Monday, October 31, 2005 

While CDC silent on Tamiflu hoarding, IDSA speaks out

So, Tamiflu. People who had never heard of the drug last year now want to have their own personal stock, as it's the one drug that has been shown to be effective against H5N1. Last week, Tamiflu manufacturer Roche announced that it was suspending shipments of the drug to the U.S.,, in an effort to decrease hoarding and make sure that enough of the drug would be available for those who actually needed it during this year's flu season. And while the CDC has had little to say on the hoarding matter, other organizations have started to speak out.

(IDSA=Infectious Disease Society of America).
Dear Colleagues,

In response to requests for guidance from our members, policymakers, and the public, IDSA and the Society for Healthcare Epidemiology of America have developed the following position statement on antiviral stockpiling for influenza preparedness.

We advocate a national stockpile with minimum treatment courses for at least 25 percent or ideally 40 percent of the U.S. population. We advocate health care institutional reserves to improve local access for treatment of affected populations, but not prophylaxis of health care workers given the current shortage of antiviral drugs. We discourage personal stockpiles. We want to remind the public that there are a number of other steps that individuals can take to protect themselves against seasonal or pandemic influenza, including cough etiquette, hand-washing, and annual influenza vaccination.

This policy statement will require continuous refinement as events change. We will continue to use IDSA’s website and e-mail alerts to keep our members apprised.

The Society owes a debt of gratitude to the members of the Pandemic Influenza Task Force, who drafted the statement: Kathleen Maletic Neuzil, MD, MPH, Chair; Kathryn M. Edwards, MD; David S. Fedson, MD; Frederick Hayden, MD; Edward N. Janoff, MD; Andrew T. Pavia, MD; and Gregory A. Poland, MD.

Sincerely,

Martin J. Blaser, MD
IDSA President

(Emphasis mine). More info at the link.

 

Cervical cancer vaccine and politics as usual

As mentioned in the comments to this post, there is a brewing controversy over upcoming guidelines outlining who should receive the "cervical cancer vaccine," a vaccine against the human papilloma virus (HPV). Briefly, the HPV vaccine is a highly effective (100% in a 2-year clinical trial) vaccine which is targeted against two specific serotypes of the human papilloma virus: HPV 16 and HPV 18. Together, these types cause about 70% of cervical cancers in the United States. Previously, Bridget Maher of the Family Research Council, a leading Christian lobby group, has said this about the HPV vaccine:

"Giving the HPV vaccine to young women could be potentially harmful, because they may see it as a licence to engage in premarital sex," Maher claims, though it is arguable how many young women have even heard of the virus.
Why all this resistance to the vaccine? HPV is a virus that can be spread by "ordinary" sexual transmission, but it can also be spread by skin contact--meaning condoms are not 100% effective in preventing transmission of the virus. As Maher also mentioned, therefore, abstinence is the best way to prevent HPV. No one is arguing this fact, as far as I know. Nevertheless, these conservative groups seem poised to fight use of this vaccine in teenage girls. Today's Washington Post has an article on the issue, here.

Because the vaccine protects against a sexually transmitted virus, many conservatives oppose making it mandatory, citing fears that it could send a subtle message condoning sexual activity before marriage. Several leading groups that promote abstinence are meeting this week to formulate official policies on the vaccine.

In the hopes of heading off a confrontation, officials from the companies developing the shots -- Merck & Co. and GlaxoSmithKline -- have been meeting with advocacy groups to try to assuage their concerns.

The jockeying reflects the growing influence that social conservatives, who had long felt overlooked by Washington, have gained on a broad spectrum of policy issues under the Bush administration. In this case, a former member of the conservative group Focus on the Family serves on the federal panel that is playing a pivotal role in deciding how the vaccine is used.

"What the Bush administration has done has taken this coterie of people and put them into very influential positions in Washington," said James A. Morone Jr., a professor of political science at Brown University. "And it's having an effect in debates like this."
This isn't small potatoes we're dealing with here. As mentioned in the article, cervical cancer strikes more than 10,000 U.S. women each year, and kills more than 3,700. These are 3,700 preventable deaths. And as one who isn't sooo far out of her teens, even as an infectious disease geek during that time, I had essentially no understanding of HPV. Sure, we learned about sexually transmitted diseases, but most of our sex education class was devoted to, "can this make me pregnant? Can this? How about this?" kind of topics. I can guarantee that probably 75% of my class had no clue what HPV even stood for, much less had an idea that infection could lead to cancer. And the equation of vaccination leading to more promiscuity? C'mon. I'd love to hear any 16-year-old girl rationalize her sexual activity could increase because she was now vaccinated against one particular STD. If she knows enough to understand HPV, then she should also know that there's still HIV, chlamydia, syphillis, herpes, hepatitis B, and others out there, and that infection with those can lead to sterility or even death.

The article notes:

The [conservative Family Research Council] is planning to meet on Wednesday to discuss the issue. On the same day, the Medical Institute for Sexual Health in Austin, which advises conservative groups on sexuality and health issues, is convening a one-day meeting to develop a position statement.
One can only hope that those who actively say they advocate a "culture of life" will put their money where their mouth is, and show that they value those 3,700 women who die of cervical cancer each year--deaths that may soon be completely preventable.

 

More on DNA vaccination for avian flu

I mentioned here a short article bio.com had on the possibility of a DNA vaccine for avian flu. MSNBC now has an extended article on that concept here.

The flu vaccine-making system that serves as the best available protection against a pandemic relies on millions of chicken eggs, takes nine months to produce each year’s flu shots and has changed little since the 18th century.

This creaky system poses a big problem if a new, deadly strain emerges once the annual and inflexible production process begins.

Several biotechnology companies are at work on a new and quicker way of making a flu vaccine they hope can replace one that requires people to be inoculated with the entire influenza virus. Their technique: extract just a few genes from the virus and inject it into people.

The nascent technology, called DNA vaccines, is a form of gene therapy that proponents argue is the best way to overhaul a 50-year-old vaccine manufacturing system.

***

DNA vaccines were first introduced about 10 years ago as a possible treatment for a variety of diseases, from AIDS to cancer. They worked great in mice, but largely failed to work in humans because the injected genes did not find their way into the cells.

Vijay Samant, chief executive of Vical Inc. in San Diego, said those initial problems have been overcome and his company is testing DNA vaccines in cancer and AIDS patients to battle those diseases.

Gary Nabel et al. have worked on a different modification of the DNA vaccine, priming with DNA vaccine and boosting with a recombinant adenovirus containing the influenza nucleoprotein gene, which is a more highly conserved protein than the hemagglutinin and neuraminidase proteins that are targeted with current vaccines. This vaccine combination worked well in their tests in mice (including challenge with the 1997 H5N1 strain), but again, the problem is that its efficacy in humans is unknown.

Friday, October 28, 2005 

Bacterial machines--real ones

Those "molecular motors" don't have nuthin' on this Bacillus cereus "cellborg."



Fully merging microbe and machine for the first time, scientists have created gold-plated bacteria that can sense humidity.

The breakthrough is the first "cellborg," heralding what might become an array of devices that could sense dangerous gases or other hazardous substances.

The bioelectronic device swells and contracts in response to how much water vapor is in the air. It’s called a cellborg humidity sensor, and it is at least four times more sensitive than those that are solely electronic. It even works even when its biological parts are long dead.

(More info and technical details in the article).

We're already using bacteria for bio-remediation, to produce insulin and growth hormone, in mining, and even to control mosquito populations. I anticipate that the applications will grow exponentially in years to come, reminding us again just what a large role these microscopic critters play in our everday lives.

 

New vaccine recommendations coming

Doctors recommend hepatitis shot for kids

Hepatitis A is a virus that causes (obviously) hepatitis, as well as jaundice, fatigue, nausea, fever, loss of appetite, and diarrhea. It's often spread fecal-orally; that is, you put something in your mouth that has fecal contamination. (Just makes you want to run to the bathroom and brush your teeth, doesn't it?) It also can be spread via sexual contact and shared needles (or other contact with blood or body fluids). It's estimated that there are ~40,000 acute cases of Hep A per year, with many of them going undiagnosed. It's one of those diseases that you don't hear about until there's an outbreak (like this one), but it causes a significant amount of morbidity in the U.S. every year. Hence, the new recommendations:

The Advisory Committee on Immunization Practices, which helps set federal vaccination guidelines, voted unanimously to recommend that a two-dose vaccination be given young children. The panel's recommendations are routinely adopted by federal health officials and are influential to doctors.

