I was very happy with NEWSWEEK recently, specifically because of its lengthy expose of Oprah Winfrey and her promotion of pseudoscience, mysticism, and quackery on her talk show. However, I haven't always been that thrilled with NEWSWEEK's coverage of medicine and science. For example, NEWSWEEK's science columnist Sharon Begley has gotten on my nerves on more than one occasion, most recently when she castigated doctors for not enthusiastically embracing comparative effectiveness research, making the unjustified slur against physicians that they "hate science." Indeed, she even managed to irritate Steve Novella with her slur, and that's not nearly as easy a thing to do as it is to irritate me sufficiently to want to lay down a heapin' helpin' of not-so-Respectful Insolence or to irritate PZ enough to type up a slapdown.
Oops, she did it again.
Last week, Begley produced an article that, quite frankly, annoyed the crap out of me, called From Bench To Bedside: Academia slows the search for cures. It never ceases to amaze me how some pundits can take an enormously flawed idea as to why a problem exists and run right off the cliff with it.
Begley begins by pointing out that President Obama has not yet appointed a Director of the NIH. That's a fair enough criticism. Personally, I'm not happy that there's no permanent NIH Director. I'd like to think, as Begley hopes, that it's because Obama realizes how important this pick is and wants to get it right. But that's about all I agree with Begley on. After that introduction, she runs straight off the cliff:
NIH has its work cut out for it, for the forces within academic medicine that (inadvertently) conspire to impede research aimed at a clinical payoff show little sign of abating. One reason is the profit motive, which is supposed to induce pharma and biotech to invest in the decades-long process of discovering, developing and testing new compounds. It often does. But when a promising discovery has the profit potential of Pets.com, patients can lose out. A stark example is the work of Donald Stein, now at Emory University, who in the 1960s noticed that female rats recovered from head and brain injuries more quickly and completely than male rats. He hypothesized that the pregnancy hormone progesterone might be the reason. But progesterone is not easily patentable. Nature already owns the patent, as it were, so industry took a pass. "Pharma didn't see a profit potential, so our only hope was to get NIH to fund the large-scale clinical trials," says Stein. Unfortunately, he had little luck getting NIH support for his work (more on that later) until 2001, when he received $2.2 million for early human research, and in October a large trial testing progesterone on thousands of patients with brain injuries will be launched at 17 medical centers. For those of you keeping score at home, that would be 40 years after Stein made his serendipitous discovery.
Whenever I see a story like this, I always wonder exactly why it took so long to move an idea from concept to clinical trial to clinical use. A while back, I wrote about John Ioannidis' study that showed that it takes between 14 and 44 years for an idea to make it "from bench to bedside." In any case, when in doubt, do a PubMed search to see what the person describing his research has published. So I did just that for Dr. Stein. He has a healthy publication record (162 publications), as well as a number of publications from the late 1960s on brain injury in rodent models. Clearly, Dr. Stein has been a successful and well-funded rsearcher. However, when I searched his name and "progesterone," I didn't find a single publication until 2006. So I dug a little deeper, and the first paper I could find by him postulating a sex difference in healing after head injuries was published in 1987. In 1986, he coauthored a review in Nature on the pharmacological attenuation of brain injury after trauma, and didn't once mention progesterone. The point here is not to cast doubt on Dr. Stein's contention that he first noticed this finding in the 1960s, but rather to point out that it must not have been a high priority in his career, because he didn't publish on it for 20 years and didn't really start doing a lot of work on it until the last few years, with a flurry of publications since 2006.
The other point is, as I have said time and time again, that a scientist can't just go to human studies (unless, of course, one believes animal rights activists who deny that animal research contributes anything to medical advancements). There has to be solid preclinical evidence. In other words, there has to be a lot of cell culture, biochemical, and animal work that all support your hypothesis, and it can take a minimum of several years to develop that evidence. Medical ethics and the Helsinki Accord demand it. Moreover, the sort of preclinical work that would have been needed to lay the groundwork for clinical trials of progesterone as a neuroprotective agent in trauma is exactly the sort of research that the NIH has funded all these years. One wonders why Dr. Stein, who clearly has a well-funded lab, didn't divert a bit of that funding earlier to do some pilot experiments to use to pursue NIH funding. Maybe he didn't have enough extra funds lying around or couldn't find a way to relate the project to one of his existing projects sufficiently to justify doing so. In any case, at the risk of sounding too harsh, I will say that the whole big pharma thing struck me as very self-serving. Whatever the case was, I strongly suspect that the full story is far more complicated than the "big pharma won't fund it because it can't patent it" hyperbole that Begley is laying down (and that sounds very much like the same sorts of excuses purveyors of "natural" therapies use to justify why they don't do any research to show that their "cures" work).
