How does a scientist or doctor become a crank?

As a physician and scientists who's dedicated his life to the application of science to the development of better medical treatments, I've often wondered how formerly admired scientists and physicians degenerate into out-and-out cranks. I'm talking about people like Peter Duesberg, who was once an admired scientist thought to be on track for a Nobel Prize; that is, until he became fixated on the idea that HIV does not cause AIDS. True, lately he's been trying to resurrect his scientific reputation with his chromosomal aneuploidy hypothesis of cancer, but, alas, true to form he's been doing it by acting like a crank. I'm talking about people like Dr. Lorraine Day, who was a respected academic orthopedic surgeon and then after being diagnosed with breast cancer degenerated into a purveyor of woo, as well as a New World Order conspiracy theorist, religious loon, and Holocaust denier. There's also Linus Pauling, another Nobel Laureate, who later in life became convinced that high dose vitamin C would cure cancer. And let's not forget Mark Geier, who, although not a distinguished scientist, did, before his conversion to antivaccinationism, apparently do a real fellowship at the NIH and appeared to be on track to a respectable, maybe even impressive, career as an academic physician. Now he's doing "research" in his basement, injecting autistic children with a powerful anti-sex hormone drug, and abusing epidemiology. There are innumerable other examples.

ERV has posted a good start in analyzing why this happens. Because her interest is HIV research, she's particularly interested in how a brilliant man like Peter Duesberg could have fallen so far into pseudoscience. However, because she is a basic scientist, her view lacks a bit when it comes to why physicians become cranks or quacks. Consequently, I thought I'd expand a bit on this topic and bring a medical perspective to the question. Because I am both a surgeon and a scientist, I routinely straddle both worlds (sometimes not being taken seriously in either). I'm not sure that this gives me any special insight, but it does give me a different perspective than ERV.

First, ERV shows great insight in pointing out that scientists are wrong all the time. Indeed, science can almost be defined as a system or a method of self-correction that brings us closer to models of how nature works. An absolutely essential part of science, therefore, is that we scientists must test our hypotheses and try to falsify them. When we attempt to do so, there are generally one of three results:

  1. The hypothesis is not falsified.
  2. The hypothesis is falsified.
  3. The results are not sufficiently clear to falsify or support the hypothesis.

When a hypothesis is not falsified, generally scientists will either try to find new ways of falsifying it until they are satisfied that it takes all reasonable challenges. Alternatively, they will build on it and refine it based on their experiments, after which they try to falsify the new versions of the hypothesis until they succeed. If the initial hypothesis is falsified, scientists generally will move on to a new hypothesis. True, they may not do so quickly or easily; after all, scientists are human too and just as prone to becoming emotionally attached to their favorite ideas and hypotheses, but move on they generally do--eventually. Of course, result #3 is the most common result; the answer is not always immediately clear. Indeed, this uncertainty may persist for years, if not decades, before some scientific questions are resolved. That's what true scientific controversies, and, once again because scientists are human, they can be quite rancorous, on rare occasions even escalating to the point of scientists yelling "bullshit!" at each other at seminars and scientific meetings. (Such meetings can actually be kind of fun.) Over time, however, evidence will accumulate, and experimental results will start pointing towards an answer. Sometimes a dramatic result, a stroke of genius, like Eintstein's Theory of Relativity or Charles Darwin's Theory of Evolution by Natural Selection, will appear like a bolt out of the blue and change everything. However it happens, once a hypothesis is roundly falsified, though, scientists will indeed, even if reluctantly, admit that the hypothesis was incorrect, form a consensus, and then move on to test other hypotheses. Or, as ERV put it:

Now here is where we get to the kook part-- Say we finally determine that MMTV does not cause any kind of breast cancer in humans. All the normal scientists on the 'MMTV causes cancer' side will say 'Aw. Man. Oh well, my bad.' and keep doing science. Admitting youre wrong in science is not a big deal because scientists are wrong all the time!

Perhaps the best illustration of this attitude among scientists was a tale told by Richard Dawkins in The Root of All Evil? about an elderly and esteemed scientist who had held to a certain hypothesis for many years. One day a visiting professor from America came to give a talk and presented evidence that conclusively refuted this professor's favorite hypothesis. Afterwards, according to Dawkins, the old man strode to the podium, shook the speakers hand, and thanked him profusely, and said, "I have been wrong these fifteen years." In response, the audience applauded uproariously. Whether this story is apocryphal or not or whether it's grown with retelling over time, it is nonetheless the ideal towards which science strives. Scientists are supposed to be willing to give up cherished hypotheses if that's what evidence and experimental results show. Of course, the difficulty in doing so tends to be proportional to both the length of time the hypothesis has been cherished and the intensity of attachment. Now, here's where "scientist" transitions to "kook":

Where one transitions from 'scientist' to 'kook' is the inability to say 'I was wrong' and move forward. In the 1980s, Peter Duesberg could have been right! No one knew what was causing this scary-ass world-wide epidemic. Yeah, it might have been HIV-1, but in the US it could have been a side-effect of some recreational drug, only surfacing when use was wide-spread and intense enough. Duesberg could have been right!

But as time went on, evidence stacked up on the side of the 'HIV-1-->AIDS' people, and nothing supported the 'drugs-->AIDS' people. If Duesberg were a scientist, he could say 'Ek. Im wrong. Good on you all.' and continued his career.

Indeed, assuming that Duesberg had done this before he had burned too many bridges by so harshly criticizing and insulting colleagues who were part of the "orthodoxy," it probably would indeed have been "no harm no foul," and Duesberg would be a happily well-funded scientists doing important research, rather than a tenured crank working in crappy basement laboratory on a shoestring budget. Heck, even after he had burned a lot of those bridges, he probably could have rebuilt them with just a little diplomacy. But he didn't, because, like all cranks, he had become so enamored of his hypothesis that he was unable to let go of it even when the contradictory evidence became overwhelming. He had become convinced that he was right and the world of HIV scientists were (and are) wrong.