Expanding the vaccination recommendation to all the states could prevent 100,000 cases and 20 deaths in the lifetimes of children vaccinated in one year. The direct costs of the vaccine program, currently at $22 million, would increase to $134 million.
Also new is the recommendation to add pertussis to the tetanus-diptheria booster shot for adults. Bordatella pertussis is the cause of whooping cough, a rare disease now but one that caused a lot of misery (and a lot of mortality) in the pre-vaccine years. Children are still vaccinated against it, but there are 2 problems: 1) insufficient vaccine coverage, as parents refuse to have their children vaccinated due to religious objections or fear of side effects, and 2) infection of infants before the vaccination has elicited immunity. The bad thing about pertussis is that the vaccine wears off after 5 years or so, meaning that adults have little or no immunity. This isn't a big deal for we "grown-ups," as pertussis doesn't cause such serious disease in adults. What it's a problem for are adults who are around incompletely vaccinated infants or children: if the adult is a carrier, they can pass the bacterium to a child, causing illness in the recipient. And there has been a resurgence of pertussis in recent years:



Since pregnant women are one group that will be in contact with both unvaccinated infants and waaaay too much fecal material, they're an ideal target for both of these vaccines. I've already passed along the recommendations to my expectant sister so that she can discuss it with her M.D.

Thursday, October 27, 2005 

More academic journals discussing ID

(And not in a supportive way). PZ and Orac discussed a recent New England Journal of Medicine editorial critical of intelligent design. Though the article had several shortcomings, it's always a bonus to see other scientists treating ID as a valid threat (not in the scientific sphere, of course, but in the "hearts and minds" of the populace). Now the Journal of Clinical Investigation, another fairly heavy-hitter as far as medical journals go, recommends to its readers, Don’t be stupid about intelligent design. Kudos to them...now come the nitpicks. :)

Neill writes,
For those who have had their heads in the sand, it is worth going over the main points of intelligent design. Intelligent design challenges both Charles Darwin’s theory of natural selection and other tenets of evolutionary theory by arguing that many organisms are too complex and their systems too intricate to have been accomplished through evolution alone. Unlike creationists, who eschew scientific theory and believe that God created the entire world in 6 days, design proponents accept many of the conclusions of science. They accept the cosmologists’ view that the universe is 13.6 billion years old or the geologists’ view that the world is 4.5 billion years old and shun the Bible’s suggestion that the world is less than 10,000 years old. They accept that mutations and natural selection may have guided aspects of the natural world.
Well...many of them accept an old earth, but certainly it's not required of ID "theory" that the earth is 4.5 BY old.

They do not define the deity involved, other than labeling it "God," saying that intelligent design has no theology behind it — a way to avoid being called religion.

And here, not all of them even label it "God;" some simply say "The Designer."

Why should you bother with all this? Because this is not a fight for only developmental or anthropological scientists to fight. We all must be informed and we all must get involved to make sure that our lay peers know the facts. The science curriculum is being changed to incorporate intelligent design in Ohio, New Mexico, Minnesota, Kansas, and Pennsylvania — it is important to make sure this does not spread to other states, and that it is overturned in the states where it is taught. One thing is unambiguous: this sort of discussion — of religion — does not belong in the classroom.

Very much agreed, but I don't know why "developmental or anthropological scientists" are singled out. Weird.

Design theorists say that scientists didn’t see evolution occur and can’t recreate it in a dish, but this is untrue — chromosomal changes, mutations, and hybridization in plants, cells, and fruit flies have shown that changes can be seen in short order (microevolution, so to speak), and the study of fossil records over thousands of years have shown us how evolution has proceeded. They also say that mutations only eliminate traits and cannot produce new features. Those who came up with this argument have clearly never heard of a gain-of-function mutation.

Ah, but silly rabbit, this is just microevolution. As ID proponent Jonathan Witt so eloquently puts it:

Microevolution says a virus can change over time; macroevolution says a virus can change into a cow.

(You just can't make this stuff up, folks). Moving on,

An oft-cited, specious argument regards how life at the microscopic level is too intricate to have evolved. In particular, they point to the example of bacterial flagellum, with its intricate, interdependent motor proteins that couldn’t possibly have formed by evolution. However, not all flagellum are complicated, and not all components are required for the appendage to work. And many of the proteins are present elsewhere in the body.

This is sloppy. "Not all flagellum are complicated?" I'd argue that they are, but they're not "complicated" in the precise way Behe defines them; the flagella is not "irreducibly complex." And the "many of the proteins are present elsewhere in the body" should have been clarified; I assume it's a reference to the eukaryotic flagellum coming from the mitotic spindle aparatus?

Anyway, overall, a good editorial and I hope it will serve to bring more awareness of the issues to the scientific community. So many scientists that I talk to are shocked that people actually buy into ID, and assume that because it's so patently absurd, it will just go away. A wake-up call never hurts.


ETA: as noted in the comments, Witt does now mention: "[Update: to be precise, most Darwinists would say a bacterium evolved into a cow.]" That's sooo much better.

 

Pili becoming a hot topic in gram-positives

Pili (singular: pilus) are bacterial organelles--thin tubes of protein that function in attachment and bacterial sex, as well as immune evasion. Traditionally, studies of pili have been carried out in gram-negative bacteria, such as E. coli and Neisseria species; very little was known about pili in gram-positives. A few recent high-profile papers have changed that.

Back in July, an Italian group analyzed the genomic sequences of 2 isolates of Streptococcus agalactiae, or group B streptococcus, in order to identify surface proteins which may be vaccine candidates. (More on other outcomes of similar research here). 3 of the proteins they identified were found to be pilus-like structures extending from the bacterial surface when visualized using immunogold electron microscopy (essentially, using gold particles stuck to antibodies)--the first ever description of pili in these bacteria, and a new target for investigation of virulence factors and vaccine candidates, as immunization with these proteins protected mice from challenge with a lethal dose of the bacteria.

Now, in this week's Proceedings of the National Academy of Sciences (PNAS for the acronymophiles), a similar structure is described in Streptococcus pyogenes, the group A streptococcus. Even more interesting is the finding that several of these pilin proteins seem to be equivalent to the T antigens in S. pyogenes.

A bit of background is in order here. Way back in the days of yore, a typing scheme for S. pyogenes was worked out based on components on the surface of the bacteria. The "A" in group A streptococcus reflects a particular type of carbohydrate this species carries, which is distinct from the "B" carbohydrate of Streptococcus agalactiae, from the "C" carbohydrate of Streptococcus equi and others in that group, etc., etc. So, this is used to differentiate between different species. Once you start investigating differences within a species, there are different methods to type them. In group B strep, they're serotyped using differences in the bacterium's capsule antigens. In group A, they're serotyped using differences in antigenic properties of a surface protein, called the M protein. (Now this is mostly done a step backward, by sequencing the emm gene, which encodes the M protein, rather than dealing with around 100 different antisera to the various M proteins. Cheaper, less messy, and more repeatable between labs). In addition to M typing, the T surface antigen has been used to further distinguish between strains, although much less attention has been paid to this antigen. It looks like that will likely change in short order with this finding.

Anyhoo, back to the paper. I mentioned the Italian group above, who carried out the research on GBS pili. This same group carried out the study on GABHS (group A beta-hemolytic streptococci). They first searched simply on genetic similarity to the GBS (group B streptococci) pili genes, and came up empty. So they took another tactic, looking for groups of closely linked genes coding for surface proteins containing LPXTG motifs (typical of cell surface-associated proteins in gram-positive bacteria) in close proximity to genes coding for variant sortase enzymes.

They went on to characterize the genes they found, expressing them in E. coli and raising antibodies against them. They found similarites between the new proteins in GABHS and the pili they'd recently identified in GBS, and when they analyzed the bacteria by electron microscopy using this antisera, they could see the structures of the pili (panel H is the negative control):



They also used antiserum to various T antigens and determined that there was indeed cross-reactivity between the T antigens and the pilin proteins they'd identified; but it remains unclear whether all T antigens are components of pili, or just the ones they've identified.

