the worst of science

Two separate scandals have rocked the climate science community in the last month or so. Both were unearthed by the indefatigible Steve McIntyre of climateaudit.org. To call Steve a gadfly is inadequate; Steve is a gad-pterodactyl. Both findings are tributes to his sheer persistence as well as his statistical acumen.

The first was, after repeated letters and inquiries from McIntyre, and insults from the scientists he was questioning, it was revealed that the Hadley Center at the University of East Anglia had lost most of the raw climate data on which their reconstruction of global surface temperature records from 1850 - 1970 are based. They made some flimsy excuse about the volume of data - in fact, a quick calculation indicates that the data collection, which they made in the 1980s, could have been stored on one or at most a few floppy disks of the time. This means that no one can now check their analysis. Since re-analysis of such data sets has often revealed significant errors, this is a major problem. There is an independent compilation by the NASA Goddard group, for which the data is publicly available, but still, this is a major black eye.

What seems at first glance to be much more significant appears to be clear evidence of cherry-picking in the tree ring data used to reconstruct climate over the last 1000 years, on which most of the claims about the unusual nature of recent climate are based. After a ten year campaign to get Hadley to release raw data about the Yamal Peninsula tree-rings, which reflect Arctic temperatures over the last 1000 years, McIntyre finally thanks to the enlightened data availability policies of the Philosophical Transactions of the Royal Society B managed to get his hands on it, and his analysis seems to indicate the data were selected to include only the trees that showed 20th century warming. The full data set, per his analysis, shows no significant change at all in the 20th century, quite remarkable for a set collected in the high Arctic where climate change should be at its most obvious. Briffa has not yet replied, and this is only a blog post (though McIntyre is being encouraged to publish it) but at first glance, his findings look really, really bad, and the media are starting to notice, here, here, and here.

So three months before the Copenhagen conference, there are major questions about the observational foundations of anthropogenic global warming, thanks to unscientific secrecy, shoddy data handling, and perhaps even fraud on the part of some members of the climate science community. It's going to take a lot more than three months to sort all of this out. This doesn't mean the data are all suspect; while one can raise legitimate questions about their methods of analysis, the NASA data set is available and can be checked by anyone. But this raises serious questions about publication standards and peer review in climate science, and before we make major policy decisions, those questions need to be answered.

Largely unnoticed, Ezekiel Emanuel, President Obama's 'Special Advisor for Health Policy to the Director of the Office of Management and Budget' recently published a paper with the above title, in the Journal of the American Medical Association (July 1, 2009). In it, Emanuel argues that individuals have an obligation to submit themselves to medical research experimentation. No, I'm not kidding.

Individuals have an obligation to participate in biomedical research because the knowledge produced by the system of biomedical research is what economists call a “public good.”

and

Individuals ought to participate in clinical trials when presented with the option. Well-functioning institutional review boards ensure that the risks are not excessive relative to the benefits of research. When the risks are significant, the obligation may be weaker. The obligation to participate applies to both healthy volunteers and patients. Both are needed to advance biomedical knowledge. For patients, there is an obligation to agree to participate in a study involving their condition when appropriate. Healthy individuals should participate in a fair share of the research for which they are eligible and needed.

Got that? (By the way, in my experience, IRBs are mostly rubber-stamp bodies that exist to cover the institution's ass when things go wrong)

To be fair, Emanuel does not propose that this moral obligation should be legally enforced. But he does think the government should run advertising campaigns to 'guilt' people into participating in experiments.

One strategy to affirm and reinforce the belief that individuals have an obligation to participate in research would be a publicity campaign analogous to get-out-the-vote efforts, which have helped convince 90% of US citizens that there is a duty to vote. The language of current advertisements could change from calling participants everyday heroes, which implies participating is supererogatory, to using language similar to recycling advertisements, which state “do your part” or “it’s your turn to participate.”