The other point that ERV makes that's worth pointing out is that being a contrarian is not in and of itself particularly impressive because scientists are wrong so often while studying various questions. Indeed, I find "contrarian" scientists who won't support their doubts of the established consensus with good science (and sometimes not even good logical arguments) of their own to be particularly annoying, like a two-year old who says "No!" to everything. Being "contrarian" is only productive if the contrarian scientist can produce actual evidence using sound experimental methodology suggesting that the consensus is not correct. That's one reason why "intelligent design" creationists are not taken seriously. They point out what they see as "defects" in evolutionary theory but do no research--and don't even try to do any research--that might suggest alternatives. The same is true of cranks of all stripes, including "alt-med" cranks, HIV/AIDS denialists, and many other varieties.

So basically the key ingredients of a scientific crank are an inordinate attraction to an idea or hypothesis to the point that he won't abandon it in the face of overwhelming evidence coupled with the arrogance necessary to believe that he is correct and the rest of the scientific community is not. This is probably true no matter what sort of science is being abused. However, when it's medical science that leads to outright quackery, there are other issues that come into play.

The first thing that one needs to take into account when considering the evolution of a medical crank is that most physicians are not scientists. As much as it pains me to admit it, sadly it's true. Indeed, I have lamented time and time again how little training in the scientific method most medical students and residents receive in the scientific method. This makes all too many physicians very susceptible to pseudoscience because they don't have a good grasp of what good scientific methodology is, and I've provided ample examples of this in this blog, particularly when it comes to physicians endorsing "intelligent design" creationism and and quackery. The second thing that needs to be considered is that there is a component of being a physician that doesn't exist for basic scientists that provides added impetus to the transition from scientist/physician to kook, and that component is direct interactions with patients. This component is a powerful contributor to physicians becoming what Prometheus likes to call them, "brave maverick doctors."

Consider this: Despite what many who do not like "conventional" physicians say, the vast majority of physicians go into medicine because they want to help people. They honestly want to help their patients, and not being able to help their patients causes them intense feelings of inadequacy and disappointment. In other words, there is a strong incentive, both positive (to get that fantastic feeling we get when we realize that we've really helped a patient) and negative (to avoid that feeling of inadequacy and frustration that we get when we cannot help a patient), to find treatments that the physician perceives to help patients. There's also the ego gratification that comes from patients telling one that he's great and has helped him enormously. The problem with this desire, however noble, is that it makes physicians uniquely susceptible to pseudoscience in the form of quackery. Here's why. "From the ground," a single physician looking at a group of his or her own patients being treated with a therapeutic modality will almost always "see" that the therapy "works." The reason, of course, is the placebo effect. Without a controlled clinical trial, the placebo effect will almost always bestow upon almost any therapeutic modality at least the illusion of therapeutic efficacy, particularly at the single practitioner level. Thus, it is not surprising that homeopathy, reiki, acupuncture, and all manner of modalities that clinical trials show to be no more effective than placebo can easily appear to be effective when a single practitioner does what is in essence an uncontrolled, single-arm observational trial by treating patients with these modalities. Add to these human tendencies a significant financial incentive, and one can see how the slide into quackery can start out as an exercise in idealism, with "start out" being the operative phrase.

For example, for all the venom I've dripped on Dr. Mark Geier (venom he richly deserves), I have little doubt that he probably honest believes that he is helping autistic children with his "Lupron protocol," as autism is a condition of developmental delay, not stasis. Many autistic children improve simply with growth and development, and without a control group and controlled, blinded randomization it's impossible to tell whether a given intervention leads to an improvement in symptoms over and above what would have occurred anyway. Unfortunately, this belief has led them into some incredibly unethical activities in the service of their belief that they are somehow "helping" autistic children and with the claim that they "know" it works. Indeed, it is rather interesting to read Dr. Geier's statement in defense of Clifford Shoemaker, in which he complains of Kathleen Seidel's activities against his pseudoscience as though he's a poor, persecuted crusader for good. Of course, poor crusaders for good rarely charge the exorbitant fees that Dr. Geier charges or skirt human subjects research ethics the way he does, but in his world-view he is a lone iconoclast.

This is where physician cranks (i.e., quacks) then become just like cranks of all scientific stripes, the sole exception being that their crankery endangers patients. They no longer try to falsify hypotheses or do trials to figure out if their remedies work. Why should they? They know they work! Instead, they cherry pick studies that support their idea and, if they do any clinical studies or science at all, it is almost universally bad science. Over time, they come to believe that they are right "because I see the evidence in my patients," as quacks like to say, forgetting utterly how easy it is to be fooled by a combination of the placebo effect, expectation, confirmation bias, and observation effect when one is a single physician treating all patients. Whether it's preexisting arrogance or a developed arrogance, these physicians will then often dismiss the "sheeple" physicians who practice evidence-based medicine as lacking the vision that they have, all the while making excuses for not doing clinical studies that would confirm or disprove the efficacy of their remedies over and above a placebo. Some, like Dr. Rashid Buttar, will charge enormous fees for their services and think it justified to the point that when they are questioned about the evidence supporting their therapies they will dance around the question and when they are finally brought in front of medical boards for their activities they will behave as an aggrieved, persecuted party, sometimes even going so far as Dr. Buttar as referring to the medical board as a "rabid dog."

I tend to consider physician-cranks to be almost a special case of scientific cranks in general. In no other field of which I'm aware can the combination of an attraction to a hypothesis and arrogance combine with an honest desire to help patients in such an incredibly toxic manner. For most scientists, the forces that seduce them into pseudoscience are largely a combination of intellect and arrogance. For physicians, care for patients and the placebo effect enter into the equation to form a perfect storm that can tempt them into even the most indefensible pseudoscience.

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Orac - You say, "Being 'contrarian' is only productive if the contrarian scientist can produce actual evidence using sound experimental methodology suggesting that the consensus is not correct." You go a "step too far" here, since sound criticism doesn't have to be based on experiment. Just prior to the quoted remarks, you even acknowledge as much (parenthetically, at least).

By bob koepp (not verified) on 27 May 2008 #permalink

I met Peter Duesberg at a Summer School I took in 1989 and he was all full of himself. He had just been flown to Italy and given $25'000 to talk on TV about his ideas on how HIV has nothing to do with AIDS, but with homosexual life style, and was still "high" on the sexiness of that.

