Damned Heretics

Condemned by the established, but very often right

I am Nicolaus Copernicus, and I approve of this blog

I am Richard Feynman and I approve of this blog

Qualified outsiders and maverick insiders are often right about the need to replace received wisdom in science and society, as the history of the Nobel prize shows. This blog exists to back the best of them in their uphill assault on the massively entrenched edifice of resistance to and prejudice against reviewing, let alone revising, ruling ideas. In support of such qualified dissenters and courageous heretics we search for scientific paradigms and other established beliefs which may be maintained only by the power and politics of the status quo, comparing them with academic research and the published experimental and investigative record.

We especially defend and support the funding of honest, accomplished, independent minded and often heroic scientists, inventors and other original thinkers and their right to free speech and publication against the censorship, mudslinging, false arguments, ad hominem propaganda, overwhelming crowd prejudice and internal science politics of the paradigm wars of cancer, AIDS, evolution, global warming, cosmology, particle physics, macroeconomics, health and medicine, diet and nutrition.

HONOR ROLL OF SCIENTIFIC TRUTHSEEKERS

Henry Bauer, Peter Breggin , Harvey Bialy, Giordano Bruno, Erwin Chargaff, Nicolaus Copernicus, Francis Crick, Paul Crutzen, Marie Curie, Rebecca Culshaw, Freeman Dyson, Peter Duesberg, Albert Einstein, Richard Feynman, John Fewster, Galileo Galilei, Alec Gordon, James Hansen, Edward Jenner, Benjamin Jesty, Michio Kaku, Adrian Kent, Ernst Krebs, Thomas Kuhn, Serge Lang, John Lauritsen, Mark Leggett, Richard Lindzen, Lynn Margulis, Barbara McClintock, George Miklos, Marco Mamone Capria, Peter Medawar, Kary Mullis, Linus Pauling, Eric Penrose, Max Planck, Rainer Plaga, David Rasnick, Sherwood Rowland, Carl Sagan, Otto Rossler, Fred Singer, Thomas Szasz, Alfred Wegener, Edward O. Wilson, James Watson.
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Many people would die rather than think – in fact, they do so. – Bertrand Russell.

Skepticism is dangerous. That’s exactly its function, in my view. It is the business of skepticism to be dangerous. And that’s why there is a great reluctance to teach it in schools. That’s why you don’t find a general fluency in skepticism in the media. On the other hand, how will we negotiate a very perilous future if we don’t have the elementary intellectual tools to ask searching questions of those nominally in charge, especially in a democracy? – Carl Sagan (The Burden of Skepticism, keynote address to CSICOP Annual Conference, Pasadena, April 3/4, 1982).

It is really important to underscore that everything we’re talking about tonight could be utter nonsense. – Brian Greene (NYU panel on Hidden Dimensions June 5 2010, World Science Festival)

I am Albert Einstein, and I heartily approve of this blog, insofar as it seems to believe both in science and the importance of intellectual imagination, uncompromised by out of date emotions such as the impulse toward conventional religious beliefs, national aggression as a part of patriotism, and so on.   As I once remarked, the further the spiritual evolution of mankind advances, the more certain it seems to me that the path to genuine religiosity does not lie through the fear of life, and the fear of death, and blind faith, but through striving after rational knowledge.   Certainly the application of the impulse toward blind faith in science whereby authority is treated as some kind of church is to be deplored.  As I have also said, the only thing ever interfered with my learning was my education. My name as you already perceive without a doubt is George Bernard Shaw, and I certainly approve of this blog, in that its guiding spirit appears to be blasphemous in regard to the High Church doctrines of science, and it flouts the censorship of the powers that be, and as I have famously remarked, all great truths begin as blasphemy, and the first duty of the truthteller is to fight censorship, and while I notice that its seriousness of purpose is often alleviated by a satirical irony which sometimes borders on the facetious, this is all to the good, for as I have also famously remarked, if you wish to be a dissenter, make certain that you frame your ideas in jest, otherwise they will seek to kill you.  My own method was always to take the utmost trouble to find the right thing to say, and then to say it with the utmost levity. (Photo by Alfred Eisenstaedt for Life magazine) One should as a rule respect public opinion in so far as is necessary to avoid starvation and to keep out of prison, but anything that goes beyond this is voluntary submission to an unnecessary tyranny, and is likely to interfere with happiness in all kinds of ways. – Bertrand Russell, Conquest of Happiness (1930) ch. 9

(Click for more Unusual Quotations on Science and Belief)

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Misguided Guide May Solve AIDS’s Biggest Problem

December 22nd, 2007

Hidden in New Yorker piece, a way of moving on from HIV hysteria

How the top ranks could rationalize flipping reality the right way up again

Can you see it? Hint included

spector.jpgThe unstoppable Michael Specter has produced an update review in the New Yorker of the latest thinking on retroviruses, which makes a number of remarkable but somewhat unconvincing claims, if you know anything about the topic.

It has one point of interest for all paradigm war observers in HIV=AIDS, however, which provides what in our view is the answer to the vexed question all informed supporters and promoters of the paradigm HIV-is-the-cause-of-AIDS secretly worry over, namely, How the heck do we get out of this debacle?

The hippopotamus in the AIDS bath

For any admission of what has really been going on in the past twenty years in HIV=AIDS – possibly over a hundred billion dollars spent, much of it public money, on an absurd, unsubstantiated, self-contradicting paradigm dreamed up by a known rascal and perpetrated by a self serving bureaucrat with the scientific grasp of a gnat on a world he prevents from reviewing it by barring respectable reporters from even mentioning the topic of all the excellent papers in the AIDS literature rejecting the tenets of the overarching but hollow belief.

Papers, that is, written not only by Duesberg but also by none other than Anthony Fauci and our heroic debunker basher John P. “I am not a macaque, but a fine scientist who tests microbicide on the nether regions of macaques” Moore of Weill-Cornell – threatens to bring the grand institutions and great names of science into such disrepute that they will never recover their authority.

Imagine if Science and Nature had to admit a failure of peer review so embarrassing that twenty years of study and discussion are revealed to have been based on a very silly and unjustified belief, one that has led to dosing hundreds of thousands of people – potentially millions – with extremely damaging drugs that have not only failed to rescue patients suffering from other, misattributed, real illnesses but actually hurried them to their graves, patients who have included some of the most important cultural figures in America?

hippounderwater.jpgImagine what effect that would have on public and charitable support and funding of these august institutional and personal pillars of the scientific community, most of which is not to blame for this vast fiasco.

Where would that leave the reputation of the Lasker Awards, who have dispensed more than one prize to those who promote this insupportable distortion of science, though they have not been followed by a prize from the Nobel committee in the usual way, a fact that gives one hope that there are those in Stockholm who are better informed on what is going on, and reluctant to give the greatest accolade to such as Robert Gallo.

After all, a Nobel is meant to recognize good done to humanity, not a self serving claim which has been bolstered by artificial support from a censoring NIH and sickened and polished off so many people, including such names as Rock Hudson and Arthur Ashe, and is now threatening the black community in America as well as so many new recruits to AIDS meme thinking in Africa and Asia.

The consequences are so dire that it is almost inconceivable that a public disavowal of HIV will ever take place at the top level, where it should take place, if those perched there were ever to meet their public responsibility in the matter.

This is the hippopotamus in the HIV=AIDS bath, so to speak, the unacknowledged problem all sophisticated observers can see, regardless of which side they fight on in public, that is to say, whether they still promote the now thoroughly debunked paradigm, or whether they are debunkers who struggle to get coverage of its utterly specious and indefensible nature into the mainstream media.

Media, that is, served by science reporters who have absolutely no interest in going up against the solid array of authority figures, scientific institutions, governments and international organizations around the world who have signed on to the paradigm as instructed by Science, Nature and the rest of the supposedly authoritative scientific journals we all know and trust, until we find out how wrong they can be.

A solution appears, hidden in Specter’s piece

But now we have a solution of how to make this transition so no one gets hurt, thanks to the fellow traveling HIV=AIDS reporter Specter, who as usual clearly has no idea at all as to the truth or falsehood of any of the material he covers in this field, but merely acts as an excellent conduit of the claims and interpretations of the fine scientists he talks to into the pages of the indispensable New Yorker, a very fine magazine that we all know and trust.

Trust until, that is, until we find out how wrong it can be if its superb reporters don’t somehow find some way to employ a little investigation on their own when dealing with scientists, who are after all as human as the rest of us, and therefore likely to include one or two bad apples who try to pull the wool over the eyes of unsuspecting, politely uncritical interpreters of their story such as the inimitable Specter.

See if you can detect the exit door to the HIV=AIDS global debacle opened by the presumably unwitting Michael in this story, which was in the December 3 issue and is now available in full at Darwin’s Surprise: Why are evolutionary biologists bringing back extinct deadly viruses?

Or you can read it here:
From the December 3 issue of the New Yorker
at http://www.newyorker.com/reporting/2007/12/03/071203fa_fact_specter?printable=true
Darwin’s Surprise Why are evolutionary biologists bringing back extinct deadly viruses?
by Michael Specter
December 3, 2007

Disabled retroviruses-fossils of molecular battles that raged for generations-make up eight per cent of the human genome.

Thierry Heidmann’s office, adjacent to the laboratory he runs at the Institut Gustave Roussy, on the southern edge of Paris, could pass for a museum of genetic catastrophe. Files devoted to the world’s most horrifying infectious diseases fill the cabinets and line the shelves. There are thick folders for smallpox, Ebola virus, and various forms of influenza. SARS is accounted for, as are more obscure pathogens, such as feline leukemia virus, Mason-Pfizer monkey virus, and simian foamy virus, which is endemic in African apes. H.I.V., the best-known and most insidious of the viruses at work today, has its own shelf of files. The lab’s beakers, vials, and refrigerators, secured behind locked doors with double-paned windows, all teem with viruses. Heidmann, a meaty, middle-aged man with wild eyebrows and a beard heavily flecked with gray, has devoted his career to learning what viruses might tell us about AIDS and various forms of cancer. “This knowledge will help us treat terrible diseases,” he told me, nodding briefly toward his lab. “Viruses can provide answers to questions we have never even asked.”

Viruses reproduce rapidly and often with violent results, yet they are so rudimentary that many scientists don’t even consider them to be alive. A virus is nothing more than a few strands of genetic material wrapped in a package of protein—a parasite, unable to function on its own. In order to survive, it must find a cell to infect. Only then can any virus make use of its single talent, which is to take control of a host’s cellular machinery and use it to churn out thousands of copies of itself. These viruses then move from one cell to the next, transforming each new host into a factory that makes even more virus. In this way, one infected cell soon becomes billions.

Nothing—not even the Plague—has posed a more persistent threat to humanity than viral diseases: yellow fever, measles, and smallpox have been causing epidemics for thousands of years. At the end of the First World War, fifty million people died of the Spanish flu; smallpox may have killed half a billion during the twentieth century alone. Those viruses were highly infectious, yet their impact was limited by their ferocity: a virus may destroy an entire culture, but if we die it dies, too. As a result, not even smallpox possessed the evolutionary power to influence humans as a species—to alter our genetic structure. That would require an organism to insinuate itself into the critical cells we need in order to reproduce: our germ cells. Only retroviruses, which reverse the usual flow of genetic code from DNA to RNA, are capable of that. A retrovirus stores its genetic information in a single-stranded molecule of RNA, instead of the more common double-stranded DNA. When it infects a cell, the virus deploys a special enzyme, called reverse transcriptase, that enables it to copy itself and then paste its own genes into the new cell’s DNA. It then becomes part of that cell forever; when the cell divides, the virus goes with it. Scientists have long suspected that if a retrovirus happens to infect a human sperm cell or egg, which is rare, and if that embryo survives—which is rarer still—the retrovirus could take its place in the blueprint of our species, passed from mother to child, and from one generation to the next, much like a gene for eye color or asthma.

When the sequence of the human genome was fully mapped, in 2003, researchers also discovered something they had not anticipated: our bodies are littered with the shards of such retroviruses, fragments of the chemical code from which all genetic material is made. It takes less than two per cent of our genome to create all the proteins necessary for us to live. Eight per cent, however, is composed of broken and disabled retroviruses, which, millions of years ago, managed to embed themselves in the DNA of our ancestors. They are called endogenous retroviruses, because once they infect the DNA of a species they become part of that species. One by one, though, after molecular battles that raged for thousands of generations, they have been defeated by evolution. Like dinosaur bones, these viral fragments are fossils. Instead of having been buried in sand, they reside within each of us, carrying a record that goes back millions of years. Because they no longer seem to serve a purpose or cause harm, these remnants have often been referred to as “junk DNA.” Many still manage to generate proteins, but scientists have never found one that functions properly in humans or that could make us sick.

Then, last year, Thierry Heidmann brought one back to life. Combining the tools of genomics, virology, and evolutionary biology, he and his colleagues took a virus that had been extinct for hundreds of thousands of years, figured out how the broken parts were originally aligned, and then pieced them together. After resurrecting the virus, the team placed it in human cells and found that their creation did indeed insert itself into the DNA of those cells. They also mixed the virus with cells taken from hamsters and cats. It quickly infected them all, offering the first evidence that the broken parts could once again be made infectious. The experiment could provide vital clues about how viruses like H.I.V. work. Inevitably, though, it also conjures images of Frankenstein’s monster and Jurassic Park.

“If you think about this for five minutes, it is wild stuff,” John Coffin told me when I visited him in his laboratory at Tufts University, where he is the American Cancer Society Research Professor. Coffin is one of the country’s most distinguished molecular biologists, and was one of the first to explore the role of endogenous retroviruses in human evolution. “I understand that the idea of bringing something dead back to life is fundamentally frightening,” he went on. “It’s a power that science has come to possess and it makes us queasy, and it should. But there are many viruses that are more dangerous than these—more infectious, far riskier to work with, and less potentially useful.’’

Thanks to steady advances in computing power and DNA technology, a talented undergraduate with a decent laptop and access to any university biology lab can assemble a virus with ease. Five years ago, as if to prove that point, researchers from the State University of New York at Stony Brook “built” a polio virus, using widely available information and DNA they bought through the mail. To test their “polio recipe,” they injected the virus into mice. The animals first became paralyzed and then died. (“The reason we did it was to prove that it can be done,’’ Eckard Wimmer, who led the team, said at the time. “Progress in biomedical research has its benefits and it has its downside.’’) The effort was widely seen as pointless and the justification absurd. “Proof of principle for bioterrorism,’’ Coffin called it. “Nothing more.” Then, two years ago, after researchers had sequenced the genetic code of the 1918 flu virus, federal scientists reconstructed it, too. In that case, there was a well-understood and highly desired goal: to develop a vaccine that might offer protection against future pandemics.

Resurrecting an extinct virus is another matter. Still, if Heidmann had stuck to scientific nomenclature when he published his results, last fall, few outside his profession would have noticed. A paper entitled “Identification of an Infectious Progenitor for the Multiple-Copy HERV-K Human Endogenous Retroelements,’’ which appeared in the journal Genome Research, was unlikely to cause a stir. Heidmann is on a bit of a mission, though. He named the virus Phoenix, after the mythical bird that rises from the ashes, because he is convinced that this virus and others like it have much to tell about the origins and the evolution of humanity.

With equal ardor but less fanfare, scientists throughout the world have embarked on similar or related projects. One team, at the Aaron Diamond AIDS Research Center, in New York, recently created an almost identical virus. In the past few months, groups at Oxford University and at the Fred Hutchinson Cancer Research Center, in Seattle, have also produced results that provide startling observations about evolution and disease. The approaches often differ, but not the goals. All of these researchers hope that excavating the molecular past will help address the medical complexities that we confront today. Almost incidentally, they have created a new discipline, paleovirology, which seeks to better understand the impact of modern diseases by studying the genetic history of ancient viruses.

“This is something not to fear but to celebrate,’’ Heidmann told me one day as we sat in his office at the institute, which is dedicated to the treatment and eradication of cancer. Through the window, the Eiffel Tower hovered silently over the distant city. “What is remarkable here, and unique, is the fact that endogenous retroviruses are two things at once: genes and viruses. And those viruses helped make us who we are today just as surely as other genes did. I am not certain that we would have survived as a species without them.”

He continued, “The Phoenix virus sheds light on how H.I.V. operates, but, more than that, on how we operate, and how we evolved. Many people study other aspects of human evolution—how we came to walk, or the meaning of domesticated animals. But I would argue that equally important is the role of pathogens in shaping the way we are today. Look, for instance, at the process of pregnancy and birth.’’ Heidmann and others have suggested that without endogenous retroviruses mammals might never have developed a placenta, which protects the fetus and gives it time to mature. That led to live birth, one of the hallmarks of our evolutionary success over birds, reptiles, and fish. Eggs cannot eliminate waste or draw the maternal nutrients required to develop the large brains that have made mammals so versatile. “These viruses made those changes possible,’’ Heidmann told me. “It is quite possible that, without them, human beings would still be laying eggs.”

H·I.V., the only retrovirus that most people have heard of, has caused more than twenty-five million deaths and infected at least twice that number of people since the middle of the twentieth century, when it moved from monkey to man. It may be hard to understand how organisms from that same family, and constructed with the same genes, could have played a beneficial, and possibly even essential, role in the health and development of any species. In 1968, Robin Weiss, who is now a professor of viral oncology at University College London, found endogenous retroviruses in the embryos of healthy chickens. When he suggested that they were not only benign but might actually perform a critical function in placental development, molecular biologists laughed. “When I first submitted my results on a novel ‘endogenous’ envelope, suggesting the existence of an integrated retrovirus in normal embryo cells, the manuscript was roundly rejected,’’ Weiss wrote last year in the journal Retrovirology. “One reviewer pronounced that my interpretation was impossible.’’ Weiss, who is responsible for much of the basic knowledge about how the AIDS virus interacts with the human immune system, was not deterred. He was eager to learn whether the chicken retroviruses he had seen were recently acquired infections or inheritances that had been passed down through the centuries. He moved to the Pahang jungle of Malaysia and began living with a group of Orang Asli tribesmen. Red jungle fowl, an ancestor species of chickens, were plentiful there, and the tribe was skilled at trapping them. After collecting and testing both eggs and blood samples, Weiss was able to identify versions of the same viruses. Similar tests were soon carried out on other animals. The discovery helped mark the beginning of a new approach to biology. “If Charles Darwin reappeared today, he might be surprised to learn that humans are descended from viruses as well as from apes,” Weiss wrote.

Darwin’s surprise almost certainly would be mixed with delight: when he suggested, in “The Descent of Man” (1871), that humans and apes shared a common ancestor, it was a revolutionary idea, and it remains one today. Yet nothing provides more convincing evidence for the “theory” of evolution than the viruses contained within our DNA. Until recently, the earliest available information about the history and the course of human diseases, like smallpox and typhus, came from mummies no more than four thousand years old. Evolution cannot be measured in a time span that short. Endogenous retroviruses provide a trail of molecular bread crumbs leading millions of years into the past.

