The uphill battle against HIV

An editorial this week in The Washington Post, “HIV/AIDS:
The Incurable Epidemic
,” cites disappointing results from two recent
studies. A separate press release from Duke University cites a “major roadblock”
in another
HIV study
. Simply put, the road to curing this virus continues to be an
uphill slog.

The first study the editorial mentions, the RV144 trial, was
hailed as a
milestone
back in September because it was the first trial ever to show
even “modest” protection against HIV infection. Many thought the results,
obtained from a set of Thai patients, suggested that a legitimate AIDS vaccine
would soon be in the making. Further analysis, however, showed that the results
were less dramatic than originally thought and may even be explained by a
statistical fluke. Though researchers maintain that the results are still important,
the new caveats strike a resounding blow against the possibility of a
commercial vaccine in the near future.

The results of the other study, which looked at a gel
designed to prevent HIV transmission to women, were released on Monday. Although
the compound, which was tested in more than 9,000 women in South Africa,
Uganda, Zambia, and Tanzania over four years, had shown early successes in the
lab and in small trials, it was a complete failure on a larger scale.

The Duke University researchers, meanwhile, were studying
mice to find the best way to make an AIDS vaccine. Their findings reveal that
the immune system, instead of being “blind” to HIV, can indeed produce cells
with the potential to combat the virus. However, these cells are killed off
before they can fully mature; apparently, they are viewed by the body as a
potential threat.

Just because these studies produced lackluster results,
however, doesn’t indicate that they aren’t meaningful. Even a failed experiment
can help guide future research; it tells scientists they need to try something
else. If they can take even a little information from the misstep to create a
better next experiment, then what appeared initially to be disappointment can
ultimately be viewed as a success.

Just look at the similarity between two statements on the
future of HIV research. Anthony Fauci, director of the National Institute of
Allergy and Infectious Diseases, said to the Post about the flawed study from September: “It does now form the
basis for … the development of future HIV vaccines.”

The senior author of the Duke study, Barton Haynes,
meanwhile, said the following: “This represents a new insight into the way HIV
effectively evades … and may offer new directions for vaccine design.”

There is hope that one day, one of these failures will lead
to a major breakthrough. In the meantime, we already have developed proven methods for preventing HIV. With enough awareness, the number of new infections
can be drastically reduced.

—Andrew Kahn

Flu may contribute to Parkinson’s, Alzheimer’s

Could the flu cause Parkinson’s or Alzheimer’s disease? The
answer may be yes, according to a new study by researchers at the University of
Tennessee, Memphis, and St. Jude’s Research Hospital. In particular, the
scientists found that the H5N1 flu strain—commonly known as bird flu—can
infiltrate deep into the brain, causing a “slow-burning” immune reaction that
may contribute to the onset of several neurodegenerative disorders.

The study, published
yesterday
in Proceedings of the
National Academy of Sciences,
was inspired by reports that neurological
symptoms seemed to occur more frequently following the 1918 “Spanish flu.”
Similar signs appeared after recent cases of H5N1 in both people and animals.
So the scientists infected 225 mice with bird flu to study the virus’s effect
on the brain.

H5N1 is a
highly virulent strain of flu, and, as it does people who contract the disease,
it killed about half the mice. The other half showed signs of infection in
their brains, but within three weeks all active signs of flu infection—along
with any neurological symptoms—were gone. 
This recovery was only surface-deep, however: The researchers found that
the surviving mice had started to produce an abnormal, clumping form of a
protein known as alpha synuclein in their brains. Abnormal clumps of protein are
one of the hallmark
signs
of Parkinson’s, Alzheimer’s and other neurodegenerative diseases.

In addition, signs of activated
microglia, the brain’s immune cells, indicated the presence of inflammation. These
factors were linked directly to brain cell death; within 60 days of infection, the
substantia nigra pars compacta regions of the mice brains showed a loss of
about one-fifth of their dopamine-producing neurons, a milder form of the
damage that occurs in Parkinson’s. The researchers also found aggregated
clusters of protein in the hippocampus, cortex and brainstem—as is often seen
in neurodegenerative diseases.

The researchers liken this to a
hit-and-run; they speculate that the flu virus causes the brain’s immune system
to turn on and then remain active long after the infection has been
eradicated.  If their theory holds, they
add, then any number of viruses that make their way past the brain’s defenses
could contribute to Alzheimer’s and Parkinson’s. (This also falls in line with
a popular theory about why some flu strains, particularly Spanish flu, become
so deadly and disproportionately kill off the young and healthy: They unleash a
“cytokine
storm,”
an ultimately fatal overreaction by the immune system.)

