Why Did Swine Flu Kill Healthy Adults?

One of the most intriguing questions about the swine flu epidemic last year was why most of the deaths occurred in healthy young adults. Why were the very young and the very old generally spared?

A recent paper in Nature Medicine provides a clue, according to a news article in Science magazine. The gist of it is that the immune system of most adults is not very effective against first exposure to the H1N1-type virus. Unable to kill the virus initially with just a normal first immune response, the immune system in some patients mounted an all-out “do or die” effort to kill the virus. The result was a severe inflammatory reaction in the lungs that ultimately killed the patient instead of the viral infection.

The theory of a hyperactive but ineffective immune system would explain why the very young and the very old were spared by swine flu. The very young do not have a fully developed immune system with which to mount even a normal immune response, much less an exaggerated one. And many older persons may have had at least some effective antibodies against H1N1 by virtue of having been exposed to the previous H1N1 strain that was around until the late 1950’s.

Does Aspirin Reduce the Risk of Cancer?

In addition to its known blood anticoagulant properties, aspirin might also help prevent cancer, according to an article published in the Jan. 1, 2011 issue of The Lancet. The authors of the study examined past data from the medical charts of over 25,000 patients in eight different studies who were taking aspirin to reduce their risk of a cardiovascular event. They found that daily doses of at least 75 mg of aspirin for at least five years reduced the overall death rate due to cancer by an astonishing 21%.

So should we all start popping aspirin? Not necessarily, says the Deputy Chief Medical Officer for the national office of the American Cancer Society in his blog post of Dec. 6. Although he finds no fault with the reported results as an interesting observation, he points out that the study was a retrospective (in the past) examination of cancer deaths in studies originally designed for other purposes – far better would be a randomized prospective (looking into the future) trial, in which both the risks and benefits of aspirin could be studied together. But such a study would take another 20 years! Who wants to wait that long?

It’s a quandary often faced in medicine – what to do when there’s tantalizing new information that seems to point in a certain direction, but no way to know for sure. No doubt, some of you will be tempted to start taking aspirin as a result of this new study. Before you do, consider carefully that taking aspirin may be a double-edged sword; risks associated with taking aspirin include (in some people) gastrointestinal bleeding and bleeding in the brain. Doctors don't generally recommend aspirin for cancer prevention in healthy persons.

Cellulosic Ethanol? Not Any Time Soon

Old conventional wisdom: ethanol made from farm and forest organic wastes (cellulosic ethanol) would soon be powering our cars and trucks. New conventional wisdom: cellulosic ethanol is dead, at least for now.

Not five years ago the government was pouring money and tax credits into various cellulosic biofuels projects. Although there were technical hurdles still to be overcome in extracting ethanol efficiently from cellulose and lignin (the primary energy storage molecules in most plants), there was optimism that the problems would be solved in short order. Today, plans for large-scale demonstration plants have been shelved, venture capital has dried up, and the industry is producing just 10% of the production goal once set by the Environmental Protection Agency. What happened?!

Lots of things happened, it turns out. Ethanol production from corn (technically easier) increased four-fold and is at an all-time high. Oil got cheaper again, technical problems in producing ethanol from cellulosic feedstocks have not yet been overcome, and investors are worried that government support (i.e., subsidies) for the developing cellulosic biofuels industry may dry up. Unless something changes, don’t expect to hear much about cellulosic biofuels for a while.

Dinosaur Proteins Found in Fossils

Paleontologists have generally assumed that the only useful information that could be obtained from ancient fossils was in the sizes and shapes of the organism’s bones. The prevailing view has been that the soft tissues and any organic molecules or cellular structures within the bones themselves would have long since disappeared, leaving behind only fossils comprised of the same minerals found in rocks.

That view is slowly changing. It now appears that under the right conditions of fossilization, organic molecules may still remain in some fossils. So far, researchers have identified molecules that appear to be collagen and even fossilized osteocytes (bone-forming cells) and red blood cells, from the bones of dinosaurs as old as 80 million years.

No one is suggesting that we could ever resurrect dinosaurs from these ancient materials – cloning dinosaurs is still in the realm of science fiction. However if we could identify the precise sequences of certain ancient proteins, we’d have a better understanding of the function of these proteins within the organism. We might also be able to more accurately map out the evolutionary relationships between organisms, both ancient and living.

Reference: Schweitzer, Mary. Blood From Stone. Scientific American Dec. 2010, pp. 62-69.

New Uses for DNA Identification

It’s now possible to synthesize a nearly infinite number of unique DNA sequences. It’s also possible to identify the sequence of even a small sample of DNA quickly and cheaply. Taken together, these two advances are likely to lead to some interesting new uses of DNA technology.

According to an article in The New York Times, in Rotterdam, the Netherlands, police are experimenting with synthetic “DNA sprays” as a way to discourage robberies or to catch robbers of local businesses. When a store is robbed, the store clerk activates a security system that sprays the robber with a fine mist containing a unique synthetic DNA sequence as the robber departs. The system also notifies police that a robbery is in progress. Suspects who are apprehended within a certain time frame can then be tested for that specific DNA sequence.

Another idea: “DNA crayons” - each with a different DNA sequence - to mark valuable items that belong to you. Items suspected of having been stolen could then be tested and returned to their rightful owners. We’ll probably hear about other practical uses of DNA technology in the future. Have YOU got any good ideas?

Obesity and Body Size Misperception

According to a recent report in the Archives of Internal Medicine, about 8% of obese individuals don’t recognize that they need to lose weight. Researchers call the phenomenon “body size misperception”. Obese individuals who misperceive their body size tend to be more satisfied with their overall health and are more likely to believe that they have a low lifetime risk of chronic diseases related to obesity, than are those who acknowledge that they are obese. Two-thirds of them actually believe that they are at low risk of developing obesity in their lifetimes, even though they already ARE obese according to the standard government definition.

But are there other possibilities for these people’s failure to acknowledge their obesity besides body size misperception? Perhaps these individuals do know that they are obese, but because they don’t think they can lose weight or don’t want to try, they are unwilling to acknowledge it even on a survey. It’s called denial. Or perhaps they just don’t accept the current definition of obesity (a Body Mass Index of 30 or above) and/or its health consequences.

How people perceive obesity and its consequences need to be explored further if we wish stem the rising tide of obesity in the U.S. and around the world.

Why is Global Warming Such a Hot-Button Issue?

Why can’t we hold a civilized conversation about global warming any more without the feeling that everyone’s minds are already made up? Some people argue that global warming is an established fact, and that human activities (most notably the burning of fossil fuels) are responsible. Others insist that the evidence in support of global warming is either not convincing, deliberately misleading, or even just plain false. It’s getting to be almost as bad as talking about abortion. How did it come to this?

One science writer suggests that part of the problem lies with a failure of climate scientists to communicate the meaning of scientific uncertainty adequately to the public. Predicting climate change far into the future IS an inexact science at the moment, but that does not mean that the climate isn’t changing. Not knowing everything is not the same as knowing nothing. I’m reminded of the common anti-evolutionist argument that evolution can’t be true because (gasp) “there are GAPS in the fossil record!”

In addition, scientists may sometimes come across as having a “we know best” attitude toward dissent, rather than a willingness to engage the dissenters in a dialogue. Scientists may need to acknowledge openly that there are things about climate change that they do not know yet. But rather than representing a failure of the scientific method, these uncertainties represent an opportunity to develop better methods and testable hypotheses so that in the future we CAN be more certain.

Patenting Human Genes - An Update

In April of this year a U.S. District Court judge issued an order invalidating the patents on several human genes held by a company called Myriad Genetics (see "Human Gene Patents Invalidated.") The company promptly appealed, sending the issue to the next judicial level, the U.S. Court of Appeals.

Last month the U.S. Department of Justice filed a friend-of-the-court brief with the Court of Appeals, supporting the position that human genes should not be patentable. In its brief the Justice Department stated that “The chemical nature of native human genes is a product of nature, and it is no less a product of nature when that structure is ‘isolated’ from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth.” (The defendants in the case had tried to argue that their method of gene isolation had somehow fundamentally changed the genes, making them patentable.) However, in a bit of a compromise, the Justice Department’s brief also suggested that human DNA that is altered in some way (i.e. is not the original human gene sequence) could still be patented.

The U.S. Patent and Trademark Office has been issuing patents for human genes for years, but the legality of the patents has never been challenged in court. The outcome of the court case could affect the commercial use of numerous human genes and gene products. For now, we await the decision of the U.S. Court of Appeals.

Alcohol and Caffeine - a Potent Mix

Last year the Food and Drug Administration sent warning letters to 27 manufacturers of alcoholic beverages containing caffeine (see this blog Nov. 15, 2009), asking the companies to justify the safety of their products. But apparently the agency has not yet followed through with its promises to review the safety information requested from the companies and then to take appropriate action if it was not forthcoming.

