Soapbox Science

A lesson from ENCODE about the limits on Human Reason

untitled.bmpDavid Ropeik is an international consultant in risk perception and risk communication, and an Instructor in the Environmental Management Program at the Harvard University Extension School. He is the author of How Risky Is It, Really? Why Our Fears Don’t Always Match the Facts and principal co-author of RISK A Practical Guide for Deciding What’s Really Safe and What’s Really Dangerous in the World Around You. He writes the blog Risk; Reason and Reality at Big Think.com and also writes for Huffington Post,  Psychology Today,  and Scientific American.

He founded the program “Improving Media Coverage of Risk,” was an award-winning journalist in Boston for 22 years and a Knight Science Journalism Fellow at MIT.

The post below was written in the days immediately after the release of the ENCODE papers and includes both a foolish factual error and a tone which, upon reflection and with feedback from many critics, is harsh. A subsequent post at Risk: Reason and Reality “New Evidence About DNA, and Old Patterns of Resistance to New Ideas”    attempts to rectify the error and make my argument more respectfully.  

In what should be another blow to the hubris of human intellect, we have a new entry in the long and ever growing list of  “Really Big Things Scientists Believed” that turned out be wrong. This one is about DNA, that magical strand of just four amino acids*, Adenine paired with Thymine, Cytosine paired with Guanine, millions of those A-T and C-G pairs linked together in various combinations to make the genes that spit out the blueprints for the proteins that make us. Or so science believed.

The problem was that, the ‘genes’ sections of DNA that coded for proteins only came to about 1.5% of the whole 2 meter-long strand. For decades molecular biologists didn’t know what the rest of the DNA…as in, nearly all of it…does. So, in a remarkable stroke of intellectual arrogance, they dismissed it as ‘junk’. Actually, the drier academics simply called it ‘non-coding DNA’. A Japanese scientist named Susumu Ohno called it junk, and the word stuck because, basically, scientists had no explanation for what most of DNA was for. So they assumed it was left over from evolution, had no current function, and was, literally, junk. As Francis Crick, one of the Nobel Prize winners for helping discover the structure of DNA, put it, non-coding DNA has “little specificity and conveys little or no selective advantage to the organism”. Right. As though nature would waste that much energy.

Well, there’s going to be a lot of editing on Wikipedia in the days and weeks to come, and it’s time to reprint the basic biology textbooks, because extensive research into the mystery of what most of DNA is doing there has discovered that the ‘junk’ isn’t junk at all. Most of it has all sorts of jobs. Science Journalist Ed Yong has written a wonderful summary of this work here. The nut of it is:

“A massive international project called ENCODE – the Encyclopedia Of DNA Elements – has moved us from “Here’s the genome” towards “Here’s what the genome does”. Over the last 10 years, an international team of 442 scientists have assailed 147 different types of cells with 24 types of experiments. Their goal: catalogue every letter (nucleotide) within the genome that does something.

“For years, we’ve known that only 1.5 percent of the genome actually contains instructions for making proteins, the molecular workhorses of our cells. But ENCODE has shown that the rest of the genome – the non-coding majority – is still rife with “functional elements”. That is, it’s doing something.”

In many ways, this puts us back to the ABCs of DNA. So toss out a lot of what you know. Only, that won’t be easy.  Given the nature of human cognition, it is innately difficult to let go of what you ‘know’ and keep a truly open mind. Just look at history. Big ideas, once set into place and ascribed to by the ‘experts’ in a given field, are hard to get people to think about in new ways. This intellectual inertia can do great harm.

Since the ancient Indians and Chinese and Greeks the belief was that ‘miasma’, bad or vile air, spread disease. In 1847 Ignaz Semmelweis realized that dirty hands were spreading disease at a Vienna obstetrical hospital and had nurses wash their hands, reducing the death toll (earning him the name “The Savior of Mothers). “It’s Miasma”, maintained mainstream doctors, whose intellectual inertia condemned countless millions to illness and death that could have been avoided with simple sanitary procedures that did not become widespread for decades. (Semmelweis died an embittered drunkard.)