I can just see the ads now; two moist-eyed, super cute kids, mourning Mommy, who died because you didn't step up and let them inject you with that experimental drug.

Dr. Emanuel is a one of the nations most eminent bioethicists. I don't want to demean his work, but I think this, and his previous papers on the allocation of scarce medical resources based on the indivdual's social usefulness, are a demonstration of the ultimate inhumanity of communitarianism. Ultimately, when the 'good' is community property, the rights of the individual become secondary to the welfare of the community. A healthy political philosophy holds the right of the individual paramount, in the confidence that enlightened self-interest ultimately benefits everybody.

The longest, deepest solar minimum in a century continues, with no end in sight. We are now in the 45th consecutive sunspot-free day, one of the longest quiescent periods of the current minimum, a minimum that NASA originally forecast would end a full two years ago.

Meanwhile, as the possibility we might be in an extended, Maunder-minimum like period increases (the original Maunder minimum caused the little ice-age of the 17th and 18th centuries) the 'climate change' community, which usually latches onto every thunderstorm as a sign of the impending apocalypse, are, like the sun, strangely quiet about it all.

Anthropogenic CO₂ might turn out to be the humanity's greatest ever stroke of luck.

Democrat Governor of Senator from Michigan Debbie Stabenow, on how she knows Global Warming is real.

"Climate change is very real," she confessed as she embraced cap and trade's massive tax increase on Michigan industry - at the same time claiming, against all the evidence, that it would not lead to an increase in manufacturing costs or energy prices. "Global warming creates volatility. I feel it when I'm flying. The storms are more volatile. We are paying the price in more hurricanes and tornadoes."

You know if Sarah Palin had said anything a tenth as stupid, the leftist pseudoscientists at scienceblogs.com would be on it like a pack of rabid dogs. Henry Payne commented:

And there are sea monsters in Lake Michigan. I can feel them when I'm boating.

Hat tip: Michelle Malkin

Rudy Baum is 'Editor in Chief' of the American Chemical Society's free member magazine 'Chemical and Engineering News' (Why C & E News needs an 'editor-in-chief' is an interesting question). He's currently in hot water for a very silly editorial he penned about the cap-and trade abortion currently stalled in Congress.

The science of anthropogenic climate change is becoming increasingly well established. The scientific consensus on the reality of climate change has become increasingly difficult to challenge, despite the efforts of diehard climate-change deniers (for brevity’s sake, CCDs).

I shall have more scathing words elsewhere about the nonsense people spout about 'scientific consensus'. But let me just note that if anything the 'consensus' has been growing weaker recently, as it becomes obvious we aren't in imminent danger of burning up or drowning under Greenland ice-cap melt water. And the 'CCDs' -- the skeptics about the direr sky-is-falling prognostications on climate change -- include people like National Academy of Sciences member and prominent molecular physicist Bill Happer. They can't be airily dismissed, least of all by a mere chemistry B.A. who dropped out of medical school.

But I did go to the trouble of looking up Mr. Baum's political contributions -- to Obama, Jim Webb, John Kerry, Howard Dean, Bill Richardson, and best of all, Al Franken. I guess that's some of that clown solidarity working.

As an ACS member of long-standing, I'd prefer if Mr. Baum left his politics at home and confined his editorials to subjects he has the scientific competence to discuss. That might stop him from writing entirely, but it's a small loss, and we can bear it.

The fraudulently named 'Union of Concerned Scientists' today issued a series of 'reports' on climate change in the midwest. Well, no, not really. The fraudulently named 'Union of Concerned Scientists' today issued a single report on climate change in the midwest, titled Confronting Climate Change in the Midwest: (insert state name here). What this bunch of leftist charlatans did was produce a single 'report', and then do a quick cut-and-paste to make it look like it was written specifically about each of four different US states. For example, the first two sentences in the 'Indiana' report read:

From its fertile croplands and many riverside communities to its economy, infrastructure, and lifestyle, Indiana has been strongly shaped by its climate. However, that climate is changing due to global warming, and unless we make deep and swift cuts in our heat-trapping emissions, the changes ahead could be dramatic.