Darwin’s theory makes sense, though, only if humans share most of those viral fragments with relatives like chimpanzees and monkeys. And we do, in thousands of places throughout our genome. If that were a coincidence, humans and chimpanzees would have had to endure an incalculable number of identical viral infections in the course of millions of years, and then, somehow, those infections would have had to end up in exactly the same place within each genome. The rungs of the ladder of human DNA consist of three billion pairs of nucleotides spread across forty-six chromosomes. The sequences of those nucleotides determine how each person differs from another, and from all other living things. The only way that humans, in thousands of seemingly random locations, could possess the exact retroviral DNA found in another species is by inheriting it from a common ancestor.

Molecular biology has made precise knowledge about the nature of that inheritance possible. With extensive databases of genetic sequences, reconstructing ancestral genomes has become common, and retroviruses have been found in the genome of every vertebrate species that has been studied. Anthropologists and biologists have used them to investigate not only the lineage of primates but the relationships among animals—dogs, jackals, wolves, and foxes, for example—and also to test whether similar organisms may in fact be unrelated.

Although it is no longer a daunting technical task to find such viruses, or their genes, figuring out the selective evolutionary pressures that shaped them remains difficult. Partly, that is because the viruses mutate with such speed. H.I.V. can evolve a million times as fast as the human-immune-system cells it infects. (Such constant change makes it hard to develop antiviral drugs that will remain effective for long, and it has also presented a significant obstacle to the development of an AIDS vaccine.)

There are retroviruses (like H.I.V.) that do not infect sperm or egg cells. Because they are not inherited, they leave no trace of their history. “We can have a fossil record only of the viruses that made it into the germ line,’’ Paul Bieniasz told me. “And, of course, most did not.” Bieniasz is a professor of retrovirology at the Aaron Diamond AIDS Research Center and the chief of the retrovirology laboratory at Rockefeller University. He has long been interested in the way complex organisms interact with viruses and adapt to them. “With flu virus, you can watch it change in real time,’’ he said. “You can watch the antibodies develop and see when and how it dies out. But with these others you are looking back tens of millions of years, so it is hard to know how a virus functioned.’’

While Heidmann was working with the Phoenix virus in France, Bieniasz and two colleagues at Aaron Diamond initiated a similar project. (At first, neither team was aware of the other’s work.) Bieniasz rebuilt the youngest extinct retrovirus in the human genome—one that was still active a few hundred thousand years ago—because it had the fewest mutations. The team took ten versions of that virus (we carry more than thirty) and compared the thousands of nucleotides in the genetic sequence of each version. They were almost identical, but where they differed the researchers selected the nucleotides that appeared most frequently. That permitted them to piece together a working replica of the extinct retrovirus. “If you have a person with a lethal defect in the heart,’’ Bieniasz explained, “and another with a lethal defect in the kidney, you could make one healthy person by transplanting the respective organs. That is what we did.

“In the past, you got sick and you keeled over and died,’’ he said. “Or you survived. Nobody could make much sense of it. But almost ten per cent of our DNA consists of old retroviruses, and that says to me that it’s pretty clear they played a major role in our evolution. We evolved remarkably sophisticated defenses against them, and we would have done that only if their impact on human populations had been quite severe. It’s very likely that we have been under threat from retroviruses many times throughout human history. It is eminently possible that this is not the first time we have been colonized by a virus very much like H.I.V.”

At the end of the nineteenth century, a mysterious series of cancer epidemics devastated American poultry farms. One bird would fall ill and the entire flock would soon be dead. In 1909, a desperate farmer from Long Island brought a chicken with a tumor to the laboratory of Peyton Rous, a young cancer researcher at the Rockefeller Institute for Medical Research, in New York City (which became Rockefeller University). Cancer was not supposed to spread by virus, but the bird clearly had cancer. Rous, who as a young man worked on a Texas cattle ranch, was mystified. He extracted cancer cells from the sick bird, chopped them up, and injected the filtered remains into healthy chickens: they all developed tumors. A virus had to be the cause, but for years no one could figure out how the virus functioned.

Then, in the nineteen-sixties, Howard Temin, a virologist at the University of Wisconsin, began to question the “central dogma” of molecular biology, which stated that genetic instructions moved in a single direction, from the basic blueprints contained within our DNA to RNA, which translates those blueprints and uses them to build proteins. He suggested that the process could essentially run in the other direction: an RNA tumor virus could give rise to a DNA copy, which would then insert itself into the genetic material of a cell. Temin’s theory was dismissed, like most fundamental departures from conventional wisdom. But he never wavered. Finally, in 1970, he and David Baltimore, who was working in a separate lab, at the Massachusetts Institute of Technology, simultaneously discovered reverse transcriptase, the special enzyme that can do exactly what Temin predicted: make DNA from RNA.

The discovery has had a profound impact on modern medicine. It not only explained how cancer can be caused by a virus but provided researchers with the tools they needed to understand the origins and natural progression of diseases like AIDS. It also created a new field, retrovirology, and, more than that, as the Nobel committee noted when it awarded the 1975 Prize in Medicine to both Baltimore and Temin, it began to erase the tenuous borders between viruses and genes.

Retroviruses cause cancers in chickens, sheep, mice, and other animals, but their effect on humans became clear only in the late nineteen-seventies, with the identification of two viruses that cause forms of leukemia. Retroviral proteins are particularly abundant in certain kinds of tumor cells, and scientists wondered to what degree they might be a cause of cancer. They were also curious about how retroviruses that infect us today differ from their ancestors. Working with mice in 2005, Thierry Heidmann found that endogenous retroviruses were present in large quantities in tumor cells. Similar viruses have been associated with many cancers (and other diseases). It is still not clear how they function, but they may help subvert the immune system, which would permit cancer cells to grow without restraint. Endogenous retroviruses also may actually protect us from viruses that are even worse. Experiments with mice and chickens have shown that they can block new infections by viruses with a similar genetic structure. Nonetheless, endogenous retroviruses are parasites, and in most cases the cells they infect would be better off without them. There is, however, one notable exception.

The earliest mammals, ancestors of the spiny anteater and the duck-billed platypus, laid eggs. Then, at least a hundred million years ago, embryos, instead of growing in a shell, essentially became parasites. While only balls of cells, they began to implant themselves in the lining of the womb. The result was the placenta, which permits the embyros to take nourishment from the mother’s blood, while preventing immune cells or bacteria from entering. The placenta is essentially a modified egg. In the early nineteen-seventies, biologists who were scanning baboon placentas with an electron microscope were surprised to see retroviruses on a layer of tissue known as the syncytium, which forms the principal barrier between mother and fetus. They were even more surprised to see that all the animals were healthy. The same phenomenon was soon observed in mice, cats, guinea pigs, and humans. For many years, however, embryologists were not quite sure what to make of these placental discoveries. Most remained focussed on the potential harm a retrovirus could cause, rather than on any possible benefit. Cell fusion is a fundamental characteristic of the mammalian placenta but also, it turns out, of endogenous retroviruses. In fact, the protein syncytin, which causes placental cells to fuse together, employs the exact mechanism that enables retroviruses to latch on to the cells they infect.

The Nobel Prize-winning biologist Joshua Lederberg once wrote that the “single biggest threat to man’s continued dominance on this planet is the virus.” Harmit Malik, an evolutionary geneticist at the Fred Hutchinson Cancer Research Center, acknowledges the threat, yet he is confident that viruses may also provide one of our greatest scientific opportunities. Exploring that fundamental paradox—that our most talented parasites may also make us stronger—has become Malik’s passion. “We have been in an evolutionary arms race with viruses for at least one hundred million years,’’ he told me recently, when I visited his laboratory. “There is genetic conflict everywhere. You see it in processes that you would never suspect; in cell division, for instance, and in the production of proteins involved in the very essence of maintaining life.

“One party is winning and the other losing all the time,” Malik went on. “That’s evolution. It’s the world’s definitive game of cat and mouse. Viruses evolve, the host adapts, proteins change, viruses evade them. It never ends.” The AIDS virus, for example, has one gene, called “vif,” that does nothing but block a protein whose sole job is to stop the virus from making copies of itself. It simply takes that protein into the cellular equivalent of a trash can; if not for that gene, H.I.V. might have been a trivial disease. “To even think about the many million-year processes that caused that sort of evolution,” Malik said, shaking his head in wonder. “It’s dazzling.” Malik grew up in Bombay and studied chemical engineering at the Indian Institute of Technology there, one of the most prestigious technical institutions in a country obsessed with producing engineers. He gave no real thought to biology, but he was wholly uninspired by his other studies. “It was fair to say I had little interest in chemical engineering, and I happened to tell that to my faculty adviser,’’ he recalled. “He asked me what I liked. Well, I was reading Richard Dawkins at the time, his book ‘The Selfish Gene’ ”—which asserts that a gene will operate in its own interest even if that means destroying an organism that it inhabits or helped create. The concept fascinated Malik. “I was thinking of becoming a philosopher,’’ he said. “I thought I would study selfishness.”

Malik’s adviser had another idea. The university had just established a department of molecular biology, and Malik was dispatched to speak with its director. “This guy ended up teaching me by himself, sitting across the table. We met three times a week. I soon realized that he was testing out his course on me. I liked it and decided to apply to graduate school—although I had less than a tenth of the required biology courses. I had very little hope.’’ But he had excellent test scores and in 1993 was accepted at the University of Rochester, as a graduate student in the biology department. He visited his new adviser as soon as he arrived. “He looked at my schedule and said, ‘I see that you are doing genetics.’ I had no clue what he was talking about, but I said sure, that sounds good. I had never taken a course in the subject. He gave me the textbook and told me that the class was for undergraduates, which made me feel more comfortable.’’ It wasn’t until the end of the conversation that Malik realized he would be teaching the class, not taking it.

The Hutchinson Center encourages its research scientists to collaborate with colleagues in seemingly unrelated fields. Malik and Michael Emerman, a virologist at the center’s Human Biology and Basic Sciences Divisions, have been working together for four years. Malik’s principal interest is historical: why did evolutionary pressures shape our defenses against viruses, and how have they done it? Emerman studies the genetic composition and molecular pathology of the AIDS virus. “Together, we are trying to understand what constellation of viruses we are susceptible to and why,’’ Emerman told me. “We know at least that it is all a consequence of infections our ancestors had. So from there we want to try and derive a modern repertoire of antiviral genes.”

They focussed on chimpanzees, our closest relatives. Chimpanzees are easily infected by the AIDS virus, but it never makes them sick. That has remained one of the most frustrating mysteries of the epidemic. How did nearly identical genetic relatives become immune to a virus that attacks us with such vigor? The most dramatic difference between the chimp genome and ours is that chimps have roughly a hundred and thirty copies of a virus called Pan troglodytes endogenous retrovirus, which scientists refer to by the acronym PtERV (pronounced “pea-terv”). Gorillas have eighty copies. Humans have none.

“We can see that PtERV infected gorillas and chimps four million years ago,’’ Emerman told me. “But there was never any trace of its infecting humans.” It is possible that all infected humans died, but it is far more likely that we developed a way to repel the virus. Nobody knew why until Emerman, Malik, and Shari Kaiser, a graduate student in Emerman’s lab, presented evidence for a startling theory: the evolutionary process that protects us from PtERV may be the central reason we are vulnerable to H.I.V.

“We thought we must have a defense against this thing that they don’t have,’’ Malik told me, picking up the story the following day. Evolutionary biologists are not given to emotional outbursts—by definition, they take the long view. Malik is an engaging and voluble exception. When an antiviral protein excites him, he doesn’t hold back. “Where but in evolutionary history can you see a story like this, with PtERV and the chimps?’’ he asked, leaping up from his chair to begin sketching viral particles on a whiteboard. “It’s simply amazing.’’

He launched into a description of the complex interactions between viruses and the proteins that we have developed to fight them. There is one particular gene, called TRIM5a, that in humans manufactures a protein that binds to and destroys PtERV. “Our version of this gene is highly effective against PtERV, which is why we don’t get infected,’’ he said. Every primate has some version, but it works differently in each species—customized to fit the varying evolutionary requirements of each. In the rhesus monkey, that single gene provides complete protection against H.I.V. infection. In humans, it does nothing of the kind. “When Michael and I started to get into this business, people had never thought much about the evolutionary meaning of that gene. But we wondered, Is TRIM5a just an anti-H.I.V. factor or is there something else going on here?”

Like the two human retroviruses that were reconstructed in France and in New York, PtERV has long been extinct; Emerman and Malik realized that they would have to assemble a new version if they hoped to learn how we became immune to it. They took scores of viral sequences and lined them up to see what they had in common. The answer was almost everything. When there were differences in the sequence, the researchers used a statistical model to predict the most likely original version. Then they put the virus back together. (Like Bieniasz, in New York, they did so in such a way that the virus could reproduce only once.) They modified the human TRIM5a protein so that it would function like the chimp version. After that, the protein no longer protected humans against the reconstructed copy of the virus. Next, they tested this modified version against H.I.V. Emerman placed it in a dish, first with H.I.V. and next with PtERV. What he found astonished him. No matter how many times he repeated the test, the results never varied. “In every case, the protein blocked either PtERV or H.I.V.,” Emerman told me. “But it never protected the cells from both viruses.”

There are several possible ways to interpret the data, but the one favored by the researchers is that because humans developed an effective defense against one virus, PtERV, at about the time we split off from the chimps, five million years ago, we were left vulnerable to a new one, H.I.V. “If we can develop a drug that acts the same way the monkey version of this protein acts—so that it recognizes H.I.V. and neutralizes it—we could have a very effective therapy,’’ Malik said. Both he and Emerman stressed that this day will not come soon. “First, we have to establish what part of TRIM5a is actually responsible for protecting monkeys against H.I.V.,” Malik said. “Then we would have to try and make it as a drug”—and one that the human body won’t reject. “The challenge is to find out how little you can change the human version and still make it effective against H.I.V. That is really what drives this whole story of re-creating that extinct virus and doing these experiments. Nobody is doing this as a gimmick. This virus could open doors that have been closed to us for millions of years. And if we can learn how to do that we have a chance to find a very effective response to one of the world’s most incredibly effective viruses.”

The Oxford University zoology department is housed in a forbidding concrete structure that looks like an Eastern European police station. The building is named for the Dutch ethologist Niko Tinbergen, whose work—with wasps and gulls, among other species—won him a Nobel Prize and helped establish the study of animal behavior as a science. Tinbergen’s most famous student, Richard Dawkins, has carried on the university tradition of aggressive independence, and so have the younger members of the faculty. I stopped by the department a few months ago to have lunch with two of them, Aris Katzourakis and Robert Belshaw, both evolutionary biologists who have made the new field of paleovirology a specialty. Just before I arrived, Katzourakis had lobbed a bomb into the field.

Nobody knows what chain of evolutionary factors is required to transform an infectious virus—like H.I.V.—into one that is inherited. Such a virus would have to invade reproductive cells. H.I.V. doesn’t do that. It belongs to a class called lentiviruses (from the Latin for “slow”), which are common in mammals like sheep and goats. Because lentiviruses had never been found in any animal’s genome, most virologists assumed that they evolved recently. Until this summer, the oldest known lentivirus was “only” a million years, and almost no one thought that a lentivirus could become endogenous.

In a paper titled “Discovery and Analysis of the First Endogenous Lentivirus,’’ published last spring in Proceedings of the National Academy of Sciences, Katzourakis, along with collaborators from Oxford, Stanford University, and Imperial College London, showed otherwise. They discovered the fossilized remains of an ancient lentivirus—the same type that causes AIDS—within the genome of the European rabbit (Oryctolagus cuniculus). “At first, I just assumed it was a mistake,’’ Katzourakis told me over lunch in the building’s cafeteria, Darwin’s Café. “We checked it twice, three times. But we kept seeing genes that are found only in lentiviruses.’’ They named their discovery “rabbit endogenous lentivirus type K,” or RELIK. An obvious next step for Katzourakis and his group will be to work with virologists who can assemble a functional version of the ancient virus—as the researchers in Paris, New York, and Seattle have done. “It’s the most promising way to explore the evolution and the impact of H.I.V.,” he said.

It might be more than that. AIDS researchers have always been handicapped by the absence of a small-animal model in which to study the effects of the disease. It is not easy to use monkeys or sheep. They are expensive and difficult to obtain, and, for reasons of ethics, many experiments on them are proscribed. “Although RELIK is an ancient lentivirus and only defective copies were identified in this analysis,’’ the authors wrote, “recent research has shown that it is possible to reconstruct infectious progenitors of such viruses,” which, they concluded, could potentially “provide a small animal model for experimental research.”

The discovery has already changed the way scientists think about viral evolution, and about H.I.V. in particular. “The most obvious implication is that we can no longer say that H.I.V. could not become endogenous,’’ John Coffin, of Tufts, told me, though he still considers that unlikely. “It opens the field to a whole new level of examination.” It also considerably alters the phylogenetic tree. RELIK is at least seven million years old, which makes it the oldest known lentivirus. “It is possible that primate lentiviruses such as H.I.V. and S.I.V.’’—its simian cousin—“are much older than people ever thought,” Coffin said.

We can’t be certain when endogenous retroviruses entered our genome, because it is impossible to watch a five-million-year process unfold. Yet in Australia a retrovirus seems to be evolving in front of our eyes. Beginning in the late nineteenth century, koalas on the mainland were hunted nearly to extinction. To protect them, as many as possible were captured and moved to several islands in the south. In the past hundred years, those koalas have been used to replenish the population on the mainland and on several other Australian islands. In many cases, though, they have become infected with a retrovirus that causes leukemia, immune disorders, and other diseases. It can even kill them. The epidemic presents a significant threat to the future of the species, and scientists have followed it closely. One group, from the University of Queensland, looked for the virus in koala DNA—and, as one would expect with a retrovirus, found it. The team also noticed that some of the babies, known as joeys, were infected in the same locations on their DNA as their parents. That means that the virus has become endogenous. Yet, when the scientists examined the koalas on Kangaroo Island, in the south, they discovered something they had not anticipated: none of the koalas were infected.

That could mean only one thing: since the infected animals had all been moved just in the past century, the koala retrovirus must have spread to Australia recently and is entering the genome now. That offers virologists and evolutionary biologists their first opportunity to learn how a virus transforms itself from something that can simply infect (and kill) its host to an organism that will become a permanent part of that host. Persistent viruses tend to grow weaker over the years. They couldn’t live for long if they killed everything they infected. How they adapt, though, is a mystery. “Events like this have obviously occurred in human evolution,’’ Paul Bieniasz told me—even with viruses like H.I.V. “We might be able to see how the koala infection settles into the genome, and whether it plays a role in helping its host fend off other viruses,” he continued. “Whatever we learn will be useful, because we could never have learned it in any other way.”