But that's not what irritated me the most about Begley's article. This is:
The desire for academic advancement, perversely, can also impede bench-to-bedside research. "In order to get promoted, a scientist must publish in prestigious journals," notes Bruce Bloom, president of Partnership for Cures, a philanthropy that supports research. "The incentive is to publish and secure grants instead of to create better treatments and cures." And what do top journals want? "Fascinating new scientific knowledge, [not] mundane treatment discoveries," he says. Case in point: in research supported by Partnership for Cures, scientists led by David Teachey of Children's Hospital of Philadelphia discovered that rapamycin, an immune-suppressing drug, can vanquish the symptoms of a rare and sometimes fatal children's disease called ALPS, which causes the body to attack its own blood cells. When Teachey developed a mouse model to test the treatment, he published it in the top hematology journal, Bloodin 2006.
A brief aside: Wow. Surgeon that I am, I didn't know that Blood was such a top tier journal. The reason I'm amazed is that I published in Blood last year. If Blood will take one of my manuscripts, it can't be that awesome, can it? (Queue false modesty.) Now, back to Begley:
But the 2009 discovery that rapamycin can cure kids with ALPS? In the 13th-ranked journal. The hard-core science was already known, so top journals weren't interested in something as trivial as curing kids. "It would be nice if this sort of work were more valued in academia and top journals," Teachey says. Berish Rubin of Fordham University couldn't agree more. He discovered a treatment for a rare, often fatal genetic disease, familial dysautonomia. Given the choice of publishing in a top journal, which would have taken months, or in a lesser one immediately, he went with the latter. "Do I regret it?" Rubin asks. "Part of me does, because I'm used to publishing in more highly ranked journals, and it's hurt me in getting NIH grants. But we had to weigh that against getting the information out and saving children's lives."
My brain hurts from the concentrated ignorance on display here.
Let's boil down Begley's thesis here. The cool basic science stuff appeared in the top hematology journal, but the first report of the application of that basic science to treat patients appeared in only in the 13th-ranked journal. Obviously journals value basic science over clinical science! Those bastards! They don't care about curing children! To them curing kids is "trivial."
And Begley's full of crap.
Begley seems blissfully ignorant of two things: How journal rankings work and the fact that different scientific journals fill different niches. Ranking of scientific and medical journals are in general based on something called the "impact factor" (IF). The IF is often used as a proxy for the importance of a journal in its field, with the higher the IF number the better. Although the algorithm that determines the IF is proprietary, it is calculated based on a two-year period and is based on the average number of citations in a year given to papers in a journal published during the two preceding years. In general, higher IF journals are viewed as more desirable to publish in. Thus, what makes the IF a proxy for a journal's importance is the presumption that more citations of its articles equates to more interesting science and novel findings that more scientists cite. This may or may not be a valid assumption. Finally, one aspect of the IF is that journals designed for a more general readership tend to have higher IFs than subspecialty journals. In other words, Cell, Nature, and Science have high IFs. Within a field, Cancer Research or Clinical Cancer Research has a higher IF than Breast Cancer Treatment and Research (an example that actually is in line with using IFs, as CR and CCR are definitely better journals than BCTR).
Here's where niches come in. Different journals have different niches. For example, the example mentioned by Begley, Blood, is not primarily a clinical journal. True, it does publish some clinical trial results, but its main emphasis is clearly on basic and translational research. It's simply silly to get all worked up because Blood didn't publish a small pilot study with six patients and conclude that journals don't value clinical research. They do, just not journals that are primarily basic and translational science journals. Publishing clinical trials is not their raîson d'être. However, I think I know why Teachey's second study was not viewed as being interesting as his first study. A mouse model that provided proof of principle that rapamycin can treat a rare blood condition, complete with scientific mechanism is indeed interesting for a wide range of researchers, basic science, translational, and clinical. A small pilot study tends to be less so.