Five years later John Snow pioneered epidemiology when he investigated a cholera outbreak in London and figured out that the people getting sick were drinking from one well…that the germ was apparently water-borne. He took it upon himself to remove (steal) the pump handle, and shut off the outbreak. Yet leading English health officials debunked Snow’s finding and clung to the idea of ‘miasma’. After all, they said, note how bad the Thames smells. It was that ‘Great Stink’ more than Snow’s discovery that water carries germs that finally got London to clean up its drinking water.

In the 1890s Dr. William Halstead, a surgical pioneer of great influence at the time, established radical mastectomy as the gold standard of treatment for breast cancer, and despite early evidence that it did little good compared to less traumatic approaches (basically, none of them worked), oncologists refused to abandon Halstead’s approach as late as the 1970’s (see The Breast Cancer Wars), condemning tens of thousands of women to unnecessary suffering and disfigurement.

Despite strong evidence questioning the efficacy of the Prostate Specific Antigen (PSA) test, many urologists still cling to it as the established way to detect prostate cancer, and cling to radical treatments rather than “watchful waiting” even for tumors diagnosed as slow growing, condemning tens of thousands of men to sexual impotence and urinary incontinence who need not suffer those harms

Consider how this intellectual version of Newton’s First Law…an object at rest tends to stay at rest (a big idea once accepted by experts tends to stay accepted)…bears on some huge current health issues. A few scientists (Carlos Sonnenschein and Ana Soto among them) are daring to question the fundamental idea of how cancer starts….the somatic mutation theory that cancer is caused from mutations to the genes that control cell growth. They have found tumors with no evidence of DNA mutation, and offer a different idea about carcinogenesis.   Many in the mainstream science community are treating them like Semmelweis and Snow.

A fresh way of doing toxicology – the study of poisons – has found strong evidence to suggest that things that are bad for us at high doses may actually either do no harm or even be good for us at low doses. (In one study that compared rats exposed to low doses of DDT to rats not exposed at all, the rats exposed to low doses of DDT had less liver cancer. Sukata, et.al, 2002 )

You will not be surprised to learn that Ed Calabrese, the main proponent of this theory, known as hormesis, is getting the Semmelweis/Snow treatment.

Because our brain is constantly called on to make choices and judgments – and rarely has all the facts or all the time necessary to go get the facts or all the smarts necessary to understand all the facts, what Herbert Simon called “Bounded Rationality”  – human cognition has developed a wonderful range of mental shortcuts for making these judgments. One of them is to default to the way things are ‘framed’. The way we learn things, especially if we learn them from ‘the experts’ or other trusted sources, establishes The Way It Is, and we tend to fight back against, to resist, information that conflicts with that initial framing. (Pluto will always be a planet to me.) It would take time, attention, effort – literally calories spent by the brain – to keep a completely open mind and think everything through afresh every time some new evidence comes in.

This resistance to new ideas is particularly acute, of course, among people who have a vested interest in The Way It Is, professionals whose careers and funding, and self-identity, depend on The Accepted Paradigm. This is uniquely true of academics, and scientists.

But this innate facet of human cognition, that narrows our thinking and causes us to resist new ideas, puts us at risk. Science is not knowledge. Science is the process of methodically testing ideas to see where the bulk of the evidence lies, and requires the effort of an honestly open mind. The ENCODE DNA evidence has great promise. But beyond all the physical things it can teach us, it should serve as another warning that, in the name of human health, and progress, we need a little more humility about what we claim we ‘know’ (come on, could all that DNA really have just been JUNK?), and a lot more humility about the innate limits on our capacity to think and reason and establish ‘the truth’ in a purely objective way.

*An ironic mistake?

Comments

  1. Report this comment

    Stuart Cantrill said:

    It is somewhat unfortunate that a sentence that tells us that DNA is made up of amino acids:

    “This one is about DNA, that magical strand of just four amino acids, Adenine paired with Thymine, Cytosine paired with Guanine, millions of those A-T and C-G pairs linked together in various combinations to make the genes that spit out the blueprints for the proteins that make us.”

    follows this one:

    “In what should be another blow to the hubris of human intellect, we have a new entry in the long and ever growing list of “Really Big Things Scientists Believed” that turned out be wrong.”

