of thawing and freezing embryos or determining which materials make the best surfaces on which to place reproductive materials in a laboratory.
Better knowledge about fetal cell feeding and chemical signalling holds the promise of identifying the reasons why miscarriages occur and the development of ways to prevent miscarriages.
Scientists are only beginning to glimpse all the intricate interactions that go on between the cells of the embryo and its environment. By using placental cells in the laboratory, Fisher said, researchers for the first time are able to "characterize the interactions" each step along the way.
Those findings may help shape stem cell treatments. Back in the IVF clinic, Cedars hopes to use the findings much sooner.
"You can take it one step further and apply it to the fetus in utero, into perhaps better ways to promote fetal health," she said, adding that some of the greatest frustrations in IVF occur when someone manages to become pregnant and then miscarries.
The researchers interviewed for the article say they think it ironic that while embryonic stem cell research is seen in some quarters as a product of killing of early stage human life the research will be used eventually to avoid miscarriages and to allow more pregnancies to be started.
Of course the opponents of embryonic stem cell research could argue that some of the information that will be discovered by human embryonic stem cell research could also be discovered by embryonic stem cell research on other species. Still, any new technique that appears to help to grow non-human embryonic cells still has to be verified as working on human embryonic cells as well. In fact, the various mammalian species differ significantly in the difficulty of doing reproductive cloning and in growing their embryonic cells in culture. So not all knowledge is going to be equally applicable across species.
Since the state of California is now going to fund human embryonic stem cell research at a high enough level to make substantial progress it seems reasonable to expect many advances in the coming years in techniques for assisted reproduction and for maintaining healthy pregnancies. The ethical arguments are going to continue. But the science is going to be done.
Public health officials are starting to sound downright scary in their pronouncements about the potential danger to humans of the H5N1 influenza strain which is spreading through populations of chickens, ducks, and other birds in Southeast Asia. Julie Gerberding, head of the US CDC, told a meeting of the American Association for the Advancement of Science (AAAS) that we are probably in a period equivalent to the historical period right before the 1918 influenza pandemic which killed tens of millions of people.
In an address to the AAAS Annual Meeting in Washington, D.C., Dr. Julie Louise Gerberding noted that the in its current form poses a relatively limited problem for humans. But, she said, the current situation "probably" resembles the period before the 1918 Spanish flu outbreak when the virus was quietly mutating into a strain that would eventually leave 50 million people dead.
"Most people who are looking at this recognize it is a very ominous situation for the globe in terms of statistical probability" of a larger outbreak among humans, Gerberding said.
Gerberding's comments Monday came just a day after Dr. Nancy Cox, the CDC's chief influenza scientist, suggested to a AAAS audience that further mutation in the avian flu in Asia could precipitate the worst pandemic in human history.
Researchers believe that prolonged contact with infected birds or consumption of raw, infected chicken meat is required for the virus to jump to humans. But once it does make the jump, it appears to be lethal: According to a report Monday in the Financial Times, the current outbreak has infected 55 humans in Asia and killed 42, a mortality rate of 76 percent.
There is some question as to whether the bird flu really does kill three quarters of the people it infects. If more people are being exposed but developing symptoms too mild to be diagnosed as bird flu then the reported deaths might represent a smaller fraction of a much larger number of infected. Dr. Cox says people who may have been exposed to the bird flu are being tested for immune responses to the flu virus as a way to determine if they managed to have mild cases of bird flu.
"Some studies are going on to get a better handle on what the real case fatality case is," she said. For example, poultry workers exposed to the virus would be checked for any H5N1 antibodies in their blood.
However, some of the previously undiagnosed human cases of bird flu infection appear to have been fatal. The disease may be occurring more often in humans than previously expected but without typical influenza respiratory symptoms.
Two Vietnamese children who died in 2004 of diarrhoea and apparent encephalitis actually had H5N1 bird flu, British and Vietnamese scientists have reported.
The cases raise the frightening possibility that there have been far more human infections with H5N1 than thought, because many cases have been overlooked by doctors watching for the fever and cough of typical flu.
The cases of the Vietnamese children suggest that other cases of bird flu are not being diagnosed.
Dr. Menno de Jong, with Oxford University's Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, said he and fellow researchers believe the boy's case, which wasn't linked to bird flu until months later, may mean that other cases with no respiratory symptoms have gone unnoticed.
The discovery of these H5N1 bird flu cases in the two children was accidental because some scientists happened to be investigating the causes of encephalitis (brain inflammation) in southern Vietnam and found the bird flu link.
One complicating factor in any analysis of antibodies to H5N1 influenza strains is that earlier and far less lethal strains of H5N1 provoked immune responses a few years ago that will show up in tests for H5N1 infections today. Yet the H5N1 of today appears to be much more lethal than the strains from 5 years ago.
Well dear reader, should you be worried about this? I think so. I would not be the least bit surprised if later this year or in 2006 or 2007 tens of millions of people died worldwide from a further mutated strain of the H5N1 bird flu. All it would take would be for that bird influenza virus and an influenza virus from humans to infect an animal or human at the same time. Then the two strains could have their DNA recombined into a strain that has the deadliness of the avian flu and the transmissibility of a human flu. The result would be a pandemic in which each of us would lose family members, neighbors, and friends.
We desperately need more rapid ways to make and scale up the production of influenza virus vaccines. The current method of growing influenza viruses in fertilized chicken eggs for months is too slow and does not scale up rapidly. But when an influenza strain with high human lethality finally springs up we are not going to have a year or two to get ready.
CDC officials are not alone in sounding the alarm about bird flu. Joseph Domenech, director of animal health at the United Nations Food and Agriculture Organization (UN FAO), says the H5N1 avian influenza is a sword of Damocles hanging over the world.
"The time is ripe today for the international community to see how the virus constitutes an enormous sword of Damocles in terms of public health and the rural economy," Domenech told AFP during an interview.
Governments should consider stockpiling vaccine against H5N1 bird flu now, before a pandemic starts, a World Health Organization report out next month will advise.
The change in policy reflects growing fears that an H5 pandemic is likely, and that there will not be time to produce much vaccine once it starts. "When we realised H5N1 is not going to be eradicated in poultry in Asia for at least another couple of years, that made the risk of H5 much higher," Klaus St�hr, head of the WHO's influenza team, told New Scientist.
That story reports that the United States government plans to stock 4 million doses. With a new strain of flu 2 doses are required for full immunity. So those 4 million doses are even more inadequate than they initially appear to be. As for the rest of the world, France and Italy are going to stockpile a couple million doses each.
If a pandemic with high rates of lethality breaks out then I predict a black market in the vaccines that are available against the virus.
Two companies have developed pilot batches of vaccine against H5N1 influenza virus.
Two companies, Sanofi Pasteur and Chiron Corp., are currently under contract to make H5N1 vaccines for the United States. Each company received a contract in May 2004 to make small pilot batches. In September, Sanofi (formerly Aventis Pasteur) received a contract to make 2 million doses. US officials have said that clinical trials of those vaccines are expected to start soon. Chiron is also under contract to make 40,000 doses of an H9N2 vaccine, another flu strain regarded as having pandemic potential.