No prizes for guessing that the first two sentences in the 'Minnesota' report!

From its fertile croplands and boreal forests to its 10,000 lakes and many riverside communities, Minnesota has been strongly shaped by its climate. However, that climate is changing due to global warming, and unless we make deep and swift cuts in our heat-trapping emissions, the changes ahead could be dramatic.

The reports were written by 'lead science writer' Barbara Freese (global warming, Freese, get it?) whose scientific qualifications apparently are a law degree and a former position as Minnesota's Assistant Attorney General. Moreover, the UCS website claims, ludicrously, that the reports are 'peer reviewed'. Who by, another attorney?

I can't wait to find out how many gullible news organizations will be willingly misled by this scam.

The left is mounting some pretty implausible defenses of John Holdren for his disturbing writings about coercive population control in the 1970’s. The White House claims that the drastic and compulsory population control measures that Holdren proposed in Ecoscience are "description … misrepresented as endorsement". Holdren’s staff released a statement:

This material is from a three-decade-old, three-author college textbook. Dr. Holdren addressed this issue during his confirmation when he said he does not believe that determining optimal population is a proper role of government. Dr. Holdren is not and never has been an advocate for policies of forced sterilization.

This defense has been echoed by some bloggers, while others argue that Ecoscience "takes a stance against such policies" Chris Mooney also reports that Holdren’s co-authors, the Ehrlichs, sent out an email observing:

We were not then, never have been, and are not now ‘advocates’ of the Draconian measures for population limitation described—but not recommended—in the book’s 60-plus small-type pages cataloging the full spectrum of population policies that, at the time, had either been tried in some country or analyzed by some commentator.

The trouble is, these defenses are disingenuous at best and downright false at worst. In the prolog to his 1968 book The Population Bomb Paul Ehrlich, wrote, and I quote:

We must have population control at home, hopefully through a system of incentives and penalties, but by compulsion if voluntary methods fail.

Later in that book he advocated a federal Department of Population and Environment, which would, inter alia, promote the "development of mass sterilizing agents", agents discussed later by him, his wife and Holdren, in Ecoscience. He said the US should have supported India in setting up a program of compulsory vasectomies:

We should have sent doctors to aid in the program by setting up centers for training para-medical personnel to do vasectomies. Coercion? Perhaps, but coercion in a good cause.

You might recall that India later did institute such a program, with horrific results. In other words, Ehrlich is lying through his teeth.

And Holdren worked closely with Ehrlich for a quarter century, starting in 1971. In Human Ecology: problems and solutions (1973), Holdren and the Ehrlichs laid out their program, not as dispassionate observers, as they now claim they were, but as passionate advocates. After a quick review of the Indian vasectomy program, and proposals for compulsory sterilization of mothers with more than three children, as well as

compulsory implantation of steroid capsules at puberty, with removal for childbearing with official permission only

they wrote

Compulsory control of family size is an unpalatable idea, but the alternatives may be much more horrifying.

That's not a rejection of the idea, it’s advocacy of it -- particularly when you consider that two years previously, Ehrlich, in a volume edited by himself and Holdren, had predicted a US population of 22 million in the year 2000 thanks to mass ecological catastrophe. It is clear Holdren and Ehrlich thought the 'horrifying alternatives' were not hypothetical, but in fact destined to occur, and that compulsory control of family size is a better alternative.

If Holdren had acknowledged he once held these views and had subsequently renounced them, I'd be less critical. But he hasn't. His writings in the 1970s evince grotesque scientific arrogance, in which he was willing to advocate draconian social authoritarianism based on pseudoscientific theories of imminent eco-catastrophe that turned out to be grossly in error.