For now, the findings are merely
informative. The study did not extend long enough to check whether full-blown
cases of Parkinson’s did occur in the mice, for instance, and more
research—especially in primates—is needed to confirm that the results translate
to humans. It’s also far too early to tell if bird flu survivors are
contracting these disorders more often. And even if verified, viral infections
are likely to just be another addition to the many risk factors, most notably
age, for such neurodegenerative disorders.

As for those worried about H1N1—the current
pandemic flu strain
—good news: It does not appear to attack the brain.

 —Aalok Mehta

A treatment for peanut allergies

For people who have peanut allergies, something as simple as going out to eat or having a candy bar can be an anxiety-producing and potentially harmful experience. Not only do they have to stay away from peanuts themselves, many of the most allergic must avoid peanut oil and any utensils that may have come in contact with a peanut.

At first reflection, this may seem a little silly to those of us without such an allergy. How often does the average person even think about peanuts? Then you realize that a chopping board may not have been washed between chopping nuts and other vegetables; that ice cream scoops may not be cleaned off after they dip into the peanut butter ice cream; that a delicious plain milk chocolate bar came down the same conveyor belt as a bar that was chock full of peanuts. If you have such an allergy, it doesn’t take much to spark a reaction that can range from wheezing to anaphylaxis, putting quite a damper on that fun evening out.

Thanks to a team of doctors at Duke University Medical Center and Arkansas Children’s Hospital there may be new hope for the 1.8 million Americans suffering from an allergy to peanuts. In a pilot study, 29 severely allergic children spent a day in the hospital ingesting increasing doses of specially prepared peanut flour. Lest any adventuresome reader think this would be a good idea to try at home, the dosage given to the children was less than a thousandth of a peanut, impossible to prepare at home. Once the children had taken enough doses to have a reaction, they were sent home with directions to take a daily dosage just under that amount. Over time, their bodies developed a tolerance to the flour and the dosage was gradually increased. Eight to ten months later, most of the children could consume the equivalent of 15 peanuts a day without having a reaction.

Even more remarkably, five of the children in the study could stop treatment for a month and still eat 15 peanuts without having an allergic reaction. Wesley Burks, allergy chief at Duke University and the lead researcher in the study, said in an Associated Press article that changes to their immune systems show that the children are truly allergy free. This kind of tolerance has not been seen before with a food allergy.

Further studies are in progress at Arkansas Children’s Hospital, and so far the results support the findings of the pilot study. If this form of treatment proves effective, it could end the threat of allergic reaction to peanuts, which accounts for 200 deaths in the United States each year, according to the article.

However, if peanuts still aren’t your thing, there’s really nothing that can be done about that. Seven-year-old Ryan Cassada, who has been allergy free for two years, may no longer face a health risk because of a peanut but he still doesn’t like them. Why? “They smell bad.”

—Juliana Avery

Outbreak of the vaccination debate

It’s hard to imagine that parents wouldn’t do everything possible to safeguard their child’s health. Yet keeping them safe can be a puzzle. A vocal group of parents questions the value of childhood vaccinations because they worry that this “preventive medicine” is not necessary and could be dangerous, particularly the supposed link between vaccination and autism. Yet choosing not to get vaccinated has its risks too—and they don’t affect just one child.

A recent USA Today article reports on some disturbing new evidence of the dangers of not being vaccinated. In Minnesota in 2008, five children were diagnosed with haemophilis influenzae type B, or Hib infection, a disease that had been virtually wiped out by vaccination. One of those five children eventually died. Outbreaks of measles, also preventable by vaccine, have affected 140 children and adults statewide in recent years.

Most people are protected by “herd immunity,” meaning that being surrounded by immunized people generally keeps even the unimmunized safe from harm. However, health officials are now concerned that anti-vaccination sentiment has led to a decrease in herd immunity, leaving more people vulnerable—especially children too young to be vaccinated or those people for whom vaccination was not effective. “By vaccinating your child, you’re doing good not only for that child, but for the community,” Kristen Ehresmann, immunization program manager for the Minnesota Department of Health, says in the story.

Ehresmann’s view is shared by a recent Newsweek article on vaccination, including concerns over a perceived link to autism, the amount of mercury in vaccines, the dangers of too many shots “overloading” the immune system and the belief that surviving an illness like chicken pox naturally is preferable to getting immunized. The article concludes that the concerns were generally without scientific backing and the benefits far outweigh the risks, pointing out that diseases such as chicken pox, often thought of as being uncomfortable but relatively harmless, can sometimes result in severe infection and even death.

