AIDS Vaccine: Should We Stop Looking?

Recently, The Independent asked the provoking question: Should we end the quest for an HIV vaccine?

A vaccine for HIV will certainly be based on a revolutionary idea.

The Problem

One of the major problems with HIV-vaccine research is that CD4+ cells like monocytes and macrophage express an IgG Fc receptor. Thus, any antibody that sticks to HIV is internalized via the FcR into the CD4+ WBC, and thus the WBC are infected by the tagalong HIV. Even antibodies that are "neutralizing" in a Petri dish increase infectivity.

Thus, I was not surprised when the recent Merck HIV vaccine study went terribly, horribly awry, actually increasing the likelihood of infection and leading to earlier death in vaccinated individuals.

No Solution?

Any antibody-stimulating vaccine will have this problem, assuming an IgG response. Passive immunization with F(ab') fragments might meet with a better result.

Should We Stop?

Seth Berkley, president of the International AIDS Vaccine Initiative, said in The Independent's survey: “Most people’s immune systems hold HIV in check for years before they develop AIDS. A small number of HIV-infected people seem never to develop the disease. There are also documented cases of individuals who have been repeatedly exposed to HIV, but have not become infected. If scientists can work out the type of immune responses that protect these individuals, it might provide vital clues about how to create a vaccine.”

The above data that Berkley notes is indeed reason for hope. However, a traditional vaccine will not evoke the anomalous immune responses that are so rarely observed.


TK Kenyon
Author of CALLOUS: A Novel, ( http://www.amazon.com/gp/product/1601640226 ) a story about free will, neuroscience, fate, Schrodinger's Cat, and the End of Days.

Amazon Oops Again!

Amazon has jumped the gun and is offering my new novel, CALLOUS, for sale ahead of its May publication date ( http://www.amazon.com/gp/product/1601640226 ) . When RABID was released last year, Amazon sold out and even sucked dry its wholesaler, so they had to backorder the book from the distributer and it took a couple weeks to get the fresh meat.

If you want to read CALLOUS any time soon, muscle your way to the head of the line and snatch a copy from some milquetoast's virtual shopping cart now!

TK Kenyon
http://www.tkkenyon.com

NPR Interview of Kristen Byrnes, Global Warming Denier

Morning Edition on NPR recently produced a puff piece about Kristen Bynes, blogger of Ponder the Maunder, a blog dedicated to refuting the idea that global warming is a man-made phenomenon.

While the issue of a 16 yo kid becoming a leading global warming contrarian is devastating for the contrary view's validity as a scientific theory, and it seems that she indeed attended a short course at UGoog in Climate Science to arrive at her pre-ordained conclusions (which is the complete antithesis of how science should be conducted,) and that NPR is succumbing to natural selection by lowest common denominator, it seems that there is more to this story.

Personally, I’m not sold on the whole idea of global warming, man-made or not. I used to be. I was upset by the enormous amounts of CO2 that we humans were venting into the atmosphere, just like we exhaust raw sewage into our oceans, etc., etc., etc. And, you know, it seemed warmer, discounting that horrendous Iowa winter of 1995 when temps hit -40F and the Iowa River froze over. You can eliminate outliers in your data, as long as you can account for them, or at least make a nice statistical argument for ignoring them. It seemed that the consensus of the scientific community is that man-made global warming is a threat, and I generally go along with scientific consensus unless there’s a valid reason to doubt, and it had better be a good one. I don’t like the contrarian position.

I do, however, like data. Hard data. Preferably raw, pre-crunched data.

Here’s what changed my mind on global warming: I read that horrible anti-GW novel by Michael Crichton, which so sticks in my mind that I can’t recall the title, and I thought that his novel was so badly written that surely its conclusions can be tossed aside with great force. Crichton is both a horrid novelist and merely an MD.

(Yes, I am arrogant to snark so widely. I hold a fiction MFA from Iowa, where I received many prizes, and have published two well-received novels. During my PhD work in microbiology, I taught medical students in a Midwestern medical school. They’re great at memorizing things but, let’s face it, medical school does not reward original thought nor critical thinking. Their exams are multiple-guess. So, I’m snarky and arrogant. Crichton has loads more money than I have and a huge house on Kauai. He can take the shot.)