Finally, they carried out a mouse immunization experiment, inoculating mice with 3 of the pili proteins, and then challenged with a strain known to be lethal to mice. ~70% survived, which was similar to the survival rate in mice challenged with the M1 protein (vaccines consisting of M protein components have long been suggested and tested, though they remain problematic due to the fact that some M proteins cause autoimmunity).

Definitely lots of interesting work going on in streptococcal genetics and pathogenesis. Now if only someone could make them more amenable to genetic manipulation, we'd be golden.

 

Playing with the template...

...so if this looks funny or you encounter any bugs, drop me a note. Gracias!

Wednesday, October 26, 2005 

Polio "graphic novella"

I guess that's what they're calling comic books these days. Check out Polio: a virus' struggle in Science Creative Quarterly. For an infectious disease geek, this is primo literature. Hat tip to PZ at Pharyngula for posting it.

 

H5N1 confirmed in Croatia; Leavitt appeases the cool kids

Croatian poultry found infected

"The Commission has been informed by the European Union reference laboratory ... that the virus isolated in wild birds in Croatia is indeed the H5N1 virus," EU Commission spokesman Philip Tod said.

Croatian authorities said they slaughtered all domestic poultry in four villages near a Nasice pond where two of 13 swans found dead tested positive for bird flu. The pond is next to the Zdenci park and all the infected swans were believed to have been from the same flock.
Germany could be next:

In Germany, officials said that preliminary tests on wild geese found dead there came back positive for bird flu. And even though the fowl died of poisoning -- not influenza -- further tests would be carried to see whether they carried H5N1.
Still, it's noteworthy to keep in mind that most of these recent H5N1 isolations have been only in birds (with the exception of recent human cases in Indonesia). You can be sure that migrating birds are being watched closely here in North America, as well.

In other pandemic flu news, Secretary of Health and Human Services Mike Leavitt said that a reason the US still doesn't have a pandemic plan finalized is because the public wasn't interested:
The Bush administration, says Leavitt, did not do more about bird flu before now because most Americans were not worried about it.

"The public," says Leavitt, "has not until recently found this to be a compelling issue."

But now, he says, the administration is paying a lot of attention — with a detailed plan to be released soon.

That's some good governmentin' there, folks! Don't worry about what's actually important--just focus on what's popular. As that Orbit gum girl says, "Brilliant!"

Tuesday, October 25, 2005 

The bass-ackwardness of ID proponents

'New recruits' said needed for intelligent design

In the Dover circus (updates continue here), a sociologist named Steve Fuller testified yesterday on behalf of the defense. What was a theme of his testimony? Recruit the younger generation to give ID theory a boost--since apparently, the senior level ID "theorists" haven't been able to come up with jack squat.
Introducing "intelligent design" to high school students could help the idea gain wider acceptance among mainstream scientists, a sociology professor testified Monday in a landmark federal trial over whether the concept can be mentioned in public school biology classes.

Fuller said minority views can sometimes have a difficult time getting a toehold in the scientific community, but students might be inspired to develop intelligent design as future scientists if they hear about the concept in school.

"You have to provide openings where you have new recruits to the theory," Fuller said. "Unless you put it into the school system, it's not going to happen spontaneously."

And later in the article:

"It seems to me in many respects the cards are stacked against radical, innovative views getting a fair hearing in science these days," he said.
Once again, it makes you wonder how such "minority views" as a bacterial cause for ulcers and symbiogenesis ever made it without a political lobby.

Edited to add: once again, Mike Argento nails it.

Fuller said intelligent design is, essentially, a half-baked idea, pretty much something the intelligent design guys have whipped up without doing much in the way of producing evidence.

And that's why it should be taught to ninth-graders in Dover.

You know, I can come up with a lot of half-baked ideas that no one in their right mind would want to teach to kids in Dover. Let's see. How about this? Cows think in Spanish. Discuss.

 

China: the next Africa?

China warns HIV cases could exceed 10 million by 2010

China, once accused of being slow to acknowledge the threat of AIDS, could have as many as 10 million HIV carriers in five years if no effective preventive measures are taken, state media said on Monday, echoing a grim UN warning.

China says it has 840,000 HIV-AIDS cases among its 1.3 billion population, but experts say at least a million poor farmers were infected in botched blood-selling schemes in the central province of Henan alone.

"If the preventive measures are slack, the number of people infected by HIV could reach 10 million by 2010," Dai Zhicheng, director of the Health Ministry's Committee of AIDS Experts, was quoted by the Xinhua Daily Telegraph as saying.

It looks as if years of denial about the extent of the AIDS epidemic in China is finally catching up with it. A background timeline:

  • 1985: first reported case of AIDS in China.


  • 1985-8: sporadic cases of AIDS, mostly in coastal cities and attributed to foreigners.


  • 1989-93: outbreak of AIDS among drug users in Yunnan province. Again, largely attributed to foreigners or "Western influence."


  • 1994-2000: HIV spreads throughout country, beginning of recognition of the problem. Steps taken to increase safety of blood supply and to address transmission.


  • 2001-present: silence begins to break. "China Plan of Action to Contain, Prevent and Control HIV/AIDS (2001-2005)" published. Additional measures taken to screen blood supply, push to begin public education about AIDS and distribute anti-retrovirals, funding increased. (Much more information can be found here).
Is it too late?

No one really knows how bad China's AIDS problem is. Many people lack access to basic medical care, and there may be large populations out there which are HIV+ but have not been diagnosed. Despite the government's recent efforts, there is still a high level of ignorance about HIV in the Chinese population. A 2003 survey showed that 17% of the population had never even heard of the disease, and an incredible 77% did not know that condoms could prevent sexual transmission. Those who are familiar with AIDS are likely to attach a stigma to patients, much like patients received in the early days of the AIDS epidemic in the United States (and still do to some degree, even today). Additionally, as the disease spreads among the heterosexual population, more AIDS orphans will result, potentially causing widespread disturbance in the population that will span the generations. Finally, China's tuberculosis problem is already severe; the spread of the AIDS epidemic and with it, a larger number of immunocompromised people, will likely worsen that problem. One can only hope that both China and the U.S. will learn from these missteps, and see that education trumps ignorance on a subject every time.

 

Grand Rounds 2.05 at Hospital Impact

Check out a slice of medical life over at Hospital Impact. There's a little something for everyone, but this post at Parallel Universes in particular caught my eye. It even made me, a microbiologist who's used to reading about this stuff, go "eww."

Sleep is supposed to be a peaceful break from all the stressful events we face daily. Unknown to most of us, however, is the fact that everytime we lie down and drift to dreamland, thousands of 'enemies' roam around our face, our arms, and bodies, feeding on our dead skin cells and imbibing whatever sweat comes out of our pores.

For those with asthma, 'ever notice if your attacks always coincide when you're lying down on your bed? Here's a clue about the usual suspects.

So bad is the situation that a news report describes your bed as a virtual ecosystem. Yes people, your bed is a forest of creatures you do not see....and I'm not talking of imaginary monsters, ok?

***

Your bed might be as dirty --- perhaps dirtier --- than your bathroom. This emphasizes the need to replace bedsheets and pillowcases more often than monthly or yearly. This is something we overlook, and before you say ignorance is bliss, I think you ought to do something about it.

I am soooo going home and throwing out my kids' pillows. I can't give up my artificial pillow, though...feather pillows drive me nuts. Guess I'll live with a few extra dust mites.

Monday, October 24, 2005 

How many mutations?

There are 2 big questions regarding influenza and species jumps. 1) What changes does the virus need to adapt to a new species, and 2) what changes does the virus need to be easily transmitted within that species? A paper in press by Gambaryan et al. (found in the journal Virology, here) sheds some light onto the first question, at least regarding H5N1. And the answer is: not many changes are necessary at all--as little as one amino acid change can alter the binding specificity.

The fact that a single amino acid substitution in the receptor binding area of the H5 HA of two human isolates, A/Hong Kong/212/2003 and A/Hong Kong/213/2003, resulted in marked affinity to a receptor optimal for typical human viruses underscores the necessity and significance of further comprehensive surveillance for the affinity of H5N1 viruses to different receptors for better understanding of their pandemic potential.
As always, EffectMeasure is one step ahead of me, and has a more thorough discussion of the results here.