As a scientist, I was shocked how little his ideas has changed over almost 20 years when I read a recent interview with Duesberg. It was a carbon copy of what he had told us students in 1989.

This sounds like it should be mandatory material for physicians to-be, at least.

By John Kingman (not verified) on 27 May 2008 #permalink

Do cranks ever 'uncrank': realize they've wasted years and reputation, and admit they were wrong?

Do cranks ever 'uncrank': realize they've wasted years and reputation, and admit they were wrong?

It's rare, but occasionally you see some movement. There was that guy who denied the Holocaust happened (David Irving?). After he was tossed in prison for a few years, he changed his position to "the Holocaust was exaggerated, and the Jews brought it on themselves."

By Tegumai Bopsul… (not verified) on 27 May 2008 #permalink

ORAC wrote:

Sometimes a dramatic result, a stroke of genius, like Eintstein's Theory of Relativity or Charles Darwin's Theory of Evolution by Natural Selection, will appear like a bolt out of the blue and change everything.

As a historian of science this statement sends shivers down my spine because it is so, so wrong. Both of the theories mentioned have long pre-histories that tend to get ignored by the "bolt out of the blue" historiographers. In the case of Darwin John Wilkins, has a nice article on Talk Origins that explains the pre-histories of the bits of Darwin's theory of evolution. On Einstein and relativity, the story starts at the beginning of the 18th century with the Clarke/Leibniz correspondence and includes a lot of stuff out of the 19th Century. Peter Galison's Einstein's Clocks, Poincaré's Maps is very good on some of the 19th Century stuff.

Don't forget Dr. Heimlich, who created the maneuver to prevent dying from choking which is probably familiar to most everyone. The success and name recognition was not good for him. Apparently, these days, he has become enamored with malariotherapy, the deliberate infection of a person with malaria in order to treat ailments such as cancer, Lyme disease and more recently, HIV.

Don't also forget William Shockley.

Part of the problem may be that people who are successful in one field think their opinions on other fields ought to be given special weight, even if they have no particular expertise. Shockley's work in semiconductor physics, leading up to a Nobel Prize, went to his head, and he began spouting off all kinds of wacky notions about eugenics and race.

I have to wonder whatever happened to that sperm bank he was involved with. Were any children conceived with his sperm?

By rglovejoy (not verified) on 27 May 2008 #permalink

rglovejoy: There's a whole book about the "Nobel Prize spermbank", The Genius Factory written by David Plotz. It's on my to-read list.

By Woobegone (not verified) on 27 May 2008 #permalink

Thony C.,

As a practical matter, what counts (in science) is not the 20/20 hindsight that allows us to see hints of, or even clear statements of, important ideas. Rather, it is the clear and compelling exposition of them, that captures the attention of other scientists, that make the proposals of Darwin and Einstein revolutionary.

It is true that some important finds are just due to following the next, logical step in a field. I have heard that is the reason Jonas Salk did not get a Nobel for his Polio vaccine. If one considers the contemporaneous reception of Darwin's and Einstein's works, they were not simply the next, logical steps.

Thorny C, I think you have missed the point that Thomas Kuhn makes in his book "the structure of scientific revolutions". The history of science is rewritten to make the paradigm breaking discovery appear to be a logical outcome. It wasn't.

For each scientific revolution, at one time there was no one who understood it; at a later time many individuals understood it. From mathematics we know that therefore there was a time when only a single person understood it. The transition from zero people understanding it to a single person understanding it can be described as a "bolt out of the blue" (more or less).

Usually the person who gets credit for the discovery is not the first person who understood the discovery, or the first person who publicized the discovery, but the last person who publicized it. That is more an artifact of the communication systems we use, how ideas are recorded and how kudos is allocated (which provides strong motivation for hogging credit) than about how scientific discoveries are actually made.

Regarding training physicians in the scientific method (please!), we must also be careful to train young scientists to admit negative results and occasionally embrace being flat-out wrong. I find that many striving young lab rats have spent so many years excelling in classes, sitting in the front row of the lecture hall, getting the best grades, and competing for Dr.P.I.'s attention in lab meetings, that they have an ingrained abhorrence of admitting fault. As mentors in science, we owe it to the next generation to teach them not only how to test hypotheses, but how to reject them and move on gracefully.

To this end, when I judge the yearly high school science fair and find a student who has admitted the failure of their research to support a hypothesis, I always give a few extra points and make sure to leave a comment conveying that this is a hard thing to do (especially in a competition!), but that it's an important part of science. And I always encourage them to pursue science!

By St.PaulScientist (not verified) on 27 May 2008 #permalink

Orac - You say, "Being 'contrarian' is only productive if the contrarian scientist can produce actual evidence using sound experimental methodology suggesting that the consensus is not correct." You go a "step too far" here, since sound criticism doesn't have to be based on experiment. Just prior to the quoted remarks, you even acknowledge as much (parenthetically, at least).

Yes and no. It is possible to nitpick just about any result. This kind of back-seat driving is rarely helpful. Constructive criticism of a scientific work is suggesting a practicable experiment that will close off an alternate hypothesis.

The most reliable indicator of a crank is how they respond if you ask them to propose an experiment to exclude their own hypothesis. Sometimes, they will refuse to do so at all, or if they do, they will propose an "experiment" that could not be done in practice due to impractical requirements for time or materials, or (often in the case of a medical hypothesis) violation of ethics. Most of the time, the experiment proposed would not in fact even answer the question. And it is never an experiment that they propose to do, but one that they demand that you do. In other words, it is not a genuine experiment, but rather a roadblock, an assertion that "You cannot prove that I am wrong unless you can accomplish this impossible thing." Behe, for example, when asked at Dover what kind of experiment would be a test of ID, replied

To falsify such a claim, a scientist could go into the laboratory, place a bacterial species lacking a flagellum under some selective pressure, for mobility, say, grow it for 10,000 generations, and see if a flagellum, or any equally complex system, was produced. If that happened, my claims would be neatly disproven.