So, I set out on my own course of study at UGoog. I expected to quickly dismiss Crichton’s objections with data and confirm the majority opinion. It seems like an overwhelming opinion. I figured it would take an hour.

Here’s what I found: the global warming data is terrible. The methods that collected the data that produced the scary graph that we’ve all seen (where temperature spikes up in the 1970’s) are beyond shaky. It’s really bad science.

I read the whole UN report, and the data that is cited in the prologue, which everyone reads, is a minor part of the whole report. Only surface temps, and only those in major urban areas, are going up. Atmospheric temperatures are not. This is to be expected by the “heat island” effect, where asphalt retains more heat than soil and re-radiates this heat at night.

Personally, I’m on the fence. The data behind GW, whether man-made or not, sucks.

Here’s the problem: whenever you say that the data sucks, people jump on you like you insulted Jesus. They label you a “denialist” and, rather than debate the data, accuse you of wanting to rape the planet.

The global warming debate has moved from the arena of science, where one is free to debate data, methods, and conclusions, and into the area of religion, where one must adhere to dogma or else risk retribution.

That’s a huge problem.

When I published a short blog post about this (http://science4non-majors.blogspot.com/2007/11/hoax-of-global-warming-john-coleman.html ), I got hate mail. Not refute mail. Not argue mail. Hate mail.

Even though my blog post encouraged recycling and conservation, people accused me of trying to destroy the planet.

The debate about global warming must return to being a debate, not a tirade, not a crusade, and not a sermon.

TK Kenyon
http://www.tkkenyon.com
http://science4non-majors.blogspot.com/

Author of RABID ( http://www.amazon.com/gp/product/1601640021 ) and CALLOUS ( http://www.amazon.com/gp/product/1601640226 ): Two novels about science and religion, with some sex and murder.

Science Debate 2008

Science Debate 2008 is a coalition of scientists and science supporters who are asking the three presidential candidates to engage in a debate concerning the future of America as the world's scientific powerhouse.

Please join and donate to this important cause. The democratic candidates have had a debate about their religious views. Surely, we deserve to know, in detail, what the plans of the candidates are for the scientific community, funding, and regulation.

John F. Kennedy dared us to dream of the moon. Our next president should inspire us, too.

Antarctica: Giant Sea Stars and Carnivorous Sponges

Giant sea stars and carnivorous sponges are among the hundreds of new animals discovered by a research mission in the Antarctic Ocean.

See more nifty pics at this National Geographic site.

AIDS Vaccine Failures: A Return To Basic Research

After the Merck's disastrous HIV vaccine trial was halted because it made people more susceptible to HIV infection and increased the severity of the course of AIDS in vaccinated people, the National Institute of Allergy and Infectious Diseases (NIAID) called a conference this week to discuss a new plan for HIV vaccine research.

After an AIDS activist group called for a halt on all vaccine research, the NIAID Director Anthony Fauci, rebutted, "Not only will we will not cut it; wherever possible, we will increase" funding for vaccine research.

AIDS vaccine research is funded by an $476 million extramural portfolio, which will shift away from product development and toward "discovery research." Right now, the share of vaccine research money that goes for "discovery," or basic research, is 47%. The NIAID will spend less on testing candidate vaccines in the lab and in clinical trials and more on the basic biology of the virus to generate ideas.

Drug Trials, Surrogate End Markers, and Death

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One thing that many people don't realize is that many clinical trials for drugs do not test the ultimate outcome for a drug. The clinical trial tests a "surrogate biomarker," which means that the drug changes an easily measured, immediate statistic rather than an endpoint.

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Blood Pressure, Cholesterol, and Your Heart

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For example, most heart-health drugs on the market test whether or not the drug lowers blood pressure or cholesterol, not whether the drug reduces heart attacks or strokes. High blood pressure and cholesterol levels are associated with increased heart attacks and strokes, but no one knows whether (1) increased blood pressure or cholesterol causes heart attacks and strokes or whether (2) bad cardiovascular health causes increased blood pressure, elevated cholesterol, heart attacks, and strokes.

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In the latter case, lowering blood pressure or cholesterol would not change the problem condition: poor cardiovascular heath, and would thus not reduce heart attacks and strokes.