One of the companies selling caffeine-and-alcohol drinks was in the news again last month after students at two universities ended up in emergency rooms with alcohol poisoning. The drinks in question, called Four Loko, contain 23.5 ounces of 12% alcohol laced with caffeine. Allegedly the caffeine overrides the natural sleepiness effect of alcohol, causing the user to underestimate how drunk he/she really is.

The company says that it is being unfairly singled out.

Some college students will abuse alcohol no matter what form it is in. But are packaged caffeine-and-alcohol drinks GRAS (Generally Recognized As Safe) or not? It should be up to the FDA to decide, and so far it hasn’t.

Meanwhile, states and municipalities are taking action. Last Thursday Michigan became the first state to ban alcohol-and-caffeine drinks. The city of Chicago is considering a similar ban.

For more on this subject, go to a previous blog post titled "Caffeinated Alcoholic Beverages Under Scrutiny."

Assessing the Long-Term Risks of Drugs

Here’s a dilemma for you; drugs that prevent or treat chronic diseases and that therefore will probably be taken for the rest of the patient’s life are generally only tested for a only a couple of years (for safety and efficacy) before they are approved. What if the drugs have adverse effects that only become apparent when they have been taken for many years?

This concern has been raised recently by the discovery that two blockbuster drugs do in fact have long-term negative effects not seen in their initial safety studies. The class of drugs known as bisphosphonates (Fosamax, Actonel, and Boniva) widely used to prevent osteoporosis can, on rare occasion, lead to degeneration of the jawbone or to thigh fractures. And a drug called Avandia, often prescribed for diabetics to prevent heart disease, has been shown to increase the risk of heart disease in certain cases.

I'm not saying that FDA approval of these drugs in the first place was a mistake, because in some cases the benefits may still outweigh the risks. Still, it would be nice to know the long-term risks as soon as possible so that patient treatment decisions can be made with full information. The question becomes, then, how to reduce the potential long-term risk without making the drug approval process even longer than it already is. Requiring 30 years of clinical trials before a drug can be approved is clearly impractical.

Once a drug is approved, currently there is no method for effectively tracking the incidence of adverse side effects over time. Some health officials are suggesting that we develop a national drug-use database and require physicians to report all adverse effects, so that long-term effects can be determined as soon as possible. But that raises concerns over confidentiality of patient information.

What do you think?

Drug Safety in the Workplace

Should a company be permitted to fire a worker for taking a drug that is legally prescribed by a physician to treat a medical condition? That’s what happened to a worker on an auto-parts assembly line who was taking hydrocodone for back pain, according to an article in The New York Times.

You might say, “That’s not fair!”, but it’s not that simple. After all, companies have a responsibility to maintain a safe work environment. Companies can be held responsible for accidents on the job and for product defects caused by impaired workers. And in “safety-sensitive” jobs, such as airline pilot, the public has a right to expect that the employee is not impaired.

The question becomes, then, how does society achieve the right balance between the rights of workers and the responsibilities of employers? At present we know very little about just how safe various prescription drugs are in the workplace, because testing for workplace safety is not part of the normal approval process for pharmaceutical drugs.

More and more companies are requiring drug tests of their employees. Employees who test positive are sometimes fired, in part because companies aren’t sure whether or not the drug creates a safety issue and just aren’t willing to take the risk. It’s a societal problem that needs to be addressed by valid scientific research into drug safety in the workplace.

Long Beach Bans Smoking in Public Outdoor Areas

The City Council of Long Beach, California voted unanimously last week to ban smoking in nearly all public outdoor areas, including parks, hiking trials, and biking paths. Supporters of the ban argued that the ban was necessary to protect children’s health.

The ban exempts public golf courses because of a potential loss of income to Long Beach (and because not many children golf). It also makes exceptions for special events like filming. Does anybody else see the double standard being applied here - that smoking is banned in public places in Long Beach unless it’s in Long Beach’s financial best interests to allow it?

Disclaimer: I’m not a smoker. I am convinced that the evidence is pretty solid that smoking is harmful for the smoker, and I wish that smokers would see the wisdom of quitting for their own good. But let’s be clear about one thing; banning smoking in public places outdoors is not likely to improve children’s health. There is no scientific evidence to support the notion that a brief whiff of smoke causes any damage to children or to adults. A better way to improve children’s health would be to encourage them to exercise more, even if they occasionally smelled a whiff of smoke while doing it.

If we’re going to ban smoking in public places, let’s at least be honest with smokers about why we’re doing it.

Canada Declares BPA Plastic to be Toxic

Canada recently declared a plastic called BPA (bisphenol A) to be a toxic substance. BPA is commonly used in the manufacture of refillable polycarbonate water bottles and in the linings of metal food and beverage cans.

BPA falls into a category of substances known as endocrine disruptors. As a group, endocrine disruptors either mimic or block the action of hormones, thereby disrupting the body’s functions. In laboratory animals, high concentrations of BPA have been shown to mimic the female hormone estrogen. Several studies reported by The Endocrine Society, a well-known scientific group, suggest that endocrine disruptors such as BPA may have adverse health affects that include infertility and cancer.

Canada and about half a dozen states in the U.S. have already banned the use of BPA in children’s products. Canada’s recent action paves the way for future bans on the use of BPA in food and beverage containers for adults as well, and for increased control over manufacturing processes involving BPA.

So far the U.S. government has taken no action, saying there is not enough evidence that the substance harms humans. But research is underway, and time will tell.

HPV Vaccination Rates in College Women

It’s been more than three years since the FDA approved Gardasil, the vaccine against the sexually transmitted Human Papilloma Virus (HPV) that is responsible for most cases of cervical cancer. How is the vaccine being accepted by young college-age women?

To find out, researchers conducted a survey of 972 female college students at a large Midwestern state university. Most of the women were freshmen or sophomores. Sixty-five % of the women reported being sexually active, and by the Spring of 2009 57% had already received at least the first of the three shots required by the vaccination protocol for Gardasil. (The vaccine was available on request at the university student health center, at a cost of $360).

Vaccination coverage of 57% in this age group within three years of vaccine availability is welcome news, considering that these college-age women were already 15 or 16 years old when the vaccine first became available. Current recommendations are that girls should be vaccinated as early as 11-12 years of age. Significantly, young women who believed that their mothers would approve of their receiving the vaccine were more likely to have been vaccinated or to have an interest in being vaccinated.

More than a third of the women reported having had three or more sexual partners, and over 25% had had vaginal sex with a casual partner (not a serious or steady dating partner) without using protection against sexually transmitted diseases. All the more reason they should be vaccinated…

Cell Phones Can't Cause Cancer?

One of the limitations of the scientific method is that it is virtually impossible to prove that something doesn’t exist or could never happen based on empirical data alone. And if that “something” has the potential for great harm, then common sense would dictate that we should err on the side of caution and continue to assume that it could exist, or might happen. It’s known as the precautionary principle.

Take cell phones and cancer, for example. Despite tens of millions of dollars spent on research, no one has ever proven that mobile phones cause brain cancer. And yet, researchers (and the public) are still unwilling to conclude that they don’t. Even the authors of a major study that once again showed no relationship between cell phones and cancer concluded: “The possible effects of long-term heavy use of mobile phones require further investigation”. Of course, that might mean more funding for their laboratory….

Physicist Bernard Leikind has taken an entirely different approach. He claims that, based on well-accepted physical principles, cell phones cannot cause cancer. He argues that the energy emitted by cell phones is not strong enough to disrupt the chemical bonds in biological molecules, period. Indeed, he claims that if it were possible for radiation energy of this type to disrupt cellular biochemical processes, there would be no life on earth because of natural sources of similar radiation energy in the environment.

Dr. Leikind has taken a lot of heat (no pun intended) from readers – see the reader-response thread after the article. But I have yet to find the flaw in his logic.

Popular Joint Pain Supplements Don't Work

The popular joint-pain supplements glucosamine and chondroitin are ineffective in reducing knee or hip pain due to osteoarthritis, according to a recent report in the British Medical Journal. The latest meta-analysis reviewed 10 previous large, randomized, controlled studies. The authors conclude that the two supplements have no effect on either patient perception of joint pain or minimum width of joint space (a clinical measure of improvement) when compared to a placebo.

Glucosamine and chondroitin are among the most popular over-the-counter supplements, with annual sales of nearly $2 billion per year. Some people swear by the two supplements because they genuinely do feel better when taking them, and I sincerely believe they’re telling the truth. But the improvements could be due to the well-known placebo effect, or to the fact that in some patients, joint pain declines over time due to natural healing processes. Anecdotal evidence can’t be generalized to a larger population.

The authors of the study see no harm in patients continuing to take the supplements if it makes them feel better. They say that neither supplement does any harm (except to lighten your wallet a little).