This is not a practicable experiment in that it does not in fact distinguish between the alternate hypotheses, because no version of evolutionary theory predicts that a flagella would evolve in a laboratory-sized volume over such a short period of time, and Behe knows this perfectly well.

HIV denialists like to demand a double-blind placebo controlled trial in which one population of HIV patients is treated with a placebo and the other is treated with antiretroviral drugs, knowing perfectly well that there is no IRB board in the nation that would countenance such a modern version of the Tuskegee Experiment.

In contrast, some scientists have achieved high regard despite having been wrong about nearly every major hypothesis in their careers--because those wrong ideas nevertheless gave rise to valid experiments which resulted in major insights

Shockley is of particular note because without the team of scientists he lead none of us would be sitting here typing on keyboards, sending data to a box the size of a shoebox, which then gets sent into a whole web of such boxes. However, his descent into Crankery may well tarnish the good work he did in semiconductors.
Many cranks or kooks start out with the best of intentions and then go off the deep end into a kind of madness.
Medical cranks or kooks (pick your favored label for them) are more dangerous, because they do harm to people in the name of their particular brand of nuttery.

One other factor is that being contrarian can be a thrill for some people, to the point that they will actually lie to themselves to maintain that thrill. It's the unconscious version of an athlete inciting a crowd to boo him, or a comedian getting on stage and reciting The Great Gatsby.

I suspect that if Shockley had not been running that team, that someone else would have made the same discoveries within a few years.

I think it is extremely unlikely that we would still be using slide rules, manual typewriters and vacuum tube powered electronics.

I think that Tesla's conceptualization of the polyphase electric motor may have changed the course of the development of electricity. He eventually became a crank too.

It would help to point out, that in a large mature field, typically about 30% of the conclusions are wrong. Either because they have been deformed to fit a particular viewpoint, or that the underlaying data does not support them.
When someone puts forward an hypothesis, it will normally only work for 80% of the scientist in the field. If you have painted yourself, by being part of the 30% 'wrong' in a corner, you will not accept the new hypothesis, and so fight back.
To bring forth a new hypothesis, it helps if you are tenacious and have a thick skin. So there is a selection pressure on this type of individual. The more successful they are in their early career, the more likely they are to believe that they are surrounded by idiots, and that they are clear sighted original thinkers.
Meanwhile, the more mature a field becomes, the more it settles into a grove, and the more difficult it is to break the consensus, if it is wrong. The cause of stomach ulcers springs to mind, a bacterial infection as a causative (not associated) agent was very much rejected.
A friend of mine, Professor Alan Ebringer, has tried for years to persuade granting agencies that his hypothesis deserves funding, but he only got peanuts. His hypothesis was that MS was cause by a specific bacterial infection, acinetobacter. Now he might be right or wrong, I don't know. But the resistance in the MS field is something to behold.

By DocMartyn (not verified) on 27 May 2008 #permalink

trrll - While it's sometimes appropriate to dismiss criticism as nitpicking or back-seat driving, the fact that a critic doesn't provide a plausible alternative hypothesis is not a good indicator that he or she is a crank. Criticisms can be directed at methods of data acquisition, the interpretation of data, the soundness of inferences based on the data, etc., etc. Criticisms of this sort, examples of which are scattered through the history of science, can be perfectly legitimate, and don't depend in the least on the availability of alternative hypotheses.

By bob koepp (not verified) on 27 May 2008 #permalink

"Apparently, these days, he has become enamored with malariotherapy, the deliberate infection of a person with malaria in order to treat ailments such as cancer, Lyme disease and more recently, HIV."

MBA, thank you for the information on Malariotherapy. I never heard of Malariotherapy before and I just found a doctor that is using that treatment for Autism. We are going to try it. This blog is a great source for Alternative Treatments. Keep up the good work.

Thanks!

YLJ, you must have a very low reading and science comprehension to think that malaria could be beneficial!

Or you are being sarcastic.

YLJ, after just seeing your comment on another blog(Autism-News-Beat), I now know you are not being sarcastic, but that you really do have reading comprehension issues.

Malaria actually is an effective treatment for some forms of syphilis. The high fever caused by the malarial infection creates temperatures too high for the syphilis bacteria to tolerate. The developer of malaria therapy, Julius Wagner-Jauregg, actually won the Nobel Prize for it, back in 1927.

By Woobegone (not verified) on 27 May 2008 #permalink

Just to be clear, though, if you even think about using it to treat autism, you ought to be locked up.

By Woobegone (not verified) on 27 May 2008 #permalink

daedalus2u: Yes, I was indulging in a bit of dramatization for purpose of education. I think it was "time to railroad", to paraphrase Heinlein. The concept of a solid-state valve had already been thought of by others, but it took Shockley and his team at Bell Labs to do it. Perhaps, in another year or so, someone at say, Marconi or Siemens would have achieved the same thing.

There actually is good physiology behind fever therapy. It isn't the high temperatures reached during the treatment, it is the immune system activation. I have a quite extensive blog about the phyiology behind it.

http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-…

My analysis was prompted by the paper by Andrew Zimmerman on acute resolution of some symptoms of autism during some episodes of fever. My conclusion is that it is NO from iNOS due to the immune system activation.

Inducing fevers is an extremely dangerous way to increase NO levels, the effect is only transient and can cause feedback over compensation which lowers NO levels chronicly (the low NO ratchet).

I agree with woobegone that malaria therapy has no place in treating people with autism, but I don't think anyone should be locked up just for thinking about it, just for trying it, and then for a very long time.

Perhaps the science schools could issue one of these with every diploma?

has, that is a great poster!

While it's sometimes appropriate to dismiss criticism as nitpicking or back-seat driving, the fact that a critic doesn't provide a plausible alternative hypothesis is not a good indicator that he or she is a crank. Criticisms can be directed at methods of data acquisition, the interpretation of data, the soundness of inferences based on the data, etc., etc. Criticisms of this sort, examples of which are scattered through the history of science, can be perfectly legitimate, and don't depend in the least on the availability of alternative hypotheses.