While some people in the “autistic community” hold the view that vaccines could be the root cause of the illness, at least one mind has changed. Alison Tepper Singer, executive vice president of communications and awareness for the advocacy group Autism Speaks, recently resigned, citing Autism Speaks’ policy on vaccination research as the reason she stepped down. While the group continues to promote the study of the link between autism and vaccines, Singer says, “Dozens of credible scientific studies have exonerated vaccines as a cause of autism. I believe we must devote limited funding to more promising areas of autism research,”

Adding support to these views is a report by The Times of London about the work of Andrew Wakefield, the doctor who originally linked autism to the vaccine for measles, mumps, and rubella (MMR). In a February 1998 article in The Lancet, Wakefield claimed that the families of eight out of twelve children in his study blamed vaccination for their autism and said that the children’s symptoms started days after vaccination. This small study helped spark the anti-vaccination fervor that exists today.

The Times’s investigation, though, showed that Wakefield manipulated the patients’ data: The children’s medical records conflicted with Wakefield’s reporting and only one patient reported symptoms within days of vaccination. In most cases, the children had medical concerns before vaccination. A second Newsweek article on the enduring effects of Wakefield’s research reports that other studies that have supported Wakefield’s results are also flawed.

Wakefield had a financial stake in demonstrating a connection between autism and vaccination. Richard Horton, the editor of the Lancet, said that had he known of this financial connection, the paper would not have been published. Horton told the press, “There were fatal conflicts of interest.”

As long ago as 2004, the Institute of American Medicine reviewed more than 200 studies and rejected the autism-vaccine hypothesis. Yet anti-vaccine fervor continues (one need only look at the Newsweek site’s comments to see this). While autism may not caused by vaccination, we still don’t know what it is caused by. So fear persists and vaccination rates decline. As in Minnesota, England and Wales also have reported a spike in the rates of measles.

No one denies that autism is a real and pressing problem, or that many parents feel genuine concern over shots they worry are unnecessary or dangerous. Yet research is showing that these concerns may be groundless and may overshadow real, known dangers. They may also be drawing attention away from finding a more likely cause for illnesses such as autism. Many people today haven’t experienced the measles or the Hib infection that hit Minnesota. But they are real and deadly and a threat—not just to individual children but to everyone.

—Juliana Avery

Some biologists pre-emptively addressing “dual use” research

Some life scientists already are taking steps to reduce the harmful potential of their research, suggests a new survey about “dual use” research—scientific work that also has military or security implications.

Without formal guidelines or government restrictions, researchers have in certain instances broken collaborations, abandoned or altered planned lines of work or restricted what they publish, says the report, which was jointly conducted by the U.S. National Research Council and the American Association for the Advancement of Science.

At a press briefing yesterday, however, report chairman Ronald Atlas said it wasn’t clear that such drastic reactions were appropriate. For example, the scientists surveyed thought there was a 51 percent chance of a bioterrorism attack somewhere in the world in the next five years and a 35 percent chance such an attack would take place in the United States, but only a 28 percent chance that anyone’s dual-use research would contribute.

Atlas, a professor of biology at the University of Louisville, also warned repeatedly about the limitations of the survey. The questionnaire was mailed out to 10,000 members of the American Association for the Advancement of Science who work in the life sciences, but only about 1,600 fully completed it. “[This] may or may not be reflective of the broader scientific community,” he said. “Be careful how you interpret the data.”

It is more useful to think of the report as a framework for how to proceed with additional research or policy projects, he said. For example, the survey suggests that scientists largely favor more self-policing of potentially dangerous research projects as well as mandatory education on the potentials and pitfalls of dual-use research. The scientists offered substantially less support for formal certifications or greater government oversight.

One potential bias in the report was a larger-than-representative response by researchers working with “select agents,” potentially harmful biological toxins already subject to government scrutiny. One-quarter of respondents had handled such agents at some point, including, presumably, a large number of immunologists, virologists and molecular biologists. Part of the reason for commissioning the report were several advances in those fields, such as 2005 work reconstructing and testing the 1918 influenza virus, which is estimated to have killed between 20 million and 50 million people worldwide.

But concerns have been raised at some point in almost all fields of biology. Even if the effects may seem less immediate and less potentially catastrophic, for instance, the field of neuroscience received such scrutiny just a few months ago, when the National Academies released the report “Emerging Cognitive Neuroscience and Related Technologies.” The paper “identifies and explores several specific research areas that have implications for U.S. national security,” including lie detection using brain scans, cognition-enhancing drugs, chemical weapons that act on the brain and brain-machine interfaces. One of the paper’s committee members, in fact, was Jonathan Moreno, a professor of medical ethics and the history and sociology of science at the University of Pennsylvania; his Dana Press book “Mind Wars: Brain Research and National Defense,” predicted many of these concerns.

Aalok Mehta

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