    (I wasn’t the first to spot this; was pointed out to me on Facebook)

  2. Report this comment

    Ashutosh Jogalekar said:

    “This one is about DNA, that magical strand of just four amino acids”

    If DNA were made up of amino acids it would indeed be magical.

  3. Report this comment

    Stephen Fairclough said:

    First, DNA is not composed of amino acids. Second, it is a pain in the butt to leave a comment.

  4. Report this comment

    J K said:

    “This one is about DNA, that magical strand of just four amino acids, Adenine paired with Thymine, Cytosine paired with Guanine, millions of those A-T and C-G pairs linked together in various combinations to make the genes that spit out the blueprints for the proteins that make us. Or so science believed.”

    Um . . .DNA is not made out of “four amino acids”. You mean bases. Proteins are comprised of amino acids. DNA codes for RNA which is eventually translated into amino acids . . . this is a really very basic error.

  5. Report this comment

    Francis Pettit said:

    Wow, how about the hubris of YOUR intellect, and the limits of YOUR reason? Virtually everything you just wrote about “Junk DNA” is dead wrong. So many factual falsehoods — where to start?

    1. No molecular biologist nor geneticist at any time in history ever asserted that non-coding DNA is equal to, or a subset of, non-functional DNA. This is a scurrilous lie. There are no quotes from ANY molecular biologist nor geneticist from the 1960’s, 1970’s or 1980’s in which he asserts that it is his personal belief that non-coding DNA is equal to, or a subset of, non-functional DNA.

    There are quotes in which molecular biologists say that non-functional DNA is a subset of non-functional DNA. That was true then and is still true; but you assert that they said non-coding DNA is a subset of non-functional DNA. That is not the same at all as what they said, and what you wrote is still a scurrilous lie.

    Before you shoot off your mouth again, I demand that you provide a reference from a molecular biologist or geneticist of the 1960’s-1980’s saying that he himself believes non-coding DNA is a subset of or equal to non-functional DNA. If you can’t, you must retract.

    In fact, T. Ryan Gregory has done an extensive search of the literature of the 60’s-80’s and proven the opposite conclusion; you can see his extensive list of references here: [http://www.genomicron.evolverzone.com/2008/02/junk-dna-quotes-of-interest-series/.]

    In fact, every molecular biologist has known since the 1960’s-70’s that DNA regulatory elements are non-coding yet essential. They HAVE to know this to do basic wet lab work. If a molecular biologist grad student said in an oral exam that non-coding DNA is all non-functional, he’d be expelled.

    Remember that Jacques Monod and co-workers got the Nobel Prize in 1965 for discovering non-coding, yet functional, regulatory elements? Or that Jack Szostak and co-workers got the Nobel Prize in 2009 for their 1980’s discoveries about chromatin, which is non-coding but functional?

    If scientists “arrogantly” call non-coding DNA ‘junk’, as you claim, then why are the Swedes handing out Nobel Prizes to people who proved non-coding DNA can be functional— and then have their research incorporated into the wet lab work of tens of thousands of scientists, every day?

    You write:

    <i>“For decades molecular biologists didn’t know what the rest of the DNA…as in, nearly all of it…does. So, in a remarkable stroke of intellectual arrogance, they dismissed it as ‘junk’. Actually, the drier academics simply called it ‘non-coding DNA’. A Japanese scientist named Susumu Ohno called it junk.”</i>

    This is at least three lies in one. Above, I already addressed the point that no molecular biologist or geneticist ever said non-coding DNA was a subset of, or equal to, non-functional DNA ‘junk.’ Next two lies:

    2. Susumu Ohno never called non-coding DNA ‘junk’. What Susumu Ohno called ‘junk’ were PSEUDOGENES, which make up about 1-2% of all non-coding DNA. So you are only wrong by a factor of 50-100x.

    Ohno was a great geneticist who provided POSITIVE arguments, not arguments from ignorance, for non-functional psuedogenes— like the argument from genetic loading. They have never been refuted and it’s rare for anyone to try. Ohno predicted lots of pseudogenes would exist, and he was right.