I hardly ever see a paper in which there is absolutely nothing to criticize. But scientists are more interested in knowledge than in criticism for its own sake. A criticism is of only minor interest unless it affects a study's conclusions. And it can affect the study's conclusions only if impacts the discrimination between the conclusions of the study and some alternate set of hypotheses. If not, it is mere nitpicking.

Daedalus2u, this is a bit toungue-in-cheek, but could sildenafil citrate (Viagra) be used in place of fever for the same NO response? I know that it is given to neonates to assist with breathing in the case of premature birth and incompletely formed lungs (I think, I could be wrong...)

trrll - So, demonstrating that Smith's favored hypothesis doesn't in fact follow from the premises he adduces is mere nitpicking. When was the last time you opened a logic text?

By bob koepp (not verified) on 28 May 2008 #permalink

Jesse, I don't think so. Sildenafil inhibits a specific phosphodiesterase (PDE5) that destroys the cGMP that is made by sGC following activation by NO in somewhat specific tissue compartments (which is why it works for ED). Effects mediated through sGC and cGMP are only one pathway by which NO has physiological effects.

Sildenafil does make some diseases caused by low NO worse, for example obstructive sleep apnea is exacerbated by a single dose of sildenafil. My interpretation is that is not unexpected because breathing is mediated by NO through non-cGMP pathways. When cGMP pathways are potentiated by inhibiting PDE5, the feedback inhibition of nitric oxide synthase by increased cGMP levels will reduce the total amount of NO produced, and so decreases effects of NO not mediated through cGMP.

This is the major difficulty in developing NO based treatment modalities. There is so much cross-talk between the different NO mediated pathways (thousands of them), that it is extremely difficult to modify one or a few without having adverse effects on others.

Every method that has been tried long term doesn't work long term. So far there has always been compensation and eventually the NO modifying treatment modality doesn't work. That includes organic nitrates, NO donors, and L-arginine.

I think the only mechanism that is going to work long term is the natural mechanism that organisms evolved to use. I am quite sure that is the one that I am working on and will be the only one that will be successful long term.

"YLJ, you must have a very low reading and science comprehension to think that malaria could be beneficial!"

What if Autism is caused by a spirochete?

So, demonstrating that Smith's favored hypothesis doesn't in fact follow from the premises he adduces is mere nitpicking. When was the last time you opened a logic text?

To argue that Smith's favored hypothesis doesn't in fact follow from the premises, you need to make a case that there is some other hypothesis that is equally (or more) consistent with the data. It is of course possible that that alternate hypothesis could be the negation of Smith's hypothesis. But you need to make that case to elevate the criticism above the level of nitpicking.

In contrast, it is typical crank behavior to seize upon some aspect of a study that was not done perfectly as a rationalization for ignoring unpalatable conclusions, even if there is no plausible way that the supposed flaw could impact those conclusions. Since there are flaws in virtually every study, this provides a convenient pretext for cherry-picking.

trrll - If you count the negation of a hypothesis as an alternative hypothesis, then you've undercut your own criticism of so-called cranks, since simply by denying some hypothesis they are (by your lights) proposing an alternative. But what exactly is the explanatory import of said alternative? You're grasping at straws to prop up an untenable view -- there's something rather crankish about this. Oh, the irony.

By bob koepp (not verified) on 28 May 2008 #permalink

trrll wrote "To argue that Smith's favored hypothesis doesn't in fact follow from the premises, you need to make a case that there is some other hypothesis that is equally (or more) consistent with the data."

I am afraid not, one does not need an alternative hypothesis. The history of science is loaded with examples of doubt about proposals, without an immediate alternative. I am not a science historian, and cannot come up with easily understood examples. Examples from my own research are too esoteric to describe here.

If you count the negation of a hypothesis as an alternative hypothesis, then you've undercut your own criticism of so-called cranks, since simply by denying some hypothesis they are (by your lights) proposing an alternative.

Only if you can provide a logical argument as to why the data constitutes evidence supporting that alternative hypothesis. Saying that "The investigators did X wrong, and therefore their conclusion is wrong" is invalid--you have to show that the data (when taking into account the impact of the supposed error) support that alternate hypothesis. The negation of a hypothesis is generally referred to as the "null" hypothesis. In statistics, the null hypothesis is generally that the difference between experimental groups was due to chance. So for example, a valid objection might be that the investigators used a one-tailed t-test when there is not basis for it, and that if the proper two-tailed test is used, then there is a higher-than-acceptable likelihood that the null hypothesis is correct, and the results were the consequence of chance. On the other hand, if the one-tailed test yields p=0.000001, then complaining that the investigators should have used a two-tailed test is mere nitpicking, because the use of the correct test still would not support the null hypothesis.

I am afraid not, one does not need an alternative hypothesis. The history of science is loaded with examples of doubt about proposals, without an immediate alternative.

Yes, there are plenty of examples of useless nitpicking and doubt in the history of science. Progress never comes from mere doubt, unless it is accompanied by some sort of reasonable experimental or observational test that will discriminate among alternate hypotheses. A hypothesis--even a wrong one--is worth much more than doubt, because a hypothesis leads to experiments which will ultimately advance knowledge, and lead to the rejection of that hypothesis if it is mistaken. Mere doubt, by contrast, is a roadblock to discovery.

trrll -
Any evidence against an hypothesis H is, ipso facto, evidence for the hypothesis not-H. This is a simple matter of logic. It has no relevance to the problem of distinguishing between crankish and legitimate criticism.

By bob koepp (not verified) on 28 May 2008 #permalink

Oooh, a video as evidence! Um, no.

That is actually a lower level of evidence than Medical Hypotheses.

For one thing that particular tick is not necessarily spread around the world, and autism is pretty much worldwide. Do the cases of autism follow the map from the NEJM that is posted here?:
http://scienceblogs.com/denialism/2007/10/a_critical_appraisal_of_chron…

This borders on all diseases being caused by Fasciolopsis buski (a liver fluke only found in Asia and the Indian subcontinent).

HCN, "Your Oooh, a video as evidence" comment is not warranted. You posted a response to my question "What if Autism is caused by a spirochete?" with a link to a previous post on this blog.

