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?