In 1963, Linus Pauling, the twentieth century’s most influential chemist, wrote an essay, with Emile Zuckerkandl, in which they predicted that it would one day become possible to reconstruct extinct forms of life. It has taken half a century for scientists to acquire the information necessary to master most of the essential molecular biology and genetics, but there can no longer be any doubt that Pauling was right. Once you are able to assemble the ancestral sequence of any form of life, all you have to do is put the genes together, and back it comes.

“The knowledge you gain from resurrecting something that has not been alive for a million years has to be immensely valuable,’’ Harmit Malik told me in Seattle. “We didn’t take it lightly, and I don’t think any of our colleagues did, either.’’ He repeatedly pointed out that each virus was assembled in such a way that it could reproduce only once. “If you can’t apply the knowledge, you shouldn’t do the experiment,” he said. Malik is a basic research scientist. His work is not directly related to drug development or treating disease. Still, he thinks deeply about the link between what he does and the benefits such work might produce. That is an entirely new way to look at the purpose of scientific research, which in the past was always propelled by intellectual curiosity, not utilitarian goals. Among élite scientists, it was usually considered gauche to be obsessed with anything so tangible or immediate; brilliant discoveries were supposed to percolate. But that paradigm was constructed before laboratories around the world got into the business of reshaping, resurrecting, and creating various forms of life.

The insights provided by recent advances in evolutionary biology have already been put to use, particularly in efforts to stop the AIDS virus. One of the main reasons that endogenous retroviruses can enter our genome without killing us is that they make many errors when they reproduce. Those errors are genetic mutations. The faster a cell reproduces (and the older it is), the more errors it is likely to make. And the more errors it makes the less likely it is to be dangerous to its host. “Viruses are accumulating and becoming more decrepit with every passing million years” was the way Malik described it to me. That realization has led AIDS researchers to contemplate a novel kind of drug. Until recently, antiviral medications had been designed largely to prevent H.I.V. from reproducing. Various drugs try to interfere with enzymes and other proteins that are essential for the virus to copy itself. There is a problem with this approach, however. Because the virus changes so rapidly, after a while a drug designed to stop it can lose its effectiveness completely. (That is why people take cocktails of H.I.V. medications; the combinations help slow the rate at which the virus learns to evade those interventions.)

Scientists at a company called Koronis Pharmaceuticals, just outside Seattle, are taking the opposite approach. They hope that by speeding up the life cycle of the AIDS virus they can drive it to extinction. The goal is to accelerate the virus’s already rapid pace of mutation to the point where it produces such an enormous number of errors in its genome that it ceases to pose a threat. Like endogenous retroviruses, H.I.V. would become extinct. Earlier this month, researchers at the University of California at San Francisco and at the University of Toronto announced an even more fascinating way to use the fossils in our genome. H.I.V. infects immune-system cells and alters them so that they can produce more H.I.V. In doing so, they stimulate endogenous retroviruses, which then produce proteins that act as a sort of distress signal. Those signals can be detected on the surface of H.I.V.-infected cells, and in theory it should be possible to develop vaccines that target them. In essence, such a vaccine would act like a smart bomb, homing in on a signal transmitted from within each H.I.V.-infected cell. The team in San Francisco found strong evidence of those signals in the immune cells of fifteen of sixteen volunteers who were infected with H.I.V. In an uninfected control group, the signals were far weaker or were absent altogether. “For a vaccine against an infectious agent, this is a completely new strategy,’’ Douglas Nixon, the immunologist who led the team, said. It’s one that could not have emerged without the recent knowledge gained through experiments with endogenous retroviruses.

There may be no biological process more complicated than the relationships that viruses have with their hosts. Could it be that their persistence made it possible for humans to thrive? Luis P. Villarreal has posed that question many times, most notably in a 2004 essay, “Can Viruses Make Us Human?” Villarreal is the director of the Center for Virus Research at the University of California at Irvine. “This question will seem preposterous to most,’’ his essay begins. “Viruses are molecular genetic parasites and are mostly recognized for their ability to induce disease.” Yet he goes on to argue that they also represent “a major creative force’’ in our evolution, driving each infected cell to acquire new and increasingly complex molecular identities. Villarreal was among the first to propose that endogenous retroviruses played a crucial role in the development of the mammalian placenta. He goes further than that, though: “Clearly, we have been observing evolution only for a very short time. Yet we can witness what current viruses,” such as H.I.V., “can and might do to the human population.”

Villarreal predicts that, without an effective AIDS vaccine, nearly the entire population of Africa will eventually perish. “We can also expect at least a few humans to survive,’’ he wrote. They would be people who have been infected with H.I.V. yet, for some reason, do not get sick. “These survivors would thus be left to repopulate the continent. However, the resulting human population would be distinct” from those whom H.I.V. makes sick. These people would have acquired some combination of genes that confers resistance to H.I.V. There are already examples of specific mutations that seem to protect people against the virus. (For H.I.V. to infect immune cells, for example, it must normally dock with a receptor that sits on the surface of those cells. There are people, though, whose genes instruct them to build defective receptors. Those with two copies of that defect, one from each parent, are resistant to H.I.V. infection no matter how often they are exposed to the virus.) The process might take tens, or even hundreds, of thousands of years, but Darwinian selection would ultimately favor such mutations, and provide the opportunity for the evolution of a fitter human population. “If this were to be the outcome,’’ Villarreal wrote, “we would see a new species of human, marked by its newly acquired endogenous viruses.” The difference between us and this new species would be much like the difference that we know exists between humans and chimpanzees.

For Villarreal, and a growing number of like-minded scientists, the conclusion is clear. “Viruses may well be the unseen creator that most likely did contribute to making us human.” ♦

Hint:

““The most obvious implication is that we can no longer say that H.I.V. could not become endogenous,’’ John Coffin, of Tufts, told me, though he still considers that unlikely. “It opens the field to a whole new level of examination.” It also considerably alters the phylogenetic tree. RELIK is at least seven million years old, which makes it the oldest known lentivirus. “It is possible that primate lentiviruses such as H.I.V. and S.I.V.’’—its simian cousin—“are much older than people ever thought,” Coffin said.”

Drug bust

December 13th, 2007

Big pharmaceuticals head for lower profits as chemists bump limit

Pfizer dumps $300 million five year upgrade as it closes facility; profits of 90% to 95% will expire along with patents

Dr. Sliskovic makes $13 billion a year for Pfizer, but gets laid off

Will Mother Nature make a comeback?

pfizerlipitorad.jpgAs Christmas approaches, please spare a thought for the sad plight of the drug companies. As the WSJ explains in a fine series of illuminating pieces, they are having a tough time coming up with new drugs just as the patents are expiring on their blockbusters. The prize example at Pfizer is Lipitor, the world’s most lucrative drug:

Pfizer Inc. will be particularly hard-hit when the patent expires as early as 2010 on Lipitor, the cholesterol-lowering blockbuster that ranks as the most successful drug ever. Pharmacists and managed-care companies will aggressively fill prescriptions with generics, reducing annual Lipitor sales to a fraction of last year’s $13 billion.

By 2012, Merck & Co. will face generic competition to its three top-selling drugs: the osteoporosis treatment Fosamax, Singulair for asthma and the blood-pressure drug Cozaar. Those three represent 44% of the company’s current revenue. Following the loss last year of patent protection for Merck’s cholesterol-lowering Zocor, sales this year are expected to fall 82% from $4.38 billion in 2005. A Merck spokeswoman said the company has several products in the pipeline that will offset its patent losses.

The rise of generics wouldn’t matter so much if research labs were creating a stream of new hits. But that isn’t happening. During the five years from 2002 through 2006, the industry brought to market 43% fewer new chemical-based drugs than in the last five years of the 1990s, despite more than doubling research-and-development spending.

grred2.jpgNowadays coming up with a successful new drug is harder than you may think, it seems: the chances of a new one making it into the market is less than 1/10,000, the drug companies claim:

It has never been easy to take a drug from the lab, through animal testing and into human trials. The industry estimates only one out of every 5,000 to 10,000 candidates makes it to human trials. And many drugs that work beautifully in animals fail miserably in people.

But those odds seem to have worsened in recent years, prompting debate about whether the cause is government regulation, corporate structure or an excessive scientific reliance on chemicals rather than biology.

Many drug-company executives blame the FDA for pulling back on approvals. “Very few products are being approved today,” said Bernard Poussot, incoming chief executive of Wyeth. The heightened scrutiny contributed to delays of two Wyeth products this past summer, the company has said.

Evidently the MacDonald’s executive who took over the helm at Pfizer is convinced that chemists can’t come up with hugely profitable breakthroughs any more by fiddling with the Periodic Table.

greed.jpgIn one measure of the greed ethic rampant in the industry, even the inventor of Lipitor, the extraordinarily successful cholesterol curber, has been laid off, and the huge research facility where he toiled is shuttered. How much extra pay did he get from a grateful Pfizer for a drug that earned the company billions of dollars, and which still pulls in $13 billion annually? Not one red cent.

In August, Dr. Sliskovic’s team stopped doing research and began transferring projects to other Pfizer sites. The labs are now being cleaned, inspected and sealed off. The 177-acre campus is a ghost town of empty rooms and boxed-up equipment.

Dr. Sliskovic didn’t seek an internal transfer. He felt that moving would be too hard on his family.

As acting head of chemistry at the Ann Arbor labs, Dr. Sliskovic earned far above the $112,000 a year paid to the average chemist of his experience level. Dr. Sliskovic says he will receive severance pay for between 18 months and two years. With two children in college and another in high school, he says, two years is the longest he could afford to forgo a paycheck.

Dr. Sliskovic has already repainted the family kitchen and living room. Now he is festooning the house and yard with holiday lights. Worried about their financial future, his wife, Cindy, took a second part-time job at the barn where they keep their horses. The irony that the drug her husband helped discover will bring in nearly $13 billion for Pfizer this year hasn’t been lost on her. As a staff scientist, Dr. Sliskovic earned no bonus or royalties for his work on Lipitor.

biotechtomato.jpgWhat will the industry do now to escape the new squeeze? The move is into biotechnology, where products are created not by chemists in test tubes but in live cells, where they don’t yet face competition from generics. Companies are currently charging over $50,000 annually for a cancer drug, and $200,000 a year for one which fights another disease, because competition from generics hasn’t arrived, and it won’t come until Congress creates a way to regulate them.

“For all our amazing advances in the last 50 years, we are still working with the tools of the first pharmaceutical revolution…using advanced chemistry to treat disease symptoms,” Mr. Taurel of Lilly said in a 2003 speech.

The future, many believe, lies in biotechnology. Unlike traditional, chemistry-based drug development, biotechnology uses biological tools to create entire proteins, often similar to those that occur in the human body. This approach has yielded successful drugs to treat diseases such as anemia, cancer and rheumatoid arthritis.

Biotech drugs are especially appealing because they face no competition from generics: No regulatory pathway yet exists in the U.S. for bringing to market generic biotech drugs. So until Congress creates such a pathway, no generic threat will exist to the $4,400 a month that Genentech Inc. charges for its cancer drug Avastin, or the $200,000 a year that Genzyme Corp. gets for Cerezyme to treat Gaucher disease. And biotechnology products tend to target specialized areas of medicine that don’t require mass advertising or armies of salespeople.

pfizerpills.jpgIf you think the vast profits still being made on certain drugs are pure plunder, however, you have to remember that research costs are enormous and the pay off is uncertain. One drug lost $800 million without going anywhere:

Investors, once huge beneficiaries of drug-industry success, have moved to the sidelines. As the Dow Jones World Index rose 75% in the six years ended Nov. 29, the FTSE Global Pharmaceuticals Index fell 19.8%.

While many patients are benefiting from lower-cost generics, others are waiting in vain for relief of their suffering. “In anxiety disorder, the field has imploded in terms of drug development,” said P. Murali Doraiswamy, chief of biological psychiatry at Duke University medical school. “Ten years ago, we had eight or nine different” anxiety-disorder drugs under development, but that has now “come to a halt.”

At last month’s big American Heart Association meeting in Orlando, Fla., there were just two high-profile studies of experimental drugs on the agenda. One, for Eli Lilly’s anti-blood-clotting drug prasugrel, posted results that left some doctors and analysts questioning whether the drug would be a big seller. Lilly, however, says it is “very pleased with the trial’s outcome.”

The other study was a postmortem on Pfizer’s torcetrapib, already known as one of the industry’s most costly failures, with $800 million in budgeted research costs.

Meanwhile the industry is fighting to keep its grasp on America’s pocket book as long as it can:

lipitor.jpgThe dearth of new products has led the industry to invest heavily in marketing and legal tactics that squeeze as much revenue as possible out of existing products. Companies have raised prices; the average price per pill has risen 63% since 2002, according to Michael Krensavage, Raymond James analyst. Companies raised advertising spending to $5.3 billion in 2006 from $2.5 billion in 2001 and since 1995 have nearly tripled the number of industry sales representatives to 100,000.

The industry spent $155 million on lobbying from January 2005 to June 2006, according to the Center for Public Integrity, on “a variety of issues ranging from protecting lucrative drug patents to keeping lower-priced Canadian drugs from being imported.” The industry also successfully lobbied against allowing the federal government to negotiate Medicare drug prices, the center said. The lobbying has drawn fire from politicians, doctors and payers, and damaged the industry’s public image.

A new era of natural treatment heralded, maybe

mothernature.jpgThe other side of the coin is how radically medical treatment might benefit if the commercial pressure from drug companies which distorts it is lessened or removed.

As one knowledge activist in the field points out to Science Guardian, “Mother Nature has been outlawed” in the US marketplace for medications ever since the Kefauver-Harris amendment to the Food and Drug Act in 1962. This ordained that drugs could not be licensed by the FDA until their efficacy was proven in trials, as well as their safety. That put in place an obstacle course of trials to prove effectiveness as well as safety that now costs as much as $400 million or more.

Chemical drug companies of enormous size can handle this financial challenge, but small vitamin companies can’t jump through the hoop. The enormous cost is too much to recover in sales without exclusive patents, and all of Mother Nature’s products are by definition in the public domain and beyond patenting.

So a pyramid of patented drugs to fight symptoms and more drugs to deal with side effects accumulates. One drug after another is marketed as an expensive analogue for natural substances already available. Each one is synthetic, and therefore something never before encountered by the human system, so it is likely to open a Pandora’s box of side effects. The result is a pyramid of accumulating toxicity. New drugs are provided to deal with the side effects of the primary drug treatment, more doctor visits and prescriptions are needed, and everyone profits except for the patient.

gravy_train.gif“Everybody is happy,” says this critic, “because everyone gets paid. But the patient doesn’t get cured. He or she only gets temporary relief, and a regimen of drugs for life. The system is antagonistic to a cure, because a cure would pull everyone off their ride on the gravy train. This is not necessarily a conscious process, but it is the economic reality.”

If this era is now moving into the past, it will be a happy development for patients, in our view. And despite some exceptions to the trend, including wonder drugs that do a great job and are still highly profitable, this does seem to be the case. Naturally, the pharmas will take over natural products soon enough, but at least they won’t have gigantic costs or patents to allow them to lever prices skyhigh.

“The era that created the modern pharmaceutical industry is in fact over,” said Richard Evans, a former Wall Street analyst and now a pharmaceutical consultant.

See full story Big Pharma Faces Grim Prognosis Industry Fails to Find New Drugs to Replace Wonders Like Lipitor by Barbara Martinez and Jacob Goldstein, December 6, 2007; from the WSJ

Big Pharma Faces Grim Prognosis
Industry Fails to Find
New Drugs to Replace
Wonders Like Lipitor
By BARBARA MARTINEZ and JACOB GOLDSTEIN
December 6, 2007; Page A1

Over the next few years, the pharmaceutical business will hit a wall.

Some of the top-selling drugs in industry history will become history as patent protections expire, allowing generics to rush in at much-lower prices. Generic competition is expected to wipe $67 billion from top companies’ annual U.S. sales between 2007 and 2012 as more than three dozen drugs lose patent protection. That is roughly half of the companies’ combined 2007 U.S. sales.

Sortable Chart: Starting in 2010, the pharmaceutical industry faces one of the biggest waves of patent expirations.

At the same time, the industry’s science engine has stalled. The century-old approach of finding chemicals to treat diseases is producing fewer and fewer drugs. Especially lacking are new blockbusters to replace old ones like Lipitor, Plavix and Zyprexa.

The coming sales decline may signal the end of a once-revered way of doing business. “I think the industry is doomed if we don’t change,” says Sidney Taurel, chairman of Eli Lilly & Co. Just yesterday, Bristol-Myers Squibb Co. announced plans to cut 10% of its work force, or about 4,300 jobs, and close or sell about half of its 27 manufacturing plants by 2010. (Please see related article.)

Between 2011 and 2012, annual industry revenue will decline, estimates Datamonitor, a research and consulting firm. That would be the first decline in at least four decades.

Patent expirations are a big problem. Drugs are granted 20 years of patent protection, although companies often fail to get a product to market before half of that period has elapsed. Once it hits the market, however, the patent-protected drug is highly profitable: Typical gross margins are 90% to 95%. When patents expire, generic makers offer the products at a price much closer to the cost of production.

Pfizer Inc. will be particularly hard-hit when the patent expires as early as 2010 on Lipitor, the cholesterol-lowering blockbuster that ranks as the most successful drug ever. Pharmacists and managed-care companies will aggressively fill prescriptions with generics, reducing annual Lipitor sales to a fraction of last year’s $13 billion.

By 2012, Merck & Co. will face generic competition to its three top-selling drugs: the osteoporosis treatment Fosamax, Singulair for asthma and the blood-pressure drug Cozaar. Those three represent 44% of the company’s current revenue. Following the loss last year of patent protection for Merck’s cholesterol-lowering Zocor, sales this year are expected to fall 82% from $4.38 billion in 2005. A Merck spokeswoman said the company has several products in the pipeline that will offset its patent losses.

The rise of generics wouldn’t matter so much if research labs were creating a stream of new hits. But that isn’t happening. During the five years from 2002 through 2006, the industry brought to market 43% fewer new chemical-based drugs than in the last five years of the 1990s, despite more than doubling research-and-development spending.

In October, Moody’s Investors Service, which rates about $90 billion in U.S. pharmaceutical-company debt, lowered its outlook for the U.S. drug industry to negative from stable. The industry was long considered among the most credit-worthy, but in recent years, Moody’s has downgraded giants Schering-Plough Corp., Merck, Bristol-Myers, Pfizer and GlaxoSmithKline PLC. In explaining its diminished outlook, Moody’s said that drugs currently in development don’t have as much commercial potential as earlier pipelines.