 

12-year-old girl "frozen in time"

Strange case of Brooke Greenberg, who is 12 years old but still looks like an infant--and no one knows why. Her parents have contacted all sorts of specialists, but can't seem to get beyond "Syndrome X" (aka, I have no idea what the hell is happening here). Just one more reminder of how little we really know about human biology and health.

 

DNA vaccine for avian influenza?

Researchers suggest might be one way to go in the event of an influenza pandemic.

"A DNA vaccine is not a panacea, however it could be useful if the situation gets out of hand," Dunnill says. "But if we're going to try it, we need to move. You can't expect to walk into a production facility, hand over the instructions, and expect them to make it on the spot. It's going to take some weeks, and we really don't know how much time we have."

A DNA vaccine could be produced in as little as two or three weeks, Dunnill says. To do it, scientists would create a "loop" of DNA that contains the construction plans for a protein on the outer surface of the H5N1 virus. When that DNA is injected into cells, it would quickly reproduce the protein and trigger immunization in much the same way as a conventional vaccine.

In contrast, producing conventional vaccines from viruses incubated in fertilized eggs can take up to six months, which is too long to effectively prevent an influenza pandemic, Dunnill says.
It's an interesting idea. For DNA vaccination, genes (or portions of genes) from the organism you want to vaccinate against are put into a plasmid (a circular loop of DNA). The plasmid also contains a promoter--a gene which will control expression of this gene--that is able to function in human cells. The plasmid is then injected, just like a regular vaccine is. However, to be functional, it has to be taken up into the human cells, and the pathogen genes on the plasmid have to be transcribed (made into mRNA) and translated into protein. Depending on what types of cells take up the plasmid, this can lead to both antibody and cell-mediated immune responses, which is something few regular vaccines can do (they depend mostly on the antibody-mediated response). The downfall with these vaccines is that they remain largely untested, but their potential to be used in an influenza outbreak might be the kick in the pants funding agencies need to provide money for scientists to work harder on these, and for regulatory agencies to provide an accelerated approval process.

Saturday, October 22, 2005 

Behe shredded

For anyone who hasn't been following the goings-on over in the ID trial in Pennsylvania, there's an excellent day-by-day update that can be found at Panda's Thumb. The latest transcript is out, and it contains some howlers. Ed Brayton points out one of them:

MR. ROTHSCHILD: Your Honor, should we suggest a time -- I mean, do you want to do that at a lunch break or find out --

THE COURT: How much more cross do you have?

MR. ROTHSCHILD: It will be inversely [edit--likely meant "directly" here] proportional to mentions of the Big Bang, I think.

THE COURT: So you're going to go all day.

MR. ROTHSCHILD: It could be quite a while.

Other ROFL moments on page 81, discussing scientists doing science:

MR. ROTHSCHILD. And you don't expect the dialogue to stop there, do you?

DR. BEHE. I don't expect it to, but it may.

MR. ROTHSCHILD. Okay. But scientists, as they do with many subjects on which there's disagreement, may continue to be making arguments and writing papers and submitting them to peer review journals and doing experiments to see if they can come up with a consensus answer on the subject?

DR. BEHE. Sure. And they may write books to try to come up with an answer,
too, as well.

MR. ROTHSCHILD. That's how you get the royalties, right?

DR. BEHE. (No response.)
Too funny...

Friday, October 21, 2005 

First Mississippi rabies case in almost 50 years

Boy dies from first U.S. rabies case in 2005
The patient had been hospitalized with encephalitis of undetermined origin in September 2005. No history of foreign travel or definitive animal exposure was identified. A greater than fourfold rise in rabies virus antibodies was demonstrated in both paired serum and cerebrospinal fluid samples. No other clinical specimens were available to allow viral characterization and identification of a likely animal source of infection.

Bats are the only known reservoirs of rabies in Mississippi, and the state has reported no human cases since 1956. Although the child stayed at a popular summer camp in Alabama and participated in an overnight caving event in Tennessee during the summer, there were no known exposure incidents at either venue. On additional investigation, it was reported that the child removed a live bat from his bedroom in the spring of this year.
From "spring" to September is pushing the edge of the rabies virus incubation period (which can vary from a few weeks to 6 months), but I suppose it's possible. I also wonder if the parents knew of the bat exposure, and if they contacted an MD--because this is freaking me out a bit. We had 2 bats in our house a few months ago. The first time, we were all sitting around in the living room when it started flying around in there. I rounded up the kids and took them outside, then just left the door open while my husband kind of shooed it outside. The second time, I was taking my son upstairs to bed, and he saw the bat flying around the upstairs landing. That time, we took the kids downstairs and shut the bat in my upstairs office, then caught it and had it tested (negative, as far as I know), but now I wish I'd caught the first one too. Additionally, we never did figure out how they got in the house (screens on all the windows, never found anything up in the attic and never saw any leaving the house at dusk), so it still worries me that perhaps one of the kids had an exposure while they were sleeping. My pediatrician, though, thought I was worrying over nothing (and admittedly, I probably am), and advised against post-exposure prophylaxis. I realize that the odds are low (and in Iowa, skunks are rabies-positive more frequently than bats), but still...my worry as a parent tends to trump my common sense as a scientist.

 

Measles vaccine doesn't cause SSPE

Measles is one of those diseases that we don't give much thought to in the United States anymore. Following an incubation period of about 10 days, flu-like symptoms appear: fever, malaise, cough, congestion, conjunctivitis. Soon, the rash appears, first near the ears, then the forehead, the face, and over the rest of the body. Complications were common. These could include a seconary bacterial pneumonia, encephalitis, myocarditis, miscarriage, and a condition called subacute sclerosing panencephalitis (SSPE).

SSPE is a progressive, generally fatal, brain disorder caused by chronic measles virus infection. It follows ~7-10 years after measles virus infection, and generally kills within 3 years from the onset of symptoms. And it's a nasty way to go: the patient suffers from behavioral changes, cognitive deterioration, vision problems, and eventually, advanced neurologic symptoms such as severe spasms, and finally, severe physical and mental impairment that leads to death. Risk factors for developing SSPE including contracting the measles virus at an early age (especially before age 2). Males also are more commonly affected than females. When the first live attenuated measles vaccine was licensed here in 1963, approximately 8 million deaths per year worldwide were the result of measles infection (or complications thereof), and ~50 cases of SSPE were reported each year in the U.S. Following vaccination, the numbers of SSPE cases have dropped dramatically; we now see only 1 or 2 cases per year, and those are almost always in patients who come from countries where measles is more of a problem than in the U.S. By any measure, the introduction of measles vaccination in the U.S. was successful at controlling the disease.

But success often breeds complacency. In the 1980s, rates of measles vaccination decreased, particularly among children less than 5 years of age, and those living in poverty. Anyone who's familiar with public health knows what comes next--an outbreak of measles infections. Indeed, an epidemic of measles occurred during 1989-1991: 55,622 measles cases and 123 measles-associated deaths were reported. From JID 189:S1:



A problem with the measles vaccine--and with many vaccines--is that one dose may not be enough to prevent an infection with the natural virus. Therefore, many children who did not receive booster shots of the vaccine were incompletely protected; several developed measles during the 1989-91 outbreak. Some parents blamed this on the measles vaccine, which also has been linked to other conditions, such as autism (more on that here). A current Journal of Infectious Diseases study (JID 192:1686-93) used brain tissue and measles virus typing to determine whether the measles vaccine strain or natural measles virus infection was responsible for these cases of SSPE.

To do this, they took brain tissue from 11 patients diagnosed with SSPE, performed reverse-transcriptase PCR (necessary because measles is an RNA virus), and analyzed the sequences of the PCR products in order to determine the genotype of the measles virus. (Measles has 22 known genotypes; the vaccine strain, for example, is genotype A). None of the sequences matched the genotype A viruses--the vaccine was not causing SSPE.

However, based on their data, they do suggest that the risk of SSPE from measles was underestimated using older data. Using estimates of measles virus infection in the 1960s and 70s, a 1982 paper suggested that SSPE occurred in ~8.5 cases/million measles virus infections. Estimates from the current JID paper put it at closer to 6.5-11 cases of SSPE per 100,000 cases of measles--7-13 times higher than the earlier estimates.