Texting and Fatal Driving Accidents

Text messages sent per month from hand-held phones increased more than 15-fold from 2002 to 2008. Over the same years the percentage of fatalities in which distracted driving was listed as a possible contributing factor increased from about 12% to nearly 16%.

Based on these data, the authors of a recent report speculate that texting while driving may have contributed to 16,000 additional driving fatalities between 2001 and 2007. The claim was reported in the Los Angeles Times and other papers, but is it true?

There are several problems with this report. First, the authors defined a fatality as caused by driver distraction whenever a distraction was merely listed as present. Other factors such as equipment failure, alcohol, or driver age were not considered. Second, distractions are anything that takes the driver’s attention away from driving, including texting or talking on a hand-held phone, reading an on-board navigation system (also increasingly popular these days), reaching for something, eating, drinking, putting on makeup, etc. Searching for street signs or rubbernecking another accident are also distractions. None of these were factored out in this study.

All the report really shows is that text-messaging volumes (in and out of cars) and the number of fatal accidents due to all distractions are both going up. The authors call it a correlation, but so what? A correlation does not prove causation. I’m reminded of the example presented by my thesis advisor years ago of the tight correlation between the rise in the number of telephones in the U.S. and the decline in the incidence of tuberculosis. Do telephones prevent tuberculosis? Hardly.

Is texting while driving a problem? Probably yes. Does this paper convince me that texting while driving has caused 16,000 additional fatalities? Sadly, no.

Thimerosal, Vaccines, and Autism

The tenth scientific study showing that autism spectrum disorders in children are not linked to thimerosal, a mercury-containing preservative once used in vaccines, has just been published in the journal of the American Academy of Pediatrics, adding one more to the nine others already published. In addition, the initial report that there is a link have been largely discredited. According to an article in the LA Times earlier this year, the doctor who first alleged that there was a link between autism and thimerosal has been rebuked by the British General Medical Council for the way his research was conducted, and the journal in which published his work declared that it should not have published the report.

And yet, one in four parents still persist in believing that vaccinations increase the likelihood of a child developing autism. Is there anything that could convince them otherwise?

Perhaps not. Resistance based on emotion (fear), may not be able to be overcome by scientific evidence, no matter how clear and convincing the evidence is. It’s too bad, really. It would be a shame if diseases like measles, mumps, or even polio made a comeback because not enough children had been vaccinated against them.

Testing Athletes for Gene Doping

Ever since winning athletic competitions has meant a lot of money, athletes have tried to increase their odds of winning by using performance-enhancing drugs. And for just as long, sports associations have tried to catch the athletes who cheat. In most cases the athletes have stayed one jump ahead by using newer-generation harder-to-detect “designer” drugs as soon as sports associations developed tests to detect the older-generation ones.

Sports associations and many athletes thought that the next level of sophistication in athletic performance enhancement through artificial means (i.e., cheating) was going to be “gene doping” – using genetic engineering techniques to introduce foreign genes into the body that would cause the body to produce performance-enhancing hormones naturally. But the athletes may have lost the detection battle before it even began. Scientists in Germany have already developed a test that they say can conclusively prove with 100% certainty that gene doping has occurred, using a blood sample as small as 200ul. The test looks for the presence of the foreign gene itself, not the protein or hormone product produced by the gene.

It’ll take about two more years for independent laboratories to validate the test, and so it may not be ready by the 2012 Olympics. But even if it’s not, blood samples could be stored and tested later.

Score one for the sports authorities, for once.

Biodiesel Fuel from Sunlight and CO2

From time to time I like to highlight innovations that have the potential to be real game-changers; good ideas still in the development stage that could alter our lives significantly within our lifetimes. So here’s one; a tiny start-up company called Joule Unlimited announced last week that it had received a patent on a bacterium that has been genetically engineered to produce diesel fuel using only sunlight, water and CO2. It’s similar to how plants produce hydrocarbons, but in this instance the hydrocarbon is diesel fuel, not a sugar or a starch.

The company expects that the process could be scaled up to produce 15,000 gallons of diesel fuel per acre, using water that is unfit for drinking (it could be wastewater or brackish water) and land that is unsuitable for farming. The process is not yet efficient enough to use the very limited amount of CO2 available in air (air is only 0.04% CO2), but it has been shown to work using the kinds of CO2 concentrations found in the effluent of coal-fired energy facilities. The company expects to begin production at a pilot plant in Texas by 2012.

Imagine a future in which the very CO2 that we’re trying so hard to get rid of these days (because it’s a greenhouse gas) becomes an asset – the raw material for creating diesel fuel. That would make CO2 an endlessly renewable energy source and solve most of the global warming problem at the same time.

With a few more good ideas like this, maybe there’s hope for our planet (smile).

Electronic Cigarette Manufacturers Warned

The Food and Drug Administration (FDA) sent letters last week to five manufacturers of electronic cigarettes (e-cigs), warning the companies that they were making unsubstantiated medical claims about their products, including the claim that the products were an aid to stopping smoking – a medical claim prohibited by the Federal Food, Drug, and Cosmetic Act. The FDA also signaled its intent to regulate e-sigs as a drugs or drug-delivery devices.

An “e-cig” (since you forgot to ask) is a battery-powered cigarette-shaped device that can be loaded with a cartridge of nicotine and other additives. When the user inhales through the device, the battery vaporizes the liquid so that it can be inhaled into the lungs. The product contains no tobacco. A wisp of “smoke” appears, but it’s just water vapor.

Several of the e-cig products contain herbal ingredients in addition to nicotine. One of the e-cig companies even sells other drugs in liquid form for use in the devices, including an erectile dysfunction drug (tadalafil) and a weight-loss drug not approved in the U.S. (rimonabant).

The names of the companies and copies of the FDA’s letters to them can be found on the FDA web site in a press announcement dated Sept. 9th. Whether this is the end of e-cigs isn’t clear.

Stem Cell Research Continues (Temporarily)

In the long-standing battle between opponents and proponents of research involving stem cells derived from human embryos, last month a U.S. District judge issued a temporary injunction against the use of federal funds for such research (see this blog, Sept. 1). The injunction not only halted funding for future research projects that would have used stem cells derived from embryos, but also threw the funding for all current research projects into doubt. Researchers wondered whether their experimental animals would have to be euthanatized and their laboratory workers laid off.

To prevent that from happening, last week the U.S. Court of Appeals (the next step up the judicial ladder) issued a temporary injunction against the lower court’s ruling. The injunction will allow the National Institutes of Health to continue funding stem cell research temporarily, until an appeal is heard by the higher court. It also gives Congress time to act to change the law, but of course that depends on whether proponents of stem cell research can muster the votes to do so.

So now it’s in the hands of the U.S. Court of Appeals and Congress. Researchers, patient advocacy groups, and opponents of embryonic stem cell research will be watching closely. It’s time to lobby your congressman, if you have an opinion.

Pre-run Stretching Doesn't Prevent Injuries

I reported last year on this blog that the U.S.A. Track & Field association (USATF) was recruiting runners for a study to try to determine whether pre-run stretching prevents running injuries (see "Stretching and Sports Injuries"). Coaches and trainers often recommend stretching before exercise, but whether it’s helpful, harmful, or neutral has remained essentially an untested hypothesis.

To test the hypothesis that pre-run stretching reduces the incidence of injuries to runners, the USATF recruited 2,729 runners, defined as persons who ran over 10 miles a week. Each runner was randomly assigned to either a “stretch” or a “no-stretch” group. “No-stretch” runners were instructed not to stretch before running even if they had been in the habit of doing so before. “Stretch” runners were instructed to follow a specific stretch routine before running. All runners were instructed to continue their normal running routine for three months and to report any injuries that caused them to stop running for at least three days.

The results of the study were released last month. Just over half of the runners complied with their assigned group protocol and successfully completed the three months of the study. The results - injury rates were precisely 16% in both groups. In other words, pre-run stretching had no effect on injury rates.

One intriguing finding was that runners who normally stretched before running but were assigned to the “no-stretch” group had a higher injury rate than those who normally didn’t stretch and were in the same group. One hypothesis is that just changing their routine (stopping stretching) may have been enough to predispose them to injury.

So if you’ve always stretched before you run and like doing it, by all means keep doing it. But if you haven’t been in the habit of stretching before running, don’t feel that you have to start.

Vaginal Gel is Effective Against HIV

Finally, there’s an HIV prevention method that’s controlled by women. This is especially important for women who are not in a mutually monogamous relationship and who cannot convince their men to use a condom. (In Africa, over 60% of HIV-infected persons are women who contracted the disease via heterosexual sex.)

In a study published last week in Science, nearly 900 sexually active women in a high-risk area in South Africa were supplied with either a vaginal gel containing the antiviral drug tenofovir, or just the gel alone as a control, over a thirty-month period. Women who received the drug were 39% less likely to become infected with HIV, compared to women in the control group.