Investors, once huge beneficiaries of drug-industry success, have moved to the sidelines. As the Dow Jones World Index rose 75% in the six years ended Nov. 29, the FTSE Global Pharmaceuticals Index fell 19.8%.

While many patients are benefiting from lower-cost generics, others are waiting in vain for relief of their suffering. “In anxiety disorder, the field has imploded in terms of drug development,” said P. Murali Doraiswamy, chief of biological psychiatry at Duke University medical school. “Ten years ago, we had eight or nine different” anxiety-disorder drugs under development, but that has now “come to a halt.”

At last month’s big American Heart Association meeting in Orlando, Fla., there were just two high-profile studies of experimental drugs on the agenda. One, for Eli Lilly’s anti-blood-clotting drug prasugrel, posted results that left some doctors and analysts questioning whether the drug would be a big seller. Lilly, however, says it is “very pleased with the trial’s outcome.”

The other study was a postmortem on Pfizer’s torcetrapib, already known as one of the industry’s most costly failures, with $800 million in budgeted research costs.

“There haven’t been any new therapies that are proven to reduce death and disability for atherosclerosis since the introduction of the [cholesterol-lowering] statins” in the late 1980s, said Richard C. Pasternak, vice president of Cardiovascular Clinical Research at Merck. Atherosclerosis, a buildup of arterial plaque, is a major cause of heart disease.

As patent expirations loom, pharmaceutical companies are reorganizing. In five years, many may look very different. They will be in new businesses. Their cost structures may be slimmer and more flexible. Some familiar names may disappear in mergers. Companies are installing new leaders, including outsiders like Pfizer Chairman and CEO Jeffrey Kindler, who in 2002 joined the company as general counsel from McDonald’s Corp.

“The era that created the modern pharmaceutical industry is in fact over,” said Richard Evans, a former Wall Street analyst and now a pharmaceutical consultant.
John McCammant of the Medical Technology Stock Letter discusses the likely repercussions of cancer drug Avastin’s rejection and a forthcoming wave of patent expirations on big drugs.

To be sure, the pharmaceutical industry is still highly profitable. Sales will continue to benefit from the Medicare drug benefit for the elderly and from growth in overseas markets. The industry will continue to produce new drugs, though at too slow a rate to sustain its size and cost structure, analysts assess. Some players, such as Merck, may fare better because of a more productive R&D operation, according to Sanford C. Bernstein & Co. research analyst Timothy Anderson.

It has never been easy to take a drug from the lab, through animal testing and into human trials. The industry estimates only one out of every 5,000 to 10,000 candidates makes it to human trials. And many drugs that work beautifully in animals fail miserably in people.

But those odds seem to have worsened in recent years, prompting debate about whether the cause is government regulation, corporate structure or an excessive scientific reliance on chemicals rather than biology.

Many drug-company executives blame the FDA for pulling back on approvals. “Very few products are being approved today,” said Bernard Poussot, incoming chief executive of Wyeth. The heightened scrutiny contributed to delays of two Wyeth products this past summer, the company has said.

Would-be blockbusters such as Novartis AG’s diabetes drug Galvus and Sanofi-Aventis’s weight-loss drug rimonabant have recently been delayed by the FDA over safety concerns.

Safety concerns have also prompted the agency to require larger studies of new drugs. Novartis CEO Daniel Vasella says this trend has done more than any other to drive up the industry’s R&D costs. He cites Novartis’s blood-pressure drug Tekturna, approved earlier this year, which had more than 6,000 patients in its late-stage trial. A decade ago, a similar study might have had fewer than 1,000 patients, according to Dr. Vasella.
[Chart]

Christopher DiFrancesco, a spokesman for the FDA, said, “The number of approvals have declined because companies are submitting fewer drugs to the FDA for approval. The threshold for what we consider to be a safe, effective drug hasn’t changed.”

Some say the industry’s ballooning research budgets may be working against productivity. Most companies use a centralized system to allocate research money, and the growing budgets have left the decision making to too few people who are too far removed from the research, suggests Mr. Evans, who worked at Roche’s U.S. subsidiary until 1998, spent several years as a Wall Street analyst and is now a consultant at a health-care-consulting firm. He calls the system “a nightmare of complexity.”

As evidence of this problem, some in the industry point to Pfizer, with an annual research budget that has grown to $7 billion, highest in the industry. Yet only a handful of drugs discovered in its internal research labs have come to market in the past decade. And late last year, the company lost its most promising hope when the cholesterol drug torcetrapib failed in late-stage trials.

In a statement, Pfizer said it has the largest pipeline of midstage drugs in company history and plans to triple the number of late-stage drugs in its portfolio by 2009.

A few companies, notably GlaxoSmithKline, have begun breaking R&D into smaller groups, though it is too early to gauge results.

Some believe the industry, which grew out of the European chemical business of the late 1800s, has remained too reliant on that foundation. “For all our amazing advances in the last 50 years, we are still working with the tools of the first pharmaceutical revolution…using advanced chemistry to treat disease symptoms,” Mr. Taurel of Lilly said in a 2003 speech.

The future, many believe, lies in biotechnology. Unlike traditional, chemistry-based drug development, biotechnology uses biological tools to create entire proteins, often similar to those that occur in the human body. This approach has yielded successful drugs to treat diseases such as anemia, cancer and rheumatoid arthritis.

Biotech drugs are especially appealing because they face no competition from generics: No regulatory pathway yet exists in the U.S. for bringing to market generic biotech drugs. So until Congress creates such a pathway, no generic threat will exist to the $4,400 a month that Genentech Inc. charges for its cancer drug Avastin, or the $200,000 a year that Genzyme Corp. gets for Cerezyme to treat Gaucher disease. And biotechnology products tend to target specialized areas of medicine that don’t require mass advertising or armies of salespeople.

So big pharmaceutical companies have spent nearly $76 billion since 2005 to buy biotech companies, according to Health Care M&A Information Service, a unit of Irving Levin Associates Inc., a Norwalk, Conn., research company. While in 2005 there were 33 deals amounting to $16.5 billion, in the first nine months of this year there were 49 deals totaling $28.7 billion, including AstraZeneca PLC’s $15.6 billion acquisition of MedImmune, which followed a bidding war against Eli Lilly, among others.

Meanwhile, Novartis and Pfizer recently announced the formation of in-house biotech units.

The dearth of new products has led the industry to invest heavily in marketing and legal tactics that squeeze as much revenue as possible out of existing products. Companies have raised prices; the average price per pill has risen 63% since 2002, according to Michael Krensavage, Raymond James analyst. Companies raised advertising spending to $5.3 billion in 2006 from $2.5 billion in 2001 and since 1995 have nearly tripled the number of industry sales representatives to 100,000.

The industry spent $155 million on lobbying from January 2005 to June 2006, according to the Center for Public Integrity, on “a variety of issues ranging from protecting lucrative drug patents to keeping lower-priced Canadian drugs from being imported.” The industry also successfully lobbied against allowing the federal government to negotiate Medicare drug prices, the center said. The lobbying has drawn fire from politicians, doctors and payers, and damaged the industry’s public image.

Aware that seven of the top 10 drug launches of 2006 were generics, pharmaceutical giants are pushing more deeply into that business. In first nine months of this year, Novartis’s generics unit, Sandoz, grew roughly three times as fast as its branded-drugs business and accounted for nearly 20% of overall revenue. “The balance is changing,” says Novartis CEO Dr. Vasella. In the coming quarters, “we will continue to see a faster growth opportunity” in generics.

After Pfizer’s antidepressant Zoloft went off-patent last year, the company’s own generics unit, Greenstone, launched a generic version of the drug.

Johnson & Johnson has its own generics unit. Other companies cut deals with generics manufacturers, licensing them the right to sell “authorized generics” that are identical to a branded drug that has gone off-patent.

Diversification is another hope. Roche Holding AG is pursuing a $3 billion hostile takeover of Ventana Medical Systems Inc., a diagnostics company that makes the test used to determine whether women with breast cancer should receive Herceptin, a targeted biotechnology drug that Roche sells in some markets.

The bid is part of a broad push further into diagnostics by the company, which said in July that Severin Schwan, who runs the company’s diagnostics unit, will take over next year as CEO.

Yet none of these moves are forestalling cost slashing. Pfizer is cutting 20% of its sales force, AstraZeneca is cutting 10% of its employees and Johnson & Johnson is shrinking its staff by 4%, according to Bernstein Research. As many as 50,000 industry positions will be displaced over the next 10 years, according to wealth-management company RegentAtlantic Capital, Chatham, N.J.

AstraZeneca, GlaxoSmithKline and Bristol-Myers Squibb have also recently suggested they will outsource at least some of their manufacturing. “There are lots of people in India, China and Eastern Europe who can make products of the same quality as ours but at significantly less cost,” says Bristol-Myers Squibb CEO James Cornelius.

The outsourcing is expected to extend to research. “We don’t do any basic research yet in the lower-cost countries, but over the next few years, to be successful you’ll have a constant emphasis on looking for that,” Mr. Cornelius says.

The coming difficulty is threatening every industry tradition. “I’m talking to you from the 44th floor of an office on Park Avenue,” Mr. Cornelius says. “A year from now, I won’t be talking to you from the 44th floor because we’re going to move downstairs out of these very expensive offices.”

–Sarah Rubenstein and Ron Winslow contributed to this article.

Write to Barbara Martinez at Barbara.Martinez@wsj.com and Jacob Goldstein at healthblog@wsj.com

See full story As Drug Industry Struggles, Chemists Face Layoff Wave; Lipitor Pioneer Is Out At Doomed Pfizer Lab; A Blockbuster Drought By AVERY JOHNSON December 11, 2007 from the WSJ.
PARADIGM LOST
As Drug Industry Struggles,
Chemists Face Layoff Wave
Lipitor Pioneer Is Out
At Doomed Pfizer Lab;
A Blockbuster Drought
By AVERY JOHNSON
See Corrections & Amplifications below
December 11, 2007; Page A1

ANN ARBOR, Michigan — In January, Pfizer Inc. announced it was closing its storied research laboratories here, laying off 2,100 people. Among the casualties: Bob Sliskovic, a 23-year lab veteran who helped create the world’s most successful drug.

The closure and Dr. Sliskovic’s abrupt change of circumstances are emblematic of the pharmaceutical industry’s declining fortunes. It was at the Ann Arbor facility in the late 1980s that Dr. Sliskovic first assembled the chemicals that make up Lipitor, the cholesterol-lowering drug that has generated about $80 billion in sales since its launch and ranks as the bestselling pharmaceutical product ever. Today, Lipitor is nearing the end of its patent life, and Pfizer hasn’t been able to come up with enough promising new drugs to replace it.

Following that initial breakthrough some 20 years ago, Dr. Sliskovic worked on several other research projects, but none panned out. His losing streak mirrors the industry’s. A byproduct of the late-19th-century chemical business, pharmaceutical research thrived for more than a century by finding chemical combinations to treat diseases. But after contributing substantially both to human health and drug-industry profits, it has failed to produce significant innovations in recent years.

High failure rates have long plagued chemistry-based drug research. Between 5,000 and 10,000 compounds are tested for every drug that makes it to market. In recent years, the problem seems to have gotten worse. Despite spending tens of billions of dollars more on research and development, pharmaceutical companies have fewer and fewer drugs to show for it. In 2006, the industry received Food and Drug Administration approval for just 18 new chemical-based drugs, down from 53 in 1996. Moreover, many of those drugs are variations of existing medicines.

Robert Massie, president of the American Chemical Society’s database of chemistry research, says some researchers are questioning how many more chemical combinations there are that are useful against diseases. “It’s like how coming out with metal drivers in golf was a huge innovation, but now it’s incremental. You’re just coming out with drivers that are a little longer or rounder,” he says.

As pills like Lipitor made out of elements from the periodic table prove harder to come by, pharmaceutical research is being superseded by the newer field of biotechnology. The latter relies mostly on biologists who make proteins from live cells.

The shift is exacting a human toll, as big drug companies like Pfizer lay off thousands of chemists, casting a pall over what was once a secure, well-paying profession. “When I started in this industry in the 1980s, you didn’t worry about things like this,” Dr. Sliskovic says of the lab closure.

It isn’t clear how many chemists have lost pharmaceutical-company jobs. But overall, 116,000 chemists were employed in 2006, down from 140,000 in 2003, according to the Bureau of Labor Statistics. During the same period, employment of biologists rose to 116,000 from 112,000. Just as the rise of biotechnology is contributing to an economic boom in Northern California, the decline of chemical-based research is hurting the Michigan cities of Ann Arbor and Kalamazoo, along with some regions of New Jersey and Illinois.

Dr. Sliskovic, a 50-year-old with a mustache and the scattered air of a scientist, was raised in Doncaster, a coal-mining town in northern England. His father, a refugee from the former Yugoslavia, found work there after World War II. As a child, Dr. Sliskovic says he was fascinated by such things as the properties that “make a mint minty.”

That interest led him to pursue a doctorate in chemistry. In 1982, his Ph.D. adviser told him of a friend who worked as a consultant for a pharmaceutical company in New York. The company was looking for chemists to do postdoctoral research. Raised with a passion for American comic books, Dr. Sliskovic says he jumped at the opportunity to come to the U.S.

Two years later, his research completed, he received a job offer from Warner-Lambert Co.’s Ann Arbor labs. “Holy cow! I accept,” he remembers saying.

Dr. Sliskovic was hired as the pharmaceutical business entered a golden era of huge profits. Its labs churned out drugs for chronic conditions such as heart disease and depression, while its armies of salesmen promoted them through aggressive marketing. Warner-Lambert assigned him to a team of three other chemists investigating a new idea: whether lowering cholesterol — the soft, waxy substance that can clog arteries — would help people avoid heart attacks. Other companies were at work on similar projects.

Dr. Sliskovic’s new boss, Bruce Roth, had invented a chemical structure that he thought would work. In the late 1980s, Dr. Sliskovic fine-tuned the compound, isolating its potent part. An early version of the compound wasn’t absorbed well by the body, so the team brainstormed about how to modify it to get more of it into the bloodstream. “We sat around the table and said ‘You try this, you try that,’ and they said, ‘Bob, why don’t you look at salt formation?'” Dr. Sliskovic recalls.

A calcium salt he tried solved the problem, and Lipitor was born. Though it would reach the market in 1997 after several rival drugs, Lipitor would turn into a blockbuster because it was more potent.

Its runaway success sparked Pfizer’s $116 billion hostile takeover of Warner-Lambert in 2000. Ahead of the takeover, Pfizer suggested one of Warner’s main appeals was its research-and-development force. “We would like to keep them all,” Pfizer’s then-research chief, John Niblack, told The Wall Street Journal in 1999. “You need a big staff to run this strategy. Warner-Lambert offers us a nice instant fix.”

With the acquisition, New York-based Pfizer inherited the Ann Arbor labs where Dr. Sliskovic worked and continued to base much of its pharmaceutical research there. Between 2001 and 2006, it invested $300 million to expand the facilities.

By that time, Dr. Sliskovic had moved on to other projects. As Lipitor traveled down the long road of animal and human testing in the early ’90s, he led a group of chemists developing drugs to prevent cholesterol from being absorbed by the body and stored in arteries. Lipitor, by contrast, works by reducing the amount of cholesterol the liver produces.
[Job Cuts]

One compound, called avasimibe, seemed to work well in animals. Despite skepticism from higher-ups, Dr. Sliskovic and his team persuaded Warner-Lambert to take it into human testing. For a while, it looked as though avasimibe could be a contender to succeed Lipitor. But it failed in an intermediate stage of clinical testing, and the company abandoned it.

Dr. Sliskovic had devoted about six years to the drug. He recalls needing pep talks from his boss about picking up and starting over. He blocked out disappointment, he says, by throwing himself into the day’s science rather than thinking about the odds of creating a marketable drug. “You’ve got to develop the hide of a rhino,” he says.

In the mid-90s, he tried to develop compounds to counter inflammation in the heart, which some scientists think can cause heart attacks. Those projects also flopped but got him interested in another area of research, inflammatory arthritis.

Dr. Sliskovic took on the challenge of finding a drug that would repair the cartilage that can break down between bones and cause arthritic pain. But the several compounds he concocted didn’t meet testing requirements. In 1999, Dr. Sliskovic was promoted to a management role that took him away from the day-to-day work of drug discovery. He says his new job required him to teach his scientists how to remain excited in the wake of failure. “It was me who started telling them, ‘Oh well, never mind. What can we do about this other project?'” he says.

But over time those failures added up. In December 2006, Pfizer killed torcetrapib, the cholesterol compound the company had placed its hopes on, because it was associated with too many deaths in clinical testing. It was a huge setback because Pfizer didn’t have much else in its research pipeline to replace Lipitor’s sales. The company relies on Lipitor for more than a quarter of its revenues, and the drug could face generic competition as early as 2010.

The company has had some successes: Pfizer appears to have a rich cancer-drug pipeline and has come up with two notable new chemical-based hits recently, the antismoking medicine Chantix and a pain drug, Lyrica, which was discovered in Ann Arbor. The company’s new chief executive, Jeffrey Kindler, has emphasized biotech after taking over some 16 months ago. In October, Pfizer opened a new biologics center in San Francisco.

By January 2007, Mr. Kindler was promising to do something radical to shake the world’s biggest drug maker out of its worsening slump. Rumors of layoffs were swirling at Pfizer. Few imagined anything as drastic as closing the half-century-old Ann Arbor labs, where Pfizer was just finishing the $300 million expansion.

Dr. Sliskovic says he learned of the closure on Jan. 22, in a morning meeting with the site’s top managers. The room went silent, he says.

After the meeting, Dr. Sliskovic called his wife on her cellphone to tell her the news. She thought he was kidding. Realizing he was serious, she offered to increase her hours at her part-time job at a pet-food store. Later, at home over lunch, his 19-year-old daughter asked whether they would have to sell the family’s three horses.

The announcement also took Michigan officials by surprise. The state, which has the country’s worst unemployment rate, was already reeling from auto-industry cuts. Pfizer was also Ann Arbor’s largest taxpayer, contributing $14 million a year into city coffers. At a press conference later in the day, local officials pledged to fight for scientists to stay in the area. Later, they pledged $8 million in interest-free loans for start-ups run by laid-off scientists or existing companies that hire them. A state-budget deadlock delayed the money for months, but it is now being handed out to scientists.

Pfizer offered about half of the Ann Arbor researchers internal transfers, mostly to its other big research facility, in Groton, Conn. But a higher proportion of those offers went to biologists than to chemists, former lab employees say. Though it is far from abandoning chemistry-based research, Pfizer has been increasingly outsourcing chemistry work to contract research organizations, some in India. Pfizer declined to comment on which scientists were offered transfers.