It is possible that treating blood pressure and cholesterol problems does not reduce cardiovascular events, but these studies have not been performed for a variety of reasons.

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First, they're very long-term, expensive, and possibly immoral. You would need to gather 20-30 years worth of data to determine whether there is a difference in heart attack rates between those folks who took blood pressure drugs and those who didn't. In the meantime, are you going to deny those drugs to people outside the study? It is possible that they will help.

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Second, no drug company wants to know that their billion-dollar drug doesn't really work. Not to mention that no drug company wants to design their clinical trials around 30-year endpoints. Witness what just happened to Schering-Plough's stock.

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Nature Article

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There's a very good article in Nature this week about this subject: http://www.nature.com/news/2008/080401/full/452510a.html

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If one is testing a drug for cancer or a viral disease, obvious surrogate markers like tumor size reduction or viral blood titer made excellent endpoints. It is very likely that these markers will correlate with increased survival rates or prolonged life, but not always. Even some cancer studies have found that reducing tumor size did not increase life expectancy.

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Diseases with less clear cut causes, like Alzheimer's, or multiple causes, like heart disease, are more problematic. These very diseases also would require very long time horizons to judge ultimate effectiveness.

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Alzheimer's Disease and Surrogate Endpoints

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Alzheimer's Disease is a particular problem because we don't know, really, what causes Alzheimer's. (Really, we don't.)

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The APOE gene has various alleles that increase risk, but even the worse one increases one's odds to around 40%. That's still less than a coin toss.

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Many people with Alzheimer's dementia have gunky plaques made of amyloid protein on their brains, but not all, and many people with significant dementia and other AD markers (like tau tangles) have few plaques, and some people with lots of amyloid plaques have no dementia. It is not known whether amyloid plaques cause neurons to die, or whether a toxic precursor protein causes neurons to die and amyloid plaques are a garbage dump for this protein.

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If the first, then reducing plaque buildup should reduce dementia.

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If the latter, reducing amyloid deposition in plaques will increase dementia.

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Wyeth Pharmaceuticals is using an unproven cognitive test to study its latest drug for AD, which is at least better than studying amyloid disposition.

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And again, are you going to deny drugs that might work to a person with Alzheimer's or a high risk of developing it?

Race-Specific Cancer Gene (Sort Of)

Using population genetics methods, scientists have found an allele (a form of a gene, due to mutation) that increases the odds for colon cancer by 10% if a person is of European ancestry (specifically Scottish ancestry) but not Japanese ancestry.

http://www.nature.com/news/2008/080328/full/news.2008.712.html

Interestingly, this allelic variation is not in the coding region of the gene but in the non-coding region, suggesting that it is a regulatory sequence that can increase or decrease the expression of a protein.

The increase is seen only for colon cancer and not for rectal cancer.

The scientists did not rule out diet or lifestyle factors as the reason for the difference in the effect of the gene.

For example, it is possible that Gene + haggis + scotch = colon cancer, while Gene + sushi + fugu does not.

Quotable Scientists: Henry Fairfield Osborn

"Evolution is the most firmly established truth in the natural universe."
--Henry Fairfiel Osborn, American paleontologist, (1857-1935)

Ring My Bell: Solar Flares Produce Oscillations

Solar flares cause recoil in the sun (like the recoil from shooting a gun,) that cause oscillations within the sun. Like a bell, the whole sun "rings" at various frequencies.

Whole paper at Nature

This finding could help us understand the physics of our sun and other stars.

Science and Religion: The Missing Link

Science education is not designed to destroy religious faith. Science is a different subject than religion. Science is concerned with the natural world and universe, not the supernatural or theological. Most scientists will deny that science destroys faith in a Deity or Deities.

However, the study of science introduces people to ideas that are at odds with what religious organizations promulgate as true. This occurs most often when religion intrudes into the domain of science and not vice versa. When religion states that it has the answers to scientific questions, such as when the Bible states that the Earth is flat (All quotes, KJV: Daniel 4:10-11, Matthew 4:8) and immobile (Examples: I Chronicles 16:30, Psalm 93:1,) science disproves these hypotheses by definitively showing that the Earth is neither flat nor immobile.