A Chinese team has also developed a vaccine against H5N1 influenza. But the initial development of a vaccine is not the hard part. The hard part is scaling up vaccine production to make doses for billions of people.
If and when a big killer bird flu crosses over into humans the most rational response should be to find ways to greatly reduce human-to-human contact while we wait for vaccine production to be scaled up. We will need to radically alter our lifestyles for a year or two while waiting for vaccines to be produced for billions of people.
Dr. Richard White and colleagues at the Medical College of Georgia have found that in older blood vessels estrogen ceases to be a vasodilator that opens blood vessels and instead becomes a vasoconstrictor that restricts blood flow.
They were studying estrogen's effects on blood vessels, focusing on its impact on the smooth muscle cells that allow blood vessels to contract, thereby regulating blood pressure and blood flow. These researchers found that estrogen targets nitric oxide synthase 1, one of three versions of the enzyme that makes the powerful vasodilator, nitric oxide.
"What we were finding is that estrogen seems to be what you might call a natural nitroglycerin; nitroglycerin also works by making nitric oxide," Dr. White says.
Then they tried to block estrogen's activity by blocking nitric oxide. "What surprised the heck out of me was after we blocked nitric oxide production and added estrogen, we got a contraction," says Dr. White. "Estrogen now had turned into a constrictor agent, an agent that would increase blood pressure."
They looked further and found that normal aging decreases levels of the cofactors L-arginine and tetrahydrobiopterin - both critical to nitric oxide synthase's production of nitric oxide.
Instead of making nitric oxide, estrogen was producing the powerful age-promoting - and apparently vasoconstricting - oxygen-free radical, superoxide.
"At first, I thought it was an artifact," says Dr. White, who recently received a $1.2 million, four-year grant from the NHLBI to pursue his findings. But using a porcine heart that is very similar to the human heart, he and Dr. Barman, along with Dr. David J. Fulton, a pharmacologist in the MCG Vascular Biology Center, found that every time they blocked nitric oxide production, estrogen became a vasoconstrictor.
"Under normal conditions, such as a pre-menopausal woman, this enzyme, nitric oxide synthase, makes nitric oxide," says Dr. White.
"But if you block the production of nitric oxide, this nitric oxide synthase now has a secondary product that normally isn't made in an appreciable form. Now it makes a compound called superoxide. It's an oxidant, and oxidation is bad in general. It causes a lot of cellular damage. But what we also have found is that now, instead of causing relaxation, it causes constriction. So you completely flip-flop the response here."
"One of the things this means is that menopause is a good thing, a sort of revolutionary endocrinology idea," says Dr. White.
"Menopause is adaptive because a woman is not supposed to have as much estrogen when she gets older because it can kill her." He holds up a graph plotting the dramatically dropping rates of tetrahydrobiopterin over a woman's life, a drop that parallels the drop in estrogen levels.
"We have to confirm it," he says of the new grant in which researchers will use different drugs to mimic aging, drugs that knock out L-arginine and tetrahydrobiopterin, to try to create an aged artery and restudy estrogen's impact.
"Estrogen is so powerful; it affects every system in your body. We are looking with tunnel vision at its effect on blood pressure control. What would this do to bone? What would this do to Alzheimer's? What happens to the brain is probably very similar," he says as critical cofactors drop that enable estrogen to relax blood vessels. "This could be a mechanism that would affect practically every system in the body."
The dangers posed by estrogen replacement therapy in older women illustrate a point I've made here before: the reason many compounds decline or increase as we age may well be an adaptation to other changes that are caused by damage accumulation that is aging. Restoring those compounds to youthful levels may raise risks of a variety of diseases. For another case which I suspect is also an example of this same phenomenon see my warning that replacement of older blood with younger blood may reinvigorate many stem cell reservoirs but at the cost of increasing the risk of cancer. Some types of rejuvenating interventions may not be prudent before other types of rejuvenation can be accomplished first. Otherwise, as is illustrated with this report above, the net result can be harmful.
One practical question arises from this study: Can we at least partially prevent the decline in nitric oxide production capability in old bodies by eating more foods that contain L-arginine? Studies of the effects of supplementary L-arginine on the vasodilation of old blood vessels seem like a wise idea. It might be possible to cancel out some of the negative effects of hormone replacement therapy in older women by L-arginine supplementation or some compound that would enhance vasodilation.
If you want to boost your L-arginine intake on speculation that this will increase nitric oxide production then nuts are good sources of L-arginine and hazel nuts, brazil nuts, and walnuts are the richest sources (at least of those nuts listed). See the table 4 at that link for more nuts and their L-arginine content. The reported heart healthy benefits of nut consumption may be coming at least in part from the vasodilatory effects of the L-arginine in them.
Young blood makes old cells act younger.
STANFORD, Calif. - Any older person can attest that aging muscles don't heal like young ones. But it turns out that's not the muscle's fault. A study in the Feb. 17 issue of Nature shows that it's old blood that keeps the muscles down.
The study, led by Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences at the Stanford University School of Medicine, built on previous work showing that old muscles have the capacity to repair themselves but fail to do so. Rando and his group studied specialized cells called satellite cells, the muscle stem cells, that dot muscle tissue. These normally lie dormant but come to the rescue in response to damaged muscle-at least they do in young mice and humans.
In older mice the satellite cells hold the same position, but are deaf to the muscle's cry for help. In the Nature study, Rando and his group first attached old mice to their younger lab-mates in a way that caused the two mice to share a blood supply. They then induced muscle damage only in the older mice. Bathed in the presence of younger blood, the old muscles healed normally. In contrast, when old mice were connected to other old mice they healed slowly.
In similar work, the group examined the livers of older mice connected to younger lab-mates. The cells that help liver tissue regenerate are less active in older animals, but again the cells responded more robustly when the livers in older mice were bathed in the younger blood. Clearly, something in the youthful blood revived the regenerative cells in muscle and liver.
Of course another possibility is that something in the aged blood is suppressing stem cells and repair mechanisms. Does their work rule out that possibility? I don't see that it does. But I haven't read the original paper.
It would be interesting to know how the effect of the young versus old blood scaled as they were blended in different ratios. For example, does one quarter young blood mixed with three quarters old blood have a quarter the effect of pure young blood or more or less than a quarter of the effect?
There is a potential bright side to this report: If blood could be made young again then possibly cells thoroughout the body in many tissue types would act young again.
"We need to consider the possibility that the niche in which stem cells sit is as important in terms of stem cell aging as the cells themselves," said Rando, who is also an investigator at the Veterans Affairs Palo Alto Health Care System. It could be the chemical soup surrounding the cells, not the cells themselves, that's at fault in aging.
One clue to what might be going on also comes from previous work. Rando had found that satellite cells in younger muscles begin producing a protein dubbed Delta in response to muscle damage. Older muscles maintained the same pre-injury levels of Delta even after muscle damage. However, in the current study he found that satellite cells in elderly mice joined to younger partners ramped up Delta production to youthful levels after an injury.