So now, in 2009, science is predicting a different eco-catastrophe, and Holdren is in the position of advising the White House on responses to it. Given his previous advocacy of drastic coercive measures to forestall an earlier (incorrectly) predicted catastrophe, isn't it reasonable to ask if he will give similar advice today?

---

Meanwhile, Nick Anthis has weighed in with the usual fact-free, copycat rant.


The mainstream media, and even more so the quasi-scentific blogosphere (need a shorter term for that!) are all a chatter about the recent Pew Survey about attitudes to science among scientists and the general public. Almost nobody, however, has drawn attention to the hideous selection bias inherent in the sampling of scientists. The Pew Research Center decided to skirt the rather difficult problem of demarcation in defining a 'scientist', and then finding an unbiased sample of scientists, by polling not scientists in general, but members of the American Association for the Advancement of Science.

Why does this matter? Because only a small and unrepresentative minority of scientists in the US are members of AAAS. I am not, and have never been a member. My wife was once, but thinks she let her membership lapse; we both have online access to the journal Science through our university, and so the main perk of membership isn't a perk for us. I don't know for sure, but would be willing to bet that fewer than 20% of my colleagues in the Department of Chemistry are members. I've never been to an AAAS meeting, and I don't recall a single one of my colleagues ever mentioning having gone to one. I doubt any of us would go unless we were invited to speak.

So who does join AAAS? I'd say it contains a large overrepresentation of scientists who are interested in public policy aspects of science. In fact, many are not really working scientists at all, but engaged in the quasi-discipline of Science and Technology Studies. Hardly a surprise, then, to find very few of the scientists polled by Pew were conservative. The surveyed scientists were also disproportionately US-born, disproportionately over 50 and disproportionately in academia as opposed to industry.

Needless to say, most commenters have totally missed the sampling bias, and as a result are drawing incredibly silly conclusions. The survey is probably useful as a barometer of public attitudes toward science. As a barometer of scientists' attitudes, it's useless. Caveat lector!

John P. Holdren is Assistant to the President for Science and Technology, Director of the Office of Science and Technology Policy, and Co-Chair of the President’s Council of Advisers on Science and Technology. His ridiculously wrong predictions in the 1980s about commodity and energy shortages drew some attention, as did his characterization as 'dangerous' those who disagree with him about climate change. Nonetheless, he sailed through Senate confirmation in March 2009. And, of course, he was defended by the usual corps of para-scientific flaks.

Far more serious evidence of Holdren's intolerance has now appeared, in an analysis of Ecoscience, a book Holdren co-wrote with the Ehrlichs in 1977. At the time, population and not climate change was the ecothreat-du-jour, and Holdren and his co-authors proposed some pretty horrific solutions: compulsory abortion, forced adoption, forced marriage of single women, addition of human sterilants to drinking water, 'coercive fertility control', and Chinese style maximum family size policies mandated by law. Needless to say, the 'population bomb' failed to materialize in the United States, and Holdren turned to proposing other means to control our lives. Nonetheless, there is an entirely appropriate word to describe what Holdren was considering, and that word is fascist. In fact, the Nazis put many of these same policies in place, in an earlier era.

If Holdren was prepared to contemplate such authoritarianism in the 1970s to control fertility in the US, what is he advising Obama to do to fight anthropogenic global warming?

Hat tip to Dgray of Darwin Central.

I've revamped this blog as a generalized science blog; frankly, I started to find reading scienceblogs.com regularly to be like watching Keith Olbermann; predictable in its nuttiness, ultimately boring, and bad for my blood pressure. So, while I ain't laying off scienceblogs.com, I'm broadening my focus, and posting more often.

Comments will be enabled just as soon as I figure out an alternative to haloscan. In the meantime, if you want to comment, email me.