Why wasn’t the treatment 100% effective? Part of the reason may be that some study participants may not have used the gel properly and consistently. Among women who used the gel as advised (both before and after sex) more than 80% of the time, the reduction in HIV infections was 54%. When the gel was used less than half the time the reduction in infections was only 28%. No one should be surprised; after all condoms, too, only work if you use them!

AIDS researchers are cheering. Although prevention wasn’t perfect, they’ve proved that pre-exposure prophylaxis controlled by women is at least partially effective. The next step will be to find more potent drugs or a more effective delivery method – perhaps a vaginal ring that releases the drug over longer periods of time.

By the way, would you like to know how the researchers monitored compliance to the study protocol (participant’s actual use of the gels)? They counted the used gel applicators returned by the women in the study and compared that number to the 181,340 gel applicators they gave out. Obviously the researchers suspected in advance that compliance might be a problem. You have to admire the researchers’ advance planning and their willingness to do what was necessary to improve the validity of their results.

Injunction Against Human Stem Cell Research

In March of 2009 President Obama issued an executive order permitting the use of federal funds for research on stem cells lines derived previously from human embryos, arguing that the researchers had not destroyed the embryos themselves. The Obama executive order effectively overturned the ban of the Bush administration on the use of human embryonic stem cells for research. At the time, I reported in this blog that the Obama order might still face a legal challenge, based on a federal law called the Dickey-Wicker Amendment of 1999.

Last week it finally happened. As the result of a lawsuit filed by several Christian groups and two doctors opposed to human stem cell research, a U.S. District Court judge issued an injunction which blocks the National Institutes of Health (NIH) from implementing the Obama order. The judge argued that the Obama executive order clearly violates the language of the Dickey-Wicker Amendment, and even some supporters of the Omama order grudgingly agree. According to Harvard ethicist Louis Guenin, allowing research on cell lines merely derived from human embryonic stem cells would be like allowing research on dead bald eagles. It’s illegal to kill bald eagles, and therefore anyone doing research on bald eagles killed by someone else would be considered complicit in the crime.

If research on stem cells derived from human embryos is to continue, it appears that Congress will have to overturn the Dickey-Wicker Amendment. Whether there are sufficient votes in both houses of Congress to do so is anybody’s guess. In the meantime, funding for future projects is on hold. And while NIH’s interpretation is that currently-funded research projects can continue for now, not everyone seems to agree. We’ll have to see how this one shakes out. For starters, I’m sure we can expect the ruling to be appealed.

The Benefits of Human Breast Milk

Colonization of the human infants’ gastrointestinal tract by bacteria occurs only after birth. It is known that human breast milk encourages colonization of the newborn’s gut by beneficial bacteria and discourages colonization by harmful ones, but how exactly does it do that? An article in the Proceedings of the National Academy of Sciences provides a tantalizing glimpse into the likely mechanisms.

About 4-12% of the macronutrient composition of human milk consists of a structurally diverse group of complex sugars called oligosaccharides. These oligosaccharides are indigestible by the infant, and so for many years scientists thought they had no function. It turns out that they are digestible by a particular group of beneficial bacteria called bifidobacteria. The presence of these oligosaccharides in human milk gives the bifidobacteria a nutritional advantage over less desirable bacteria in the human infant’s gut. In other words, these oligosaccharides are produced in human milk specifically to provide nutrients to beneficial bacteria, rather than to nourish the infant.

Some of these oligosaccharides have another interesting property; they bind to certain harmful bacteria, thus preventing them from attaching to the epithelial cells lining the gut. Researchers think that these oligosaccharides may flush out harmful bacteria during that very vulnerable time in early life when the infant’s immune system has not yet developed fully.

Oral Immunotherapy for Food Allergies

Some people have food allergies so severe that even the slightest contact with the food can lead to a life-threatening allergic response. A rare but potentially fatal allergic response to peanuts, for example, is why most airlines no longer serve peanuts on their flights. Other sufferers are equally allergic to milk or to eggs, commonly used as ingredients in many food products and recipes. Is there anything that can be done for people with life-threatening food allergies aside from having them try to avoid the food?

Current research efforts are focused on oral immunotherapy (OIT). OIT consists of exposing the patient to miniscule quantities of the allergen in a supervised research setting (under close medical supervision), and then if an allergic reaction fails to occur or remains mild, slowly increasing the dose over days or months to “desensitize” the patient.

Researchers caution that the technique is not yet ready for widespread clinical use, however. The risk of an adverse reaction to the first dose is fairly high, and little is known about the safety of OIT when done at home under a variety of conditions. In addition, it is not known how long desensitization lasts if/when regular desensitizing dosing is ended. There is a danger that desensitized patients might develop a false sense of security once they become partially desensitized or quit their therapy altogether.

Nevertheless, OIT might become a useful therapy for severe food allergies in the future, once we better understand how to perform it safely. For sufferers of truly severe food allergies, the risks associated with desensitization would have to be balanced against the risk of accidental exposure to the allergen and perhaps even death.

Kidney Disease and African Sleeping Sickness

Natural selection can actually favor an otherwise harmful allele of a gene, if that allele somehow confers a survival advantage in some individuals and populations. The one textbook example of this phenomenon has always been sickle cell disease, a genetically inherited disease that results in deformed red blood cells and can lead to early death. Sickle cell disease is prevalent in persons of African ancestry because the allele that causes sickle cell disease also protects the person with that allele from malaria, a disease which is widespread in Africa.

Now there’s a second example of this phenomenon. Researchers have found that two different alleles for a gene involved in the production of a blood protein; a) are associated with a rare inherited kidney disease, and b) protect against the parasite that causes African sleeping sickness. Not surprisingly, the two abnormal alleles and the kidney diseases they cause are four to five times more common in African Americans than in persons of European descent.

Researchers are wondering how many other genetic diseases we’ll find that also confer protective advantages against certain infectious diseases. Researchers are also hoping to develop new treatments for African sleeping sickness that are based on the proteins these abnormal alleles produce.

Maximum Heart Rate for Women

Many serious exercisers pay close attention to their heart rates while exercising. That’s because they generally are advised to keep their heart rates within 65-85% of their maximum heart rate for a safe but relatively strenuous workout designed to improve aerobic capacity and endurance.

According to a formula for maximum heart rate that is now 40 years old (it was developed in the 1970s), your maximum heart rate should be around 220 beats per minute (bpm) minus your age. The formula is a population average, of course, and shouldn’t be taken as an absolute number for each individual. More importantly, the old formula was based solely on men subjects. Now a new study of over 5,000 healthy women indicates that a better population-based formula for women is:

Maximum Heart Rate for Women = 206 – (0.88 x age)

Admittedly the new formula has the disadvantage that it can’t be calculated in your head, but it’s easy enough to do with a calculator. And the difference may be significant: By the old formula, a 40-year-old’s 65-85% target range would have been 117-153 bpm. By the new formula, the target range for a 40-yr-old woman would be 111-145 bpm. Six to eight beats per minute might not sound like much, but over an hour’s workout it could make the difference between pushing yourself too far and getting discouraged, and just getting a good healthy workout.

The new study focused only on women subjects. Perhaps someone ought to confirm or revise the old formula for men, too!

Rapid Eye Movement (REM) Sleep

Humans go through several stages of sleep during a typical night. One of them is the period during which we have complex dreams, called rapid eye movement (REM) sleep. During REM sleep our eyes move about rapidly beneath closed eyelids, even though our bodies typically remain completely motionless.

The explanation for rapid eye movement during REM sleep has always remained somewhat of a mystery - until now. In the June issue of Brain, researchers report that the most likely explanation is that our eyes are trying to follow the action in our dreams. They came to this conclusion after studying the direction of eye movements in a group of subjects who have a particular sleep disorder in which they physically act out their dreams while sleeping. The patients’ eye movements tracked their physical actions with a consistency of nearly 90%. The eye movements in these patients were no different than in normal subjects who did not move physically during sleep, leading the authors to suggest that the “follow-the-dream-action” explanation for REM activity may hold for normal subjects as well.

Dietary Supplements Deceptive Sales Practices

Dietary supplements are regulated as food products, not as drugs. Manufacturers are free to make vague claims of effectiveness, such as “improves heart health” or “boosts brain function”, but they cannot make medical claims such as “lowers high blood pressure” or “prevents Alzheimer’s”. And although their products are supposed to be safe, they’re not required to submit any data to prove it.

Now a Senate document reveals that even though the products may be labelled correctly, in sales conversations (“off-label”, so to speak) retail sales representatives of dietary supplements products are openly engaging in “deceptive and questionable sales tactics” – in other words, they’re lying to make a sale.