    Before you spout any more falsehoods about Ohno, you should look at this transcript of a conference from 1973 in which Ohno discussed junk DNA (which was his term for pseudogenes, not non-coding DNA as you falsely claim) and you should read the responses of the scientists then; this from T. Ryan Gregory’s blog:

    [http://www.genomicron.evolverzone.com/2008/02/quotes-of-interest-ohno-1973-and]

    3. Intellectual arrogance had nothing to do with it. Proponents of junk DNA like Ohno advanced POSITIVE arguments, not arguments from ignorance, that most of the genome is non-functional. These arguments include:

    a. Genetic loading argument
    b. Sequence non-conservation between species
    c. Less complex organisms often have much, much more DNA (e.g. onions, Paris japonica (flower), some amoeba and salamanders with more DNA than humans)
    d. Related species with very different amounts of DNA
    e. More essential DNA sequence would mean too many accumulated deleterious mutations per generation

    These POSITIVE arguments have never been refuted, and the ENCODE project never addressed them. Now that’s intellectual arrogance!

    And this is a last, but important, falsehood.

    4. The Encode project did not demonstrate that 80% of the human genome has function. They only claim that by <i>redefining the word function</i> to mean “any molecular interaction between any part of a DNA element and any other molecule.”

    ENCODE did not prove 80% function by the ordinary layman’s definition, “contributing to essential biochemical processes that affect visible phenotype, fitness or viability of the cell.”

    Rather, ANY molecular interaction counts as “function” for them. By ENCODE’s super-broad definition of “function”, randomly generated DNA sequences would have function. By their super-broad definition of “function”, all transposons and retrotransposons would have “function”! If you caught a virus and it inserted its DNA in your genome, they’d call that functional too!

    Thus, the ENCODE consortium is guilty of equivocation, because they have only proved 80% “function” with the definition 80% “function” = “ANY molecular interaction”, but they equivocate when they imply to the general public that they have proven 80% “function” = “essential to viability or visible phenotype.” No, they have not proven anything re: the second, layman’s definition.

    They call 80% of the genome “functional” because:

    A. many DNA elements are transcribed into RNA, often at extremely low levels, maybe one RNA molecule per living cell. They simply ASSUME that extremely low-level transcription is “function”, but they don’t have evidence the low-level expressed RNA’s are functional. So this simply substitutes a “junk DNA” problem for a “junk RNA” problem.

    B. Transcription factors are found bound to many DNA elements. ENCODE assumes without evidence that all kinds of transcription factor binding designate the whole region as “functional.” There is a lot of experimental evidence AGAINST ENCODE’s assumptions; see for example this paper: [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2910615/.]

    C. Many DNA elements are sensitive to chewing up by the enzyme DNAse I, which indicates that some kind of protein binds somewhere thereabouts. ENCODE assumes without evidence that all kinds of protein binding designate the whole region as “functional.”

    ENCODE’s assumptions might be right, but until they’re proven, the ENCODE consortium is guilty of equivocating by switching between two definitions of the word “functional.”

    The intellectual arrogance here is all your own. You should apologize to your readers for this long string of falsehoods, and you should especially apologize for your scurrilous slurs on Susumu Ohno!

  6. Report this comment

    David Winter said:

    I’ve seen some pretty terrible opinion pieces spring forth from the ENCODE results – but this has to be the worst.

    Skipping over the clanger about DNA having “amino acids”, almost every factual claim in this piece is wrong.

    No one ever claimed only protein-coding sequences are “genes”. No one ever claimed all non-coding sequences were junk, the coining of the term “junk DNA” was not an act of hubris or an argument from ingnorance, ENCODE doesn’t establish that most of the genome is not junk.

    If David Ropeik doesn’t believe me about these points he might start by reading the Wikipedia article he himself links to, but presumably didn’t read, describing Ohno’s positive (mutational load) argument for the existence of junk DNA. Contrast that without Ropeik’s own profoundly ignorant statement “come on, could all that DNA really have just been JUNK”.

    If David Ropeik wants to be taken seriously on this topic he might consider learning a little about the history of this idea, and the results the the ENCODE actually presented.