So, among the Reverend Jeremiah Wright's remarkable sermonic rants, through which presidential contender Barack Obama now admits he sat, was the claim that "we" (i.e. America) started the AIDS virus. That's a statement that anyone with a modicum of genetic knowledge should be able to refute. And you would think the sciencebloggers would be all over it, as they were on McCain for his recent goof about Thiomerosal, and Huckabee about evolution. Well, gosh, no they weren't. Soros sockpuppet Ed Brayton (exactly why is he a scienceblogger anyway?) has spent at least two posts defending Obama, while Josh Rosenau tries to shift the conversation to John McCain.

Surely, since this myth is being broadcast, and is unfortunately quite widespread, in the African-American community, Barack Obama, if he's as pro-science as our leftist pals on scienceblogs claim he is, should be actively working to dispel it? Is he? Nope, no more than the sciencebloggers are challenging him to do so.

Chirp, chirp, chirp. Say, it's rather early for crickets!

---

(Added 4/23/08) Well, a month later, the sciencebloggers are finally noticing that Obama and Clinton are fudging on the 'vaccine-autism' link. Better late than never, I suppose.

The Terra Sigillata blog, in honor of the day, quotes some words by Martin Luther King on the subject of science and religion.

"Science investigates; religion interprets. Science gives man knowledge which is power; religion gives man wisdom which is control. Science deals mainly with facts; religion deals mainly with values. The two are not rivals. They are complementary. Science keeps religion from sinking into the valley of crippling irrationalism and paralyzing obscurantism. Religion prevents science from falling into the marsh of obsolete materialism and moral nihilism."

The blogger very properly gives a source for the quote, which in turn took it from "The Words of Martin Luther King, Jr," published in 1984 by Coretta Scott King.

Problem is, like most of King's published work, including his doctoral thesis, the words are not really his. Googling the first four words finds you this (full passage edited by myself):

Science investigates; religion interprets...Science is the response to the human need for knowledge and power. Religion is the response to human need for hope and certitude...Science and religion are not rivals. They are each other’s complement and man’s binocular vision. In the past science frequently aided religion to correct its perspectives and religion has delivered science from the pitfalls of naturalism, materialistic monism, and moral nihilism.

Rabbi Hillel Silver, 1930, in 'Religion in a Changing World' (New York: Richard R. Smith, 1930)

http://www.lerwill-life.org.uk/spirit/scienceandreligion.html

King was an incurable plagiarist. Of course, merely mentioning that indisputable fact will usually get you branded a racist. King's plagiarism is so completely ignored by the media I really can't blame the Terra Sigillata blog for missing it. But as a general rule, if you're quoting King, odds are you're really quoting someone else.

I had no intention of giving revere two successive WOSB awards -- there's plenty of other junk available on scienceblogs -- but this couldn't escape remark.

When the highly toxic fumigant methyl bromide was banned under the Montreal protocol as a greenhouse gas, growers started looking for a replacement. Now the EPA has approved one, methyl iodide. If you know any chemistry, you might suspect that replacing one halogen with another might not solve the problem.

Well, let's see, the Montreal Protocol banned ozone-depleting chemicals, not greenhouse gases. Methyl bromide is actually still in use in the US, under a critical use exemption. Replacing the bromine with an iodine does solve the problem, because methyl iodide (iodomethane) decomposes quickly on exposure to light, and so doesn't make it to the stratosphere. In fact, since methyl iodide will replace methyl bromide, it will lessen ozone-depletion. Hard to believe anyone could be wrong so often in such a short paragraph.

The honor of being the first recipient of our 'worst of scienceblogs.com' award goes to revere, the collective sobriquet of some self-described, anonymous 'senior public health scientists and practitioners'. Their winning post Bisphenol A. What's all the noise about? wins not only for its content, but for the near rabid way the blogger(s), revere, responds to scientific challenge.