In testimony before a U.S. Senate committee, the General Accounting Office (GAO) reported that it had staff members ask questions of sales representatives such as: Is ginkgo biloba safe to take with aspirin? Can ginseng cure cancer? Is it okay to replace my blood pressure medication with garlic supplements? All too often they got “yes” answers when the correct answers are “no”. These answers are not just harmless sales advice – they are potentially dangerous advice and they are against the law. Action may be taken against some sellers as a result of the investigation. But for all practical purposes, it’s still “buyer beware” when it comes to the safety and efficacy of dietary supplements.

You can hear clips of some of the undercover calls at http://www.gao.gov/products/GAO-10-662T.

First Human Stem Cell Therapy Trial

The first clinical trial of a therapy based on human stem cells has received final approval from the Food and Drug Administration (FDA) and will get underway shortly, according to a press release from Geron Corporation, the company sponsoring the research. During the first phase of the trial, researchers will inject precursor cells to neural support cells called oligodendrocytes into the spinal cords of patients who have suffered recent spinal cord injuries and who have almost no chance of recovery of function otherwise. The hope is that the precursor cells will differentiate into mature oligodendrocytes (the cells that produce myelin) and that the myelin will form new sheaths around damaged nerves.

The trial was planned several years ago but held up by the FDA over concerns that the therapy could increase the risk of tumors forming in the spinal cord if the injected cells were not free of embryonic stem cells. The first phase of the trial is designed to test the safety of the procedure. It will be years before the technique becomes widely available for the repair of spinal cord injuries, even if it does eventually prove to be both safe and effective.

Stem cell researchers will be holding their breath. A failure in this first approved trial could set back the whole field of stem cell therapy research for years.

Familial DNA Searches

DNA testing is a modern way to positively match DNA left at a crime scene to a suspect. But what if police have DNA from a crime scene but no suspect? Most states have DNA banks only of convicted felons already in prison, so a criminal with no prior record would almost certainly go undetected.

One method being used in California is to look for partial matches between DNA from a crime scene and the state’s database of DNA from convicted criminals. A partial match, while not implicating the criminal himself, would suggest that a close relative might have carried out the crime. California used the method this month to identify a person previously convicted on a weapons charge as “probably related” to a long-sought-after Los Angeles serial killer known as the Grim Sleeper. The person’s father eventually was arrested and charged with ten murders.

This is new ethical ground for us all. As a society we need to understand the costs vs. benefits of these types of searches. The benefits are obvious – another killer identified. But the costs will be freedom lost – the freedom, for example, not to be put under suspicion and investigated for a crime unless there is reason to suspect you of an offense. Suspicion of relatives based on partial DNA matches is likely to fall disproportionately on African Americans, since they already represent a disproportionate fraction of the prison population.

Because of these concerns, California wisely put some safeguards in place for familial DNA searches. Currently, such searches require that all other investigative leads have been exhausted, that the crime is murder or rape, and that the criminal is still committing crimes – i.e. is still a threat to society. Other states considering familial DNA searches should consider similar safeguards.

Cotton Pests Infest GM Cotton

It was bound to happen, given enough time. In western India, a species of cotton bollworm has now developed the ability to infest genetically modified (GM) cotton that was specifically engineered to resist bollworm infestation.

GM cotton has become increasingly popular with farmers – so popular that approximately 50% of all cotton planted worldwide is now GM cotton. The largest users (and cotton growers) are China, India, and the United States, in that order. With so much GM cotton being planted, we could have anticipated that the cotton pests would adapt eventually. But it’s surprising how quickly it happened – bollworm-resistant cotton was only first planted in India in 2002.

Realistically, we can expect the current generation of GM crops to remain useful for several more decades. In the meantime I’m sure that researchers at Monsanto will be working on new ways to thwart the pests, just as the pests will be slowly adapting. It’s just part of the ongoing battle between species for survival.

A New (Extinct) Human Ancestor

Scientists have discovered two partial skeletons of a new species of the genus Australopithecus near Johannesburg, South Africa, which they named Australopithecus sediba. The new australopithecines, nearly 1.95 million years old, appear to be closely related to both A. Afarensis and A. africanus.

Of course, paleoanthropologists are already debating where to place A. sediba in the human family tree; direct human ancestor, or evolutionary dead end? Regardless of the outcome, the new find is significant in that it fills some gaps in our understanding of evolutionary processes leading to humans. For instance, it appears that changes in the shape of the pelvis occurred before brain enlargement, and that the legs underwent adaptive changes for upright walking before the arms took on smaller, more human-like proportions.

Using Bacteria to Fight Bacteria

A recent article in the New York Times is a good primer on the astonishing variety of bacteria that colonize our bodies, and what they may be doing there. It turns out that our individual microbiomes (all of the microbes in a defined environment within our bodies) are quite different. And at any one time, each of us probably has only about 20% of the species of bacteria that can inhabit the human body.

An interesting new idea is that the “good” bacteria in certain people’s microbiomes might actually be used to treat certain diseases. Doctors have actually cured several stubborn cases of severe diarrhea caused by a particularly difficult bacterium to treat (Clostridium difficile) by transplanting human fecal matter from a healthy person into the patients’ colons! Granted, having a fecal transplant in order to cure disease sounds a bit strange. But apparently the “good” bacteria in the fecal transplant outcompete the C. difficile and wipe them out.

Someday maybe there’ll be ointments or pills containing especially “good” bacteria for treating certain antibiotic-resistant infections such as flesh-eating Staphylococcus aureus or diarrhea-causing C. difficile. Using bacteria to kill bacteria – like using fire to fight fire.

Reference: Zimmer, C., How Microbes Defend and Define Us. New York Times, July 13, 2010.

Heritable, Non-Genetic Behavioral Patterns

Why do abused children grow up to be abusive parents? Why do people raised in lower socio-economic environments tend to have more long-term health problems? Why is it so hard for drug addicts to kick their habit?

For possible answers, behavioral neuroscientists are turning to a hot new field called behavioral epigenetics. Behavioral epigenetics is the study of inherited changes in behavior or gene expression that are caused by factors other than changes in DNA, i.e., that are epi- (Greek: over, above) genetics.

According to epigenetics theory, environmental factors such as the degree of nurturing (or lack of it) by one’s parents early in life can alter the chemical structure of DNA (specifically, the degree of methylation of DNA and its associated histones). This in turn affects how and when certain genes are turned on and off. In theory, such chemical alterations in DNA could last for multiple generations (i.e., be heritable) even though the nucleotide sequence of the genes themselves hasn’t changed.

So far, there’s very little evidence to suggest that epigenetic mechanisms influence human behavior, mostly because human brain tissue is not readily available for research. However, laboratory studies show that rats raised by less-nurturing mothers tend to be more prone to stress as adults and to exhibit increased methylation of certain genes. It’s worth keeping an eye on this developing field to see where it leads.

It's Official: She Can Compete

It took more than 10 months for a committee of the IAAF, international track and field’s governing body, to decide that Caster Semenya could compete in track and field events as a woman. As you may recall, Ms. Semenya’s gender was called into question after she completely dominated the 800-meter event in the world championships last August in Berlin (see this blog, Sept. 7, 2009.) A statement released yesterday by the IAFF on their Web site (www.IAAF.org) reads in full:

Caster Semenya May Compete. “The process initiated in 2009 in the case of Caster Semenya (RSA) has been completed. The IAFF accepts the panel of medical experts that she can compete with immediate effect. Please note that the medical details of the case remain confidential and the IAAF will make no further comment on the matter.” (IAFF statement)

Remember the old “Where’s the beef?” commercials for Wendy’s chain of restaurants? One might ask, “Where’s the proof?” Out of fairness to all athletes in sports, sports governing bodies should develop understandable policies, guidelines, or criteria for gender assignment in sports. But it won’t be easy (gender IS ambiguous, sometimes), so I’m betting the IAAF won’t even attempt it.

The Wendy’s commercial ended with the remark, “(I don’t think there’s anybody back there…)” IAAF, are you listening?

Studying Human Behavior

What drives human behavior? In a provocative paper published online in Behavioral and Brain Sciences last week, it is argued that much of what we believe we know about human behavior is skewed by the fact that most psychological studies are performed on WIERDs – subjects from Western, Educated, Industrialized, Rich, Democratic societies. Indeed, most human subjects used in psychological studies are from the United States, according to an article published several years ago in American Psychologist by Jeffrey Arnett. And most of the subjects are psychology undergraduate students – hardly representative of the world’s cultures as a whole.

How might this affect the results? Take for example, perception of self. Textbooks generally describe people has having a tendency to rate their own abilities as above average and to be motivated to maintain a positive image of themselves. But this may not necessarily be true for non-WEIRD cultures, who may place more emphasis on family relationships and less on personal choice or ability.

There’s nothing inherently wrong with studying WEIRDs, of course, as long as it is understood that the conclusions may not generalize to all cultures.