What does all this mean, and why does it matter?

In 1999, measles still caused 873,000 deaths per year, and accounts for almost half of the 1.6 million vaccine-preventable deaths in children every year. The Red Cross and associated agencies began a campaign in 2000 to reduce this number, akin to the polio and smallpox eradication efforts. They concentrated on sub-Saharan Africa, where 95% of the measles deaths worldwide occurred. By 2003, deaths were already down by 39% (to just over 500,000 in that year). Still, 500,000 vaccine-preventable deaths every year is way too many. And resistance to this vaccination remains, and by some accounts, is growing, in the United States. People forget that these "benign childhood diseases" can, and do, kill, and that vaccines are a public health intervention that has saved many millions of lives around the world.

The eradication of smallpox due to vaccination was a public health milestone. We no longer have endemic polio or measles in the United States, and global elimination of those diseases has been discussed. But this only works if everyone plays their part, and doesn't allow the small risk of side-effects outweigh the large benefit of vaccination.

 

Excellent avian flu article on DailyKos

Just in case there's anyone reading who didn't come here from DK (their traffic is just a wee bit higher than mine :) ), go read this piece by DarkSyde.

One morning, ten years ago, I awoke in a different body. The new body looked superficially like the old. But gone was the healthy 33 year-old, and in its place was a stiff, pale wretch, aching as if I'd been beaten by sticks in my sleep, delirious from fever, with lungs wheezing like a rusty harmonica. The next day I had to be driven to the ER because, in a rare moment of clarity between waves of delirium, I realized I couldn't drive; It was that bad.

After having my vitals checked, I found myself being hustled quickly into a cardio ICU ward! The diagnosis was influenza leading to pneumonia complicated by pericarditis.

And it only gets better. Two thumbs way up.

Thursday, October 20, 2005 

"God is to engineering what Michael Brown is to hurricane relief"

That's my new favorite anti-ID quote, spoken by Mark Blumberg, at the University of Iowa Freethinkers' panel discussion on intelligent design last evening. Dr. Blumberg was discussing what a piss-poor design the human vertebral column is, and concluded his talk with the comment above. The other speakers, Scott Robinson and Evan Fales, also did a great job of conveying the issues. On the ID side was physicist Fred Skiff, one of the "dissenters from Darwinism." I'm sure Skiff is a nice guy and apparently a good physicist, but...wow. A biologist, he ain't. He conflated abiogenesis with evolution, wrote off anything that's "macroevolution" as being "overly reductionist," said scientists claim that science is a worldview (and that's in textbooks?), made a complete strawman of those opposed to teaching ID (suggesting that scientists want to "make it illegal to challenge a scientific theory"), and then pissed off both the scientists and philosophers by saying that Epicurial materialism equals hedonism. And man, he just does this wierd thing with his eyebrows that makes it difficult to watch him speak.

The best question blunder of the evening came from a pro-ID student who was trying to respond to Blumberg's comments that physicists (and others) shouldn't tell biologists what to teach. Both Blumberg and Robinson are officially listed in the department of Psychology, so this student tried to tell them that they were just as unqualified to speak on evolution as Dr. Skiff. Guess he slept through the part where they both talked about their graduate training in basic biology (Robinson even discussed his background in paleontology and zoology at length). Boo-yah.

 

Update on avian influenza

New reports from Indonesia, Russia, and China, so I'm going to do them in one meta-post. (Hat tip to H5N1 for several of the links).

First, The Guardian has a nice cliff notes version of the infections, deaths, and other issues on a country-by-country basis here. One revelation about China I'd not seen yet:

The authorities revealed in August 2004 that the H5N1 virus had been found in pigs but denied claims that they had kept an outbreak of bid flu secret for over a year.

Yikes. You'd think they would have learned their lesson from SARS...

Note that the situation in China, Vietnam, and Russia are all new. In Russia, avian flu has been found in 2 additional Siberian villages (warning: commercial audio on that site) and 19 more are being investigated. In China, H5N1 is back as well. In Vietnam, more ducks are dead, but the report lists it currently as just an "influenza A" strain. All of the countries claim the outbreaks are local, and have taken measures to stem the spread.

Thailand also has a new death, a 48-year-old man who apparently cooked and ate an infected chicken. His son is currently ill with flu-like symptoms.

Finally, the UK appears to be planning an ambitious project: buying enough H5N1 vaccine to cover every citizen. Best of luck to 'em.

 

I love Mike Argento

If you've been following the intelligent design trial out in Dover, PA (covered in detail here), you've probably come across some of Mike Argento's writing. If you haven't, for FSM's sake, go read some.

One of the things Behe, a professor of biochemistry at Lehigh University and one of the grand poobahs of the intelligent design movement, pointed out to show that scientists still debate the idea of evolution is that scientists don't know anything about sex.

He had a slide that referenced an article from the science journal "Nature" titled "Why Sex?"

You know, if you have to ask...

Seriously, I guess, he quoted the article as saying, "Scientists come with a profusion of theories."

Interpret that any way you wish.

He said the article reported that "major factors of the evolution of reproduction are still obscure." The article said, "After decades of theorizing about the evolution of sex, biologists are at last beginning to test their ideas in the field."

It's really kind of sad because a lot of these guys are middle-aged and if they're just getting around to it...

The article says, "How sex began and how it thrived remain a mystery."

It usually begins with a few drinks and maybe dinner and then...

 

Oh, Mike Seaver, what happened to you?

I liked him so much better during his "Tiger Beat" days. Next thing they'll tell me is that Boner has become a monk...

(But on the plus side, "argument from banana" is now my favorite creationist argument).

Wednesday, October 19, 2005 

What the hell is going on with Tularemia? or, a Rant about public health problems

It's situations like this that really irk me.

I mentioned the tularemia detection in DC here almost 2 weeks ago, already annoyed that there hadn't been more information about it. There has been some discussion on the ProMed list, but it's hardly been a blip in the mainstream media. Yesterday, there was an article in Salon

The background:


On Sept. 24, 2005, tens of thousands of protesters marched past the White House and flooded the National Mall near 17th Street and Constitution Avenue. They had arrived from all over the country for a day of speeches and concerts to protest the war in Iraq. It may have been the biggest antiwar rally since Vietnam. A light rain fell early in the day and most of the afternoon was cool and overcast.

Unknown to the crowd, biological-weapons sensors, scattered for miles across Washington by the Department of Homeland Security, were quietly doing their work. The machines are designed to detect killer pathogens. Sometime between 10 a.m. on Sept. 24 and 10 a.m. on Sept. 25, six of those machines sucked in trace amounts of deadly bacteria called Francisella tularensis. The government fears it is one of six biological weapons most likely to be used against the United States.


Tularemia is a naturally-occurring, albeit rare, disease. The bacterium, Francisella tularensis, can infect a wide variety of animals, and can be spread in a number of ways: via ticks, contact with infected animals (this used to be a disease that was fairly common in hunters and trappers, and is nicknamed "rabbit fever"), drinking contaminated water, and airborne spread if the pathogen is aerosolized in some manner. (When I was first taking infectious disease epidemiology, it was mentioned that at least one pulmonary case was due to a rabbit puree which had been created when an infected rabbit was run over by a lawn mower. Similar cases in landscapers have been documented in Martha's Vineyard). It also is a potential biowarfare agent, due to the fact that it can spread fairly easily via aerosol, and that the infectious dose is incredibly low: as few as 10 inhaled organisms can cause disease.

So, when this bug was detected in 6 sensors in our nation's capital, at the same time as a large march in the area, wouldn't you think that would be some headline news? Hell, at least the second section?

Yet it's barely a blip on the nation's radar. Even many infectious disease folks I've spoken to haven't heard of it, and certainly the public at large is largely ignorant that anything happened. And that would be fine--I understand very well the conflicting desire to inform people about what was detected by the sensors, and at the same time, to educate them about how the tests work, the false positive rate, and other issues so that no one freaks out about something that may turn out to be a false alarm. But some of the revelations in this article are stunning. For example:

The DHS scrambled for three days to confirm just what may have been in the air that day. On Sept. 27, it turned for help to the Centers for Disease Control and Prevention. The CDC did its own tests, and on Sept. 30 -- six days after the deadly pathogens set off the sensors and well into the incubation period for tularemia -- alerted public health officials across the country to be on the lookout for tularemia, the deadly disease caused by F. tularensis.