  7. Report this comment

    Martin Hafner said:

    You state that “resistance to new ideas is particularly acute, of course, among people who have a vested interest in The Way It Is, professionals whose careers and funding, and self-identity, depend on The Accepted Paradigm. This is uniquely true of academics, and scientists”. This is definitely not the case for the critics I am aware of. E.g., as I already pointed out in a comment at another Nature blog Larry Moran’s and T. Ryan Gregory’s foremost concern is the legitimacy of ENCODE’s definition of function which is at least debatable and ENCODE’s hyped conclusion that there is likely no Junk DNA which is not compatible with biological knowledge established during the last four decades. The last time this happened, the researchers that you denounce as conservatives afraid of losing funding were right: Don’t you remember the bets on gene numbers during the Human Genome Project. Numbers went up to hundreds of 1,000 genes. Genome scientists were quite surprised that the numbers were quite low and not much different from those of other species. They shouldn’t have been because it has already been laid out in the early seventies that due to mutational load the human genome cannot contain more than 30,000 genes. It was exactly the same research that led to the conclusion that much of the human genome must be Junk. Thus, it is quite ironic that it is challenged again by ”Big Science”.
    To characterize critics of ENCODE as not being open minded is false, unfair and actually un-informed. What else than checking the methodology and discussing the presented conclusions in the light of older research and current knowledge would you expect from your peers?
    I guess it is not the worst thing for a scientist to be skeptic about research that is hyped as the latest Kuhnian paradigm shift. And this is what you actually do above.
    IMHO it is the finest duty of scientists to thoroughly question and discuss published research. Dr. Moran and Dr. Gregory don’t question ENCODE’s measurements. They just legitimately ask if signals have been separated from noise properly and point out that if this were not the case one should be reluctant to accept ENCODE’s conclusion regarding Junk DNA.

  8. Report this comment

    Martin Hafner said:

    IMO at least some of the ENCODE researchers want to invoke the impression that they have achieved some paradigm shift in the Kuhnian sense. Thus, it is indeed necessary to check their data and their conclusions. If either fails the claim that 80% of the human genome is functional would be at best pre-mature. The main problem of projects as huge as ENCODE is that they are mainly technology rather than hypothesis driven. Suggesting that allegedly nearly every bit of DNA is biochemically interfering with something in some cell type is stretching what could have served as a hypothesis. It stretches it to a degree that renders it worthless because it cannot be falsified due to the possibility that some of the alleged something remains inaccessible to technology. Adapting assumptions in hindsight with respect to observations would have been fine but their definition of “functional” is over the top. Extraordinary claims need extraordinary evidence. ENCODE surely is quite a technological leap but paradigm shifts surely need more than that. They need to be corroborated by hard evidence that can stand scrutiny..

  9. Report this comment

    David Ropeik said:

    Dear Readers,
    My most humble apologies for making a high school mistake with the line about DNA being made of amino acids (rather than playing a role in producing them). I am embarrassed that my haste led to this dumb mistake. I hope you accept this apology, and share it with any else with whom you might have shared the error.
    Most of all, I hope the foolish factual error doesn’t keep you from considering the larger point this episode offers, that human cognition contributes to resistance to new ideas and open minds. Please note the nature of some of the comments to this piece (on the merits of the case, thank you, rather than my dumb mistake), and the same resistance to the ENCODE work in a lot of the reaction to those findings. To be fair, skepticism…challenging ideas…is part of science. I’m talking about a more fundamental intellectual/cognitive recalcitrance, and I offer other examples to demonstrate the pattern of which I speak. Again, my embarrassed and sincere apologies for a foolish error made in haste.

  10. Report this comment

    Ashley Ng said:

    Is modern medicine and science permeated with an “intellectual inertia” as the author purports?

    If we look beyond the basic errors and inaccuracies regarding the DNA which were established by Watson and Crick and which have been already critiqued in some depth by other respondents, we are asked to ponder whether his central thesis is correct.

    I did not have to ponder long to reach my conclusion.

    The narrative the author has created seems to imply that science and modern medicine are wedded to conspiracy, parochialism and a willingness to inflict rather egregious medical harm without justification. To do this he has heavily cited historical examples to make his case, some of which refer to medical practises which have been abandoned for over half a century. Rather than “intellectual inertia”, I would argue modern science are medicine are driven by the opposite.