Reference: Henrich, Joseph et al. The Weirdest People in the World? Behavioral and Brain Sciences 33 pp. 61-83.

Lucy's Older Brother

Remember “Lucy”, the first nearly complete skeleton of Australopithecus afarensis, an extinct species of early human ancestor? Well, now partial remains of her older “big brother” have been found, though technically he’s not her brother because he lived nearly half a million years earlier. But at 5 – 5 ½ feet tall he is big by early human ancestor standards. Kadanuumuu, or “big man”, as he was nicknamed, had a rib cage and shoulder blade (scapula) more like a modern human than a chimpanzee. In addition, his legs were long compared to his arms, another feature that is more humanlike than apelike.

This second Australopithecus afarensis partial skeleton strengthens the hypothesis that although early human ancestors were not entirely humanlike, they also did not resemble modern apes or chimpanzees.

Details were published online on June 21 in the Proceedings of the National Academy of Science, ahead of the print version.

China's Future Water Shortage

China is depleting its underground water reserves in an effort to increase its agricultural productivity, according to a news article in Science magazine. Hundreds of thousands of wells were drilled in the North China Plain over the past 40 years, turning the plain into a fertile corn- and wheat-farming region. But the water table in the North China Plain is now falling at an alarming rate. Many of the wells are expected to run dry within the next couple of decades, putting at risk China’s ability to feed its growing population.

Water in deep underground aquifers exchanges only slowly with surface water. According to experts, some of the water now being drawn out in the North China Plain aquifer has been underground for 30,000 years. It might be that long again before it could be replaced naturally. In other words, water in deep underground aquifers should be thought of as a non-renewable resource, like coal, oil, and gas.

Reducing the Duration of Muscle Cramps

The cause of muscle cramps during extreme exercise is somewhat of a mystery. The usual explanation is that dehydration-induced electrolyte imbalance leads to inappropriate firing of the motor neurons to the muscle. The usual treatment is physical stretching until the cramping stops, followed by rehydration with salts and water to restore fluid and electrolyte balance.

Is there anything that can shorten the duration of a cramp? Apparently there is – pickle juice! A recent study shows that the duration of cramps deliberately induced in a muscle in the big toe is reduced 37% by drinking about 2 ½ tablespoons of pickle juice as soon as the cramp starts. (Cramps were induced in a muscle in the big toe, because deliberately inducing muscle cramps in a larger muscle was thought to be too painful.)

Interestingly, the pickle juice worked within 1 ½ minutes – too fast to be due to replenishment of body fluids or salts. Researchers speculate that the acetic acid in pickle juice triggers a neural reflex originating in the esophagus or stomach, which somehow inhibits the excessive firing rate of motor neurons to the cramping muscle.

Whether pickle juice will reduce the duration of cramps in major muscle groups in athletes remains to be seen.

Teens and the Rhythm Method of Birth Control

According to a recent government survey of teen sex entitled “Teenagers in the United States: Sexual Activity, Contraceptive Use, and Childbearing, National Survey of Family Growth, 2006-2008”, teens aged 15-19 increasingly are relying on the rhythm method for birth control. Among sexually active teens, 17% reported using the rhythm method in 2006-2008, compared to just 11% in 2002.

The rhythm method, also known as periodic abstinence, is moderately effective as a birth control method. Approximately 25% of women who rely on the rhythm method will become pregnant in a year. (Approximately 85% of women who use no birth control method at all will become pregnant in the first year.) However, the rhythm method is much less effective than birth control pills or condoms, which have failure rates of less than 5% per year if used properly.

The new findings coincide with both an increased number of teen pregnancies and an increased acceptance of unwed pregnancy by teens. In the survey, 2/3 of all teens said they agreed or strongly agreed with the statement, “It is OK for an unwed female to have a child”. Sex-education messages to teens may have to change if this trend is to be reversed.

For more on birth control methods, see a previous blog post titled "Birth Control Method Failures."

Do Skin Sutures Need to be Kept Covered and Dry?

I’ve always heard that skin sutures should be covered and kept dry for a couple of days in order to prevent infections – at least that’s the usual standard medical advice. But does getting recent sutures wet really lead to more infections?

To answer that question, a couple of years ago a team of Australian researchers randomly assigned over 850 patients who needed skin sutures into one of two groups. Patients in one group were asked to keep their sutures dry and covered, while the patients in the other group were allowed to remove their bandages and get their sutures wet within the first 48 hours.

The results of the study indicated that there were no differences in the incidences of infection between the two groups. The results indicate that it would be perfectly okay to take a shower without increasing the risk of infection of recent skin sutures. But I wouldn't suggest going swimming in a scummy lake or river....

Improving Rice Yields, Feeding the World

Two groups of scientists working independently have identified a variant of a gene in rice that can increase rice crop yields by 10%, according to a news report in Science. Neither group knew of the other’s work until their work was near completion, but when they learned of each other’s work they agreed to publish simultaneously.

Rice is a staple of a large fraction of the world’s population. Breakthroughs such as this one will help improve crop yields and feed the still-rising world population. They’re made possible by modern DNA technology and genetic engineering – techniques that allow crop scientists to sequence genomes, identify specific genes with specific actions, and then splice the genes into other plants of interest.

Beating the EPO Blood Doping Test

Synthetic erythropoietin, called EPO, was widely used by endurance athletes in the 1990s to boost red blood cell production and blood oxygen carrying capacity. The use of EPO declined after 2000 when the World Anti-Doping Agency (WADA) developed a test to detect EPO in urine.

But now, WADA believes that athletes could be beating the current EPO urine tests by “microdosing” – injecting very small (micro) doses of EPO at night. EPO is excreted so rapidly into the urine that most of an injected dose will be eliminated from the body within eight hours. Thus, microdosing is likely to go undetected as long as urine samples are not demanded in the middle of the night.

Microdosing works because the effects of the erythropoietin outlast the hormone itself. Researchers now know that even such small, intermittent doses of EPO will boost the body’s production of red blood cells significantly over time. They aren’t publishing their dosage information to avoid providing a recipe for blood-doping, but they suspect that athletes already know.

Removing Carbon From the Atmosphere

How can we absorb all that excess carbon dioxide that is being released into the atmosphere by the burning of fossil fuels? Preserving Earth’s forests and planting more trees might help, but it won’t be sufficient. One idea is to use carbon-scrubbing machines that would pull the carbon dioxide out of the air. The recovered carbon dioxide could then be used in such products as high-carbon cement, dry ice, or synthetic gasoline. Or it could be stored deep underground again.

Current technology would need to be improved before carbon-scrubbing is economically feasible. But the basic techniques are in place already – they’ve been used in submarines for decades.

Reference: Lackner, Klaus S. Washing Carbon Out of the Air. Scientific American pp. 66-71, June 2010.

Did Neanderthals Mate With Modern Humans?

When modern humans (Homo sapiens) migrated out of Africa around 140,000 to 100,000 years ago, it is likely that they ran into their more primitive cousins the Neanderthals (Homo neanderthalensis), who were already living in Europe. Both species probably evolved separately from the same ancestor, Homo erectus.

Did the two groups mate when they met? All we really know is that the Neanderthals disappeared about 28,000 years ago. Some scientists hypothesize that they were attacked or simply out-competed by modern humans; others claim that the two groups interbred, causing Neanderthal features to be absorbed into a larger population of modern humans.

Now there is new evidence that perhaps they did interbreed. Using modern DNA analysis techniques, scientists have determined that the Neanderthals have more genetic variations in common with present-day humans in Europe and Asia than with modern humans in Africa. These data suggest that interbreeding may have occurred if/when the two species met in Europe, before modern humans migrated out of Europe to Asia.

How Safe is Live Kidney Donation?

It’s been about 60 years since the first live kidney donor operation. There have been scattered reports that kidney donation is safe, but most published studies have been limited in scope and used inappropriate control groups against which to compare mortality statistics.

A recent report strengthens the hypothesis that live kidney donation is relatively safe. The report compares mortality data for essentially all 80,347 live kidney donors in the United States between 1994 and 2009 to a carefully matched control group of people who were eligible to donate but were not asked to do so. Mortality statistics were followed in both groups for up to 12 years (median 6.3 years) after donation by the live kidney donor group.

The results indicate that there is a small risk of death from the surgical procedure itself, as would be expected of any similar major surgical procedure. Early post-surgical (three-month) mortality was 3.1 per 10,000 kidney donors, compared to 0.4 deaths in the control group over a similar three-month period. After that, however, there were no differences in survival between the donor and control groups out to 12 years.

The results support the hypothesis that there is no long-term mortality risk associated with live kidney donation except for the usual risks of surgery. Presumably a follow-up study will be done in years ahead to extend the definition of “long-term” to beyond 12 years.