"It is alarming that health officials ... were only notified six days after the bacteria was first detected," House Government Reform chairman Tom Davis, R-Va., wrote in an Oct. 3 letter to Homeland Security Secretary Michael Chertoff. "Have DHS and CDC analysts been able to determine if the pathogen detected was naturally occurring or the result of a terrorist attack?"
(Emphasis mine) 6 days for notification of health officials? These are the very people who should be warned ASAP. They should, theoretically, have some training in bioterrorist events, and know that in the early stages, it's pretty unlikely that a positive sensor means a bioterrorist attack, so the "public fear" issues that may keep some reporters from holding a story back shouldn't apply there. It should have been especially critical to notify them, as people from all over the country had flocked to the peace rally right where all those detectors went off. Luckily, tularemia isn't spread person-to-person, but the local health departments should have at least been put on alert to keep an eye out for potential cases.

Moving on,
"It is not unreasonable that this is a natural occurrence," says Von Roebuck, spokesman for the CDC. "There are still no cases of tularemia."
I'll discuss his "no cases" assertion a bit later, but regarding the naural occurrence scenario, sure, it's not totally unreasonable. I've seen estimates from 150,000 to 300,000 people involved in the September rally; lots of people around, kicking up dust. Would it be enough, though, and is tularemia even present in D.C.? Ideally, when any environmental sensors of this type are installed, the background levels of contamination should be determined first, so you know how much "noise" there is in the environment. I don't know if this was done with tularemia in D.C. (though I have to say, I doubt it). Had it been, we could already have data on the presence of naturally-occurring tularemia there. For instance, there certainly are a lot of squirrels in that area, and tularemia may be endemic in them. Testing of the rodent population there could further that hypothesis. One could also look at the molecular epidemiology of the pathogen population to see if the strain(s?) of tularemia isolated from the sensors matched up with ones found naturally in D.C. I'd assume some of this is being done now--at least, I hope it is.

BUT--according to the Salon article, those marchers would have to have been kickin' up some major dust:

There was another troubling thing. One of the sensors that went off was located at the Lincoln Memorial on the far western end of the Mall. Another was located near Judiciary Square, roughly two miles to the east and two blocks north of the Mall. A third was at the Army's Fort McNair, more than two miles from the Lincoln Memorial down the Potomac River past the Mall, on the point of land where the Washington Channel and Anacostia River meet. The locations of the other three sensors have not been disclosed.
It seems pretty unlikely that the soil could have been that contaminated, yet they'd never had a sensor pick this up before.

As far as the earlier assertion that there haven't been any cases, well, maybe there have, maybe not. Tularemia is also one of those pathogens that causes a "flu-like illness:" fever, chills, headache, muscle aches, cough, and weakness, with serious cases progressing to pneumonia and respiratory failure. It's very treatable with antibiotics, so it's certainly possible that many people have simply gone to their physician and were treated without ever having the causative pathogen isolated. The Salon article found several people who reported symptoms similar to those caused by F. tularensis; some went to the doctor, at least one did not. Had more been made of this in the national media, perhaps more people would have checked in with their physicians, and we could at least have samples to test for the bacterium. As it stands now, we don't know whether people were really infected, or not; and if they were, whether it was due to an actual terrorist event, or not.

Feeling safe yet?

In September, I wrote a post over on Panda's thumb discussing the 2001 anthrax attacks; y'know, the ones that were very obviously bioterrorism, yet we still have no clue about. And today on Effect Measure, Revere discusses administration policies (specifically, funding cuts) and their effects on public health and beyond:

The cuts are independent of the concern for influenza. They are a consequence of the wrecking-ball policies of the Bush Administration and the Republican-controlled congress (and shame to the democrats who helped). You don't stop a wrecking-ball in mid-swing. It has too much inertia and will continue to destroy critical infrastructure even as bandaids like supplementary avian flu funding try to cover the worst of the damage.

It's not just public health. It's dams, bridges, levees, the shredded safety-net for our most vulnerable neighbors. While pursuing military adventures abroad and obsessed with terrorists at home, the BushCo's left us defenseless and dangerously vulnerable in our own homes, workplaces and communities.

(Emphasis mine). And that's exactly the problem. We keep hearing over and over how we're "fighting the terrorists" and "taking the war to them," yada yada yada, yet we may have just been attacked in our own national capital with a real WMD, and no one's paying attention. All the attention to avian flu has been great, but the Powers That Be really need to wake up and realize that if they really want to do something to increase our safety, they should be investing more money here at home in better public health programs that will benefit everyone, instead of throwing some money here and there at different hot topics and hoping that will make them go away--it's crystal clear that's simply not working.

 

"Clusters" of H5N1 infection?

In response to this post in the pandemic influenza series, Curtis asked in the comments section:

What will be the 'trigger' to watch for, either in the press or on a site like ProMed, that will tell us that avian flu has gone to a probable pandemic stage?
I replied:

That's really hard to say. Most likely several confirmed reports of human-to-human transmission, particularly ones where there has been a documented chain of several human hosts with no bird exposure.
Over on H5N1, there's a link to an article by Helen Branswell, discussing an article which will appear in the November issue of Emerging Infectious Diseases. The manuscript contains data suggesting that several of these clusters (with possible cases of human-to-human transmission) may have already occurred.

(Continued below)
Clustering of human cases of H5N1 avian flu infections has occurred on at least 15 occasions since late 2003 and limited human-to-human transmission of the virus may have occurred in several of these groupings, researchers will report in an upcoming issue of the scientific journal Emerging Infectious Diseases.


However...
But key information on several of the clusters - the most recent documented in the paper occurred in early July - is still outstanding, illustrating some of the problems international health authorities will likely face if they try to put into action a plan to extinguish an emerging pandemic at source.

"Part of the reason to highlight this is to suggest any cluster should be viewed as a worrisome event and should be thoroughly worked up so that we can ascertain if it's person-to-person (spread) or rule it out," said Sonja Olsen, acting director of the U.S. Centers for Disease Control's International Emerging Infections Program, which is based in Bangkok.
The article also contains a comment from Michael Osterholm of CIDRAP on the clustering and pandemic potential:

But Dr. Michael Osterholm, who is skeptical that containment of a pandemic could be achieved, said when a pandemic virus starts to spread, the clusters of cases won't look like the ones Olsen and her co-authors found.

"The cluster or clusters signalling this will look very different. Even in the first week to 10 days, there may be 20, 30 or more cases in a given area," said Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
So Curtis, that might give you a better idea of what to look for--and keep an eye out for the report in EID.

(Edited to add: the paper is out today. You can find it here).

 

Great cartoon

You've probably seen parodies of intelligent design suggesting that the idea that storks carry babies should be taught as an "alternate" to reproductive "thoery." GrrlScientist at Living the Scientific Life links a new twist to the theory, complete with avian flu connection, here:

 

Tangled Bank #39 up and running

For those of you unfamiliar with the Tangled Bank, it is

a version of the "Carnival of the Vanities" for science bloggers. A Carnival is a weekly showcase of good weblog writing, selected by the authors themselves (that's the vanity part). Every other week, one of our crew will highlight a collection of interesting weblog articles in one convenient place, making it easy for everyone to find the good stuff.

Two things will distinguish us from the original "Carnival of the Vanities": 1) we are specifically restricting ourselves to articles in the field of science and medicine, very broadly defined, and 2) we've got a different name. Our weekly compendium of great science weblog articles will be called the Tangled Bank, after Charles Darwin's famous metaphor.
Lots of good stuff today; head over to The Questionable Authority to check it out.

Tuesday, October 18, 2005 

What a week for prions

I swear I hadn't intended to do a prion focus this week, but the stories just keep popping up. In this week's Science, Seeger et al. report that prions can be excreted in urine.

Prions were originally thought to be confined to the brain, spinal cord, and lymph tissue. Around 2 years ago, researchers had confirmed that they could be detected in muscle tissue as well. Earlier this year, investigators showed that the presence of inflammation in other organs allowed for the infiltration of prions. Infected organs included the liver, pancreas, and kidneys. Following up on those studies in the current report, they've now shown that inflammation of excretory organs can lead to spread of the prion via the urine.