However, there is a less optimistic interpretation to this result: The body may have evolved to produce stem cell growth suppressor compounds as the body ages in order to suppress cell divisions that could produce cancer cells. So blood that causes old stem cells to grow and repair tissue more vigorously might increase the risk of cancer. My guess is young blood would do that to older people.
The young blood effect was confirmed using cells grown in culture.
The group confirmed their results by putting satellite cells from old and young mice in a lab dish with either old or young blood serum. Old satellite cells in old serum and young satellite cells in young serum both behaved as expected. But when old satellite cells were bathed in young serum they cranked up their production of Delta and began dividing. Likewise, young satellite cells decreased the amount of Delta they produced when in a dish with older serum and divided less frequently.
Rando said that it may be a general phenomenon that a person's inability to repair tissues with age-whether it's muscle, liver, skin or brain-is a matter of the regenerative cell's environment rather than the cells themselves.
Rando said that finding the youth-promoting factors in the blood is no small task. "It's as big a fishing expedition as you can possibly imagine," he said. With thousands of proteins, lipids, sugars and other small molecules in the blood serum, deciding where to look first would be tantamount to a roll of the dice. What's more, there's no evidence that the same blood component is responsible for reviving the different types of cells.
"Another approach is to pick factors that are good candidates and see if any of them or some combination recapitulate the effect of the younger blood," Rando said. His group is now looking for likely targets. He said that for some degenerative diseases such as Alzheimer's or muscular dystrophy, such blood-borne factors may be able to reactivate the regenerative cell's ability to repair tissue that has been damaged.
This is an important report. But I repeat my caution above: If the presence or absence of some compound(s) in the blood is reducing the repair ability of a variety of tissue types (and it seems likely other tissue types will also be found to be affected by young versus old blood) then there is a decent chance that this reduction in repair ability was selected for to achieve some benefit, most likely a reduction in cancer risk.
Having stated the caution the ability to turn up repair capabilities could still be therapeutically useful for people who have dire needs for repair of some organ or tissue type. For example, turning up repair temporarily after major surgery or an accident could be worth the increased risk of cancer in some cases.
Suppose that changes in levels (either increases in suppressor molecules or decreases in cell growth stimulating molecules) of one or more compounds in the blood as we age happens in order to reduce the risk of cancer. Well, this is problematic for hopes to derive maximal benefits from replacing aged stem cell reservoirs with youthful stem cells. The old stem cells could be replaced with younger cells. There'd be immediate gains from lowered risk of cancer and relative improvements in the vigor and health of adult stem cells. So that is still worth doing. Yet the young replacement stem cells would still be restrained by levels of compounds in the aged blood. Here's the problem: If some but not all stem cell reservoirs have their stem cells replaced with younger stem cells it might not be safe to change the blood to make it more like young blood. It might be necessary to rejuvenate all stem cell reservoirs before the blood can safely be made more like young blood.
Here is an analogy: Imagine you have a car. It is old and it has 4 bad axles that will fall off if the car is driven too fast as well as a steering column that will fall apart at high speeds. Suppose you know how to replace the 4 axles but not the steering column. Well, if you replace only the 4 axles you still can't safely drive your car at high speeds. But with humans this problem is even tougher because there are many stem cell reservoirs located near every muscle and organ that would need to be rejuvenated before they could all have their level of stimulation by the blood safely raised to youthful levels.
Once really effective anti-cancer treatments (even treatments that kill all precancerous cells) are developed then most (all?) safety worries from making blood young again would go away. Any cancers that popped up in response to having youthful and growth-stimulating blood could quickly be slain or they could be slain even before the blood was rejuvenated. So great cancer-slaying treatments would make rejuvenation treatments easier to implement.
An Israeli research team at the Weizmann Institute of Science in Rehovot, Israel has discovered that tissues can be transplanted from organs in developing pig embryos to produce functioning organs in mice if the tissues are extracted from pig embryo organs during an optimal time window that is specific to each organ. (same article here)
Scientists at the Weizmann Institute of Science have determined distinct gestational time windows for the growth of transplanted pig embryonic liver, pancreas and lung precursor tissue into functioning organs in mice. These findings -- appearing this week in PNAS online Early Edition -- could help enhance the chances for successful implementation of embryonic pig tissue in the treatment of a wide spectrum of human diseases.
The study, led by Prof. Yair Reisner of the Institute's Immunology Department, involved the extraction of embryos from sows at various stages of pregnancy and implantation of organ-committed cell tissue into immunodeficient mice. His novel approach did not involve the growth of any tissue in culture. The analysis of embryonic-tissue at various gestational ages revealed a unique pattern of growth and differentiation for each organ.
The potential of embryonic pig tissues as a new source for organ transplantation in humans has been advocated for more than two decades. Transplant too early, however, and the risk is undifferentiated embryonic tissue that can develop into undesirable and possibly malignant tissue, a type of tumor known as "teratoma." Transplant too late and the risk is that the tissues will have reached the stage where they have been marked with certain identifiers that trigger rejection by the new host.
The study demonstrated that maximal liver growth and function were achieved at the earliest teratoma-free gestational age (four weeks). The growth and functional potential of the pancreas occurred later (six weeks) and its optimal transplant age limit was defined by a decline in the insulin- secreting capacity beyond 10 weeks gestational age. Development of mature lung tissue containing essential respiratory system elements was observed at a relatively late gestational age. The sequence of transplanted organ development paralleled that of normal embryonic development in which the liver and pancreas precede the lungs.
"Disappointing results in past transplantation trials may be explained, at least in part, by these results," explains Reisner. Early studies that attempted to cure diabetic patients by implantation of pig embryonic pancreas, made use of late gestation tissue which is now shown to be inferior compared to the optimal six weeks gestational time.
In previous studies, Reisner's group demonstrated that transplanted human and pig kidney embryonic tissue could grow into miniature, functioning human or pig kidneys inside a mouse. His novel approach was a matter of timing: gestational age proved to be the key to successful kidney growth from transplanted embryonic tissue.
Some pretty simple knowledge (the optimal time to take the cells from each organ) may make possible trans-species organ cell transplants (a.k.a. xenotransplantation).
The key is to take cells from an organ during the period soon after it has started to form.
Growing new organs in humans from embryonic pig tissues may be feasible, researchers report, but the cells need to come from specific stages of an embryo's development. Using pig tissue to replace human organs could help patients with diseases such as diabetes, Parkinson's disease, and liver failure, but researchers have so far faced a challenge of balance. On the one hand, stem cells taken from very early in an embryo's development tend to develop tumors after transplantation, whereas tissue from adult organs face rejection by the recipient's immune system. Taking cells from an embryonic organ soon after it has begun to form may strike the ideal balance. To investigate the best time to harvest embryonic cells, Yair Reisner and colleagues took embryonic pig tissue that had begun to form particular organs at various developmental stages and transplanted them into mice. The researchers studied three types of organs--liver, pancreas, and lung--and found unique growth patterns. Optimal time windows were clearly seen for each organ. The authors say these findings may help in part to explain the failure of previous transplantation trials of pancreatic islets in diabetic patients.
This research was sponsored by a American-Israeli tissue transplantation biotech company called Tissera.