Paying Living Donors for a Kidney

Arguments against paying living donors for a kidney generally focus on two ethical concerns; 1) that payments might induce a potential donor to ignore the risks associated with kidney donation, and 2) that payments might exploit poor people, who would have a greater incentive to donate than wealthier persons.

To test these concerns, a team of researchers polled 342 potential donors in Philadelphia. The study found that potential donors’ perception of the risk of kidney donation is completely unaltered by how much money is offered for their kidney ($0, $10,000, or $100,000). The study also found that although a potential donor’s willingness to donate is influenced by money (more money, more willingness to donate), the effect of money was the same across all income strata. In other words, there was no evidence that payments would either induce donors to ignore risk or specifically exploit poor people.

Based on these data, perhaps payments should be offered to donors on a trial basis. It’s worth knowing whether potential donors’ actual choices would be the same as their hypothetical choices on a survey.

Medical Spas Warned about Lipodissolve

Medical spas are making big bucks on a procedure called lipodissolve, the latest fad for getting rid of unwanted fat. The procedure involves the injection directly into subcutaneous fat deposits of two active ingredients that allegedly break the bonds in the molecular form of stored fat. The active ingredients may also disrupt the cell membranes of fat cells, causing death of the cells. Goodby, fat! But does it work?

In fact, the products used in the lipodissolve procedure have never been evaluated and approved for that purpose by the U.S. Food and Drug Administration (FDA). The safety and efficacy of the lipodissolve procedure is unknown. So this month the FDA sent warning letters to six U.S. medical spas and to a Brazilian firm that advertises the lipodissolve procedure over the internet, warning them to stop making false or misleading statements about the products used in the procedure. The letters warned that assertions that the products used in lipodissolve are safe and effective, have an outstanding safety record, or are superior to other fat-loss procedures are unwarranted and are in violation of the federal FDA Cosmetic act. The companies must take action to correct the violations and to prevent future ones or they will face legal action.

Inflammation and Type 2 Diabetes

Scientists have long suspected that inflammatory processes play a role in certain chronic diseases, such as Type 2 diabetes and atherosclerosis, and now there’s preliminary evidence. In a clinical trial involving 104 patients, an anti-inflammatory drug related to aspirin called salsalate lowered blood levels of hemoglobin A1c levels and triglycerides slightly in Type 2 diabetics. (Hemoglobin A1c levels are the “gold standard” for monitoring long-term effectiveness of glucose control in diabetic patients.)

Scientists caution that no one should start taking salsalate just yet to try to prevent or treat diabetes or atherosclerosis. Larger clinical studies involving many more patients will be needed before salsalate is becomes a standard treatment for these diseases. Nevertheless, these preliminary findings bring us just a little bit closer to an understanding of the link between obesity and inflammation, and whether (and if so, how) inflammation contributes to chronic diseases such as Type 2 diabetes.

Antibiotic-resistant Gram-Negative Bacteria

You’ve probably never even heard of Acinetobacter baumannii or Enterobacter aerogenes. But these and other little-known gram-negative bacteria are killing tens of thousands of hospitalized patients every year, according to some estimates.

Gram-negative bacteria (so-called because of the way they are stained during the Gram staining protocol) have a cell wall structure that makes them more difficult to kill with antibiotics in the first place. But some strains of these bacteria are now resistant to every modern antibiotic we have.

In an ironic twist, two antibiotics (colistin and polymyxin B) that are somewhat effective against these resistant bacteria are still effective only because they were essentially abandoned decades ago, when it was learned that they can cause nerve and kidney damage. Now it’s become an unpleasant trade-off at times; risk death from the bacteria, or risk possible nerve and kidney damage from the antibiotics.

New antibiotics are needed, but so far there do not appear to be any “magic bullet”-type antibiotics on the horizon. This is a battle we’re slowly losing.

Human Gene Patents Invalidated

Basing his decision on legal arguments that human genes are products of nature and hence cannot be patented, in March of 2010 a U.S. District Court judge invalidated several patents held by a company called Myriad Genetics on the human breast cancer genes, BRCA1 and BRCA2. Myriad Genetics sells a kit used to test for the two genes for about $3,000. The company tried to argue that their method of isolating the genes changed the genes, and thus made them patentable. But the judge ruled that such an argument was just a trick to circumvent the prohibition on the direct patenting of DNA.

About 20% of human genes have already been patented. A number of biotech companies were planning to make a hefty profit by developing and selling patent-protected genetic tests or by selling the patent rights to others. Whether all of those patents could ultimately be invalidated is unclear. With potentially billions of dollars at stake, the decision is likely to be appealed.

Medical and research organizations and patients are pleased by the decision. If it holds up on appeal it should provide wider access to human genes currently under patent protection, and ultimately make genetic tests like those for BRCA1 and BRCA2 less expensive.

DNA Mutations Between Generations

How often do errors in DNA replication occur between generations – i.e., how many times are new mutations found in a child that were not present in a parent? These new mutations created between generations would represent a “human mutation rate”. Undoubtedly they would contribute to human evolutionary change.

The human mutation rate per generation has been difficult to measure, but several different laboratories have now come up with numbers that are remarkably similar. According to the most recent estimate, the answer is about 60 DNA nucleotide base errors per generation. That sounds like a lot, but given that there are 3 billion nucleotide base pairs (6 billion bases) in the DNA in a human cell, that’s just one error in every 100 million bases. DNA replication and repair mechanisms are remarkably accurate, it seems.

And that’s why human evolution has occurred so slowly, over several million years.

Re-creating Undifferentiated Cells

People who object to the use of embryonic stem cells (ES cells) for research or for therapeutic purposes continue to hope that induced pluripotent stem cells (iPS cells) might just be the answer. If adult cells could somehow be coaxed back (induced) into a state where they were once again capable of differentiating into all kinds of cells (i.e. were pluripotent), then embryonic stem cells just wouldn’t be needed any more.

Researchers announced several years ago that they had, in fact, found a way to create iPS cells. But are currently available iPS cells just as good as ES cells? In the first side-by-side comparisons of iPS and ES cells, two groups report that they are not. Both groups report that while iPS cells can differentiate into many cell types, they just are not very efficient at it, at least not yet.

The results are a disappointment, perhaps, but don’t count iPS cells out just yet. Scientists are still in the early stages of understanding how to create iPS cells in the first place. As the techniques improve, perhaps they’ll begin to look more and more like ES cells after all. And that would be a scientific advance welcomed by all.

Potential Alzheimer's Drug Flames Out

A closely-watched drug that was supposed to offer hope to Alzheimer’s sufferers failed miserably in Phase III trials this month, according to a press release from Pfizer, one of the pharmaceutical companies involved in its development. In all likelihood all further research on the drug will stop.

It wasn’t supposed to end like this, although looking back it may not be as surprising as it sounds. The drug, called Dimebon, was actually an antihistamine previously sold only in Russia. The Phase I and Phase II trials (efficacy in animals and limited safety tests in humans) were performed in Russia, and then the drug was patented and brought to the United States for Phase III trials and future marketing as an Alzheimer’s treatment. Apparently it doesn’t work.

Although people sometimes complain (rightly) that the drug approval process in the United States is expensive and time-consuming, there’s a good reason for the process. It protects us all.

Caffeine Made Easy

Remember Sweet’n Low, the first really convenient sugar substitute? Well, now somebody has finally come up with a similar easy-to-use product containing caffeine. Fein energy crystals (pronounced FEEN) are being promoted as an energy-boosting product that can be added to any drink, including water. Fein has no calories, no artificial ingredients, and no taste, according to the company marketing it. Drop a single stick of FEIN into your drink of choice and you’re getting 75 mg of pure crystalline caffeine, roughly the amount of caffeine in some energy drinks. And Fein costs less than 70 cents per stick. You probably won’t find it in stores yet, but it’s available over the internet.

Henceforth, getting that caffeine buzz (if that’s important to you) will be as easy as sweetening your tea. This is not an endorsement; just a fact.

Should Older Women be Vaccinated Against HPV?

The U.S. Centers for Disease Control and Prevention (CDC) recommends that all girls and women between the ages of 11 and 26 be vaccinated against the strains of human papillomaviruses (HPVs) that cause cervical cancer. But what about older women; wouldn’t they benefit as well?

The answer appears to be no, or at least not very much. A study of over 9,000 Costa Rican women conducted over a seven-year period found that older women (over 40) tend to get fewer new HPV infections. They also found that HPV infections do not progress towards cancer any faster in older women than in younger women.

Cancer develops in only a small fraction of women who have an HPV infection during their lifetimes, and most HPV infections clear up on their own within a couple of years anyway. Even among women who do develop cervical cancer as a result of an HPV infection, it takes about 25-30 years on average for the cancer to develop fully to the metastatic stage. Therefore, vaccinating older women is not of much use. The ideal time to vaccinate women and girls is before they become sexually active so that they never have an HPV infection in the first place.