    As we enter into the 21st century, the principles on which science and medicine are based still require the veracity of observations to be scrutinised. This is not a conspiracy. This is good practice.

    A recent example which supports the need for healthy skepticism, with appropriate internal and peer review is found when recalling the “faster than light neutrino” experiment in 2011. Further checks by the OPERA consortium suggested their initial interpretation may have been flawed due to a technical error in a cable http://news.sciencemag.org/scienceinsider/2012/02/breaking-news-error-undoes-faster.html

    Science is littered with examples where initial claims could not be independently verified. This issue was recently raised by Glenn Begley, the then vice president and head of global Hematology and Oncology research at AMGEN who with colleagues, identified 47 of 53 “landmark” cancer publications which could not be replicated http://www.reuters.com/article/2012/03/28/us-science-cancer-idUSBRE82R12P20120328

    Healthy skepticism is not a luxury. It is a an essential requirement for today’s research and publication filled world.

    The prosecution of his argument using the example of “hormesis” http://en.wikipedia.org/wiki/Hormesis as a model of toxicology which proposes a U shaped response curve to toxins, with “beneficial” biological effects observed as “low doses” compared to their toxic effects at high doses, needs to be addressed. The model of hormesis is in contrast to the linear no-threshold model adopted by the EPA, FDA and NRC, unless there is evidence to the contrary http://www.radscihealth.org/rsh/Papers/FrenchAcadsFinal07_04_05.pdf. There is difficulty in adopting any theory as an underlying biological principle if there are examples which run contrary to the hypothesis, let alone adopting the theory as a basis for public health policy http://www.ourstolenfuture.org/Commentary/JPM/2006-1005hormesisflawed.html. Toxicology and establishment of toxic thresholds for public policy has been an active area of research and valid debate. How can the argument be prosecuted that not adopting one example of a theory is demonstrative of “intellectual inertia”, and that debate and peer review which argues against any given theory is an example of parochialism and bias? Debate and scrutiny rigorously based around evidence has been the cornerstone of the scientific method since the null hypothesis.

    The author also argues that researchers who have proposed that there are be a non-somatic mutation mechanisms that contribute oncogenesis have been ostracised by the scientific community, using “hormone” related malignancies in which no somatic mutations have been identified as an example. This has been far from the case. Hormone related oncogenesis is not a novel concept nor is it championed by a disparaged minority.  Diethylstilbestrol, a synthetic oestrogen was strongly associated with the rare clear cell adenocarconima of the vagina and cervix and breast cancer in daughters of women exposed to the drug during pregnancy http://www.cancer.gov/cancertopics/factsheet/Risk/DES. Concern regarding this drug was raised by physicians and resulted in the subsequent FDA warning in 1971 http://toxipedia.org/display/toxipedia/Diethylstilbestrol+(DES) ~ hardly an example of “intellectual inertia”.

    The mechanism of hormone related tumours is also an area of active research, especially in relation to breast cancer. Rather than being scientific pariahs, researchers who find insights into these mechanisms have been lauded. One example of this research is here: 

    http://eureka.australianmuseum.net.au/856F25B0-93F5-11E1-8A69005056B06558?DISPLAYENTRY=true

    Rather than being stricken with intellectual inertia, science and medicine has embraced ideas which have stood the test of time and have been validated. Take for instance the field of epigenetics: modifications of the genome which result in altered transcription without somatic mutation. Epigenetics has been extensively studied and serves as as a basis for developmental biology, cellular differentiation, and can lead to human genetic disorders associated with genomic imprinting such as with uniparental disosmy http://www.mayoclinic.com/health/angelman-syndrome/DS01048/DSECTION=causes. Epigenetic modification has become an intense area of research for clinical therapeutics. As an example, the agent Azacitadine  was the first drug in myelodysplasia which was shown to provide patients with this condition a survival benefit over best supportive therapy http://www.google.com.au/#q=azacitidine&hl=en&tbo=d&ei=Zx5PUM-7OK6ZiQerp4GoCQ&sqi=2&start=10&sa=N&bav=on.2,or.r_gc.r_pw.&fp=c279e1aece2ce2e8&biw=543&bih=653 .