Other labs are working on making pigs genetically more compatible with humans by transferring human genes into pigs in order to grow up organs that are highly compatible with humans. See my previous posts "Human Genes Put Into Pig Sperm"and "Genetically Engineering Pigs for Xenotransplantation" for some details. The promise of the genetic engineering approaches is that potentially fully grown organs could be transferred from pigs to humans. Such transfers of fully formed organs might require immunosuppressive drugs to make them compatible. Whereas the transfer of starter cells from early embryo proto-organs may provide greater immunocompatibility.
The obvious advantage of transferring fully formed organs is that they can be used to save people's lives in cases of acute organ failure. When the liver or another vital organ has stopped working entirely there is not enough time to transfer some cells and wait for those cells to grow up into a complete organ. Full sized organs are needed to deal with emergencies. However, in cases where an organ is failing slowly the ability to gradually grow a replacement alongside of it offers the potential for a more immunocompatible replacement.
My guess is that in the future both the use of starter cells to grow replacement organs in a human body and the transfer of fully grown xenotransplants will become commonly used treatments for organ failures. These treatments might even be used in a complementary fashion. Get an emergency full sized xenotransplant organ with immunosuppressive drugs to meet an immediate emergency need and then once the patient is stabilized and healthy transfer in some more immunologically compatible cells to grow yet another organ that will serve as the permanent replacement.
In the longer run it seems reasonable to expect the development of techniques that allow the growth of full sized immunologically compatible organs. Alternatively, full sized organs will be grown up and then immune system modification therapies will be developed that will be able to adjust an immune system to teach it that a transplant organ should be treated as native tissue.
People overestimate the amount of extra time they will have in the future to do additional tasks. (same article here)
If your appointment book runneth over, it could mean one of two things: Either you are enviably popular or you make the same faulty assumptions about the future as everyone else. Psychological research points to the latter explanation. Research by two business-school professors reveals that people over-commit because we expect to have more time in the future than we have in the present. Of course, when tomorrow turns into today, we discover that we are too busy to do everything we promised.
The study appears in the February issue of the Journal of Experimental Psychology (JEP): General, which is published by the American Psychological Association (APA).
Gal Zauberman, PhD, of the University of North Carolina at Chapel Hill, and John Lynch Jr., PhD, of Duke University, also learned from paper-and-pencil questionnaires (respondents to seven different surveys numbered 95, 68, 241, 61, 264, 48 and 130) that that this expectation of more time “slack,” a surplus of a given resource available to complete a task, is more pronounced for time than money.
The authors suspect that’s because every day’s a little different: The nature of time fools us and we “forget” about how things fill our days. Money is more “fungible,” freely exchanged for something of like kind -- such as four quarters for a dollar bill. Write Zauberman and Lynch, “Barring some change in employment or family status, supply and demand of money are relatively constant over time, and people are aware of that. Compared with demands on one’s time, money needs in the future are relatively predictable from money needs today.”
Participants believed that both time and money would be more available in “a month” than “today,” and believed it more strongly for time than for money. A deeper investigation of a psychological phenomenon called “delay discounting,” in which people tend to lessen the importance of future rewards, showed that people also discounted future time more than both gains and losses in future money.
The best time to ask someone for a favour is at least several weeks in advance, a new study suggests. The research finds that people consistently over-commit because they expect to have more time in the future than they do right now.
Yes, I believe I do this. Most of the time future of one's life a couple of months from now looks simpler than the future of one's life tomorrow. More of the detailed clutter of tasks for tomorrow are clear in one's mind than is the case for days further out in the future.
Is this tendency to underestimate the number of more distant future tasks simply a result of having longer lists of tasks to do tomorrow versus a month from now? Or is something deeper at work? The ability to think of all the tasks one has to do a month from now may have been maladaptive. The ability to think in detail about the many detailed tasks one might do weeks into the future was probably a counter-productive distraction from concentration on more immediate needs.
Now, researchers at Johns Hopkins have discovered that sudden emotional stress can also result in severe but reversible heart muscle weakness that mimics a classic heart attack. Patients with this condition, called stress cardiomyopathy but known colloquially as "broken heart" syndrome, are often misdiagnosed with a massive heart attack when, indeed, they have suffered from a days-long surge in adrenalin (epinephrine) and other stress hormones that temporarily "stun" the heart.
"Our study should help physicians distinguish between stress cardiomyopathy and heart attacks," says study lead author and cardiologist Ilan Wittstein, M.D., an assistant professor at The Johns Hopkins University School of Medicine and its Heart Institute. "And it should also reassure patients that they have not had permanent heart damage."
In the Hopkins study, to be published in The New England Journal of Medicine online Feb. 10, the research team found that some people may respond to sudden, overwhelming emotional stress by releasing large amounts of catecholamines (notably adrenalin and noradrenalin, also called epinephrine and norepinephrine) into the blood stream, along with their breakdown products and small proteins produced by an excited nervous system. These chemicals can be temporarily toxic to the heart, effectively stunning the muscle and producing symptoms similar to a typical heart attack, including chest pain, fluid in the lungs, shortness of breath and heart failure.
Upon closer examination, though, the researchers determined that cases of stress cardiomyopathy were clinically very different from a typical heart attack.
"After observing several cases of 'broken heart' syndrome at Hopkins hospitals - most of them in middle-aged or elderly women - we realized that these patients had clinical features quite different from typical cases of heart attack, and that something very different was happening," says Wittstein. "These cases were, initially, difficult to explain because most of the patients were previously healthy and had few risk factors for heart disease."
For example, examination by angiogram showed no blockages in the arteries supplying the heart. Blood tests also failed to reveal some typical signs of a heart attack, such as highly elevated levels of cardiac enzymes that are released into the blood stream from damaged heart muscle. Magnetic resonance imaging (MRI) scans confirmed that none of the stressed patients had suffered irreversible muscle damage. Of greatest surprise, the team says, was that recovery rates were much faster than typically seen after a heart attack. Stressed patients showed dramatic improvement in their hearts' ability to pump within a few days and had complete recovery within two weeks. In contrast, partial recovery after a heart attack can take weeks or months and, frequently, the heart muscle damage is permanent.
The researchers collected detailed histories and conducted several tests, including blood work, echocardiograms, electrocardiograms, coronary angiograms, MRI scans and heart biopsies, on a total of 19 patients who came to Hopkins between November 1999 and September 2003. All had signs of an apparent heart attack immediately after some kind of sudden emotional stress, including news of a death, shock from a surprise party, fear of public speaking, armed robbery, a court appearance and a car accident. Eighteen of the stressed patients were female, between the age of 27 and 87, with a median age of 63. The results were then compared to seven other patients, all of whom had suffered classic, severe cases of heart attack, called a Killip class III myocardial infarction.
When results from both groups were compared, the researchers found that initial levels of catecholamines in the stress cardiomyopathy patients were two to three times the levels among patients with classic heart attack, and seven to 34 times normal levels.
Catecholamine metabolites, such as metanephrine and normetanephrine, were also massively elevated, as were other stress-related proteins, such as neuropeptide Y, brain natriuretic peptide and serotonin. These results provided added confirmation that the syndrome was stress induced. Heart biopsies also showed an injury pattern consistent with a high catecholamine state and not heart attack.