Thus, science contradicts many edicts of religion when religion ventures out of its territory.
Science truly undermines religious faith, however, because it teaches people to think. Science teaches people to search for testable, real-world answers to problems and questions rather than rely on superstition, magical thinking, or laziness.

When asked, "Why is the sky blue?" a person of faith can only answer that God decrees it or formulate an inaccurate scientific answer. A person with some science background understands water vapor in the air refracts incoming sunlight toward the blue end of the visible light spectrum. Scientific endeavors, such as rockets and telescopes, have shown that there is no solid firmament above the Earth, as the Bible states.

When asked, "Why did I get sick?" a person of faith can only answer that God willed it, while a microbiologist could isolate the bacteria or virus that caused the infection and provide antibiotics or antivirals to eliminate the infection.

At a magic show, a person who relies on faith to explain the world can only marvel at the wonders. A person with a scientific background notes the smoke and mirrors and the rabbit under the podium, noting that the hat must have a removable panel.

When confronted with horrors in the world, a person of faith can only say that God willed it, perhaps to give Christians something to do. They might pray for God to provide food for the starving. A scientist, however, creates fertilizers, dams, or new strains of drought-resistant crops.

Science teaches people to think of logical, physical causes for events. This makes people less gullible.

By making people less gullible and intellectually lazy, yes indeed, science undermines religious faith.

TK Kenyon, http://www.tkkenyon.com/ Author of RABID and CALLOUS: Two novels about science and religion, with some sex and murder.

A Psychopharmamusical!

And you thought Hair had a lot of drug references.

Genetic Link to Autoimmune Diseases Type 1 Diabetes and Sjogren's: Hox11 gene

This fascinating paper from the Faustman lab at Harvard links a developmental gene, Hox11, to the later development of the autoimmune diseases Type 1 Diabetes and Sjogren's syndrome.

http://www.nature.com/icb/journal/vaop/ncurrent/full/icb20086a.html

Also important, it links the hearing loss often seen in Type 1 diabetes directly to the Hox11 gene malfunction, not the later autoimmune attack.

This paper suggests that treatment of Hox11 deficiency in people with mutations could prevent Type 1 diabetes, Sjorgren's syndrome, and hearing loss.

Figure from the paper showing deterioration of the ear in Hox11 genetically modified mice:

Comparison of NOD and C57BL/6 cochlear structures. (a) A schematic area of interest in the cochlea. (b–g) Histological cross-sections of the mouse cochlea were processed and cochlear structures were compared between NOD and C57BL/6 animals at 5–8 weeks of age. Structural abnormalities were found in the spiral ganglion, spiral ligament and organ of Corti in the NOD mice. (b and c) The spiral ganglion cells of the NOD mouse were greatly deteriorated (arrow, b), relative to the C57BL/6 control (arrow, c), with only the Schwann cell nuclei remaining. (d and e) There was also atrophy of the spiral ligament, as seen by the loss of cells in the NOD specimen (arrow, d), which is in sharp contrast to the fully populated spiral ligament in the control (arrow, e). (f and g) The organ of Corti of the NOD specimen appeared to be deteriorated and to have many fewer cells (arrow, f), including hair cells, compared to the control (arrow, g). Defects similar to those observed in the NOD cochlea were present in the NOD-SCID cochlea as well.

Instant Nanotech Test for Mad Cow Prions

Researchers at Cornell University have developed a nanatechnology platform to detect prions at low concentrations that, hopefully and soon, will be used to detect Mad Cow Disease prions in blood -- instantly.

That's right. Instantly.

Mad Cow disease prions are responsible for the transmission of bovine spongiform enchelalopathy to humans, causing new variant Creutzfeld-Jakob disease (nvCJD,) an incurable neurodegenerative disease, much like Alzheimer's plus Parkinson's, but kills people in just a couple years.

Right now, the "gold standard" of prion detection is to remove brain matter from an animal that is suspected to be infected (and is dead), inject that into another animal, wait for a long time, then kill the other animal and necropsy its brain. This can take years and (get this) only detects the prion infection 31% of the time.

That's a terrible assay.

The new nanotech assay technique developed by Harold Craighead and company use a "tuning fork" technique. A nano-sized tuning folk is coated with antibodies against the abnormal conformation of the prion protein.