Just as much as you can't prove what causes Autism, you can't prove that a spirochete bacteria does not cause Autism. Can you? If we knew what causes it, why would we call it Autism Spectrum Disorder? I am not saying that spirochetes cause Autism...I don't know it all. Some of you seem to think you do. I am simply throwing it out there as a maybe. Maybe the epidemic of Autism is actually a huge misdiagnosis of several different ailments and maybe this accounts for a double digit percentage of the misdiagnosed cases?

Did you watch the video link? What do you have to say about it? I challenge you and the Skeptics' Circle to debunk Kathleen Dickson and the many claims that she makes in her many YouTube videos.

http://youtube.com/watch?v=WHyyPTIg0Eo&feature=related

Let me say again...I am not saying that spirochetes cause Autism, I am just simply asking all of you extremely intelligent scientists to take on Kathleen Dickson's claims about Lyme and fraud.

I know the answer in our case...we now have a positive lab test for Lyme and we are treating it.

What is the lab test for Autism? What are the biomarkers? What kind of blood test do you have?

What peer reviewed case defintion is there for Autism?

How about a defintion that we can test!

First off, I am an engineer. I am a parent of child who had seizures when he was 2 days old. I'll believe you if you can tell me how a tick got to the fifth floor of the hospital to put an invisible bite on a newborn.

Autism is solely a behavioral based diagnostic. And that diagnostic criteria has changed much over the last 15 years. It was only when my son was 18 that it was even mentioned by a school psychologist.

You wrote "Just as much as you can't prove what causes Autism, you can't prove that a spirochete bacteria does not cause Autism. Can you?"

Well, I cannot prove a negative. But since the tick that spread Lyme Disease (it is named after a location) is not present over entire country or the world, the premise is pretty unlikely.

It is up to you to show that the infection is nationwide, countrywide and has been infecting children who ended up autistic for over a century. Also, if it causes autism, you have to show that autism can appear in adults.

When Kathleen Dickson publishes in a real peer reviewed journal indexed at PubMed, then we can have a serious conversation. Until then she is a crank.

Great article!

I think it is important to publish the data no matter what the results, because a result that is negative and disproves the hypothesis is just as important in getting to the "truth". I have noticed a lot of younger people think they can only publish if they get a positive result that proves their hypothesis, and forget that a negative result is just as important.

storkdok - It's interesting. I'm a graduate student in neuroscience, and everyone I've spoken too about this agrees that in an abstract sense, a "negative result" is just as worthy as any other.

Yet there is also a perception that negative results are less likely to get published in decent journals. There is clearly a lot of truth in this, even if there are some honorable exceptions. To a large extent what gets you published is your results, not the soundness of your methods. No-one likes this situation and everyone agrees that in an ideal world negative results would be as publishable as positive ones, but people accept it as a fact of scientific life.

The paradox is that the only reason that negative results are difficult to publish is that scientists make it so. It's not just journal editors and reviewers - any scientist who has ever got annoyed by reading a really well-designed study which gave "the wrong result" is indirectly a part of the problem. Which is all of us! You have a situation in which the same people lament that the system is a bad one, while perpetuating it.

By Woobegone (not verified) on 29 May 2008 #permalink

Any evidence against an hypothesis H is, ipso facto, evidence for the hypothesis not-H. This is a simple matter of logic.

However, as I pointed out before, a criticism may be evidence neither for the hypothesis H nor for the hypothesis (not H). Which brings me back to my point: the distinction between valid criticism and crankish nitpicking is that valid criticism is linked to it evidentiary value with respect to some kind of hypothesis (even if the hypothesis is that the results are a consequence of chance).

trrll - OK, so it now appears that what distinguishes crankish from legitimate criticism of a hypothesis is the cogency of the reasons being proffered, which is entirely independent of whether some alternative hypothesis is being proposed. So let's move beyond the red herring of "What's the alternative?", and address the real (and very complex) issue of how to distinguish between cogent/legitimate and crankish criticisms.

By bob koepp (not verified) on 29 May 2008 #permalink

HCN, I hate to go off the rails into crankitude, but consider the possibility that Lyme (or some other infection) might be transmitted to a fetus in utero or during birth.They tell the ladies not to clean the catbox for a reason, and it isn't because, as some have done before :), a pregnant woman is more likely to topple over. Pains are taken during birth to lower risk of transmission of HIV from mother to baby. (And in the neonate, needle pricks and blood transfusions and IV lines are not unheard of interventions, and potential vectors for spread of disease or infection of many varieties.)

Also it does not follow that adult Lyme infection would produce autism in an adult if it did so in children. One could be true and the other need not be true.

I'd like to make a slightly different comment on the valid point raised by Thony C ("bolts from the blue" are rarely that in science) and the valid criticisms of that point (what are seen as obvious foreshadowings now weren't so obvious at the time).

I want to focus not on the history of the science, but the history of the scientists, because there's something to be learned here, it seems to me, on the crank-vs.-scientist issue. The two scientists cited by Orac, Darwin and Einstein (particularly Darwin), took great pains to try to ensure the correctness of their ideas prior to publishing them. Cranks frequently seem to focus on the revolutionary nature of Darwin's and Einstein's theories at the time they were first published, thinking that this somehow confers scientific blessing on heterodoxy itself. Not nearly enough attention is paid to the tremendously elevated need for care, caution and confirmation when one's ideas are running counter to a lot of good work by a lot of good scientists over a long period of time.

SKBW: You are being an uber crank. And you are really reaching.

The in utero part is particularly stupid because I also happen to have a rare genetic pheromone condition that makes ticks and leeches hate me. I've had ticks run off my arm, and in a leech infected creek I was the only kid to come out without a leech. I got it from my father.

Plus the comparison to toxoplasmosis is even more stupid: It is a protozoa that is present in most warm blooded animals! Not a bacterial infection passed by deer ticks (which actually don't live out this far west... oh, and deer don't wander around in the middle of this city).

Lyme cranks come back when you have real research.

Also, Lyme cranks: my next two children are perfectly fine.