Note that 18 out of the 19 patients diagnosed with stress cardiomyopathy were women. Do men suppress their emotional responses and thereby lower their risk of stress cardiomyopathy?
I predict that some day people will have embedded drug dispensers in their bodies that have integrated sensors that will be able to detect the chemicals released by a severe emotional stress episode. The sensor devices embedded in a body will have integrated drug dispensers that together will act like an extension of the endocrine system. The artificial endocrine organs will be able to react to the severe stress reaction by releasing compounds that will damp down the stress response to put the stress response back within a safe range by neutralizing the catecholamines and other compounds released in response to severe emotional stress.
Severe emotional stress is bad for your health. To the extent that it is practically possible structure your life to avoid circumstances and events that will elicit intense emotional feelings of stress.
Professor Malcolm Horne of the University of Melbourne's Howard Florey Institute has found that a drug which blocks the D2 receptor on dopamine neurons eliminates cocaine cravings in rats previously addicted to cocaine.
The Howard Florey Institute’s Prof Malcolm Horne and his team successfully cured cocaine addiction without withdrawal symptoms in rats - a discovery that could help develop drug addiction treatments for humans.
Cocaine increases dopamine, the body’s own ‘feel good’ drug produced by the brain. Repeated use causes tolerance for the drug so that withdrawal results in low levels of dopamine and continuous use is required to keep dopamine at normal levels, and even higher doses to get the ‘high’ levels of initial use. Cocaine withdrawal is often accompanied by mental and physical symptoms.
The Florey scientists cured cocaine addiction in rats by fooling their brain cells into thinking that there was a shortage of dopamine. As a result, their brain cells made more dopamine, which meant cocaine was not needed to increase dopamine levels and the addiction was cured.
Dopamine production and nerve cell endings capable of releasing dopamine were increased when the D2 receptor was blocked by the drug.
Dopamine is released by specialised nerve endings in the brain called terminals. The amount of dopamine is sensed by the D2 receptor, which regulates whether more or less dopamine needs to be released. Horne’s team discovered that the number of terminals increase or decrease according to the levels of dopamine and found that when dopamine levels are high, the D2 receptor not only shuts down dopamine synthesis, it also reduces the number of terminals. When dopamine is low, it gives the signal to produce dopamine and make more terminals.
Prof Horne’s team gave a drug that blocks the D2 receptor to cocaine addicted rats and found that they could increase the number of terminals even while the animals had free access to cocaine. With time, the rats stopped seeking cocaine, and even when re-exposed to the drug some weeks later, did not relapse in the way that would be expected. The rats’ normal dopamine levels had increased, curing the addiction and removing withdrawal symptoms such as anxiety.
The news release excerpted above and various Australian media reports on this study do not provide a name for the antipsychotic medication used by Professor Horne's team. However, many antipsychotics bind to D2 receptors including risperidone and olanzipine. Some of those drugs bind at serotonin receptors and other sites as well. So without more details from Horne's lab we can not be certain that the effect he saw was really due to the D2 receptor blocking effect. Still, if it works on humans the mechanism of operation is of secondary concern.
The paper that will provide the details is not out yet but you can watch for it in the journal Neurobiology of Disease.
D2 receptor blockers can cause the pituitary to make too much prolactin with all sorts of undesirable side effects.
Symptoms of hyperprolactinaemia include amenorrhoea, galactorrhoea, infertility, loss of libido and erectile dysfunction. Resulting hypogonadism may cause osteoporosis.
My guess is that many of those effects come from prolonged use of a D2 receptor blocker drug. This may not be a problem for cocaine addicts since Horne's work showed that the antipsychotic drug he used did not have to be taken indefinitely. The D2 receptor was blocked by the antipsychotic drug he used, more dopamine was produced by the brain, compulsion to use cocaine dropped, and then administration of the antipsychotic was halted.
The ability to cure drug addictions would reduce crime, child abuse, birth defects from pregnant moms on drugs, brain damage, and a whole host of other problems. Therefore we all stand to gain enormously from the development of effective treatments for curing drug addiction.
The Bush Administration proposes to not allow biomedical research funding to keep up with inflation and therefore is effectively proposing cuts in biomedical research funding.
Under the president's request, the budget of the National Institutes of Health, which doubled from 1998 to 2003, would rise by 0.7 percent, to $28.7 billion next year. That is much less than what would be needed to keep pace with the costs of biomedical research, which are rising more than 3.5 percent a year.
For the National Science Foundation, Mr. Bush will request $5.6 billion in 2006, an increase of 2.4 percent, budget documents show. Mr. Bush requested an increase last year as well, but Congress ended up making a small cut in the agency's budget for this year.
At the Food and Drug Administration, buffeted in recent months by concerns about drug safety, the budget would increase by 4.5 percent, to $1.9 billion.
Aside on the FDA budget increase: What we need are more drugs in the drug pipeline, not more regulation of the drug development process.
The Bush Administration announced almost a year ago that funding of most categories of research was not going to keep up with inflation. The latest announced NIH budget increase for FY 2006 is even smaller than the 2% increase for fiscal year 2005.
The US federal budget is running a large deficit. Cuts have to be made. But medical research is a penny-wise pound-foolish place to cut spending. What we need are better treatments that are more cost-effective. Advances in medical science and in supporting technologies will some day yield treatments that are both much cheaper and much more effective. During transition phases early and less effective treatments cost more than not being able to do anything at all to treat a disease. But more advanced treatments that attack problems at the root level will inevitably cost less.
If we delay efforts to find cheaper and more effective ways to treat diseases then the avoidable cost in the long run of using less effective and more expensive treatments is going to dwarf the sums saved by cuts in medical research.
Stanley Kurtz lays out a gloomy future due to medical spending increases for an aging population.
The Congressional Budget Office estimates that the combined cost of Medicare and Medicaid alone will consume a larger share of the nation’s income in 2050 than the entire federal budget does today. By 2050, the combined cost of Social Security, Medicare, Medicaid, and interest on the national debt will rise to 47 percent of gross domestic product — more than double the level of expected federal revenues at the time. Without reform, all federal spending would eventually go to seniors. Obviously, the system will correct before we reach that point. But how?
The industrialized countries with aging populations are faced with a future of much higher taxes and benefits cuts as well. The unfunded liabilities for the care of old people are literally orders of magnitude larger than the amount spent on medical research. Take that $28.7 billion dollar figure cited above for the NIH research budget. Sound like a large number? The new Bush Administration proposal for the fiscal year 2006 budget is $2.57 trillion dollars for an economy that will be somewhere in the neighborhood of approximately $12.5 trillion per year based on an increase from the fourth quarter of 2004.
Current-dollar GDP -- the market value of the nation's output of goods and services -- increased 5.3 percent, or $152.1 billion, in the fourth quarter to a level of $11,967.0 billion. In the third quarter, current-dollar GDP increased 5.5 percent, or $157.4 billion.