First, a little background. Some time ago, the hypothesis was advanced that big, hydrophobic (i.e. greasy) molecules, of about the right shape, and especially if they contained polarizable atoms such as chlorine, might bind to steroid receptors. Steroids, like the sex hormones estrogen and testosterone, are themselves hydrophobic, so the cell receptors that detect these hormones are hydrophobic. 'Xenestrogens' -- molecules like bisphenol A and dieldrin, a pesticide -- don't fit the shape of the steroid binding site, but they do have the right electrostatic properties. So, it was hypothesized, those receptors might either be turned on by the xenestrogens (agonism), or the xenestrogens might block the real hormones from acting on the receptors without turning the receptors on themselves (antagonism). And alterations in sex hormone response are obviously bad for adults, but they're even worse for fetuses and infants, causing birth defects and developmental disorders. I'll post elsewhere why Greenpeace and their environmentalist fringe cohorts embraced the xenestrogen theory like a harpooned, dying whale; here I'll just point out that it's on its face a plausible, testable, and perfectly scientific hypothesis.

Problem is in the numbers. When people measured the binding constants of bisphenol A (BPA) to the nuclear estrogen alpha and beta receptors, they found it binds about 100 times less well than estrogen, its real target. More seriously, the binding constants for BPA are around 1 micromolar (1 uM). That means, if you expose the receptor to a 1 uM solution of BPA, half the sites will be occupied -- either turned on weakly, or blocked. But the highest measured levels of BPA in human plasma are more like 0.01 uM, or about 100 times lower than the binding constant. At that level, less than 1% of the sites are occupied, and the chances of a physiologically relevant effect are zero.

OK, plausible hypothesis refuted, right? Well, not if your scientific career depends on the hypothesis. Within the last few years, it has been proposed that estrogen receptors on the cell membrane respond to xenestrogens at much, much lower levels. If that were so, it would rescue the entire xenestrogen hypothesis, and raise significant concerns about the levels of BPA in the environment. BPA, by the way, is a building block of the polymer polycarbonate, an incredibly useful plastic because of its clarity and toughness, used in everything from the lenses of my eyeglasses, to baby bottles. Polycarbonate is a polymeric carbonic ester of BPA; in its manufacture, a little BPA remains in the polymer, but also the links between BPA and the carbonate groups can slowly be degraded by exposure to water, leading to release of BPA.

Revere's post ont he subject is really vague on specifics; so I asked him via a comment, how he reconciled the binding constant data with the reported biological effects. I was surprised, to say the least, by the response. Instead of answering, he answered with ridicule:

Mr. Harbison: You're right. Nothing designed like a bumblee could possibly fly. But it does. The literature showing effects at environmental levels is getting quite large. But you're safe. It's impossible! LOL.

I responded

The epidemiological literature showing effects of EM fields on health is also quite large. Nonetheless, physicists discount them, because of lack of a feasible mechanism. You, on the other hand, have postulated a mechanism, and that mechanism is disruption of the endocrine system. In fact, the people who are pushing bisphenol A as an ED (endocrine disruptor: RWP) have volunteered the estrogen receptor for the job. The biochemistry of binding of small molecules to hormone receptors is well known. And the numbers don't add up. Unless you can provide me with a receptor with a dissociation constant for bisphenol-A in the neighborhood of 10 nM, you're in the same category as the EMF crowd. The antagonism of estrogens will be insignificant, and there will be no physical basis for the effect. It's a shame you don't take the scientific method a little more seriously, and approach scientific challenge so defensively.

This, it turns out, wasn't as persuasive as I though it would be. Revere, remarkably, has a soft spot for the discredited idea that low intensity, low frequency, EM fields have physiological effects, and provided a link to a really bad paper claiming some basis for this. That was easily dealt with. But then revere decided to go the ad hominem route:

Gerard: Yes, that bumblebee can't fly. Everyone is wrong but you. Some scientist. Just disregard the evidence it if doesn't match your preconceived notions. As for ideological bias, what's the name of your blog again? The Right Wing Professor? (as Gerard knows, this is not snark; that's actually the name of his blog). BTW, the way a real scientist would phrase the point he makes is this: "given some numbers I have on binding constants (which estrogen receptor, which model system, under what conditions?) what is the explanation for the observed biological effects?" Instead Gerard says, "I have these numbers and they imply that the biological effects being seen in studies which I haven't bothered to critique but whose reliability I question a priori because they disagree with my libertarian bias not to interfere with the vaunted market can't possibly be true." Some scientist.