    It is bordering on sophistry to suggest that there is an ongoing systematic conspiracy to suppress best medical practice in the 21st century. I need to discuss in more detail the two examples the author uses regarding the Halstead mastectomy and PSA screening.

    The Halstead radical mastectomy was introduced in 1822 and was one of the most disfiguring and disabling treatments for breast cancer. The author is correct in that it was only abandoned as lack of superiority to more localised forms of surgery. What he fails to mention was that up until that time, no proper trial had been undertaken to compare outcomes. The NCI instituted the first controlled study in breast cancer surgery led by the surgeon Bernard Fisher, which led to this conclusion. If there was truly an intellectual inertia, the Halstead procedure would still be performed today.

    There is an argument prosecute as to “why wasn’t this done sooner?”. To put this question into context, the first published randomised control trial was in 1948 regarding the use of “Streptomycin treatment of pulmonary tuberculosis”. The medicine of early last century, is very different to the medicine of today. Evidence based medicine is very much part and parcel of modern medical practice. There are, for instance, over 132,000 clinical trials currently registered at http://clinicaltrials.gov/ ~ a far cry from the number of trials over half a century ago.  Of note, what the author should have mentioned, was Halstead’s original observations regarding patient outcomes were grossly misrepresented, and would not stand the test of today’s scrutiny.

    The controversy surrounding PSA, however, is a more recent and relevant example. The controversy surrounding PSA is in its validity as a screening test in asymptomatic men. Here the author confuses the PSA as a diagnostic test for prostate cancer. To be clear, the PSA does not diagnose prostate cancer. The diagnosis of prostate cancer is a more involved process that includes PSA, physical examination and prostate biopsy. It is incorrect to suggest that men with an elevated PSA on a “screening test” will automatically proceed to radiation therapy or radical prostatectomy rather than “watchful waiting”. The issue of what is the “best” treatment for an individual diagnosed with prostate cancer, which may be limited in stage, spread beyond the confines of the prostate, and sometimes unfortunately, metastasised beyond, requires advice based on current clinical evidence, with treatment tailored to the individual’s circumstance ~ as well as their wishes. Once again, however, the fact that utility of PSA is being debated as a screening investigation argues against intellectual inertia. All public health screening measures are subject to assessment and revision as new evidence becomes available. This is not a sign of intellectual inertia, but  the opposite; vigorous scrutiny of the evidence and rigorous debate http://www.abc.net.au/science/articles/2012/05/22/3508167.htm

    So, do the so-called “experts in the field” conspire against paradigm shifting novel theories and continue to ostracise their proponents? As I have argued above, scientific scrutiny is not a sign of “intellectual inertia”, but a requirement to validate the observations and evidence used to support a hypothesis. Paradigm shifts are more often than not, a culmination of an evolution of theories based upon strong evidence rather than conversions on the road to Damascus. No substantive change in scientific theory or medicine occurs, or more importantly, should occur without solid evidence to back it. The evidence must precede the revelation. 

    The author rightly uses the example of John Snow’s quest to characterise the nature of the outbreak of cholera. This was an example of solid epidemiological research to associate cases of cholera with proximity to water contaminated with human waste used to guide public health policy. This was scientific evidence. Unsurprisingly, miasma, a concept propagated by unsubstantiated belief, is a theory which has been confined to the dust-bin of history.

    Do we still ostracise proponents of novel theories? Not if the theories have been proven to be valid. The example of Barry Marshall and Robin Warren was strangely neglected by the author. Their discovery was that a bacteria, Helicobactor pylori was the major cause of peptic ulcers in humans, which went against the current thinking at that time. Through good science, and the demonstration of (self-inflicted) Koch’s postulates , they were able to substantiate their hypothesis. Nowadays, rather than denigrate the proponents of novel paradigm shifting theories, once they have been validated, Stockholm are more inclined award them Nobel prizes (if they are lucky).

    Experts in the field are by no means always right. Neither are they always wrong. The author somewhat misrepresents the scientific method and the need for evidence based medicine. Personally, I don’t believe this blog deserves the title of the “worst scientific blog, ever”. Overlooking the simple errors of fact, however, we are still left the use of selective historical references to reinforce a narrative, and the near sophistry which the author uses to make his argument to obfuscate the modern scientific method and current medical practice. There are lessons to learnt from the past. However, the arguments he makes are probably best left to historical debate and the allegations drawn against current practice somewhat misguided..