But, barring cuts in entitlements, in 2050 Medicare and Medicaid alone may cost proportionately more than all of the US federal government today. So their costs alone could become be about 2 orders of magnitude more than is currently spent by the US federal government on medical research.
Of course government spending is only one portion of total medical spending. So even if medical entitlements programs are scaled back the portion of total GDP that goes to medical costs could be much higher than it is today.
While projections from current trends yield a bleak financial situation in 2050 it seems reasonable to assume that medical science is going to advance greatly by 2050. Even without higher levels of funding for medical research the rates of advance of biotechnology and biomedical science are likely to produce effective and cheap treatments by 2050. Some of those advances will produce cheaper treatments. Therefore I am less concerned about financial crises brought on by aging populations in the Western industrialized countries in 2050 than I am in the medium term, say 2025. We need to make medical advances come sooner so that we can cut costs, reduce the incidence of degenerative diseases, and increase the number of years people can work before Western countries get caught up in economic stagnation caused by higher taxes.
Here is another financial way to state my basic argument: Western governments have committed themselves to provide enormous quantities of medical care in the coming decades that those governments can not afford to deliver. The political debate on how to handle these commitments tends to center around whether to raise taxes, cut benefits, impose price controls, or inject more market forces into medical care. All four of those responses have either substantial downsides or insufficient upsides or both. Some of the approaches will even make the problem worse while also producing lower living standards. Let us consider each potential response in turn.
First off, taxes can be increased. But taxes raised beyond some point cease to produce a net revenue gain because people will respond to high tax rates by working less. This will slow economic growth and therefore in the long run will reduce the size of the underlying economy available to be tapped to pay for old age benefits. The United States could end up like European countries that have slower economic growth, lower per capita GDPs, higher taxes, and lower labor market participation rates.
Benefits cuts are still not happening in the United States and still seem a distant prospect. In fact, Republican President Bush added a new expensive drugs benefit a couple of years ago. No politician wants to propose benefits cuts and therefore government finances will get worse before cuts become politically feasible. Yet benefits cuts seem inevitable in the 2010s, 2020s, and beyond since the working population will oppose tax increases that are large enough to pay for all promised benefits.
Price controls are really backdoor benefits cuts. Price controls will produce decreases in the quality of service and will produce queues and rationing of the sort seen in Canada and Britain. Price controls also (and most importantly in my view) reduce incentives for development of new treatments by reducing the profits from new treatments. Hence price controls will make the financial crunch even worse by delaying the development of cost effective treatments.
Then there is the injection of more market forces into medicine. I'm all for this and favor health savings accounts for this reason. However, my judgement is that market forces alone can not prevent medical costs from becoming a huge weight on living standards because the public is going to demand governments to pay for medical bills that individuals can not afford. We are therefore politically limited in how much market forces will be allowed. Also, markets transfer the bulk of the benefits of innovation to customers and therefore underreward and underfund innovation. Markets provide even worse incentives for funding the scientific research needed to develop better medical treatments. If the government, as such a huge buyer of medical care, wants to benefit from innovative cost-saving biotechnology then the government will need to fund more research that will enable the development of that biotechnology.
Given that the four major alternatives discussed above have major downsides why not consider science as a potential solution? After all, science will eventually produce solutions that cheaply cure or prevent all the major diseases. The only question is when. Acceleration of the rate of advance could not only reduce the size of future liabilities but could also have the very attractive added benefit allowing us all to get healthier and stay healthier for much longer.
The biggest reason I can see for why medical research isn't taken seriously as a policy tool to solve the problem of unfunded old age medical care entitlements is that it is hard to predict the rate of advance of medicine. If a government wants to build a road across a continent it can get fairly realistic cost and time projections. Then the government can set out to build the road fairly confident that the goal can be accomplished in a time frame and for a cost not too far from original projections. But science by its very nature seems unpredictable. We have been pursuing the development of cancer cures for decades with tens of billions spent to date and still can't cure most cancers.
But the unpredictable nature of science ought to be considered in light of the substantial downsides of all the alternatives. We have a huge problem with aging populations. The problem doesn't get the attention it deserves in part because tallies of numbers of tens of trillions of dollars of liabilities and descriptions of trends in dependency ratios of workers to retirees and children are rather bleak to discuss and depressing to ponder. Debate on the issue easily deteriorates into a partisan battle about the New Deal and the proper role of government. Ideologues are quick to run to take up defensive positions against perceived ideological attacks by the other side, leaving them ill-disposed to think through rational analyses of the problems posed by aging populations. Does the US Social Security old age retirement program face a financial crisis? Perceived (and in some cases real) attacks on its very moral legitimacy prevents the financial problems of Social Security from being discussed rationally in too many cases. Ditto for programs for medical care for the aged. We need to move beyond the ideological sparring and look for better solutions.
Precisely because scientific research takes a long time to produce desired results we need to greatly increase the push to advance biomedical science and biotechnology now. We can't wait until the budget deficits are even larger, taxes are even higher, medical care rationing has become commonplace, the economy is stagnating, and the task of finding money to allocate to research is even more difficult. As things stand now medical treatment spending is going up faster than inflation while medical research spending is going up more slowly than inflation. Medical research spending ought to rise as fast as medical treatment spending rises.
My modest proposal for funding medical research: Change the major medical entitlements programs to require that 10% of all medical entitlements budgets go to fund medical research. Then when medical entitlements spending inevitably goes up medical research spending will go up proportionately. Yes, that will make the financial numbers for the medical entitlements programs look worse in the short run. But the money thereby spent will produce much larger savings for those programs in the longer run and will also produce treatments that will lead to great improvements in the health of the vast majority of people.
The Scientist has additional details about the NIH budget.
The proposed NIH budget would provide $15.5 billion for new (competing) and continuing (non-competing) research project grants, a 0.4% increase of $56 million. This would fund about 38,746 total projects, 402 less than this year. The average new research project grant would be funded at $347,000, about the same amount as in FY 2005.
One question I have: Is the current allocation of money in the NIH between staff researchers and grant-funded researchers optimal? My guess is that less funding for NIH staff and more funding for academic researchers would produce more total research progress. Anyone have any useful insights into this?
Aging minds do pick up some advantages.
Hamilton, ON. February 2, 2005 – The long-held belief that older people perform slower and worse than younger people has been proven wrong. In a study published today in Neuron, psychologists from McMaster University discovered that the ageing process actually improves certain abilities: Older people appear to be better and faster at grasping the big picture than their younger counterparts.
"Going into the study, we knew that ageing changes the way people see the world," says Allison Sekuler, one of the senior authors and a Canada Research Chair at McMaster. "But these results are an unusual twist on the standard 'ageing makes you worse' story, and they provide clear insight into what is changing in the ageing brain."
Using computer-generated stimuli, the researchers monitored how much time subjects needed to process information about the direction in which a set of bars moved. When the bars were small, or when the bars were low in contrast (light gray vs. dark gray), younger subjects took less time to see the direction of motion. But when the bars were large, and high in contrast (black vs. white), older subjects outperformed the younger subjects.
"The results are exciting not only because they show an odd case in which older people have better vision than younger people, but also because it may tell us something about how ageing affects the way signals are processed in the brain" says Patrick Bennett, the other senior author, also a Canada Research Chair at McMaster.