In April, about 80 laid-off Pfizer chemists from Ann Arbor traveled to nearby Detroit to hear a talk by career consultant Lisa Balbes. Ms. Balbes told them the story of a former chemist who now uses her skills to enhance acoustics in stereo systems. Her message: Start thinking about different career paths.

As winter turned into spring, Dr. Sliskovic found himself going to a parade of goodbye parties for colleagues. Dr. Roth, his former boss, left in April for Genentech Inc., the biotech pioneer based in South San Francisco. Dr. Sliskovic organized the send-off. In early May, David Canter, the head of the Ann Arbor site, threw a dinner party for other departing employees. A band played songs parodying Pfizer and the executive who symbolized headquarters’ decision-making: John LaMattina, Pfizer’s Connecticut-based head of research. To the tune from Evita, they sang, “Don’t Cry for Me, LaMattina.”
[Scott Larsen]

A few weeks later, Dr. LaMattina himself announced his retirement, as part of Mr. Kindler’s broad reorganization of top company executives.Martin Mackay, who succeeded Dr. LaMattina as research chief and played a major role in the research restructuring, says the company was “very aware” of its impact on the community. “We made this decision after very careful and thorough review of all possible alternatives,” Mr. Mackay said in a statement.

Scott Larsen, one of the chemists who attended the going-away party, came to Pfizer four years ago when the company merged with his former employer, Pharmacia Corp. He applied for a transfer to Groton but didn’t get an offer. He tells his two sons, who are both in college and love science, not to go work for a drug company.

In August, Dr. Sliskovic’s team stopped doing research and began transferring projects to other Pfizer sites. The labs are now being cleaned, inspected and sealed off. The 177-acre campus is a ghost town of empty rooms and boxed-up equipment.

Dr. Sliskovic didn’t seek an internal transfer. He felt that moving would be too hard on his family.

As acting head of chemistry at the Ann Arbor labs, Dr. Sliskovic earned far above the $112,000 a year paid to the average chemist of his experience level. Dr. Sliskovic says he will receive severance pay for between 18 months and two years. With two children in college and another in high school, he says, two years is the longest he could afford to forgo a paycheck.

Dr. Sliskovic has already repainted the family kitchen and living room. Now he is festooning the house and yard with holiday lights. Worried about their financial future, his wife, Cindy, took a second part-time job at the barn where they keep their horses. The irony that the drug her husband helped discover will bring in nearly $13 billion for Pfizer this year hasn’t been lost on her. As a staff scientist, Dr. Sliskovic earned no bonus or royalties for his work on Lipitor.

Former Pfizer scientists have founded 23 companies in the area. Dr. Sliskovic says he would prefer to do the creative work of discovering drugs instead of the rote chemistry some such companies do for drug makers.

Instead, he dreams of being involved in another blockbuster. Sometimes, he says, he lies in bed at night wondering if it will happen. “If the best thing I did was Lipitor in 1988, it’s like being the high-school athlete who was on the football team and that was that,” he says.

Write to Avery Johnson at avery.johnson@WSJ.com

Corrections &Amplifications

Lyrica, a pain drug sold by Pfizer Inc., was developed in Warner-Lambert Co. and Pfizer’s laboratories in Ann Arbor, Mich., but was discovered at Northwestern University in Evanston, Ill. This article incorrectly said the drug was discovered in Ann Arbor.);

HIV is HIV vaccine!- Abraham Karpas

December 3rd, 2007

Review by Honest Abe, elite Cambridge virologist, of AIDS science in 2004 reveals vaccine to HIV is…HIV!

Text if read by intelligent HIV+ people might cause doubts about need for poison

Backs up Fauci, who said that HIV induces protective T cells to proliferate

Should Karpas share in Duesberg’s Nobel for solving AIDS? Maybe

vaccine.jpgOver at Aetiology, a blog run by epidemiologist Tara Smith, who is convinced that HIV is the culprit in AIDS and that there is no need to review the literature more than she has, the comment section has reached 1072 comments and counting, since her post on Mbeki: still in denial went up on November 6th.

We regret to say we have contributed to this flurry, since we really should have been posting here much of the material we cited, and others familiar with the literature, such as Robert Houston and MacDonald, cited.

This morning, however, it seemed right to post the important sections of Human retroviruses in leukaemia and AIDS: reflections on their discovery, biology and epidemiology, Abraham Karpas’s 2004 review of AIDS science, and we did so. What it shows, as the thread has brought out, against the heavy resistance of paradigm defenders such as Christopher Noble, “franklin”, Roy Hinckley, and “Elk Mountain Man”, is the crucial flaw in HIV-AIDS theory, which is that

HIV vaccinates against HIV!

There is no reason to believe that any person with a healthy immune system will not produce antibodies in short order which will neutralize (kill) HIV in their bloodtsream, and Karpas confirms this without blinking.

“The immune response to HIV can be compared to that of a live viral vaccine. It explains why most HIV-infected patients remain well for years.”

bigkarpas.jpegThe second important point we wanted to make, after Robert Houston, is that Karpas’s belief at the time was that the virus mutates away from the immune syste’s aim and this is one explanation, though not the whole story, of why HIV is able to make a comeback in the end and defeat the imune system which defeated it in the first place, was already proved false by Rapid evolution of the neutralizing antibody response to HIV type 1 infection, the Douglas Richman et al paper of 2003 which found that antibodies not only kept up with mutation, but a quarter of the time actually responded more powerfully to the new versions of HIV-1.

Karpas went to press too early to take this result into account, it appears. But if he had read Richman, perhaps he would have come out with the same kind of idea that NIAID director Anthony Fauci seemed to be suggesting (to those alert enough to read between the lines) in the review we dealt with earrlier here, which is that the imaginative solution to the entire billion dollar problem of finding a vaccine to prevent AIDSis: use HIV itself as a vaccine!

For the only conclusion that reasonable people can come to in reading Karpas’s paper is that the harmless virus HIV vaccinates against the harmless virus HIV, just as Peter Duesberg has long stated in unrefuted and irrefutable papers drawing on the literature of the field.

The only issue now, since this is the final solution to AIDS, and save a considerable expense (vaccine researchers are busy trying to use up more than a billion, and Bush has asked for $30 billion in tax money) and some serious suffering on the part of no account (to HIV researchers, apparently) gays and blacks in Africa and now here, is: Does Karpas deserve to share in the Nobel with Duesberg, who pointed out all this first, in Cancer Research in 1987?

We think he does.

Here for the inspection of readers is what Karpas wrote on key points, which is already posted on Aetiology, and discussed earlier, with some preceding Comments for context (later Aetiology Comment posts will be added here, rather than in the Comment section to Cleaning Out The Stable (6) as hitherto:

(Some preceding Aetiology Comments, already copied into Comments here earlier under Cleaning Out The Stable, can be read if you click this tab, which will expand them for reading as a sort of introduction:

Noble and the rest of you wackjobs, if you are so sure that hiv is the cause of aids, please send us links from pub med for the 3-4 first scientific papers that prove hiv causes AIDS, Koch had orginal expiriments that proved causality, so did shyh ching lo……..so your Idol moores rocket ship analalogy is the biggest joke of them all. Waiting…………………………….

Posted by: cooler | December 2, 2007 9:05 PM

The irony arises from repeatedly referring to it as the Kraft-Dunning Effect, illustrating the overconfidence fueled by ignorance that lies at the heart of the effect.
Posted by: franklin | December 2, 2007 6:02 PM

In a classic example of the Kruger-Dunning effect, the better irony arises, franklin, from your inability to appreciate wordplay. Perhaps one should call it the Kruger-Ebbing effect, to make it clearer through the fog that obscures your brain, the one that the monkey meme sits on, invisible to you but visible to all who read what you write. But then you would complain that I spelled it wrong…sheez.

Anyhow the corpus of Krafft-Ebing is what one keeps thinking of in observing your behavior, and that of your fellow trio members, here. In fact, there seem to be five influences at work at once: 1) Kruger-Dunning 2) Krafft-Ebing 3) Moore-Noble 4) HIV meme 5) The Duesberg-Bialy litmus test for scientific intelligence, or its absence.

In case you didn’t know the Duesberg-Bialy effect (discovered at New AIDS Review, as it happens by the humble blogger) is the following:

The absence of a sense of humor correlates very highly – 99.9999% – with the inability to percieve the Grand Canyon sized flaws in the HIV=AIDS hypothesis.

It is not yet known why this is, but the favored theory is that those brilliant fellows such as yourself who lack the wit and mastery of the topic that allows one to see what is really going on are distracted by the monkey meme jumping up and down on their head.

HIV blocked from T cells

By the way, franklin, if you guys are so familiar with the literature that you know our interpretation is wrong when we see Fauci, Karpas and other commentators of irreproachable mainstream authority acknowledge that HIV is a pussy which the immune system chases up a tree and keeps it there, how about this quote (you recognize it, I hope, and who wrote it):

“However, quantitative studies of the frequency of HIV-infected cells in vivo suggest that single cell killing by direct infection with HIV may not be the predominant mechanism of CD4+ T-cell depletion. In this regard, the proportion of HIV-infected, peripheral blood CD4+ T cells in individuals in the early asymptomatic stage of HIV infection is typically in the range of 1 in 1000 to 1 in 10,10,000 (Pantaleo et al) Although this frequency increases with disease progression,the proportion of HIV infected peripheral blood CD4+ T cells rarely exceeds 1 in 100 even in patients with advanced HIV disease….the data illustrate the difficulty in accounting for CD4+ T-cell depletion solely by direct mechanisms.”

Gee. No direct cell killing by HIV. Parade past us all the excuses and imaginative claims offered to fill this Grand Canyon of contradiction of the first mechanism assumed by the HIV brigade, then read Zvi Grossman on how none of them have the slightest data to back them up and how exactly how HIV kills T cells remains a “conundrum”.

Neutralizing antibodies

Meanwhile try contradicting my description of the overcoming of HIV by the healthy immune system as “DEFEAT” again, when Richman’s paper is NAMED Rapid evolution of the neutralizing response to HIV type 1 infection. What do you think neutralizing means?

“We report here that in most patients, potent neutralizing antibody responses are generated early after infection, at first to the autologous infecting HIV variant and then to subsequent variants.”

“During the natural course of early HIV infection, fully functional envelope variants continuously emerge and compete for outgrowth in a RAPIDLY EVOLVING NEUTRALIZING ANTIBODY RESPONSE.”

Gallo himself saluted neutralizing antibodies to HIV in 1985 in Nature (Jul 4-10;316 (6023):72-4,

“Natural antibodies capable of neutralizing HTLV-III infection of H9 cells were detected in most adults AIDS and ARC patients but in no normal heterosexual controls.”

The only way HIV escapes these antibodies is to retreat to some hiding place protected from the antibodies in the bloodstream, folks. It doesn’t make any kind of comeback until the antibodies army is weakened by some other sickness, which HIV doesn’t have a chance to cause.

Karpas explains

Why the established paradigm exploiters insist on maintaining that the defeated HIV is the threat is a scientific mystery, but it may have something to do with money After all, even Abraham Karpas, professor of virology at Cambridge and one of the generals of the campaign to support HIV to the tune of $30 billion even though it doesn’t do anything, has this to say about the credentials of his colleagues:

“The history of AIDS research involves huge rewards, unscrupulous ambition, disregard for common principles of scientific conduct, battles over priority leaving injustice uncorrected, and terrible consequences in the wider world.”

Written about Gallo’s record in the early stage of HIV research, from which the asinine theory emerged, but also applicable to the whole crowd of scientific deceivers and their hangers on such as the trio here in the years since.

A sad reflection on human motivations to peddle murder rather than medicine.

Posted by: Truthseeker | December 2, 2007 9:27 PM

darin writes YOU REGARD THE PRESENCE OF ANY NUCLEIC ACID WHICH IS DETERMINED BY YOU TO BE “FOREIGN” (whatever that means) AS ORIGINATING IN AN EXOGENOUS VIRUS.

Regardless of whether you can actually SEE such a virus, regardless of whether you have a way of detecting virus particles or even “virus-like particles” (whatever THAT means!!!, I read some papers from just a few years ago on “HCV-virus-like particles” being FINALLY (finally!!!) detected, 20 years on now…)

THE NUCLEIC ACID SEQUENCE IS YOUR GOD-KING, YOUR DEITY, YOUR SOVEREIGN. YOU WORSHIP IT.

Once again you appear to have completely misinterpreted reality. “Any” nucleic acid sequence? Hardly. A nucleic acid sequence contains genetic information. If that information is not consistent with a virus that nucleic acid won’t be labelled viral.

Posted by: Dale | December 2, 2007 10:12 PM

“In a classic example of the Kruger-Dunning effect, the better irony arises, franklin, from your inability to appreciate wordplay.”

Your efforts at argumentation consist entirely of wordplay. You know fully well that Karpas, Richman and Fauci do not support your interpretations and yet you continue to argue about this.

This complete and utter disregard for the truth only demonstrates your dishonesty. It is difficult to tell whether your chosen moniker of “truthseeker” is meant to be an ironic wordplay or youreally are self-deluded.

Posted by: Chris Noble | December 2, 2007 10:20 PM

“Your efforts at argumentation consist entirely of wordplay. You know fully well that Karpas, Richman and Fauci do not support your interpretations and yet you continue to argue about this.”

Don’t be silly, Chris. They agree with what they wrote.

This complete and utter disregard for the truth only demonstrates your dishonesty. It is difficult to tell whether your chosen moniker of “truthseeker” is meant to be an ironic wordplay or you really are self-deluded.
Posted by: Chris Noble | December 2, 2007 10:20 PM

Is that a machine you crank out this repetition on?

Face up to the simple truth that the bigger men in HIV=AIDS have made clear to us:

HIV+ people have vaccinated themselves.

Repeat:

HIV+ people have vaccinated themselves.

Still can’t get it? Let’s leave you forever with a quote:

It takes two to speak the truth. One to speak, and another to hear. – Henry David Thoreau.

Posted by: Truthseeker | December 2, 2007 10:31 PM

Truthseeker (sic),

Again you demonstrate that you can only support your erroneous conclusions about HIV by misrepresenting the scientific work of others, either because you are lying or because you are unable to understand the science.

You quote from a paper:

…the data illustrate the difficulty in accounting for CD4+ T-cell depletion solely by direct mechanisms.

Then draw the following conclusion:

Gee. No direct cell killing by HIV.

Perhaps you should look up non sequitur.

Posted by: franklin | December 2, 2007 10:37 PM

Don’t be silly, Chris. They agree with what they wrote.

Don’t be disengenous. You know fully well that they do not agree with your interpretations and extrapolations of what they wrote.

I am not disagreeing with what Karpas, Richman and Fauci have written. I am disagreeing with your interpretations such as

…ordinary levels of antibodies seen in any healthy person exposed to HIV are sufficient to defeat it.

You are playing a juvenile game whereby you are pretending that I am disagreeing with Karpas, Richman and Fauci. I am not.

I have stated exactly why you are wrong. You continue to fill this webblog with overly verbose empty rhetoric.

Grow up!

Posted by: Chris Noble | December 2, 2007 11:00 PM

“During the natural course of early HIV infection, fully functional envelope variants continuously emerge and compete for outgrowth in a RAPIDLY EVOLVING NEUTRALIZING ANTIBODY RESPONSE.”

I acn only think of the term cognitive dissonance at this point although I suspect that Truthtwister will simply parrot this criticism back.

Somehow Truthtwister manages to avoid the part of this sentence which states that fully functional envelope variants continuously emerge. An honest person would not equate this to “defeat”. What does “fully functional” mean? What does “continuously emerge” mean?

As another example of cognitive dissonance Truthtwister failes to quote this sentence

The question then arises why such a strong selective pressure fails to appreciably impact levels of virus replication as does chemotherapy.

Richman is saying that ART is better at reducing viral replication than the normal human immune response.

Posted by: Chris Noble | December 2, 2007 11:15 PM

What does “fully functional” mean? What does
“continuously emerge” mean?

Dr. N

What does “early HIV infection” mean? As stated here the quote is a perfect tautology within the HIV belief system. If no “fully fuctional”, envelope variants emerged during “early infection”, it wouldn’t be much of an “infection” would it now?

Karpas then hypothesizes that HIV, AFTER EARLY INFECTION, never becomes completely latent (never fully “defeated”, just resorting to scattered, ineffectual for years, guerilla warfare) because the explanatory lentivirus model demands it or the HIV construct would merge into the “ordinary” opportunistic infection scenario, as Adele in one of her few bright moments has told us it is.

Posted by: Molecular Entry Claw | December 2, 2007 11:54 PM

What does “early HIV infection” mean?

The paper by Richman covered the time period of 0-39 months post infection.

HIV is never latent except perhaps in a small percentage of elite controllers. It is a persistent chronic infection as distinct from viruses such as herpes simplex that form persistent latent infections.

Stop trying to put words into Karpas’ mouth. The only thing you are demonstrating is your dishonesty.

Posted by: Chris Noble | December 3, 2007 12:10 AM

Truthseeker (sic),

Maybe you’re not lying, after all.

At least not on all of the points you argue.

When it comes to Richman et al. (2003) it seems just as likely to me that you simply do not understand the paper, because the passages you quote disprove your thesis that HIV is defeated by the immune response in “any healthy person exposed to HIV” (free full text available here).

As Chris has already pointed out, the second passage you quoted indicates that despite the neutralizing antibodies made by the infected patients, “fully functional envelope variants continuously emerge.”

Even in the patients with the greatest production of neutralizing antibodies, the virus is not defeated, but instead continuously evades the immune response via evolution of resistant mutants.

The question then arises why such a strong selective pressure fails to appreciably impact levels of virus replication as does chemotherapy. During the course of HIV evolution, the envelope protein has acquired the ability to retain function (i.e., bind receptors) while tolerating multiple and repeated changes in several highly variable regions containing numerous glycosylation sites (32). Although drug-resistance mutations confer much greater fitness in the presence of antiretroviral drugs, they typically do not exist as common polymorphisms in untreated patients because they impair the replication of wild-type viruses. In contrast, during the natural course of early HIV infection, fully functional envelope variants continuously emerge and compete for outgrowth in the presence of a rapidly evolving neutralizing antibody response.

The antibody response evolves rapidly, but the authors show that the virus evolves even more rapidly.

They demonstrate the more rapid evolution of the virus by studying virus and antibodies isolated from the same blood sample.

The patients’ antibodies are less effective at neutralization of the virus present in the blood sample from which the antibody was derived than virus present in earlier blood samples from the same patient.

Because the evolution of the antibody response does not keep up with the evolution of the virus, the antibody response “fails to appreciably impact levels of virus replication” and fails to defeat the virus.

I certainly hope that you wouldn’t lie about such an elegant experiment.

Somehow, I would prefer to believe that you simply don’t understand it.

For, in my opinion, to purposely lie about this work is to besmirch a thing of beauty.