I'm sorry, but this is just screaming "the stupid, it burns!"

Lyme cranks: are you all now lobbying for the return of the Lyme disease vaccine?

http://www.cdc.gov/vaccines/vpd-vac/lyme/default.htm

"The vaccine for Lyme disease is no longer available. It was discontinued by the manufacturer in 2002, citing low demand. People who were vaccinated are no longer protected against Lyme disease, as protection was not long lasting. There are vaccines available for dogs but no vaccine available for cats."

"It is up to you to show that the infection is nationwide, countrywide"

HCN, Lyme is found in all 50 states http://www.lymediseaseassociation.org/Maps/usa_total.jpg and I am not saying it causes all Autism. I don't think it causes Autism at all. I think many children have been misdiagnosed.

"Lyme cranks: are you all now lobbying for the return of the Lyme disease vaccine?"

If you watched the video I linked to previously, you would have heard Kathleen Dickson explain the fraud with the patents for Lyme disease vaccines and that the vaccines were discontinued because they gave people Lyme and after the vaccine was discontinued, the CDC never added the bands used in the vaccine back to the Western Blot IGG/IGM test. So you can test positive for the bands that were used in the vaccine but by CDC criteria you don't have Lyme. That does not make sense. That is why many cases are missed.

More than 90% of patients diagnosed with Lyme never present wih a bullseye rash or remember a tick bite.

In the case of my son, we now have a positive Western Blot test result for Lyme and we are treating it appropriately.

What is the lab test for Autism? What are the biomarkers? What kind of blood test do you have?

"When Kathleen Dickson publishes in a real peer reviewed journal indexed at PubMed, then we can have a serious conversation."

What peer reviewed case defintion is there for Autism?

HCN, my point in posting was not to posit that Lyme is THE root cause or even A root cause of autism spectrum disorders, far from it.

However, it's not scientific wicky-wack that Borrelia may be transmitted in utero in mammals including humans.
I wonder at your resistance to that idea? Do you have the idea that THAT is controversial?

I don't think you would react that way to someone telling you the same thing about syphilis.

I don't expect your son has Lyme. But no tick in the nursery would have been required to give it to him.

"If you watched the video I linked to previously, you would have heard Kathleen Dickson"

Videos prove nothing, evidence does. As a matter of fact I do particularly wish to watch silly videos.

Link to peer reviewed research, and then you might have something. I am not resistent to actual evidence. Neither of you have some actual evidence, or reading comprehension.

Stop creating a bunch of wild scenarios and get some real documentation. I repeat (just in case you did not understand): videos do not count.

The video contains all the science and evidence you need. You're too arrogant to take the time to watch it. Many studies are discussed and debunked in the clip.

C'est la vie

HCN, was your 8:35 post a comment on any of my posts to you?

It's not really clear to me if you are or not. You are not calling in utero transmission of Borrelia a "wild scenario" are you? You are clear that I do not propose Lyme as a cause of autism, correct?

Both of you work on your reading comprehension.

If the video had real evidence, then that real evidence would be written up in a paper indexed at www.pubmed.gov. Do you understand? Forget videos, provided real peer reviewed scientific documentation.

trrll - OK, so it now appears that what distinguishes crankish from legitimate criticism of a hypothesis is the cogency of the reasons being proffered, which is entirely independent of whether some alternative hypothesis is being proposed. So let's move beyond the red herring of "What's the alternative?", and address the real (and very complex) issue of how to distinguish between cogent/legitimate and crankish criticisms.

I don't think you are going to solve the demarcation problem between science and crank this way. I don't think there are any simple rules that will neatly divide the two. There will always be a gray area in the middle.

I don't think anyone is saying there is a blanket rule that anyone who criticises an orthodox theory without providing an alternative is a crank.

Nevertheless, when sombody spends most of their time finding real and imaginary problems with the "orthodox" theory rather than trying to come up with a better alternative then this is a good sign that they are a crank.

By Chris Noble (not verified) on 29 May 2008 #permalink

Do you need to work on your reading comprehension? The papers are discussed in the video. You want papers? Watch the video. I don't need to site anything. They're in the video.

Why didn't you answer my questions?

If you want questions answered, cite the papers that the video uses. If they exist, you can watch the video and pull them from www.pubmed.gov. Should be easy.

Well, I did google Kathleen Dickson. I would suggest you find some reliable documentation not from her. It seems that she has had a few issues with her campaign (legal and personal). I know this sounds like an ad hominem, but do not despair! A simple PubMed search finds lots and lots of stuff, though it is up to you to present what you think is relevant in order to prove your points.

http://lyme-rage.info/kathoct05.html

http://mysite.verizon.net/emcsweegan/LD.html

Chris Noble - I agree that there's probably no bright dividing line between crankish and legitimate criticism of scientific hypotheses. And I agree that someone who spends most of their time finding imaginary problems probably has crankish tendencies. But why include real problems in this mix? Wherever the critic's reasoning is sound, i.e., wherever it exposes real problems, it demands our respect, period. Note that I say it's the reasoning, not the reasoner, that demands our respect.

You acknowledge that there is no "blanket rule" to the effect that a critic who doesn't provide an alternative is a crank. But suppose there's a sound rule that, say, 90% of such critics are cranks. That would be an interesting statistic, but I don't think it could justify a failure to apply one's own reason to try to determine whether the criticisms are in fact cogent in particular cases.

By bob koepp (not verified) on 29 May 2008 #permalink

HCN, could you clarify if you are speaking to me?

I haven't pointed you to any videos so it seems that you are talking to others. I don't want you to watch any videos if you are referring to me.

I'll ask again - you understand what I tried to explain - that transmission of Borrelia in utero occurs in mammals, including humans? You understand that a tick bite in a NICU would not be the only means a neonate could have contracted it?

SKBW, frankly I don't care what your ideas are about until you come up with some real documentation. But I will tell you again that there is absolutely no way for myself or my kid to get a tick bite in the middle of the city on the wet side of the mountains, and definitely not on the 5th floor of a hospital.

Next time come with evidence and documentation.

PalMD said "Um, guys? Guys???"