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    David Ropeik said:

    Dear Ashley

    thank you for a very thoughtful and detailed reply, but it seems to misconstrue my case. No where did I intend to argue that “…there is an ongoing systematic conspiracy to suppress best medical practice in the 21st century.” That stretches my argument far beyond what I was trying to say, though in retrospect my tone was too exuberant and my wording too loose. I was suggesting that human cognition tends toward resistance to new ideas, not just because of appropriate skepticism about such ideas but because cognition tends to default to ‘the way it is’, and that there is indeed a history of resistance to ideas in medicine, and many many more in many fields of science, where that resistance conflicted with what a truly open minded consideration of the evidence might have led to. Halstead’s influence was such that other surgeons made it really hard to conduct the studies necessary to overturn the radical mastectomy paradigm he and they championed. The champions of PSA testing are doing the same today with getting patients to enroll as possible ‘no testing’ controls in blind study to test the efficacy of PSA screening. Sonneschein and Soto are meeting intellectual hostility, as is Calabrese. This is not a ‘systematic conspiracy’, but a facet of human nature, and is particularly true for some whose self identities and careers have been built on ‘the way it is.’
    So while I respect and honor and have learned from your eloquence, you set up and then easily blow down only a straw man, not the general idea I suggest.
    but may I add that I was duly chastised by many commenters about various facets of a too-zealous post, and have re-written my thoughts and re-state my case in my blog at BigThink.com, “Risk: Reason and Reality”, and you may find that of interest. http://bigthink.com/risk-reason-and-reality/new-evidence-about-dna-and-old-patterns-of-resistance-to-new-ideas

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    Francis Pettit said:

    Wow, Ashley, that was great. By I’m 100% certain all your science and logic went right over Ropeik’s head.

    Thanks for writing it out though. Are you the Ashley Ng of Melbourne? If I lived in Melbourne, you’d sure be my doctor!

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    Francis Pettit said:

    Ropeik has shown that he simply does not care about his numerous factual errors. He doesn’t care a bit that he slandered Susumu Ohno and misrepresented Ohno’s ideas, and those of many other scientists! He got his history of science wrong— and doesn’t care!

    Ropeik: <i>there is indeed a history of resistance to ideas in medicine, and many many more in many fields of science, where that resistance conflicted with what a truly open minded consideration of the evidence might have led to</i>

    NO, you describe <b>yourself</b>: there is indeed a history of resistance to new ideas <b>from you, on your blog</b>. <b>Your resistance conflicted with what a truly open minded consideration of the evidence might have led to</b>. Do you understand that?

    You have been shown to be factually wrong on many points, but you cannot admit it, because you are closed-minded, Ropeik, and will not go where the facts demand.

    I included links to a transcript of a conference from 1973 where Susumu Ohno introduces the concept of Junk DNA, and scientists dispute him.

    Why, Ropeik, did you not follow that link? It is directly relevant to the facts you claimed were so important. You did not follow that link because you have a closed mind, and will not go where the facts lead. <b>You present yourself as the EXPERT, but when we challenge your factual errors, you tell us we are not permitted to challenge the expert!</b>

    <i>This is not a ‘systematic conspiracy’, but a facet of human nature, and is particularly true for some whose self identities and careers have been built on ‘the way it is.’</i>

    You describe yourself. You preserve things ‘The Way It Is’ and we meet intellectual resistance from you, no matter how many facts and what evidence we have on our side, because you are crippled and retarded by a closed mind!

    Ropeik: <i>Human cognition tends toward resistance to new ideas, not just because of appropriate skepticism about such ideas but because cognition tends to default to ‘the way it is’</i>

    No, that describes YOUR human cognition. You’ve been proven wrong on many facts, but you refuse to admit because YOUR cognition defaults to ‘the way it is.’

    Ropeik seems to have learned all his science from “The Politically Incorrect Guide to Science” (book by creationist Tom Bethell, from right-wing American publisher.) I read that book— Ropeik sound just like Bethell— especially about evolution, hormesis and cancer!

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