Posted by: franklin | December 3, 2007 12:11 AM

The question then arises why such a strong selective pressure fails to appreciably impact levels of virus replication as does chemotherapy.

“Richman is saying that ART is better at reducing viral replication than the normal human immune response” (Dr. N)

What Richman does, Dr. N, is point to one of the many paradoxes raised by an explanatory model which is forced to assume that HIV is mutating furiously as answer to “strong selective pressure”, aka known as a potent antibody response.

The paradox is, as stated, that an antibody response which is so powerful that it forces HIV to perform evolutionary acrobatics which outpace many times over in a single infected person the worldwide evolution of an average influenza strain during the course of an entire year is supposedly still not potent enough to dent the viral load.

That is like carpet bombing an Iraqi village all night only to discover in the morning that all major structures are still intact and Al-Qaeda holding a soccer tournament in the town square.

Posted by: Molecular Entry Claw | December 3, 2007 12:22 AM

Why do HIV enthusiasts pretend that they don’t know the obvious? Antibodies afftect what’s accessible in the blood and may have little effect on virus in the lymph nodes or inside cells, where replication could continue.

This does not mean that an antibody response is without benefit. The low rate of infected T-cells, “1 in 1,000 to 1 in 10,000” acccording to Dr. Fauci in his chapter from Fundamental Immunology (2003, p. 1294) that Truthseeker quoted above, indicates that the immune response is doing an effective job in curbing the virus in the blood. Or as a Cambridge virology professor put it:

“The immune response to HIV can be compared to that of a live viral vaccine. It explains why most HIV-infected patients remain well for many years.” – Abraham Karpas

In his review (Biology Reviews 79:911-933, 2004), Karpas mentioned the hypothesis that “mutants emerge that manage to evade the immune response and lead to disease progression and death…” He quickly noted, however, that “this cannot be the only reason” for AIDS mortality. As D.D. Richman et al. note in their paper, “Rapid evolution of the neutralizing antibody response to HIV type 1 infection” (PNAS, April 1, 2003), in a third of the HIV patients they studied the neutralizing antibody response was actrally stronger against the mutant variant than against the original strain of HIV.

Posted by: Robert Houston | December 3, 2007 12:23 AM

Robert Houston:

What Richman does, Dr. N, is point to one of the many paradoxes raised by an explanatory model which is forced to assume that HIV is mutating furiously as answer to “strong selective pressure”, aka known as a potent antibody response.

No Robert. Richman et al. are not forced to assume that “HIV is mutating furiously.”

Richman et al. experimentally demostrate that the antibody response does not neutralize the virus present in the same plasma sample from which the antibodies are derived as effectively as it can neutralize virus isolated from earlier plasma samples from the same patient.

They experimentally demonstrate that the virus evolves in such a way that it escapes from the neutralizing anitbody response of the host.

This is known as the scientific method.

Posted by: franklin | December 3, 2007 12:33 AM

Robodoc N,

I think we’ve all got today’s talking point upload. Words are being put in Karpas’s mouth. Now I may have confused Richman and Karpas at somepoint, though I doubt it, but apart from that show me you pathetic overpaid, whatever you’re paid, spambot where I put words in Karpa’s mouth.

Posted by: Molecular Entry Claw | December 3, 2007 12:39 AM

My apologies Robert.

MEC stated:

What Richman does, Dr. N, is point to one of the many paradoxes raised by an explanatory model which is forced to assume that HIV is mutating furiously as answer to “strong selective pressure”, aka known as a potent antibody response.

No MEC. Richman et al. are not “forced to assume that HIV is mutating furiously.”

Richman et al. experimentally demostrate that the antibody response does not neutralize the virus present in the same plasma sample from which the antibodies are derived as effectively as it can neutralize virus isolated from earlier plasma samples from the same patient.

They experimentally demonstrate that the virus evolves in such a way that it escapes from the neutralizing anitbody response of the host.

This is known as the scientific method.

Somehow, it seems less surprising that MEC would not recognize the scientific method.

Again, my apologies, Robert.

Posted by: franklin | December 3, 2007 12:45 AM

Here’s your scientific method Frankie,

As D.D. Richman et al. note in their paper, “Rapid evolution of the neutralizing antibody response to HIV type 1 infection” (PNAS, April 1, 2003), in a third of the HIV patients they studied the neutralizing antibody response was actually stronger against the mutant variant than against the original strain of HIV.

And THAT quote was brought us by the real Robert Houston

Posted by: Molecular Entry Claw | December 3, 2007 12:46 AM

MEC,

Try bringing your head far enough out from under the sand to look not just at “quotes” but at the actual data:

The patients’ antibodies are less effective at neutralization of the virus present in the blood sample from which the antibody was derived than virus present in earlier blood samples from the same patient.

Posted by: franklin | December 3, 2007 12:50 AM

I have stated exactly why you are wrong. You continue to fill this webblog with overly verbose empty rhetoric. Grow up! Posted by: Chris Noble | December 2, 2007 11:00 PM

You are always ready to stop people enlightening you and other HIV loyalists with your wearying, pedestrian, heavy footed, mechanical, predictable, monkey meme repetitive and insulting responses, Chris, which do certainly convince one you are incapable of seeing beyond your own nose, yes.

OK how’s this for brevity:

HIV+ people have vaccinated themselves.

Period.

Just in case you crank your meme machine again, let’s say it slightly longer, so readers can see it clearly.

After several weeks at most, all HIV+ people have vaccinated themselves against HIV, period, because antibody neutralization is completely effective, reducing virus presence and activity to a vanishing point, where it stays for as many years as you otherwise stay healthy, and even if you fall fatally sick will barely manage a resurgence from negligible reservoirs outside the bloodstream.

Once they are self-vaccinated, HIV will never trouble them in any way that paradigm partners such as yourself can justify from the published literature, even though you read it through paradigm loyalist spectacles with the HIV meme monkey tying your optic nerve into a knot.

Karpas wrote it, I quoted it, your posts have confirmed it, your friends also confirm it, so I bid you Goodbye, since the case is proved.

It would be appreciated if you would now kindly switch off your repetition/red herring/contradiction/contempt/accusation Kruger-Dunning-Moore-Noble-Krafft-Ebing meme machine and not have the monkey crank out yet another “you misinterpret/you lie/you misinterpret/you lie/you misinterpret/you lie/you misinterpret/you lie” post so that we don’t have to deal with your uniform autoreplies again.

We all understand that you three don’t understand, Chris. The only objective is to help readers understand that.

You have been a big help, thanks.

“Antibodies neutralize HIV” – Abraham Karpas, Anthony Fauci, Douglas Richman, Robert Gallo, Margaret Johnson, David Ho, Nancy Padian, John P. Moore, Peter Duesberg, Harvey Bialy, Henry Bauer, Gordon Stewart, Rebecca Culshaw, Darin Brown, Robert Houston, Claus Jensen, in fact every intelligent student of HIV?AIDS except Chris Noble and his acolytes here.

Posted by: Truthseeker | December 3, 2007 1:19 AM

This does not mean that an antibody response is without benefit.

Nobody is saying otherwise. There is, however, a large gap between that and HIV being “defeated”. You appear to be going to a great deal of effort to confuse the issue. The evidence shows that HIV viral titres rise to a high during the acute infection stage and then fall to a non-zero “set-point”. At no stage is HIV “defeated”. It is never latent.

HIV continues to replicate after the acute infection period and continues to cause CD4+ cell depletion.

A large proportion of the damage is done in the initial acute infection stage.

HIV pathogenesis: the first cut is the deepest

Posted by: Chris Noble | December 3, 2007 1:25 AM

Karpas wrote it, I quoted it, your posts have confirmed it, your friends also confirm it, so I bid you Goodbye, since the case is proved.

Karpas most definitely did not write: “ordinary levels of antibodies seen in any healthy person exposed to HIV are sufficient to defeat it” and he most definitely did not write “because antibody neutralization is completely effective”

You know perfectly well that Karpas does not agree with you and yet you continue to claim that he does.

The only things that you have proven are your powers of self-delusion and your inability to admit to a mistake.

Posted by: Chris Noble | December 3, 2007 1:36 AM

At no stage is HIV “defeated”. It is never latent.

It is “never latent”? A mistyping, Chris?

You still are missing the fundamental distinction between the factual concession Karpas makes (HIV is neutralized by antibodies) and the imaginary claim he tries to make (it makes a comeback against a healthy immune system and defeats it after all):

Factual concession:

“This does not mean that an antibody response is without benefit.” Nobody is saying otherwise. There is, however, a large gap between that and HIV being “defeated”. You appear to be going to a great deal of effort to confuse the issue. The evidence shows that HIV viral titres rise to a high during the acute infection stage and then fall to a non-zero “set-point”. – Posted by: Chris Noble | December 3, 2007 1:25 AM

Imaginary claim:

At no stage is HIV “defeated”. It is never latent. HIV continues to replicate after the acute infection period and continues to cause CD4+ cell depletion.

A large proportion of the damage is done in the initial acute infection stage.- Posted by: Chris Noble | December 3, 2007 1:25 AM

Inadvertent factual concession:

HIV pathogenesis: the first cut is the deepest. -Posted by: Chris Noble | December 3, 2007 1:25 AM

Yes. After the initial multiplication of HIV before the immune system gears up, HIV is quickly put down.and there is no further revival. But there is no “cut” before, during or after.

HIV does nothing except vaccinate you against HIV.

You are vaccinated by harmless HIV. Period.

Chris, you seem to be unaware that the vaccine project is planning to spend billions, and here you are being told that the best vaccination against HIV is HIV itself.

Why don’t you just believe what Karpas tells you, claim some of the money for yourself, take a holiday, and stop annoying everybody with misleading objections to good science?

Just a suggestion.

Posted by: Truthseeker | December 3, 2007 1:59 AM

Truthseeker (sic):

You still are missing the fundamental distinction between the factual concession Karpas makes (HIV is neutralized by antibodies) and the imaginary claim he tries to make (it makes a comeback against a healthy immune system and defeats it after all)

Why do you maintain that the continued replication of HIV in the face of the neutralizing immune response is imaginary, given that Richman has provided experimental verification of the virus eluding even the most potent immune responses that they observed?

Richman demonstrates a neutralizing antibody response and the evolution of the virus to escape the response. Neither is imaginary. Both have been empirically demonstrated.

You simply choose to bury your head in the sand and ignore the data that you so helpfully brought to our attention.

Posted by: franklin | December 3, 2007 2:15 AM

It is “never latent”? A mistyping, Chris?

Unlike you I write what I mean and I mean what I type.

At no stage is HIV latent. It seems that at this stage of the conversation you are still not aware of the distinction between latent and chronic infection.

Natural history of acute and persistent human infections

Inadvertent factual concession:

It was neither inadvertent nor a concession. Why do you play these silly word games?

Why don’t you just believe what Karpas tells you, claim some of the money for yourself, take a holiday, and stop annoying everybody with misleading objections to good science?

I am not objecting to anything Karpas has written but rather your persistent misinterpretations.

Your rhetorical attempt to pit me against Karpas is simply pathetic. You know perfectly well that Karpas does not agree with you.

Posted by: Chris Noble | December 3, 2007 2:52 AM

Why do you maintain that the continued replication of HIV in the face of the neutralizing immune response is imaginary, given that Richman has provided experimental verification of the virus eluding even the most potent immune responses that they observed?

Because my wits have not been frightened out of me by the story of the nightmare Virus, which allows me to see that whatever life the virus might still manage to have coaxed out of it by Richman matters not a jot, because the Virus is so effectively neutralized by antibodies that it couldn’t overcome the healthy immune system which imprisoned it safely away from the bloodstream and which keeps it locked up safely for the duration.

In biology quantity rules. As Moore points out in one of his sadly neglected masterpieces, they chuck 40-500 times as much Virus at cells to prove it is toxic as occurs in vivo. Naturally it proves toxic.

Franklin you underestimately the level of rationalizing BS going on even though you do it yourself!

Franklin, a word in your ear. Here’s a plan. Forget about Chris and John Moore, and repeat five times after me:

Harmless HIV does nothing but vaccinate you against harmless HIV.

See if it fits the scientific literature, which it will, without exception, except that part of the literature which consists of data management, paradigm imposed misinterpretation and so forth.

Then have lunch at Nello’s with Anthony Fauci and David Ho, and tell them that you have a short cut to the HIV vaccine. HIV itself.

Show them Karpas’ paper as evidence you know what you are talking about.

Anthony Fauci will say something like, “Franklin, who have you told about this? Anybody else?” He will look at David Ho meaningfully.

You should reply, “I have put it in a sealed bank box to be opened at my death.”

Fauci will suddenly become very friendly, swear you to secrecy, and give you a check for $500 million.

If you don’t bother to mention this to Chris Noble, no one will blame you. However, it might be as well to give him and Hinckley $100 million just in case they start investigating why Fauci didn’t respond to THEIR phone calls on the same topic.

My commission is merely $10 million, since it is your status as family that will get you the lunch with Fauci and Ho. They probably wouldn’t see me at all.

Good luck!

Posted by: Truthseeker | December 3, 2007 2:58 AM

You still are missing the fundamental distinction between the factual concession Karpas makes (HIV is neutralized by antibodies) and the imaginary claim he tries to make (it makes a comeback against a healthy immune system and defeats it after all):

This sentence highlights the fundamental dishonesty of Denialists. They cherry pick isolated bits of papers that they falsely believe support their position and ignore the rest that refutes that position.

Posted by: Chris Noble | December 3, 2007 2:59 AM

Because my wits have not been frightened out of me by the story of the nightmare Virus, which allows me to see that whatever life the virus might still manage to have coaxed out of it by Richman matters not a jot, because the Virus is so effectively neutralized by antibodies that it couldn’t overcome the healthy immune system which imprisoned it safely away from the bloodstream and which keeps it locked up safely for the duration.

This is a classic Duesbergian misdirection. The vast majority of CD4+ cells are in lymphoid tissue and not in circulating blood. Not coincidentally this lymphoid tissue is the major reservoir for HIV and it is where it is doing its damage. Far from being locked up safely HIV is continuously replicating in lymphoid tissue at all stages of infection.

Posted by: Chris Noble | December 3, 2007 3:19 AM

At no stage is HIV latent. It seems that at this stage of the conversation you are still not aware of the distinction between latent and chronic infection.- Posted by: Chris Noble | December 3, 2007 2:52 AM,/i>

Neither statement is true.

You still are missing the fundamental distinction between the factual concession Karpas makes (HIV is neutralized by antibodies) and the imaginary claim he tries to make (it makes a comeback against a healthy immune system and defeats it after all):

This sentence highlights the fundamental dishonesty of Denialists. They cherry pick isolated bits of papers that they falsely believe support their position and ignore the rest that refutes that position. Posted by: Chris Noble | December 3, 2007 2:59 AM

The above statement reflects the foolishness of those who cannot see what part of a paper is based on data and what part based on imaginative argument, which doesn’t refute anything, especially the data in the other part of the paper.

The foolishness arises from the HIV meme which monkeys about with the already strained reasoning powers of those whose only scientific role is teacher’s pet.

Sorry Chris but you are trying to manoever your next roadblock into our path when we are already gone.

There is a limit to which one can carry on dancing with a monkey with a wooden leg, even if it is a meme.

Adieu!

Posted by: Truthseeker | December 3, 2007 3:19 AM

The above statement reflects the foolishness of those who cannot see what part of a paper is based on data and what part based on imaginative argument, which doesn’t refute anything, especially the data in the other part of the paper.

No, it demonstrates that the sole criterion you use to decide which part of a paper to cite is whether you can spin it to support your position. You are quite happy to cite Karpas as an authority when a sentence can be twisted to mean something that appears to support your claim but you have no trouble dismissing every thing else he says that clearly refutes your position.

You can’t have your cake and eat it too. This schizophrenic attitude to the literature is characteristic fro Denialists.

The paper by Richman et al that you cited is a classic example. It details direct experimental evidence that HIV continues to replicate despite the antibody response.

Even the title should give you a few clues: Rapid evolution of the neutralizing antibody response to HIV type 1 infection.

Why would the antibody response continue to evolve over a period of 39 months if HIV has been put out of action?

Posted by: Chris Noble | December 3, 2007 3:34 AM

At no stage is HIV latent. It seems that at this stage of the conversation you are still not aware of the distinction between latent and chronic infection.- Posted by: Chris Noble | December 3, 2007 2:52 AM,

Neither statement is true.

I can only conclude once again that you are either knowingly lying or are too stupid to have a clue what you are talking about.

The very paper by Richman et al that you yourself cited demonstrates that HIV is never latent.

Posted by: Chris Noble | December 3, 2007 3:55 AM

Baghdad Bob (AKA Truthtwister) said:

“Karpas wrote it, I quoted it, your posts have confirmed it, your friends also confirm it, so I bid you Goodbye, since the case is proved.”

Now TS, if only you would read it:

“90%…deadly…10 years” – A. Karpas

Posted by: Roy Hinkley | December 3, 2007 7:44 AM

“Truthseeker” or, more aptly, truthtwister (with props to Hinkley),

Your insistence on calling yourself a seeker of truth is irking me out of my silence of several weeks. You and your fellow “journalist,” Robert Houston, pretend to objectivity. Yet you both keep yourselves as far from facts as you can, and the extent of your “objectivity” is revealed in most of what you write, including Robert Houston’s reference to scientists as “HIV enthusiasts.” Anyone who can call a Joseph Sonnabend or any prominent AIDS doc or researcher an “HIV enthusiast” has never spent enough time with such people to learn of their passion and compassion and hatred of the virus.

Until you have some basic knowledge of biology, chemistry, mathematics, etc., it is pointless to argue with you about science. Nothing lost there, since science is clearly not the sticking point with you. Your objection is to facts or authority in general, it seems.

Is that perhaps why you try to provoke others with your self-consciously un-PC remarks?

Such as calling Tara “delectable” above (i.e. delicious, for cooler’s benefit)?

Or writing that jen is just another “female know-nothing”?

Or questioning Adele’s gender, deciding she must be a (male) “gay activist,” a term you use with the utmost of disgust?

Your apparent problems with society’s acceptance (relatively speaking, of course) of women as more than vacuous eye candy for British “gentlemen” who use the royal “we” and of gay people as worthy of something more than dismissal as “activists” would be a good place for you to start in assessing your unwillingness to be objective re science.

Posted by: ElkMountainMan | December 3, 2007 11:51 AM

Now TS, if only you would read it:
“90%…deadly…10 years” – A. Karpas
Posted by: Roy Hinkley | December 3, 2007 7:44 AM

Why do you truncate this quote till it its absurdity is unrecognisable, Roy? It reads in full:

Sexual intercourse has now spread the virus around the World; and there are probably some 70 million infected. 90% of those infected with HIV develop the deadly disease of AIDS within ten years of infection: the death toll from the disease has been enormous.