I pointed out that Revere hadn't actually provided any evidence. So, to give him his fair dues, he did (while simultaneously accusing me of not knowing there were two types of estrogen receptors, something I'd mentioned previously in the discussion). He linked specificially to two papers. These are Zsarnovszky A et al. Endocrinol. 2005;146[12]5388-5396 and Wozniak AL et al. Environ Health Perspect. 2005;113:431-439.
Our crappy librbary doesn't have the first, so I've sent away for it via interlibrary loan. I did, however, find the second paper, as well as a follow up in Steroids 72:124–134 (2007), and was, frankly, shocked. The investigators applied estrogen (E2), diethylstibestrol, or DES, an authentic synthetic estrogen, as well as several 'xenestrogens', to some prolactin-producting tumor cells, and measured increases in intracellular calcium (an indication of membrane-mdediated signaling) as well as prolactin release. Or so they said in the abstract Their actual data tell an entirely different story.

This is the calcium release data, measured by observing the fluorescence of a dye whose optical properties change when it binds calcium.

Some explanation is needed; the x axis is BPA concentration, and it's in logarithmic units. -12M means 1 picomolar (1 pM = 10-^-12M), or one trillionth of a mole in 1 Liter of solution. -10 is 100 pM, -9 is 1 nanomolar (1 nM = 1000 pM) and -8M means 10 nM. So, in addition to the untreated cells, they've looked at the concentration over a concentration range spanned by a factor of 10,000. On the y axis, they have the change in fluorescence on adding BPA, as a ratio of the original fluorescence. And it's tiny! Adding 1 pM BPA causes about a 1.2% increase in calcium release. Problem is, add 100 times more, and the very small 1.2% response goes down to 1%!Add 10 times more, and you get an increase to about 4%; add times times more still, and it goes back down to about a 2.5 % increase.
This, my brothers and sisters in science, is what we technically call 'noise'. There is absolutely no physically reasonable response that explains these data as presented. The effects are tiny and show no discernable trend. This becomes abundantly clear if we lose the rather weaselly way the authors presented their data, and simply plot what they measured against what they added, on a linear scale.

The only reasonable conclusion from that graph is that there is absolutely no evidence of any response to BPA, and in fact the data rather suggests there is no response. This is the exact opposite of the conclusion the authors drew.
This is a lengthy post already, and I won't belabor the prolactin release data, except to say there is no time delay in the response, whereas the basic physics of binding very dilute molecules to receptors say there have to be diffusion-limited kinetics (think about it this way: two molecules very far apart have to find each other in order to interact, and that takes time). The concentration graph is equally funky, showing a response at 1 pM and 10 nM, but no response at 10 pM, 100 pM, and 1 nM!

This is genuinely bad science; the data don't support the conclusions, in fact they contradict the conclusions. It's clearly agenda-driven, and it ignores some very basic physics of extremely dilute solutions. Moreover, there is at least one very plausible explanation about why the data are so bad. BPA is, as we said, ubiquitous. Biomedical research labs are full of plastics: they use plastic tubes, plastic pipette tips, tubing, plastic in their water purifiers, etc. Unless you take very stringent steps to eliminate BPA, it is very likely all their solutions have some quite signficant concentration of it. The authors said nothing about this, and so its reasonable to assume they didn't take such steps.

So, after the personal attacks, the defensiveness, etc., this incredibly flawed paper is what revere had to support his point. I think it's more likely than not he never read the paper he cited; he certainly didn't read it with any attention to detail. And that's just bad science, something that's far too prevalent on scienceblogs.com.