(Continued below)
Obviously, this has big implications in the health care field. Right now, the only way to definitively diagnose a prion disease is at autopsy, by digging into the brain. If this could be detected in the urine or other organs, a definitive diagnosis could then be made prior to death. However, even in those mice who were excreting prion, the concentration was low, and inflammation also had to be present, so we're unlikely to see any diagnostic tests based on this anytime soon. A more immediate implication of their findings relates to work such as this study of chronic wasting disease (CWD), a prion disease of deer and elk. Briefly, the authors gathered mule deer and put them in one of three environments: a pen into which a prion-infected deer was present; a pen in which a ~2-year-old, naturally infected deer carcass was present; or a pen where an infected deer had been present ~2 years prior. (Additionally, they had control deer, which were not exposed to the prion). Their results?
None of the unexposed deer were infected. One or more introduced deer became infected in two of three paddocks containing a naturally infected deer, in two of three paddocks containing a decomposed deer carcass, and in one of three paddocks contaminated with residual deer excreta within 1 year of exposure.
It wasn't known exactly how the deer contracted the disease, especially in areas where there had been no infected deer for at least 2 years. This new paper opens up the possibility that they were exposed via an environment contaminated with prion-bearing urine. It remains to be seen whether such a finding will hold outside of the lab, and be replicated in animals that are a better model than mice.

 

Intelligently designed avian flu?

Ah, how rare is it that my interest in stomping creationists and my interest in infectious disease collide. But I guess that when there's a topic as hot as avian influenza, it's inevitable that even the folks at the DI will sit up and take notice, as Casey Luskin has in this post: Avian Flu: An Example of Evolution?

First, as Luskin admits in the article, the answer to his titular questions is, "well, duh; of course it is." And alas, it doesn't get any better from there.

Allow me a moment to rant a bit here. It's painful for any expert in a field to read articles authored by those who are very clearly not trained in that area. I can't tell you how many times I've had to listen to local news media call Streptococcus or anthrax a "virus," for instance--something that probably doesn't bother normal people, but that makes me want to throw my TV out the window. (OK, or just write the station a nasty email). So, the little details that Luskin gets wrong are like nails on a chalkboard to me. For starters, there have not been 60 people "infected," as Luskin claims; there have been 60 recorded deaths, but we have no idea how many infections--certainly many times that number. As you'll see, this is probably the most minor of his blunders.

Second, Luskin claims:

Scientists suspect that this new "Avian Flu" strain of the flu virus arose because two flu viruses (probably one previously in humans, and another in birds), swapped genetic material in a process known as "reassortment."

Um, huh??? No, Casey, scientists don't claim this at all (and there's no link in his article where the statement by these mystery scientists is laid out)--and since this is central to your article, you really should have done some reading in this area. The thing scientists are concerned about is that this may happen--but it hasn't happened yet. The H5N1 viruses that are circulating are all bird, baby--no swapping has been detected. Kinda blows the whole "no new information--it's all horizontal transfer" thesis of the post, eh?

Luskin goes on to say:

So our fight to combat the Avian Flu is undoubtedly a fight against evolution. The question is, has there been a net increase in genetic information through this "evolution"? The Avian Flu is essentially the swapping of genes--but its genes probably came from other pre-existing viruses.

Nope; not as far as we can tell. We're not sure at this point why these particular strains of influenza are so nasty, and are able to infect so many different types of animals, but it's much more likely at this point that it's due to the accumulation of minor point mutations (antigenic drift) rather than the reassortment--or antigenic shift--that he's referring to.

Keeping these blunders in mind, let's look at Luskin's next point:

One new twist on the Avian Flu is that it can infect organs other than the lungs and cause damage to greater parts of our bodies. This more widespread attack has caused some fatalities. The fact that the Avian Flu can activate this protein in other places probably has something to do with its new configuration of genes. But we're really not dealing with anything new.

Since no significant "new configuration of genes" has occurred, Mr. Luskin, wouldn't this ability to infect a wider range of organs--likely due to subtle changes in the influenza virus proteins--now be a "gain of information?" If not, what then, pray tell, would constitute such a gain?

After a discussion of mutation limits, he continues...

Viruses are masters at taking what already exists and swapping it around to dodge our immune system. And that's what has happened here. It's still a virus, and there's probably nothing "new" in terms of new genes. This does not show that evolution can create new genetic information.

But as I pointed out above, that's not what's happened here; and indeed, that's not what happens in many pathogen species that show high levels of antigenic diversity. For example, let's take a look at the bacterium once thought to be the cause of influenza, Haemophilus influenzae:

To facilitate evasion of the immune response generated by the human host, H. influenzae has evolved several molecular mechanisms by which to alter the antigens on its surface.

Point mutations. Antigenic diversity of proteins occurs most simply, and perhaps most commonly, by spontaneous point mutations in the genes encoding protein antigens, such that the physical topography of the molecule is altered and antibodies directed against the original antigen do not recognize the altered one.

Would this be "new information?" Why or why not?

Gene amplification. The Hib capsular genes have been studied in detail and are located in a chromosomal region characterized by two tandem 18-kilobase repeats. The quantity of type b capsular material expressed is proportional to the number of tandem repeats present in an isolate, with a maximum of five repeats identified. Nonencapsulated variants arise at relatively high frequency (0.1 to 0.3%) and are characterized by deletion of one of the tandem repeats such that the remaining copy lacks bexA, a gene required for polysaccharide export.

Does this constitute "new information?" Why or why not?

Phase variation. Phase variation is a method by which organisms alter the expression of surface molecules in a reversible fashion. Phase variants arise from the background population of bacteria at relatively high frequencies and may be selected during changing environmental conditions. Two H. influenzae surface molecules, pili and LOS, undergo phase variation, and the genetic mechanisms responsible for this variation have been, at least partially, elucidated. The factors that stimulate, or facilitate, phase variation of these antigens have not been defined, although the presence of a specific antibody may result in enhanced survival of either organisms expressing an alternative antigenic form of phase variable antigens, as in LOS, or organisms not expressing the antigen at all, as in pili.

And here?

Horizontal gene transfer and recombination. H. influenzae, like other human mucosa commensals such as Neisseria gonorrhoeae and S. pneumoniae, is naturally transformable in that it possesses specific mechanisms for importing DNA from the environment.

I guess we already know the answer to this one.

In her review, Dr. Gilsdorf also notes that:

Another potential mechanism for antigenic variation in bacteria is posttranslational modification, such as glycosylation, phosphorylation, sulfation, or sialylation, of surface proteins.

As Andrea Bottaro's post on prions pointedly reminds us, the genetics sure as heck ain't the end of the game. What about this type of regulation of antigenic variation? And while the mechanisms of antigenic variation listed above are fairly common in a variety of bacterial species, there are certainly others not listed above to take into consideration as well. A bit more complicated than Luskin makes it out to be, methinks.

Ah well, back to the nails on the chalkboard:

But there's good news. Scientists are working on creating antibodies.

Funny, I thought we were working on creating vaccines. But hey, what do I know?

And then, just when you think it can't possibly get any worse, the final coup de grace:

In conclusion, viruses are constantly trying to out-evolve your immune system. That's how they survive. All they can do is mutate certain non-essential portions of their DNA within a mutation limit, and try to acquire other pre-existing genes to create combinations your antibodies haven't seen before. But in the end they're still always viruses. (Emphasis mine)

No. He did not write that, did he?? "But they're still viruses!" has to be one of the most moronic phrases in the anti-evolution bag of tricks. I know I shouldn't expect it, but for whatever reason, I tend to hold the DI and their mouthpieces up to a slightly higher level than the other creationists. I have my mental ladder, with Kent Hovind down at the bottom, Ken Ham et al. up a rung, 'cause at least even they think Hovind's a nut, and then the DI up a rung above that, since at least they're not trying to force everyone to believe the world is 6000 years old. But then Luskin has to go and obliterate what little, tiny, minute scintilla of props that I gave to the DI for being less crazy than the other creationists. At least he did encourage getting flu shots--I suppose I should take some comfort in that. And also, since their website is devoted to correcting inaccuracies in the media...