For many other assays, the added weight of the antigen (in this case, the prion) would be enough to change the pitch of the nano-tuning fork when a vibration in the assay liquid sets the fork vibrating. However, because prions are so light, this doesn't work. The researchers used secondary antibodies and metal conjugates to increase the weight of the prions, thus the added weight changed the pitch of the vibrating fork by a detectable amount.

This assay would be invaluable to eliminate prion-infected cows from getting into our food chain, which caused the outbreak of new variant Creuzfeld-Jakob Disease in England a decade ago.

This assay could also test biomedical stocks, such as human growth hormone obtained from human cadavers (yep! that's where it comes from.) for nvCJD prions. Several doctors in France were just indicted for involuntary homicide for not being vigilant enough concerning cadaver HGH and thus infecting over 100 French children with nvCJD.

It's especially a concern when slaughterhouses are unscrupulous about slaughtering and processing "downer" cows, which are sick and possibly infected with mad cow prions.

TK

Best Scientific Images of the Year II

Wellcome has awarded their prizes for best scientific images of the year, and they are pretty.

This micrograph, taken with a laser scanning confocal microscope (see post below,) is a picture of colon cancer cells. The fluors used are not labelled, but I shall make some educated guesses.

Blue here is a nuclear stain, meaning that it stains DNA in the nucleus of the cell, such as DAPI or BOBO.

The green fluor is a cytoskeleton stain. The cytoskeleton component stained here appears to be filamentous actin, because I see some stress fibers through the cells. The stain is probably phalloidin (a toxin from death cap mushrooms) conjugated to a fluor.

The red color is more ambiguous. It seems to colocalize with the cytoskeleton in some cells (red + green = yellow) but is more diffused and cytoplasmic in others. Could be an actin binding-protein or another component of the cytoskeleton.

TK

Best Science Photos of the Year

Wellcome has named its best scientific images of the year, and several are from my own favorite microscope, a laser scanning confocal. Personally, I like Zeiss. Zeiss is nice.

This is a micrograph of an HIV virus. (This image is not from a laser scanning confocal microscope. Viruses are too small to be seen with a LSM. You need an electron microscope to see viruses, let alone viral structures.)

The core in the middle is the RNA chromosome and associated core proteins. The blue half-shell is the viral capsid. The yellow proteins are the ride-along gooey things called the tegument.

TK

White Whale (Shark): Not Quite Moby Dick, But Big and White and Fishy

This albino whale shark was spotted off the Galapagoes. Nifty video.

Expelled! Again!: "Framing Science" People Pandering to Opiated Masses

Lunge:

First, PZ Myers, noted and eminent science blogger and professor, was not admitted to a pre-screening of the film Expelled!, an ID drive-by documentary on evolution, and blogged about how he was thrown out at the whim of the producers. (Previous post: here.)

Myers's guest, Richard Dawkins, was admitted without fuss (as the producers probably did not recognize him, and when asked to show identification, he produced his British passport under his legal name, "Clinton Richard Dawkins.")

It must be noted that both Myers and Dawkins appear in the film Expelled!, for which they were interviewed under false pretenses, and the piecemeal editing of their interviews was journalistically unethical.

Parry:

After some brouhaha, Matthew Nesbit, a professor of communications, blogged:
"As long as Dawkins and PZ continue to be the representative voices from the pro-science side in this debate, it is really bad for those of us who care about promoting public trust in science and science education. Dawkins and PZ need to lay low as Expelled hits theaters. Let others play the role of communicator, most importantly the National Center for Science Education, AAAS, the National Academies or scientists such as Francis Ayala or Ken Miller. When called up by reporters or asked to comment, Dawkins and PZ should refer journalists to these organizations and individuals."
At the risk here of being arch, isn't "communications" what people who flunk out of business major in?

More to the point, Nesbit is utterly wrong. He compares the evolution vs. ID debate to politics, comparing Myers and Dawkins to, "Samantha Power, Geraldine Ferraro and so many other political operatives who through misstatements and polarizing rhetoric have ended up being liabilities to the causes and campaigns that they support."

This comparison is a fallacy.

Science is not politics, which is convincing a majority of the people that your political theory is the correct one to vote for on the day of elections in the majority of the voting districts. Politics seeks to create consensus.