The U.S. Birth Rate is on the Rise

A record 4.3 million babies were born in the U.S. in 2007, according to a summary of birth statistics published each year in the journal Pediatrics. The birth rate (number of births per 1,000 women) has been climbing for a couple of decades, though it is nowhere near what it was 100 years ago. The record high number of births is due both to a recent trend upward in the birth rate and the larger U.S. population now than 100 years ago.

A noteworthy trend in the data is that women are having their babies later than they did just 15-20 years ago. Birth rates were lower in 2007 than in 1990 for women under 30, but higher in 2007 for women over 30. Also noteworthy is a continued rise in the number of births to unmarried women; it’s now a record 40% of all births.

Athlete Caught Doping with Growth Hormone

British rugby player Terry Newton has the distinction of being the first athlete ever caught doping with growth hormone to boost muscle mass. He’s been banned from rugby competition for two years.

Until recently athletes had assumed that human growth hormone doping was undetectable, because the synthetic form of growth hormone looks exactly like natural growth hormone. But then scientists discovered that the body actually produces several different forms of the hormone, and that by examining the ratio of these different forms in blood they could tell if the pure synthetic form had been administered. Anti-doping agencies also began requiring random blood tests rather than just tests after athletic events, because the hormone disappears from the blood just days after administration. It was a random test that caught Mr. Newton.

The U.S. National Football League and Major League Baseball have shown interest in the test but so far it has not been instituted, in part because it requires a blood sample.

Feeding the World in 2050

Forty years from now will there be enough food to supply the world’s growing human population? Perhaps the best answer is “It depends”. It depends on how much we can improve the energy efficiency of producing and transporting food. It depends on what we are willing to eat (“Excuse me sir – would you like the beef or the crickets?”). It depends on what we do about climate change, how much damage we do to the environment, and how efficiently we use our precious supplies of fresh water. It depends on whether we’re willing to use genetically modified crops.

A special section of Science magazine available online examines some of these and other issues on the subject of food security. There are some pretty interesting and thought-provoking ideas out there. There’s even an article on what kinds of careers might be available for persons interested in this subject.

New Stem Cell Guidelines

The National Institutes of Health (NIH) is about to change its definition of human embryonic stem cells (hESCs) in light of recent trends in stem cell research.

In March of 2009 President Barack Obama signed an executive order once again permitting the use of hESCs in research. According to the executive order, the NIH is charged with ensuring that NIH-funded research in which hESCs are used is ethically responsible, scientifically worthy, and conducted in accordance with applicable law. NIH does that by setting strict guidelines for what types of cells may be used and how they must be derived.

According to the current NIH guidelines, part of the definition of hESCs is that they are cells “derived from the inner cell mass of blastocyst stage human embryos”1. But the definition apparently had the unintended consequence of excluding some cell lines that were derived from even earlier, morula-stage cells (Review Figure 21.5 in Johnson’s Human Biology). The revised language will read, “derived from early stage human embryos, up to and including the blastocyst stage”, so that these more recent cell lines may be used in federally funded research projects.

The new guidelines do not change the rigorous ethical standards for deriving human cell lines. They just make more stem cell lines available to researchers.

1 Federal Register vol. 75, no. 35, Tuesday, Feb. 23, 2010, p. 8085-8086.

Bacterial Resistance to Antibiotics

The prevailing thought has always been that bacterial resistance to antibiotics comes about by a process of natural selection. When antibiotics kill most but not all of a bacterial population, the bacteria that survive are those that were most resistant to the antibiotic. These resistant bacteria then flourish, passing their resistance genes on to other bacteria and outcompeting their more vulnerable kin. The more times an antibiotic is used, then, the more likely it becomes that the surviving bacteria will be resistant to it.

But now researchers have found another mechanism for bacterial resistance to antibiotics. It turns out that antibiotics induce the formation of toxic molecules within bacteria called reactive oxygen species, or free radicals, that help kill the bacteria. But if the concentration of antibiotic is below the threshold for killing the bacteria outright, the free radicals cause mutations in the bacteria, some of which by random chance may confer drug resistance. In other words, antibiotics speed up the process of bacterial evolution in the surviving bacteria.

The finding opens a new avenue for research – finding molecules that prevent this bacterial mutagenesis, thus perhaps delaying the development of antibiotic resistance.

Platelet-Rich Plasma Therapy Revisited

About a year ago I described PRP (platelet-rich plasma) therapy as an exciting and potentially effective new treatment for injuries to tendons and ligaments (see "PRP Therapy for Connective Tissue Injuries"). Apparently athletes and other patients were asking for the treatment, even though insurance companies were reluctant to pay for it. I asked, “Does it work?” and mentioned that several clinical trials were currently underway to find out.

The results of several of the clinical trials are now in, and the results are not encouraging. In one study of patients with Achilles tendon injuries, PRP therapy was no more effective than an injection of saline (the control). In another study of tennis elbow, PRP therapy appeared to be slightly more effective than injections of steroids (the standard treatment these days). However, some scientists have criticized the tennis elbow study for not having a control group. Steroid injections are known to reduce pain in the short-term but to slow healing in the long-term. So the jury is still out on whether PRP therapy for tennis elbow is actually better than no treatment at all.

No doubt, studies with other tendon/ligament injuries using different study protocols will be done in the future. In the meantime, enthusiasm for PRP therapy has cooled just a little.

Carbon Dioxide and Forest Growth

Plants require carbon dioxide (CO2) for growth. How are they affected by the rise in atmospheric CO2 that occurred over the last century, as a result of human activities such as the burning of fossil fuels? Do plants use more CO2 (i.e, grow faster) when more CO2 is available?

There is some evidence that they may. A study of 55 forest plots in the Eastern United States reveals that the tree biomass is increasing at a faster rate now than in several decades past. After factoring out other known factors, the most likely causes appear to be increases in atmospheric CO2 and in temperature. This may be good news, for it means that as the atmospheric CO2 rises, some of the excess CO2 may naturally be stored in Earth's forest biomass. This could be slowing the rate of rise of CO2 (and global warming) that would otherwise occur.

Smoking and Breast Sagging

A couple of years ago a plastic surgeon and his colleagues did a study in which they interviewed 132 women who had requested breast lift surgery or breast augmentation. The goal of the interviews was to try to determine whether there was any truth to the commonly held belief that breast-feeding causes breast sagging later in life.

The results showed no difference in the degree of breast ptosis (sagging) between women who had breastfed and those who had not. However, factors that did correlate with breast sagging included the woman’s age, how many pregnancies she had had, and whether she had smoked.

Yes, you read that right - smoking. It is well known that smoking damages elastin, the protein fibers in skin responsible for skin’s youthful appearance and elasticity. That’s why chronic smokers are much more likely to have wrinkled skin than non-smokers. It would not be much of a stretch (no pun intended) to hypothesize that healthy elastin supports breast tissue and helps maintain breast shape.

One more reason not to smoke?

Snus - Smokeless Tobacco Made Easy

Now available over the internet and in stores; Snus (rhymes with loose), a smokeless tobacco product containing nicotine that originated in Sweden. Snus comes in colorful tins and is packaged in small tea bag-like packets. It’s real advantage over traditional smokeless chewing tobacco is that no spitting is necessary - the small amount of juice produced can just be swallowed. It’s likely to become popular among teens who want their tobacco use to go undetected, patrons of bars and restaurants where smoking is not permitted, and smokers who want to quit.

The tobacco companies are looking to attract a whole new generation of tobacco users and to shore up profits in the face of declining cigarette sales. R.J. Reynolds launched a nationwide marketing campaign for “Camel Snus” in 2009. As usual, the company denies that it aims its marketing campaign toward underage users.

So far there is no evidence that Snus use may be a risk factor for cancers of the mouth and throat. Nevertheless, it is a tobacco product. It’s worth remembering that there were no clear health risks associated with cigarettes, either, when they first became popular in the 1940s.

Living With Cystic Fibrosis

Sixty years ago, before doctors knew very much about cystic fibrosis, most children with the disease died before school age. Today people with the disorder are living well into their 30s. Today we know that cystic fibrosis is a genetic disorder and we know what causes the symptoms.

What we don’t have is a cure. Prolonging the life of cystic fibrosis patients is largely based on improvement of care, including medicines that alleviate some manifestations of the disease and physical therapy to keep the lungs clear. What works for one patient doesn’t always work as well for the next.

An effective tool in the improvement of care for cystic fibrosis patients has been the establishment of a national registry of patients. The registry, which is managed by the Cystic Fibrosis Foundation, currently collects and stores patient records from more than 100 cystic fibrosis treatment centers across the country. The pooled data has proven very useful in learning what works best for which kinds of patients, and why. It’s like having the collective experience of thousands of doctors right at your fingertips.

The concept of a using a national registry of patients to improve patient care has proven so successful that other patient groups are copying it.