The misreporting of the evolution issue is one key reason for this new site. The newsmedia in the U.S. seem to have rediscovered the evolution controversy recently. Unfortunately, much of the news coverage has been sloppy, inaccurate, and in several cases, overtly biased.

...I'm sure someone will rush right in and correct Luskin's sloppy, inaccurate, and in some cases, overtly biased piece, so that the evolutionnews site lives up to the lofty standards they expect of others.

 

Witnessing endosymbiosis?

The most recent issue of Science has an intriguing report by a pair of Japanese scientists. They describe their discovery of a protist that appears to be in the early stages of an endosymbiotic process. For those of you who may be unfamiliar with the term, endosymbiosis refers to a specific association between two or more species: that one species lives inside the other one, the host, working together as one organism. The best examples we have of this involve engulfment of prokaryotes by eukaryotic cells: mitochondria in our own cells, and chloroplasts in plants.

(Continued below)


(Full-size picture can be found here)

Though there are several lines of evidence that support these ideas. Mitochodria and chloroplasts contain DNA, RNA, and ribosomes, all of which are similar to those of prokaryotes. Like free-living prokaryotes, mitochondria and chloroplasts divide by binary fission. Additionally, mitochodrion and chloroplasts each have two membranes. The outer one appears to be a product of membrane infolding by the host cell, but the inner one is probably the ancestral prokaryotes plasma membrane. Finally, DNA sequence comparisons have even identified the nearest modern relatives of the organelles: a species of rickettsia for mitochondria, and cyanobacteria for chloroplasts. However, there are always nay-sayers, who argue that because we haven't seen this happening, we don't have any good evidence that endosymbiosis happened with our ancestral cells.

In their current paper, Okamoto and Inouye state:

Here we describe a flagellate (Fig. 1A--see below) that appears to be in the formative stages of an ongoing endosymbiosis. The flagellate, which we tentatively refer to as Hatena ("enigmatic" in Japanese), will be formally described as a member of a recently elected division Katablepharidophyta. Hatena is currently uncultivable, so cells from natural populations were used for investigations. Nearly all the cells had a green "plastid" with an eyespot at the cell apex. However, this plastid was inherited by only one daughter cell (Fig. 1B), indicating the structure is a symbiont.




Fig. 1. (A) Hatena (ventral view). All green, symbiont-possessing cells have an eyespot at the cell apex (arrowhead). Scale bar, 10 µm. (B) A dividing cell (ventral view). The symbiont is always inherited by only one of the daughter cells. Scale bar, 10 µm. (C) The ultrastructure of eyespot integration (longitudinal view). E, eyespot granules. Scale bar, 400 nm. Inset: A magnified view of the membranes. The inner and outer plastid membranes (arrowheads), the single symbiont-enveloping membrane (double arrow), and the host plasma membrane (arrow) are tightly layered. Scale bar, 50 nm. (D) The life cycle of Hatena, based on observations of natural populations. Hatena alternates between a host phase that harbors a green endosymbiont and a predator phase that acquires the endosymbiont after division. Solid line, observed steps in the process; broken line, hypothetical steps.

It's not just simply an engulfment, either. The symbiont keeps some of its own organelles (such as its nucleus, mitochondria, and plastid), but loses others (such as its flagella and cytoskeleton). Additionally, the symbiont-derived eyespot (the arrow in figure 1A) seems to always be located in the same place within the host cell--at the juncture of four membranes derived from the symbiont, the symbiont's plastid, and the host. Finally, in experiments using symbiont-free hosts and a different strain of the Nephroselmis symbiont did not result in the phenotypic changes observed with the symbiont strain, suggesting specificity.

This isn't the first time a phenomenon like this has been observed in the lab. An endosymbiotic relationship between Amoeba proteus and a symbiont termed "X-bacteria" was first observed ~40 years ago. But of course, while biologists marvel at fascinating phenomena such as these, creationists can just sit back and spout, "but they're still amoeba!" What a boring life that must be.

Monday, October 17, 2005 

And speaking of prions...

We still don't know what's going on with Idaho, where there have been 9 suspected cases of Creutzfeldt-Jakob disease in 2005.

Let me back up a bit. CJD comes in several forms. It can be inheirited, it can appear spontaneously, or it can be acquired (so-called "variant" CJD). It's the latter form--"mad cow disease," or if you want to be technical, bovine spongiform encephalopathy, that has made most of the headlines, as an outbreak occurred in Britain due to contaminated beef (more on that here). Typically, the variant form has affected young people, while the other forms affect those who are older. So far, we don't know of any variant forms which originated in the United States. (One man was diagnosed with vCJD in Florida, but he had previously lived in the UK, and it's assumed he acquired the disease there). It seems that tests are ongoing in the Idaho cases. This article from September 28th mentions:

Additional tests are under way at the lab to determine what form of CJD was responsible in the three confirmed cases.

"Generally, 85 percent of the tests come back as the sporadic, or naturally occurring form, 14 percent come back as the familial form that is passed down through generations and less than 1 percent come back as the variant form," said Tom Shanahan, spokesman for the Idaho agency.


So, why are these cases attracting national attention? As noted in the article linked above, Idaho officials have never recorded more than three cases in a single year, and the disease usually infects only one out of every 1 million people worldwide. Idaho's population is only ~1.3 million; therefore, 9 possible cases in a single year is high. It could be a statistical blip, or it could be something more dangerous. If any of these cases turn out to be vCJD, expect the news media to take a short break from all their avian flu coverage and go back to hyping mad cow disease.

 

Looks like H5N1 has made its way to Greece

Or so claims MSN.

Greece said on Monday it had detected one turkey with bird flu on the eastern Aegean island of Chios, becoming the first EU country where the virus has spread to.

“The Center for Veterinary Institutes has informed us that one of nine poultry samples has tested positive to birdflu (H5) antibodies,” the agriculture ministry said in a statement.

State-run television quotes authorities as saying first bird flu case has been confirmed in Greece and tests and for the deadly H5N1 strain are pending.


Not too shocking, considering other nearby countries have found the same thing. But note that this is just an H5 antibody test (meaning the birds have been previously exposed to an H5 serotype virus); it doesn't appear the virus has actually been isolated there yet. I'm sure we'll hear more about this in coming days, as this would mark the first EU country where the virus has been found.

 

Intro to prions at Panda's Thumb

Andrea Bottaro has an excellent review of prion genetics over at Panda's Thumb. Prions are, of course, the transmissible agents that cause diseases such as kuru and Creutzfeldt-Jakob in humans, and related disease such as "mad cow" disease, scrapie, and chronic wasting disease in animals. Though there was initially much controversy about these agents in the early years (most notably, because they did not contain any nucleic acids), Bottaro notes that this is a "heresy" that the science community has embraced (similar to the ulcer & Helicobacter connection I mentioned a couple weeks ago):

Spurred by a host of new findings in molecular and cellular biology, in recent years an increasing number of determined biologists have come to envision processes that contradict century-old biological assumptions and seem to defy the expectations of Darwinian evolutionary theory…

Naaah, I am not talking about ID. I am talking about prions, the specter of Jean Baptiste de Lamarck, and “heretical” views about biology. And what must be truly baffling for conspiracy-minded ID advocates, the inflexible “Darwinist orthodoxy” seems to positively dig this “heresy”. Now, that must hurt…


And as I pointed out here, this is yet one more reason why, if ID proponents really want to teach a "controversy," they should lay off evolutionary theory and attack the germ theory of disease.

About me

  • I'm Tara C. Smith
  • From Iowa, United States
  • I'm a mom and a scientist, your basic stressed-out, wanna-have-it-all-and-do-it-all Gen Xer. Recently transplanted from Ohio to Iowa, I've spent most of my life in the midwest (with 4 years of college spent out east in "soda" territory). My main interest, and the subject of my research, is infectious disease: how does the microbe cause illness? What makes one strain nasty, and another "avirulent?" Are the latter really not causing any disease, or could some of those be possible for the development of chronic disease years down the road? Additionally, I've spent a lot of time discussing the value of teaching evolution, and educating others about "intelligent design" and other forms of creationism. My interest in history of science and medicine is also useful as a way to tie all of the above interests together. [Disclaimer: the views here are solely my own, and do not represent my employer, my spouse, that guy who's always sitting by the fountain when I come into work, or anyone else with whom I may be remotely affiliated.]
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