The results suggest that as we age, the ability of one brain cell to inhibit another is reduced. That sort of inhibition helps young people find an object hidden among clutter, but it can make it hard to tune into the clutter itself. When the young brain sees big, high-contrast bars, it effectively tunes out because there is no object hidden in the bars. But older brains do not inhibit information in the same way, so they do not tune out the bars, and they can actually perform the task better.
"As we get older, it becomes harder to concentrate on one thing and ignore everything else," says Bennett. "It takes more effort to tune out distractions. We've seen it in cognition and speech studies, and now we see it in vision. Although we don't know if those are all linked, we think the visual effect is due to changes in the effectiveness of inhibitory neurotransmitters in the brain." Neurotransmitters are chemical substances that can modify the way in which brain cells talk to one another. Some neurotransmitters enhance brain signals, and others inhibit them.
Is this change in ability the result of aging or of the accumulation of mental abilities? Is it desireable to be able to reverse this aspect of aging? What would be the consequences of restoring a more youthful reaction to high contrast and low contrast signals?
Hermundur Sigmundsson of the Norwegian University of Science and Technology, Trondheim Norway, found that in simulated driving conditions dyslexics took longer to react to flashing signs.
The six dyslexic drivers took on average 0.13 seconds longer to react during the rural drive than the non-dyslexic controls and were 0.19 seconds slower in the city, where the simulated environment was more complex. In both tests the controls took around 0.6 seconds to respond, so the dyslexic drivers were experiencing a delay of 20 to 30 per cent (Brain and Cognition, DOI: 10.1016/j.bandc.2004.11.007).
The article says this level of delay is worse than what happens as a result of moderate drinking.
Some people see this result as offensive to dyslexics.
Dr John Rack, of the Dyslexia Institute, said: "It's a small study and it's an overgeneralisation and oversimplification of what dyslexia is.
"It could really be quite offensive, I feel, to the many, many dyslexic people who are actually quite talented and skilled in those areas."
Perhaps some will be offended. But is it true? If this result is true is it true for all dyslexics? Are there dyslexics who can react very rapidly to sudden changes on roads? Also, does the average person who gets into a car accident have slower reaction times than the average person who does not get into a car accident?
In the future wouldn't it make sense to use objective tests of speed of responses to simulated road events to measure how well or poorly each prospective driver will do on the road? Even if dyslexics have slower reaction times on average surely there are non-dyslexics who naturally have reaction times that are worse than the average.
Also, picture devices in cars of marginal drivers or alcoholics that would test their reaction times and accuracies every time a bad driver wanted to start the car and go somewhere. Anyone unable to reaction in a timely manner could be denied the ability to make the engine start.
The more that different categories of people are compared the more differences will be found between those categories. This is inevitably going to lead to calls for rules changes that take into account the knowledge of these differences.
A study on brain development shows another example of differences in how the different brains react to road situations. Full development of a brain area involved in the tendency toward behavioral inhibition in the face of risks does not occur until age 25.
A National Institutes of Health study suggests that the region of the brain that inhibits risky behavior is not fully formed until age 25, a finding with implications for a host of policies, including the nation's driving laws.
"We'd thought the highest levels of physical and brain maturity were reached by age 18, maybe earlier -- so this threw us," said Jay Giedd, a pediatric psychiatrist leading the study, which released its first results in April. That makes adolescence "a dangerous time, when it should be the best."
Suppose it becomes possible to measure brains to show that some people never fully develop the part of their brain that causes them to inhibit risky behavior. Should those adults be kept off the road just because they are too prone to risks when behind the wheel? Or if some people develop tendencies to risk-aversion earlier should they be granted drivers licenses earlier than the majority of the population?
The problem with judging people only by what they do is that for many actions waiting for people to do undesired things (like cause a car accident) causes too much damage. We are going to gain greater abilities to predict what people might do. How to reconcile the coming greater abilities to predict human behavior with the legal ideal to treat all equally before the law?
University of Florida Department of Mechanical and Aerospace Engineering professors James Klausner and Renwei Mei have developed a method to use power plant waste heat to lower the cost of water desalination.
Since power plants need water for cooling purposes and desalination plants need heat, why not combine the needs of both? The professors - James Klausner and Renwei Mei - calculate that their process would shave a sixth of the cost from today's most efficient technology.
If we either develop cheaper energy sources or more of the world becomes industrialized then there will be no world scale shortage of drinkable water. If people can afford to pay for water it can always be produced by desalination. Alarmist talk in some circles about future water shortages assumes a high rate of poverty. Waters shortages will become a bigger problem in the future only where severe poverty will continue to be a problem.
Employing a major modification to distillation, Klausner's technology relies on a physical process known as mass diffusion, rather than heat, to evaporate salt water.
In a nutshell, pumps move salt water through a heater and spray it into the top of a diffusion tower – a column packed with a polyethylene matrix that creates a large surface area for the water to flow across as it falls. Other pumps at the bottom of the tower blow warm, dry air up the column in the opposite direction of the flowing water. As the trickling salt water meets the warm dry air, evaporation occurs. Blowers push the now-saturated air into a condenser, the first stage in a process that forces the moisture to condense as fresh water.
Klausner said the key feature of his system is that it can tap warmed water plants have used to cool their machines to heat the salt water intended for desalination, turning a waste product into a useful one.
He has successfully tested a small experimental prototype in his lab, producing about 500 gallons of fresh water daily. His calculations show that a larger version, tapping the waste coolant water from a typically sized 100-megawatt power plant, has the potential to produce 1.5 million gallons daily. The cost is projected at $2.50 per 1,000 gallons, compared with $10 per thousand gallons for conventional distillation and $3 per thousand gallons for reverse osmosis.
Because the equipment would have to extract as much heat as possible from the coolant water, it would need to be installed when a plant is built, he said. Another potential caveat is that a full-scale version of the mechanism would require a football field-sized plot on land, likely to be expensive in coastal areas where power plants are located, Klausner said. Presumably a utility would sell the fresh water it produces, recouping and then profiting from its investment, he said.
Limited quantities of energy and intelligence are the two biggest factors holding down the rate of economic development. Every technology that increases the efficiency of utilization of energy or lowers the cost of energy spurs economic growth. Anything that raises human intelligence levels will do the same. Also, computer technologies effectively increase the efficiency of the use of human intelligence by unburdening many tasks from human minds. So computers are brain utilization efficiency increasers.
While only done in rats so far the therapy may make dental repairs and replacements easier to do.
ANN ARBOR, Mich.---A University of Michigan research team has found that introducing a growth factor protein into a mouth wound using gene therapy helped generate bone around dental implants, according to a new paper in the February issue of the journal Molecular Therapy.
In a patient with a sizeable mouth wound, replacing a tooth takes more than simply implanting a new one---the patient also needs the bone structure to anchor the new tooth in place. Such reconstructive surgery today involves either taking a bone graft from the patient's chin or jaw, which leaves a second wound needing to heal, or using donated bone from a tissue bank, which yields unpredictable results.