I tried to send them your way, but they didn't take the hint!

I'm not telling you that you got a tick bite, that's irrelevent. It's also irrelevent whether your son was ever exposed to Lyme for the point I tried to explain to you, which is your remarks indicating you believed a tick bite would be necessary to transmit the virus to him.

Do you or do you not understand that Borrelia can be transmitted from mother to childin utero? This is not a subject of scientific controversy, and am surprised you think it is.

You mention exposure to ticks as least as regards them running quickly away from contact with you, so perhaps you are not as far from a potential insect vector as you think. But that is not my concern.

I just wish to point out to you that it does not follow that lyme would necessarily produce autism specturm illness in adults if it did so in infants, and that a tick bite is not the only vector of infection for lyme, and it can be transmitted through other vectors including exposure in utero.

And BTW, HCN, what is it you are wishing to have "documented"? What evidence is it you are desiring? I posit no link between autism and Lyme disease.

YLJ asks what is the peer reviewed definitions of autism....are you serious?a quick search of pubmed reveals nearly 6,000 articles, and I wasn't even trying.

Autism Spectrum Disorders are very clearly defined in the literature. True there is no blood marker, but that doesn't mean it's not a diagnosable condition. There are no blood markers for traumatic brain injury, depression, psychosis, intellectual disabilities, dyslexia, ADHD, anxiety disorders, OCD,personality disorders, but they can all be diagnosed without the need for blood samples. Autism, as a neurobehavioural developmental condition, is diagnosed primarily by behavioural markers which are clearly laid out in the ICD-10 and the DSM-IV. Research is showing clear neurological differences in frontal lobe ability and neuropsychological differences, e.g. the research on central coherence and executive functioning in autism.

Are you seriously suggesting that because there is no lab test for autism that it doesn't exist? Because that is probably one of the most ignorant things I've seen written.

by the way, the most accepted diagnostic criteria for autism is available here, if you're interested in looking at it.

http://www.cdc.gov/ncbddd/autism/overview_diagnostic_criteria.htm

The video contains all the science and evidence you need.

I guess you don't understand this, YLJ but when clinical and scientific evidence is generated properly, it is written up in a peer-reviewed scientific journal and can be found on an internet database run by the NIH called Pubmed. It does not, in fact, appear in videos on youtube. If this person really has good evidence, she should be citing papers and studies. What are the papers and studies she cites?

You're too arrogant to take the time to watch it.

No, like I said above, HCN- and every other non-crank here- knows that videos are worthless. It has nothing to do with arrogance and everything to do with good science.

Many studies are discussed and debunked in the clip.

Fine. What are the studies referenced and who are the authors? Where are they published?

R, "quick search of pubmed reveals nearly 6,000 articles, and I wasn't even trying."

You weren't even trying? What ever that means. So the search returned 6000 articles with Autism in the title. Some of those "published articles" contain names like, Blaxill, Holmes, Geier, Haley, Nicholson, Burbacher, and many others that you label as cranks. So how much weight should you really put on your "peer reviewed" BS?

This is a quote from Richard Horton, editor of some rag called....hmmmm....what was the name of that medical journal? Oh yea....the British medical journal named The Lancet. Mr. Horton has said that "The mistake, of course, is to have thought that peer review was any more than a crude means of discovering the acceptability -- not the validity -- of a new finding. Editors and scientists alike insist on the pivotal importance of peer review. We portray peer review to the public as a quasi-sacred process that helps to make science our most objective truth teller. But we know that the system of peer review is biased, unjust, unaccountable, incomplete, easily fixed, often insulting, usually ignorant, occasionally foolish, and frequently wrong."

You're hedging way too much on peer reviewed.

Autism does not have a distinct set of biomarkers. I am not saying it does not exist. I am saying that too many other diseases and disorders or syndromes have been pooled into it. Misdiagnosed!

Come on, you guys have been trying to explain away the reason for the increase from 1 in 10,000 to 1 in 166 for years. Maybe misdiagnosis plays a big part and maybe Lyme is responsible for as many as 1/3 of that 166? There are probably several other disorders misdiagnosed as Autism.

All I can tell you is my own situation. My son was diagnosed by a neurologist as having Autism spectrum disorder.( which really means...we don't have a clue but he seems to act like kids that fit this profile and if we give him this Autism diagnosis, you will qualify for boo coo government services". We now have a positive lab result for Lyme Disease. Shouldn't we follow a course of treatment for Lyme Disease even though he is Autistic? I know several parents in this same boat.

I am not saying that if Autism does not have a blood test then it's not real. I am saying that without a definite lab test, a blood test, you can't be totally sure. Can you?

HCN, Was that hit piece you linked to on Kathleen Dickson peer reviewed? It was written by a someone she has accused of fraud. What else would he say about her?

It just floors me that you would not watch one minute of what Kathleen Dickson had to say in the video but you take the word of someone that trashed her as gospel, as if it were peer reviewed?

"A lie repeated a thousand times becomes the truth."

Dr. Kary Mullis a biochemist and the Nobel Laureate states that there is not one study published in a scientific scholarly journal with peer review that shows that "HIV is the probable cause of AIDS". Please site that study for me so that I (and Dr. Mullis) can go and read it.

Isn't it generally accepted that HIV is the probable cause of AIDS? Where are the peer reviewed studies to prove it?

I guess AIDS was created by some wack job like Kathleen Dickson since it is not peer reviewed???

Peer reviewed is over rated and is only measured by the "Impact Factor"!

"In order for scientists in many fields to attract and maintain funding it is necessary to publish in elite, prestigious journals. Such journals are generally identified by their impact factor. The small number of high-impact journals is susceptible to control by an elite group of anonymous reviewers.[citation needed] Results published in low-impact journals are usually ignored by most scientists in any field"

Maybe it's because I'm still an apprentice lab rat, and generally get stuck with some crummy lab partners, but it some of this absolutely stupefies me. How can you not accept that there's even a tiny possibility that you might be wrong? I mean, I practically have it drilled into my head that I know jack squat right now (hence the classes and all), but it can't have been so long since some of these formerly good scientists have made a mistake, can it?