Science is the truth. Myers and Dawkins should not be compared to Power and Ferraro, but to Galileo, Darwin, and Copernicus. No matter what the ID guys believe, they're wrong. Convincing more people that creationism is valid will not make it less wrong. Religionists' balking at evolution is just another example of irrational, superstitious flailing.

Nesbit's whole philosophy, "Framing Science," in which mostly non-scientists try to reconcile science with religion, which are several systems of contradictory and unsubstantiated beliefs, is a waste of time.

Yes, we should try to break it gently to religionists that they've been utterly wrong all these years, but eventually, the obvious truth of science will prevail. It's only a matter of time, another scientific concept.

I admit, when I saw Nesbit's blog and its title, "Framing Science," I thought it was a provocative anti-science blog, like when the cops "frame" someone for a crime. Perhaps that wasn't the best moniker for their movement. You would think that a communications major might have thought of that.

Another non-scientist "framing" guy, Chris Mooney, blogged that the PZ Myers controversy is giving the film loads of free publicty, is thus counter-productive, and also suggested that Myers should refrain from more discussion.

Riposte:

Nesbit's post led PZ Myers to this sputtering reply, which is perhaps less eloquent than his usual posts but heartfelt, in which he said in part, "Fuck you very much, Matt. You know where you can stick your advice."

Again, scientists are not politicians, who strive to form consensus or convince voters, or religionists, who seek to silence the opposing viewpoint.

People should go see that film and laugh at it for the dreck it is. The public should understand that Dawkins and Myers were interviewed under false presenses (the film makers told them it was a documentary about science and education, not a religion drive-by of evolution,) and with shoddy journalistic ethics (including the old trick of setting the camera and the interviewer at 90 degrees to each other, and thus the subject looks back and forth between the camera and the interviewer, producing a "shify-eyed" effect that is associated with lying or unreliability.)

Scientists seek the truth, and when we find it, we tell other people the truth. If there are contrary opinions, we debate the evidence and logically decide whose model is more accurate.

That's the problem with non-scientists like Mooney and Nesbit. They're operating in the rhelm of opinion, not truth. They're seeking to sway people with propaganda, not evidence and logic. They're using the enemy's faulty weapons against the enemy, who designed them, have the blueprints, and know where the weak points are.

Evolution is model with huge amounts of scientific evidence backing it up.

Sure, all models are wrong, but some models are useful.

Evolution is a useful model. It explains the past and, contrary to what ID guys will tell you, it accurately predicts future results.

ID and creationism in general do not accurately predict future results, except perhaps that creationists lie to themselves and others and will continue to do so.

Mooney and Nesbit are in the wrong on this issue.

Myers and Dawkins should not shut up.

Scientists tell the truth. Politicians and religionists seek create consensus or to silence the opposition. Pandering to their illogical and ignorant views will only endow them with a false sense of superiority, to go along with their false view of the universe and their false beliefs.

To PZ Myers and Richard Dawkins: Once more into the breach!

TK Kenyon

Your genes might be selfish, but your brain isn't.

Social psychologist Elizabeth Dunn of the University of British Columbia (UBC) in Vancouver, Canada, performed a series of studies on, admittedly, small groups to determine what contributes more to happiness: giving money away or spending it on yourself. She gave people money, told them to either donate it or splurge with it, and then quantified happiness levels.

http://sciencenow.sciencemag.org/cgi/content/full/2008/320/2

In the spirit of Christmas cheer (even though this is Easter weekend,) either donating the money to charity or buying a gift for others produced more happiness than keeping it or spending it on oneself.

This empirically tested and quantified altruism is a lovely addition to the study of ethics. The studies should be replicated with larger sample sizes, but they are worth reading.

TK Kenyon

Creationist Movie Doesn't Have A Clue

At the new creationist movie called Expelled, eminent science blogger PZ Myers was waiting to get in for a screening.

A cop pulled him out of line and told him that he couldn't go in and that he had to leave the premises immediately, or he would be arrested.

But wait! There's more. There's so much more. I laughed so hard that I had an asthma attack. A bad one. And then I read it again.

Read THE REST OF THE STORY at Pharyngula.

Oh, man, I wish I had been there.

TK Kenyon