You do know the date this was written, and examined, and revised, till Karpas and the peer reviewers and editors of Bio. Rev. were satisfied it was accurate? 2004, in case you overlooked it.

So we have them all agreeing that 90% of those infected with HIV develop AIDS within ten years.

How does this jibe with the current claim that the mean latent period of HIV is ten years or more? That would indicate that 50% or fewer would be showing AIDS symptoms by the ten year mark, wouldn’t it? Indeed that is the case – fewer, in fact, as the predictions fail and fail, kept up only by the medications being applied earlier.

Now the UN has corrected the 70 million guess, which was pessimistic to say the least in 2004, to 33 million today.

Don’t you recognise what is happening? These guys go overboard in pushing the view of AIDS towards the doomsday scenario of maximum sick and dead people, as they make as many claims as they can in that direction to keep the disbursements from the public purse flowing in an era where you have to compete for every penny, especially when you already have more than your fair share.

It is almost childishly transparent in this case.

Yes, Karpas is an honest man when contemplating facts. When trying to keep his fellow Fauci Club members happy, however, having burst their balloon with his observations of how HIV gets stopped and rolled back to a negligible set point by any healthy person’s antibodies (pace the three HIV meme monkeys sharing silently in this thread), he rushes to prove he is a fully paid up loyal member of the HIV=AIDS Maximum Funding Regardless of Absurd Hypothesis Killing Gays and Blacks Club, and talks nonsense about 90% being ill in ten years, and 70 million infected.

Roy, as the only bright and creative and somewhat careful and thoughtful person here defending the absurd paradigm, at least unleash your sophisticated reading of journal review texts and in this case see the blindingly apparent.

Harmless HIV vaccinates against harmless HIV.

That is the only conclusion for which we have any data for this exceptionally rewarding but otherwise overwhelmingly inert retrovirus.

Perhaps you are a physicist who doesn’t understand what is going on in biology as far as funding pressures warping common sense goes, but just as an example from another field, why not skim that Kruger-Dunning paper just for laughs?

Its brilliant topic of study which it proves several different ways is that dim people do not realize how dim they are. The funding is from the NIMH. Yes, the review committee sat around one day contemplating this proposal and funded it. In other words, public money was spent proving that the sun rises in the East and sets in the West.

This is the pretty pass we have reached in the semi-sciences of psychology and disease study. You may be shocked to hear me label disease study a semi science, and claim that disease is an active arena for such collegial boondoggles. But that is what appears to be the case, from SARS to bird flu. The outstanding example of jobs-for-the-boys peer review is HIV=AIDS, and it has encouraged all kinds of imitation, it appears.

Of course, I am writing this in the fond belief that you are not a player in this sphere who is well aware of what I say, but an unwitting fellow traveler from a cleaner arena such as physics.

Your friend,

Baghdad Bob II

Posted by: Truthseeker | December 3, 2007 12:06 PM

I must say that this amusing (and quite tedious) thread has showed a few glimmers of solid reasoning. I salute Truthseeker for actually engaging some of these AIDS knuckleheads, who really don’t think about these issues (let alone falsify them), but merely close ranks with their better paid brethren of the orthodoxy to recapitulate standard, scientific-sounding garbage.

HIV develops its own vaccine!

SARS is bullshit, so is avian bird flu, so is west nile, so is the dreaded swine flu of the 70’s, .. the list endless, and in a few years we may just have to add HIV to it.

Posted by: Barney | December 3, 2007 1:27 PM

Barney,
The fact of the matter is HIV is on the list of dead virus campaigns, except that the great protectors and purveyors of the paradigm wish to keep the status quo because God forbid they should loose their funding. Want to stop HIV AIDS? – drop the funding.

Posted by: Carter | December 3, 2007 2:22 PM

“Truthseeker” or, more aptly, truthtwister (with props to Hinkley),…etc etc etc. Posted by: ElkMountainMan | December 3, 2007 11:51 AM

By the mighty Virus you cannot even read the posts properly, Mr Elk, so you really don’t deserve a reply to this series of rank misstatements and misreadings, almost one per sentence. We would sympathise with you if any were true, but none of them are.

One might observe, however, that you fit neatly into the Duesberg-Bialy litmus test of intelligence in this affair, being somewhat humorless in your perceptions of what we wrote. That’s one cause of what “irks” you, it is clear, in this very inaccurate reading of posts you have skimmed on return from your holiday.

The absence of a sense of humor correlates very highly – 99.9999% – with the inability to perceive the Grand Canyon sized flaws in the HIV=AIDS hypothesis.

But just for the record, who said Joseph Sonnabend lacked compassion? The problem is that he loves the Virus nearly as much as all its other scientific husbands, who we observe married to it for its money. He may not be thinking straight because he is a doctor in the midst of dealing with the tortures visited upon the HIV congregation by its priests, but he knew enough to resist until he was threatened with being cut off by the powers that be, when he compromised.

We cannot see into his soul and cannot say why it happened, but it looks suspect to us, since nothing had changed in the data to make HIV any more likely a candidate for causing the effects of drugs, conventional illness and nutritional deficit, which are obviously the real causes of AIDS illness and deaths to anyone who reads the literature with any objectivity.

Oh sorry, are we talking to someone with the HIV meme sitting in his brain? Then you believe that he just grew more enlightened, right, as “overwhelming evidence” accumulated?

OK we’ll have to leave it at that, though referring you to the recent posts recording the rout of Christopher Noble et al trying to maintain that HIV is not powerfully neutralized by the immune system of any healthy person in a manner equivalent to any good vaccine.

But kindly do not babble about how we don’t credit data and good scientific reasoning, that we scorn authority, etc when we don’t. We recognize the authority of good scientists who are not politically influenced to skew their judgement away from what good data and precise reasoning indicate.

Nor accuse us of scorning gays when we only scorn the ignorance and prejudice of gay activists who profit from the monetary disbursement of drug companies into their organisations and then by some remarkable coincidence reliably agitate on behalf of the HIV paradigm and the drugs sold on that rationale which injure and eventually kill them and their friends.

Sorry, but that is the height of non-science to us, since the reasoning and objective data of good science as found in the literature is our touchstone in viewing events in this catastrophically misunderstood plague. You imply this measure is yours also. Then what a pity you don’t feel responsible enough to get yourself together and get a proper grasp on events and what we are saying, instead of firing off objections to statements we didn’t make and attitudes we don’t have. So typical of the masochistic self injury of the gay activists in this field to be so righteous when wrongly informed. Do you really want to mimic them?

And by the way we don’t have any problem whatsoever with society’s acceptance of women as more than eye candy, we support it totally, in fact unlike you we accept it as going without saying. In any circles we have anything to do with there is no mention of color or sex as affecting credentials in any public role, polticial or academic.

Sorry that you still seem to feel this is an issue, so when we delight in Tara’s superattractive image as posted by herself proudly on her site you start worrying about whether we take her mind seriously or not, when it has nothing to do with that. We would take her mind more seriously if it showed a more critical and independent scrutiny of HIV=AIDS, but that has nothing to do with her appearance.

Are you suggesting that attractive people are dumber than plain people? Why would that be? Is that what you think, since it occurs to you and not to us? If anything we imagine that they would be brighter, since they would get more attention and support in life.

While we are repeating quotes, let’s just repeat this one from Houston for the third time:

“The immune response to HIV can be compared to that of a live viral vaccine. It explains why most HIV-infected patients remain well for many years.” – Abraham Karpas

Let’s see how Chris Noble’s hand cranked autoresponse you liar/you misinterpret/you liar/you misinterpret/you liar Krafft-Dunning-Kruger-Ebing-Moore-Noble-HIV meme machine deals with that one.

Guess it lacks a reverse gear, so we can’t expect much except the same old same old, a pattern which suggests to us he is not even there half the time, he has just set the meme machine to respond automatically to certain posters while he is off somewhere else entirely doing something useful in his life down under..

Posted by: Truthseeker | December 3, 2007 2:47 PM

Meanwhile back at the ranch…

“Investigators found that Brodie [Scott J. Brodie] falsified data in 15 instances — in published and unpublished journal articles, and grant proposals. The research in question included cellular responses to the HIV virus.”

Kinda make one think what kind of science Tara et al. are really supporting, doesnt it?

Click for Seattle Times article UW: Researcher faked AIDS data, altered images by Nick Perry and Carol M. Ostrom

Posted by: carter | December 3, 2007 3:05 PM

Thanks Carter. From that news story:

“It was a very traumatic investigation to be involved with,” Liggitt said. “We got to look at the underbelly of science.”….

He said medical research and HIV research in particular is highly competitive, with the National Institutes of Health making cutbacks and many researchers competing for limited funding. Getting published can help bolster a researcher’s push to land the next grant, he added.

“It’s ugly out there,” Liggitt said. “There are a lot more desperate people because of the cutbacks.”

Oh dear, it seems that Fauci didn’t manage to keep funding up as high as he promised his faithful at last year’s HIVNET meeting after all.

I dont have any sympathy for these guys working on a false and murderous premise which takes a disproportionate amount of funding anyway, so much of it wasted on examining an innocent retrovirus.

They shouldn’t go into science unless they have something to offer science in genuine passion and talent. Find something else which suits you, for God’s Sake, instead of trying to live off deceit in an area which professes truthseeking.

Once in though, I can see they become trapped, what with wives and children and all.

This HIV=AIDS scam that Gallo launched without knowing it would grow so big can be viewed as a trap for all the people involved, with no one able to come clean now without being ruined. How Science, Nature, the Academy of Sciences, the NIH, the NSF, the New York Times, Harvard, etc etc etc can survive any correction is problematical, to say the least. That is why I posted on Saturday that the dissenters may as well give up.

Posted by: Truthseeker | December 3, 2007 3:45 PM

By the mighty Virus you cannot even read the posts properly, Mr Elk, so you really don’t deserve a reply to this series of rank misstatements and misreadings, almost one per sentence. We would sympathize with you if any were true, but none of them are.

Truthseeker, ElkMountainMan is an old friend, who, like the paper tyger virus, should have remained in the aloof scientific recesses where he is no doubt germinating. However, since by his own words he has been coaxed out of his 6 foot deep chromatin slumber as a reincarnated authority on Political Correctness, moral philosophy, and the satiric genre, maybe he would now like to elaborate, in his own name, on his comments about Christine Maggiore, Al-Bayati and the baby killer connection?

How about it Mr. PC Elk, were your statements concerning those matters just for fun? There’s a free trip to LA and instant fame for you if you can explain to Al-Bayati face to face in a public, non-anonymous venue why you find his work distasteful and his conclusions strange.

Posted by: Molecular Entry Claw | December 3, 2007 4:19 PM

“There are a lot more desperate people because of the cutbacks.”

Um, well Truthseeker, you know as well as I do it ain’ just cutbacks. The whole freakin ordeal with HIV is just plain desperate!

Each and every post by the apologists here has a very strong and distinct smell of desperation!

Posted by: Carter | December 3, 2007 5:01 PM

MEC,

Did you perhaps mean “ruminating,” not “germinating?” Your would-be linguistic master, the twister of truth, would not be pleased. But no matter; whatever I am doing in my “scientific recesses” is of little importance alongside the situation I read about this morning on the blog of Mark and Chris Hoofnagle.

http://scienceblogs.com/denialism/2007/12/hivaids_denialism_is_deadly_th.php#more

It seems that the Liversidge-emulating “gatekeepers” at the MSN Aids Myth Exposed board are encouraging an HIV-positive mother to avoid any medical care for herself and her infant. Chiming in is one “rebecca veronica,” whom several denialists in the past have identified as Rebecca Veronica Culshaw. (Truthtwister, you may not be familiar with this minor denialist but cooler has vouched for her “hotness,” so you can safely listen to her. To use your words, Culshaw is a real female know-nothing, and not just some gay activist who likes to get a kick out of a female name.)
((On the contrary, Culshaw is a fine mathematician and logician who has written an excellent book, Science Sold Out. – Ed.SG/NAR))

Culshaw and sidekick former academic Darin Brown tell the young mother to continue breastfeeding her baby, since there is nothing healthier and the “orthodoxy” doubt that mother to child transmission ever happens.

Lies, stupidity, and ignorance conspiring against an innocent mother and her child: a sad and lamentable state of affairs. How do these denialists sleep at night?

Posted by: ElkMountainMan | December 3, 2007 7:30 PM

HIV Is Not the Cause of AIDS
By Peter H. Duesberg

Science, Vol. 241, pp. 514-517, July 29, 1988.

Human immunodeficiency virus (HIV) is not the cause of AIDS because it fails to meet the postulates of Koch and Henle, as well as six cardinal rules of virology.
1) HIV is in violation of Koch’s first postulate because it is not possible to detect free virus (1, 2), provirus (3-5), or viral RNA (4, 6, 7) in all cases of AIDS. Indeed, the Centers for Disease Control (CDC) has established guidelines to diagnose AIDS when all laboratory evidence for HIV is negative (8).
2) In violation of Koch’s second postulate, HIV cannot be isolated from 20 to 50% of AIDS cases (1, 9-11). Moreover, “isolation” is very indirect. It depends on activating dormant provirus in millions of susceptible cells propagated in vitro away from the suppressive immune system of the host.
3) In violation of Koch’s third postulate, pure HIV does not reproduce AIDS when inoculated into chimpanzees or accidentally into healthy humans (9, 12, 13).
4) In contrast to all pathogenic viruses that cause degenerative diseases, HIV is not biochemically active in the disease syndrome it is named for (14). It actively infects only 1 in 104 to > 105 T cells (4, 6, 7, 15). Under these conditions, HIV cannot account for the loss of T cells, the hallmark of AIDS, even if all infected cells died. This is because during the 2 days it takes HIV to replicate, the body regenerates about 5% of its T cells (16), more than enough to compensate for losses due to HIV.
5) It is paradoxical that HIV is said to cause AIDS only after the onset of antiviral immunity, detected by a positive “AIDS test,” because all other viruses are most pathogenic before immunity. The immunity against HIV is so effective that free virus is undetectable (see point 1), which is why HIV is so hard to transmit (9, 12, 13). The virus would be a plausible cause of AIDS if it were reactivated after an asymptomatic latency, like herpes viruses. However, HIV remains inactive during AIDS. Thus the “AIDS test” identifies effective natural vaccination, the ultimate protection against viral disease.
6) The long and highly variable intervals between the onset of antiviral immunity and AIDS, averaging 8 years, are bizarre for a virus that replicates within 1 to 2 days in tissue culture and induces antiviral immunity within 1 to 2 months after an acute infection (9, 17). Since all genes of HIV are active during replication, AIDS should occur early when HIV is active, not later when it is dormant. Indeed, HIV can cause a mononucleosis-like disease during the acute infection, perhaps its only pathogenic potential (9, 17).
7) Retroviruses are typically not cytocidal. On the contrary, they often promote cell growth. Therefore, they were long considered the most plausible viral carcinogens (9). Yet HIV, a retrovirus, is said to behave like a cytocidal virus, causing degenerative disease killing billions of T cells (15, 18). This is said even though T cells grown in culture, which produce much more virus than has ever been observed in AIDS patients, continue to divide (9, 10, 18).
8) It is paradoxical for a virus to have a country-specific host range and a risk group-specific pathology. In the United States, 92% of AIDS patients are male (19), but in Africa AIDS is equally distributed between the sexes, although the virus is thought to have existed in Africa not much longer than in the United States (20). In the United States, the virus is said to cause Kaposi’s sarcoma only in homosexuals, mostly Pneumocystis pneumonia in hemophiliacs, and frequently cytomegalovirus disease in children (21). In Africa the same virus is thought to cause slim disease, fever, and diarrhea almost exclusively (22, 23).
9) It is now claimed that at least two viruses, HIV-1 and HIV-2, are capable of causing AIDS, which allegedly first appeared on this planet only a few years ago (20). HIV-1 and HIV-2 differ about 60% in their nucleic acid sequences (24). Since viruses are products of gradual evolution, the proposition that within a few years two viruses capable of causing AIDS could have evolved is highly improbable (25).

References and Notes:

J. Albert et al., J. Med. Virol. 23, 67 (1987).
L.A. Falk, D. Paul, A. Landay, H. Kessler, N. Engl. J. Med. 316, 1547 (1987).
G.M. Shaw et al., Science 226, 1165 (1984).
D. Richman, J. McCutchan, S. Spector, J. Infect Dis. 156, 823 (1987).
C.-Y. Ou et al., Science 239, 295 (1988).
M.E. Harper, L.M. Marselle, R.C. Gallo, F. Wong-Staal, Proc. Natl. Acad. Sci. U.S.A. 83, 772 (1986).
A. Ranki et al., Lancet ii, 589 (1987).
Centers for Disease Control, J. Am. Med. Assoc. 258, 1143 (1987).
P.H. Duesberg, Cancer Res. 47, 1199 (1987).
H. von Briesen et al., J. Med. Virol. 23, 51 (1987).
D. Gallo, J. Kimpton, P. Dailey, J. Clin. Microbiol. 25, 1291 (1987).
J.W. Curran et al., Science 239, 610 (1988).
G.H. Friedland and R.S. Klein, N. Engl. J. Med. 317, 1125 (1987).
J. Coffin et al., Science 232, 697 (1986).
A. Fauci, ibid. 239, 617 (1988).
J. Sprent, in B and T Cells in Immune Recognition, F. Loor and G.E. Roelants, Eds. (Wiley, New York, 1977), pp. 59-82.
H.A. Kessler, J. Am. Med. Assoc. 258, 1196 (1987).
R.C. Gallo, Sci. Am. 256 (No. 1), 47 (1987).
Centers for Disease Control, AIDS Weekly Surveill. Rep., 18 April 1988.
R. Baum, “AIDS: The molecular biology,” Chem. Eng. News (23 November 1987), pp. 14-26.
R.M. Selik, E.T. Starcher, J.W. Curran, AIDS 1, 175 (1987).
R. Colebunders et al., Lancet i, 492 (1987).
K.J. Pallangyo et al., ibid. ii, 972 (1987).
F. Clavel et al., Nature 324, 691 (1986).
J. Sonnabend, in New York Native (9 May 1988), p. 19.

Posted by: cooler | December 3, 2007 7:35 PM

———————————————————–

TS: What did Karpas really say?