---

Ian Musgrave had the following comments on the above. I'm posting them here in full; I will have my own response to his response later.
Your post on xenoestrogens raised a number of issues; unfortunately, you misunderstand the science in this paper. As I have had a fair bit of experience with measuring intracellular calcium, and have measured intracellular calcium in endocrine cells (eg Ann N Y Acad Sci. 1995 Jul 12;763:272-82. Endocrine. 1998 Aug;9(1):71-7. J Immunol. 2006 Jun 15;176(12):7489-94.), so I would like to comment if I may.

Firstly, endocrine cells such as the GH3 ones used here are a bit of a challenge to measure intracellular calcium ([Ca2+]i) accurately, as they are excitable cells and produce spontaneous oscillations when activated. This necessarily means that the data from activated cells will be somewhat noisy. However, it can quite clearly be seen in the original traces that activation only occurs when drugs (either estrogen, bisphenol A, nonylphenol etc.) are added. Before drug addition, cells are quite stable (see traces in figure 1). Furthermore, when the drugs (including estrogen) are placed on membrane associated estrogen-receptor deficient cells, no activation is seen (figure 3). As the receptor deficient cells still respond to other activators, we can conclude that the effect is specific to membrane bound estrogen receptors. Furthermore, when calcium is omitted from the medium, or in the presence of a calcium channel blocker, the response goes away (eg see figure 6, while the response is not modified by the calcium store releaser thapsigargin). All these results strongly suggest that the effect of BPA (and nonylphenol and endosulfan) are, like estrogen, produced through the membrane associated estrogen receptor.

Part of your critique rests on the apparent size of the response. Firstly, you re-interpret the ratios as percentages. You can't do that as the response is strongly non-linear, a o.o4 increase in fluorescence ratio is not a 4% increase in [Ca2+]i. It has to be interpreted in relation to calibration stimuli such as the 20mM K+ stimuli and the thapsigargin stimulus. In resting GH3 cells, basal [Ca2+]i is roughly 80 nM, the thapsigargin data indicate that estrogen is producing around a 200 nM increase in [Ca2+]i, and a quick back of the envelope calculation for the 20mM K+ stimulus gives roughly the same value. This would mean that the increase produced by BPA is roughly 80-100 nM [Ca2+]i. This is a substantial and physiologically relevant increase.

Another part of the critique rests on the supposed "unphysiological" changes in the graph of BPA. However, biological data is noisy, and we almost never see ideal concentration-response curves in real experiments. The curve for BPA is perfectly compatible with standard biological and experimental variation (and what about nonylphenol, which has pretty much a standard concentration response curve). Also, on the curve, using log values is not "weaselling", it is standard and accepted practice for displaying concentration response curves (in part because of the equations governing receptor occupancy follow log distributions). Pick up any copy of the British Journal of Pharmacology and you will see almost every article using the same approach.

The time course experiments are perfectly ok as well. The smallest time point used was 1 minute (which was the fastest practical under the circumstances), but free diffusion and mixing of ligands with receptors happens on the order of seconds, and the response, especially for excitable cells like GH3 or PC-12 cells (the ones I have worked most with), and indeed be maximal or near maximal within 1 minute (even in slow poke tissues like ileal smooth muscle the response to muscarinic agonists is pretty well maximal by 1 minute)

In summary, the data displays exactly what we would expect if BPA and nonylphenol are acting via estrogen receptors. The increases in fluorescence ratio are consistent with physiological changes in [Ca2+]i, that the "wobblyness" of graphs is with experience of biological and measurement variation. Thus it can be concluded that BPA (and nonylphenol and the other xenoestrogens) act on GH3 cells at low (nanomolar) concentrations that are similar to those of estrogen itself, and act on the membrane bound estrogen alpha receptor via a calcium dependent mechanism.

Cheers! Ian