William Giannobile, professor of periodontics, prevention and geriatrics, led a team at the U-M School of Dentistry that delivered the gene encoding for bone morphogenetic protein-7 (BMP-7) to large bone defects in rats in an attempt to turn on the body's own bone growth mechanisms. The study showed that animals that got the BMP-7 treatment produced nearly 50 percent more supporting bone around dental implants than those receiving the conventional treatment.
"This study represents a proof-of-concept investigation. We are encouraged about the promise of this treatment," said Giannobile, also an associate professor of biomedical engineering and director of the Michigan Center for Oral Health Research.
More work will need to be done before the approach can be tested in humans, Giannobile added. He said he optimistically would like to see initial trials begin in humans in four to seven years.
One can imagine gene therapy of this sort being used in conjunction with cell therapies being developed to grow new teeth.
Johns Hopkins University scientist Craig Stark and graduate student Yoko Okado have shown using functional magnetic resonance imaging (fMRI) of the brain that the prefrontal lobe is less active when minds are forming inaccurate memories.
Using advanced, non-invasive imaging techniques, Yoko Akado and Craig Stark compared the areas of the brain that were active when a subject was encoding a complex event and afterwards, during exposure to misleading information. For example, subjects were asked to watch a vignette comprised of 50 photographic slides showing a man stealing a woman's wallet, then hiding behind a door. A little later, the subjects were shown what they thought was the same sequence of slides but unbeknownst to them the second set of slides contained a misleading item and differed in small ways from the original--the man hid behind a tree, for example, not a door.
Two days later, the subjects took a memory test, which asked them to recall details such as where the man hid, and which presentation--the first, second, or both--contained that information. Memory for a misinformation item was scored as a false memory only if the subject attributed the item to either the original presentation or to both the original and second slide presentations.
Stark and Akado found clear evidence that the subjects' brain activity predicted if their memories of the theft would be accurate or false. Consistent with findings from numerous previous studies that have reported that areas such as the hippocampus are highly active during memory formation, Okado and Stark found activity in the left hippocampus tail as well as perirhinal cortex was correlated with successful encoding of an item in memory, even when the memory that was formed was for a false item. But in subjects who had formed false memories, it was noticeable that activity in other brain areas such as the prefrontal cortex was weak during exposure to the second sequence of slides compared to during the original viewing.
Okada and Stark suggest that activity in the prefrontal cortex is correlated to encoding the source, or context, of the memory. Thus, weak prefrontal cortex activity during the misinformation phase indicates that the details of the second experience were poorly placed in a learning context, and as a result more easily embedded in the context of the first event, creating false memories.
Are people who take a more critical view of what they see less prone to false memory formation? Is there a type of brain that can be recognized on scans that is less prone to being fooled by misleading images?
The real problem is in how to detect whether a memory is true or false after the fact. Might brain scans studies eventually show that during memory recall false memories show a different pattern of brain activity on average as compared to accurate memories?
The research paper, published in the jourrnal Learning & Memory is available online here and here as PDF and here in HTML. Also, here is an excerpt from the abstract.
Two interaction patterns between encoding phase (Original Event and Misinformation) and type of memory (true and false) were observed in MTL and PFC regions. In the left hippocampus tail and perirhinal cortex, a predictive item-encoding pattern was observed. During the Original Event phase, activity was greater for true than false memories, whereas during the Misinformation phase, activity was greater for false than true memories. In other regions, a pattern suggestive of source encoding was observed, in which activity for false memories was greater during the Original Event phase than the Misinformation phase. Together, these results suggest that encoding processes play a critical role in determining true and false memory outcome in misinformation paradigms.
Fun goods are much preferred as long as they are not compared to more practical goods.
In a study that sheds new light on how consumers choose between pleasurable or practical products, a University of Washington researcher has found that people are more likely to buy fun products, but only if the situation allows them the flexibility to rationalize their purchases.
According to Erica Okada, an assistant professor of marketing at the UW Business School, goods can be broadly categorized into hedonic goods that offer enjoyment and utilitarian goods that offer practical functionality.
For example, she said, in the wide product category of automobiles, sports cars are more hedonic and sport utility vehicles are generally more utilitarian. Between a sports car and an SUV, consumers may find the prospect of buying a sports car more appealing, but in a side by side comparison, consumers are much more likely to buy the SUV to avoid feeling guilty for buying something that is perceived more as a want than a need.
She found that when a hedonic product and a utilitarian one of comparable value are each presented singly for evaluation, the hedonic alternative tends to elicit a higher rating. However, when the two are presented side by side, the utilitarian alternative is more likely to be chosen.
So then is the secret of the growth in popularity of Sports Utility Vehicles the presence of the word Utility in the middle? Makes sense. People can spend a lot of money on a fancy vehicle and defend their choice by saying it is practical. This suggests that marketers need to relabel various products to make them seem more utilitarian. How about Emergency Work Energy Boost Ice Cream marketed to people who need to work long hours to complete projects?
Or how about selling sports cars based on the idea that their low profiles make them more able to handle heavy crosswinds when trying to evacuate an area ahead of a hurricane? Show an animation of SUVs getting blown into a Lousiana Bayou while practical people escape New Orleans in advance of hurricane winds and massive flooding. Maybe sports cars need to be sold with 4 wheel drive and wide tires designed to keep going on icy roads. Or how about a battery hybrid sports car? People could buy it to protect the environment.
People view hedonic (pleasurable) versus practical goods differently in terms of time and money spent to acquire them.
In addition, Okada found that the difference in the need for justification also affects the combination of time, or effort, and money that people choose to expend in order to acquire hedonic versus utilitarian items. Specifically, she said people have a relative preference to pay in time for hedonic goods, and in money for utilitarian goods.
"Consumers are generally willing to pay a premium for convenience, and go the distance for a bargain," she said. "Given a choice between paying in time versus money, individuals are more likely to go the extra mile and find a good deal on the DVD player – that is, pay in time – and more likely to pay a higher price monetarily at a convenient location for the food processor."
Maybe selling hedonic goods with a promise on the part of the seller to donate some percentage of the sale to some charity (say helping kids who have cancer) would give people the opening they need to rationalize the purpose: "I'm doing it for the kids" or "I'm doing it to save the Siberian tigers from extinction". Each type of hedonic good may need a different ideal charity that its sales could be paired up with. Who or what do you need to help to allow you to feel good about buying a sports car? Abandoned children perhaps? Is it best to medical research in order to justify the eating of ice cream? Surely research could provide the answers to these questions all broken out by demographic profiles and hot guilt buttons to cool down. Of course, this all has to be done in ways that do not dampen the pleasure of the purchase.
Something like a sports car could be sold with real life inspiring stories of practical uses of the product: "I was called in to do emergency heart surgery at this rural hospital in the middle of the night and I was the only one in 250 miles who could do it. If I hadn't sacrificed my plans for a fourth vacation home to buy the Lamborghini there is just no way I could have driven 150 miles an hour to make it to the hospital in time so save the heart and life of that mother of 4 children who had been severely injured in a car accident. Those kids have their mom to take care of them thanks to my Lamborghini. I can't possibly give it up."