The entire quote should be put up at once, before the handcranked Noble meme machine is launched. I believe it is worth going through with an index finger, mumbling the words out loud, to get the full impact of what it reveals:

“The immune response to HIV can be compared to that of a live viral vaccine. It explains why most HIV-infected patients remain well for years. Other viruses that establish lifelong infection, such as herpes viruses, tend to remain latent in the body and the only other exogenous retrovirus known to be capable of infecting humans, the adult T-cell leukaemia HTLV-1, causes disease in less than one in a thousand of infected individuals. In man infection with HIV is probably never latent, because the virus appears to mutate continuously in every infected individual due to its highly error prone reverse transcriptase (RT) which lacks the proof reading capabilities of other RNA polymerases. This has two consequences: 1) In nearly every infected individual, despite a vigorous immune response that is protective for many years, eventually one or more mutants emerge that manage to evade the immune response and lead to disease progression and death; (2) in drug-treated individuals, a drug resistant virus emrges and treatment fails to halt disease progression. The continuous mutations of the replicating virus cannot be the only reason for the very high mortality of HIV infection in man, because the viruses HIV-1 and HIV-2 do not cause disease in their natural hosts, the chimpanzee and the sooty mangabey monkey, respectively. Disease occurs only when the viruses cross species.

In addition to its high mutation rate, HIV can also evade the immune response by direct cell-cell contact through fusion between infected and non-infected cells: the virus can be transferred without being exposed to agents of the immune response, such as neutralising antibodies. This is facilitated by the affinity of viral glycoproteins expressed on the surface of infected cells for CD4 molecules on neighboring uninfected cells. Probably this process is particularly important in the lymph nodes, where presentation of foreign antigen to lymphocytes by cell-cell contact is an essential step in initiating immune responses.

Early after infection with HIV, cell-mediated immune responses can be detected in infected individuals… It is possible that when cytotoxic T-cells are lost a high level of neutralising antibodies can by itself delay disease progress….

Most HIV infection in the world is not confirmed by tests:

Most test methods can give false positive readings, so it is important to check any positive reading by a screening assay with a confirmatory test…..many third world countries are not in a position reuglarly to confirm positive readings obtained by the routine screening methods such as an ELISA. Since nearly 90% of the HIV infected live in third-world countries, this means that the majority of positive reactions are unchecked.

(Karpas developed his own alternative test method in 1985 which “contains its own controlled confirmatory test”):

The cell test showed that most of the healthy HIV-infected individuals have a very high level of anti-HIV antibodies whereas, in contrast, patients who progressed to AIDS had a low level of antibodies that decreased further with disease progression. Studies of such sera with Western Blot correlate with the cell test titration studies… The sera from the AIDS patients are missing numerous antibodies and even the antibodies which are present are at low concentrations…. We have assayed for the presence of neutralising antibodies in over 100 healthy HIV-1 infected individuals and without exception found that the sera contained significant levels of such antibodies….(We carried out) one of the earliest studies trying to explore and explain the differences in the immunological state between healthy HIV-infected individuals and AIDS patients (in 1985). Our studies have demonstrated that healthy HIV-1 infected individuals who were not viraemic had high levels of neutralising antibodies against the virus and a CD4+ T-cell count within the normal range while AIDS patients with very low numbers of CD4+ T-cells and high levels of HIV-1 were devoid of neutralising antibodies and had low levels of other antiviral antibodies (Karpas et al 1988).

Studies from the USA of long-term survivors have also found high levels of neutralising antibodies (Cao et al 1995, Pantaleo et al, 1995). Although polymerase chain reaction (PCR) assays for the presence of HIV-1 RNA in the plasma revealed significant levels of RNA in some individuals, the biological assay for viral infectivity failed to reveal the presence of infectious virus, suggesting that the HIV-1 in the bloodstream had beeen inactivated by the neutralising antibodies. In addition, this indicates that PCR does not distinguish between infectious (live) and neutralised (killed) virus.

Yes, sir, neutralise= kill.

Also helpful are someone else’s antibodies:

We have recorded similar observations with AIDS patients who were treated with passive immunotherapy (PIT). AIDS patients before the infusion of hyperimmune plasma were HIV-1 viraemic as monitored by the isolation of infectious virus from the plasma. After the infusion of hyperimmune plasma, infectious virus could not be isolated but many remained PCR positive.

Translation: Neutralising antibodies reduce HIV to vanishing set point. The pussy is treed by the dogs of the immune system.

Ultimate conclusion, as we said before:

HIV vaccinates you against HIV.

Here’s a bonus. How about AZT? Nasty stuff. Killed thousands, right?

Confirming this, Karpas continues, showing what a mistake AZT, and how beneficial IN AND OF ITSELF it must have been to stop using high doses of the poison – a proven useless poison which reportedly they are still mixing in small amounts into the cocktails:

The first drug that was approved for use in people with HIV disease was azidothymidine (AZT), a chemical developed years earlier as an anti-cancer drug but abandoned because of its high level of toxicity…. Not surprisingly, an early study of bone marrow in patients who had been receiving AZT revealed that all developed anaemia with a varying degree of other white blood cell deficiencies. AZT inhibits HIV replication by blockingg the viral RT and there is no doubt that initially the effect is very dramatic. In the early short-terms trials, AZT appeared to be beneficial. However, within a few weeks to a few months of AZT treatment, replication-competent, AZT resistant HIV strains emerge followed by disease progression, A placebo-controlled trial, lasting two years, revealed that AZT did not imptove survival and was associated with more side-effects. In the British/French Concorde trial which involved 1700 patients and lasted three years, follow-up revealed a statistically significant increase of deaths in the AZT treatment arm as compared to those in the placebo (J. Derbyshire, personal communciation, 1994). The other nucleotide analagues that have been approved for use, such as ddC and ddI, are also highly toxic and of short term benefit….

(With regard to protease inhibitors and HAART) Protease inhibitors are less toxic than AZT but when used alone , the virus quickly develops drug-resistant mutants. However, when a protease inhibitor was used together with two RT inhibitors it marked the first significant progress in anti-HIV treatment, The combination of drugs has been named highly active antiretroviral therapy (HAART). Following the initiation of HAART treatment approximately 80% of AIDS patients improved clinically; and coincidentally their CD4+ T-cell counts increased and the plasma viral load dropped significantly or completely disappeared. (Hogg et al 1997). The length of the beneficial effects of HAART differs between the individual patients and ranges from a few months to several years. For some the toxic side effects are more pronounced than for others. In most individuals who can tolerate the drug combination over prolonged periods, a wide range of pathological conditions develops due to toxicity, many of them, such as lipodystrophy, have never been seen before in AIDS while liver damage and vascular conditions are common. As a result the HAART treatment of AIDS patients has changed from combating opportunistic infections to reducing toxic side effects…

Meanwhile HAART fails to eradicate replication competent HIV-1:

A recent study of a group of patients who have been treated successfully for up to 30 months with triple therapy, replication-competent HIV-1 was routinely isolated despite the fact that even the plasma assay for HIV-1 PCR was negative (Finzi et al, 199; Wong et al 1997).

Some AIDS researchers suggested that drug treatment should be initiated early in the course of HIV infection (Ho, 1995) but so long as the available drugs have only a limited period of effectiveness, and are toxic, that may be misguided. In most HIV-infected individuals, the immune system manages to limit the damage caused by the virus for many years – far longer (on average nine years) than any drug cocktails available that have the added disadvantage of being toxic.

Hey, why not try borrowing antibodies from healthy patients? It worked!

After our early study demonstrated that healthy HIV-infedcted individuals had high levels of neutralising anitbodies, while AIDS patients had none, we investigated the possibilitiy of using passive immunotherapy as a form of treatment in AIDS. This began in 1985, transfusing blood plasma from healthy HIV-1 infected individuals to AIDS patients (Karpas et al, 1985)….(There was ) some evidence of benefit when the patients were treated for two years…(Other studies suggested that PIT is beneficial but) Unfortunately, double-blind, placebo-controlled trials have not been able to muster financial support in the UK….

(Meanwhile they have found) an increasing number of plasma donors who have been donating continuously for 3-7 years without a decline in numbers of CD4+ T-cells or antibody level or other signs of disease progression (Abelian et al, 2001). The mechanism of these effects is not understood. Defining it might help us to understand why HIV overcomes the immune system, and could open up new avenues for the development of therapeutic strategies against this deadly virus.

After you read enough of this stuff, you realise that Karpas is a reviewer who is severely handicapped by the HIV meme, which here, for example, prevents him from seeing the obvious – that the simplest explanation of “the effects” is that HIV is not deadly or even harmful at all.

Following all this you can read Richman’s paper, which Karpas didn’t see before going to press, and see that mutation is no answer to the question: How come the virus makes any kind of comeback with antibodies around to neutralise it?

Because Richman showed that the antibodies keep up very well with viral mutation, leading the dogs of the immune system to chase all the new variants of pussy cat virus up a tree just as fast as before, sometimes faster.

What a mess. All any thinking gay has to do is read this paper, I would think, and he wouldn’t cooperate with this latter day pellagra. But Alas! they all will doubtless read it like ElkMan with the monkey meme in their noggin, just like Karpas, and not see where the dividing line comes between evidence and misinterpretation.

Maybe one should borrow that meme machine from Noble and turn it on Karpas: “you liar/you misinterpret/you liar/you misinterpret/you liar/you misinterpet”.

World AIDS Day! – HIV rules

December 1st, 2007

Bush pushes for $30 billion, decks White House with 28 ft ribbon

Skeptics confounded, HIV world conquest complete

Drink hemlock, Socrates

aidslogo.jpgToday is World AIDS Day 2007, and our best congratulations to Bob Gallo, Anthony Fauci, David Baltimore and John Moore are in order. Congratulations all! You and human foolishness together have conquered the world!

The top generals of the propaganda campaign for world domination of the HIV-means-AIDS scientific hypothesis, otherwise known as the AIDS meme, must be grinning like skulls over their success over the past year in stamping out the last remnants of the ridiculous and doomed resistance to their favorite and now globally accepted bad idea.

Today, they stand atop the highest pyramid of government funded research, intensely felt activism, and 100% institutional and government support, that has ever accumulated for an unproven hypothesis in the history of human disease.

Yesterday George Bush again requested Congress to double the funds for AIDS from $15 billion to $30 billion, money which will allow drug companies to send harmful potions to the dark continent for Western and African witch doctors to give African men, women and children who “have AIDS”:

bushaids.jpg“Every year American taxpayers send billions of their hard-earned dollars overseas to save the lives of people they have never met,” he said.

But “in return for this extraordinary generosity, Americans expect results,” the president said, adding that his program demands measurable progress, accountability and the involvement of local partners. The result: The number of people in sub-Saharan Africa receiving treatment for AIDS has gone from 50,000 five years ago to nearly 1.4 million now, he said.

“We have pioneered a new model for public health,” Bush said. “So far, the results have been striking.”

In May, the last time he devoted a speech to the topic, Bush asked Congress to double the $15 billion that the U.S. committed over the program’s first five years to therapy, testing and counseling through the President’s Emergency Plan for AIDS Relief. The program is active in 120 countries, with a concentrated focus on 15, including Namibia, in sub-Saharan Africa, Asia and the Caribbean.

He also did the right thing and hung a 28 foot high red ribbon on the White House:

In honor of Saturday’s World AIDS Day, the White House hung a red ribbon — 28 feet tall and 8 feet wide — in the North Portico of the mansion to symbolize the fight against AIDS. It will stay up for two days and, on Saturday, guests who visit the White House will receive a red ribbon sticker and a fact card.

Among the “facts” to be printed on the card, no doubt, is the recalculation of how many Americans are “getting AIDS” each year, which has been raised from 40,000 to 60,000:

WASHINGTON — A new government estimate of the number of Americans who become infected with the AIDS virus each year is as much as 50 percent higher than the previously accepted level, sources said Friday.

For more than a decade, epidemiologists at the Centers for Disease Control and Prevention have pegged the number of new HIV infections each year at 40,000. They now think it is between 55,000 and 60,000. HIV, or the human immunodeficiency virus, causes AIDS.

Take that, UN statisticians!

Meanwhile Bishop Tutu has joined the activist march against President Thabo Mbeki in South Africa, urging his compatriots to push aside the doubts of a leading politician who so far is the only one in the world to have studied the case of HIV=AIDS and shut his door against the HIV meme. For God’s Sake Let’s Get cracking Against AIDS” says the fatuous prelate, and stop wasting time on worrying about whether we have the cause of AIDS correct:

“We are facing a monumental crisis which is being exacerbated by wasting time on futile debates on the causes of Aids.

“We are fiddling while people are dying. We need to stop arguing and start saving lives.

“People who would be alive today have died needlessly. We are to be held culpable for that.

“For God’s sake, let’s get cracking,” he said.

Meanwhile Hillary is not to be left out, and has jumped on the same bandwagon:

hclinton.jpgIn an address that melded her personal faith and her campaign vow to battle AIDS, Democratic presidential candidate Hillary Clinton on Thursday said that if elected, she would boost U.S. spending on the disease and encourage abstinence and the use of condoms to eradicate it.

“AIDS remains a plague of biblical proportions,” the New York senator told hundreds of church members gathered at the annual Global Summit on AIDS and the Church at Saddleback Church in Lake Forest. “Where ignorance and prejudice builds, AIDS thrives. Stigma is one of the real evils that has to be combated.”

During her lengthy appearance, Clinton cited Scripture, talked about the role faith played in her upbringing and value system, and reiterated a $50-billion plan announced days ago to fight AIDS and malaria.

The plan would increase U.S. spending to fight AIDS by about 20%, according to David Bryden, a spokesman for the Global Aids Alliance. All of the Democratic presidential candidates have committed to the same funding proposal, he said.

Foolish critics, too

All around the world, over the past year, the last ragtag remnants of resistance to this have been vanquished. What looked early last year as a possible rebel success with the publication in Harpers magazine of a 15 page exposure of drug corruption and failure of scientific theory in HIV failed to gather momentum, and is now forgotten, as East Coast media quietly reasserted the status quo, led by Michael Specter in the New Yorker.

The feisty, acutely intelligent group blog You Bet Your Life, started by a witty lawyer on the West Coast and taken over by Harvey Bialy, the fiercest and most scientifically informed of HIV=AIDS dissidents among journalists and science writers, gained considerable traction in the scientific community but eventually ran out of steam when Bialy was taken ill, and has not been resumed since mid summer. The fine contents, however, are still there for the perusal of newcomers.

Not that human weakness is confined to the supporters of the HIV meme by any means. The first court case attracting world wide attention to this topic, in Adelaide, saw the judge dismiss a knowledgeable pair of Perth dissidents as unqualified to give him an opinion on the merits of HIV as cause of AIDS, as part of the defense of the unfortunate Parenzee, whose crime was to make love to women without informing them of his HIV meme status.

What ruined the credibility of the two otherwise knowledgeable commentators, who have published well informed critiques of the paradigm even though they work outside the field, like most of its critics, was their insistence that the very existence of HIV was still unproven, a stance of such political naivete that it guaranteed the outcome of the case, whatever the merits of their argument.

aidsdayribbon.jpgMeanwhile, the blog AIDSTruth.org run by John P. Moore of Weill-Cornell Medical Center in New York, whose microbicide research is well funded by a drug company to the tune of $500,000, so far in vain, has flourished, printing copious stories in a spirit of defeating all critical thought in the arena, though inadvertently provoking questions by carrying apologia by mainstream researchers which seemed to confirm rather than deny the revelation of their studies that there were great flaws in the paradigm, the best example of this being Nancy Padian confirming that heterosexual transmission of HIV was as low as once in 10,000 bouts.

All in all, the year has been a triumph for John Moore, however, and we congratulate him and the other promoters of the HIV=AIDS paradigm for establishing the supremacy of this belief with an overwhelming defense against any and all dangers of critical inspection and doubt.

No doubt it will be easy for them to conquer the remaining one third of the population of the developed world who as yet have not heard much if anything about their glorious triumph of scientific activism.

United Nations, (PTI): One in three people in the world’s major industrialised countries “know little or nothing” about the deadly HIV/AIDS pandemic and 25 per cent believe that the problem has been “greatly exaggerated” by the media, a poll said….

The World Vision “Index of Concern,” a tool for understanding the level of concern each country feels towards the issue, finds that Canada leads the seven nations surveyed for the highest level of empathy its residents feel toward those affected by HIV and AIDS globally, with Japan ranking last. The others in order are France, Germany, US, Italy and UK.

After all, they have persuaded the local population here that AIDS is a bigger problem than global warming. In this report,Survey finds Americans more concerned about AIDS than climate, we learn that they would be willing to pay even more in taxes to support the Bob Club in the manner to which they have become accustomed:

A telephone survey has found Americans are more concerned about the global AIDS epidemic than climate change. But 25 years after the first confirmed case of the disease, 30 percent of Americans say they know little or nothing about it.

The survey of 1002 Americans was conducted by Canadian research firm IPSOS and paid for by Christian humanitarian organization World Vision. The survey was conducted in September, but the results were released to coincide with World AIDS day, which is Saturday.

Americans ranked the war in Iraq, poverty and hunger, and the global economy all above AIDS, when read a list of issues.

Half the Americans surveyed said they would be willing to pay more in taxes to help pay for prevention, treatment, research, and care for AIDS patients, but the same number said they have no personal connection with AIDS.

Perhaps that $30 billion can be expanded, as Hillary promises, if she gets into the White House.

World AIDS Day 2008 looks like being an even more glorious celebration than today, for the generals of HIV=AIDS.

Drink up, Socratic enquirers: why dissidents may never win

socrates.jpegAll this reminds us of the death of Socrates, who drank hemlock after an Athenian court convicted him of alienating the youth of the city by teaching them to question the beliefs of their betters. While the dissenters from HIV=AIDS may not have to kill themselves, it seems pretty certain that they will have to find something else to do if things continue this way.

It may be that the world doesn’t wish to be saved from the belief that HIV=AIDS. Just as Socrates exposed the sham foundation of the civic virtues of Athens, and had to be expelled from the body politic, so dissenters may be exposing far too many of the human motives of politicians, officials, editors, writers, doctors, health workers, and activists, let alone scientists, to be acceptable to responsible people.

There comes a point where a cover up is necessary, when too much would tumble down in an enquiry. Perhaps some members of the leadership of this society might be persuaded to look long enough at HIV=AIDS and its empty rationale to understand its lethal absurdity, but they will probably also decide that we cannot afford to change the story.

After all, at the cost of a few thousand lives of gays in America and Europe, and a few million ill people in Africa and elsewhere, we can preserve the dignity and authority of Bishop Tutu, Nelson Mandela, President Bush, President Clinton, Bono, Hillary Clinton, Elizabeth Taylor, Oprah Winfrey, Barack Obama, and Magic Johnson, as well as their scientific advisors Anthony Fauci, Mark Wainberg, David Baltimore, John P. Moore, John Maddox, Daniel Koshland and the current editors of Science, Nature, the New York Times, the New Yorker and every other magazine and newspaper mentioning the topic of AIDS.

Is this not a fair deal? The senators of Athens thought so, and Socrates took his hemlock like a man, not disagreeing with them. if you don’t believe us, read The Death of Socrates by Emily Wilson, the latest biography of Socrates, reviewed here by Adam Kirsch:Welcoming a True Trial of Conscience.


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