Let's look at Teachey's BJH article. It's a nice study, but clearly a very preliminary pilot study. Such pilot studies do not generally make it into the top tier journals, no matter how interesting the science is, because, well, they're so preliminary and small (and thus could be wrong). Begley seems to think that not considering such studies as being top tier is akin to considering curing children of deadly diseases to be "trivial." She also seems to think that not placing such a study in a top tier journal will fatally delay the application of such cures. However, no treatment is going to be approved on the basis of such a small pilot study; at a minimum, a larger phase II study would still have to be done, and that is the study that would be likely to show up in the higher tier journals, particularly if it was well-designed to include some cool correlative science studies that confirmed the mechanism in humans. In either case, Begley doesn't make a good case that Teachey's study's not being published in Blood has somehow delayed the fruits of his research from reaching sick children. Much work still needs to be done before Teachey's discovery becomes common practice.
Begley is closer to the mark (albeit still exaggerating) when she discusses how the importance of IFs can distort how and where scientists decide to publish. In brief, scientists tend to want to publish in the highest impact journals because articles in such journals are viewed as being more meaningful than in lesser journals. Where she goes off the mark is her assumption that it is those horrible basic scientists, with their insistence on knowing molecular mechanisms that keep clinical research in the ghetto of lower tier journals, are somehow keeping teh curez from teh sick babiez!!!! For instance, after lionizing Berish Rubin for having chosen to publish in the lesser journal rather than keep teh curez from teh babiez, she castigates an unnamed scientist:
Not all scientists put career second. One researcher recently discovered a genetic mutation common in European Jews. He has enough to publish in a lower-tier journal but is holding out for a top one, which means identifying the physiological pathway by which the mutation leads to disease. Result: at least two more years before genetic counselors know about the mutation and can test would-be parents and fetuses for it.
This is so vague as to be useless. "A genetic mutation common in European Jews"? What mutation? What is the significance of this mutation in carriers? To what disease or defect does it predispose? Begley doesn't say. I realize she's probably doing so in order not to give a huge clue as to who this evilly careerist scientist who doesn't care about patients may be, but without that information I have no idea whether this discovery is so potentially important to patients that delaying its publication until he figures out how this mutation does its dirty work. In any case, validating a new genetic mutation as a risk factor to the point where developing a screening test for it is an incredibly difficult task, requiring clinical trials and validation to carry out. The process of FDA approval for a new genetic test is not trivial. In any case, all we're left with is a bunch of self-serving anecdotes to support her dislike of basic science. (I'm half tempted to ask, with great satisfaction, why does Sharon Begley hate basic science?)
There's a deeper problem, though, with Begley's essay. Having both an MD and a PhD and doing translational research myself, I think I have some perspective on this. The problem is that Begley seems to buy into the Magic Bullet model of scientific progress, a.k.a. the "big breakthrough." While it's true that big breakthroughs so sometimes occur (think Gleevec, for instance), the vast majority of science and scientific medicine is incremental, each new advance being built upon prior advances. It's also very frequently full of false starts, dead ends, and research that looks promising at first and then peters out. If a big breakthrough could be conjured by willpower and risky research, we'd have the cure for cancer by now. These disease processes are incredibly complex, and sometimes the research to understand and treat them are even more complex.
But it's more than that. Begley may have a point when she mentions that clinical researchers are often stymied when their their grants are reviewed by basic scientists, but I can tell you that this goes both ways. If you're a basic scientist and want to get funded by the NIH, your project had better have a practical application to human disease. Just studying an interesting biochemical reaction or a fascinating gene because it is fascinating science is not enough. If you can't show how it will result in progress towards a treatment for a disease, it is incredibly unlikely that your grant will be funded by the NIH.
Discoveries can't be mandated or dictated, no matter how much Begley seems to think that just changing the emphasis of the NIH to more translational research or funding riskier projects would do it. Don't get me wrong; there's no doubt that the NIH has often been far too conservative in what grants it funds, and that risk averseness becomes worse the tighter its budget gets and the tighter the paylines it can fund. However, the NIH is also the steward of taxpayer money. Fund too many risky projects, and it is likely that nothing will come of the vast majority of them. As in everything, there needs to be balance. Ideally there should be a portfolio of research that is balanced between the solid, but not radical, science that is likely to reliably lead to incremental progress and riskier projects with a higher potential payoff but a much higher risk of producing nothing.
Finally, Begley doesn't appear to understand that, without basic science, there can be no translational science. Translational research depends upon a constant flow of new observations and new discoveries in basic science. Sometimes, it can't be predicted where those new discoveries will come from. Sometimes they come right out of left field. I know; a project I'm working on is just such a project. It resulted from a serendipitous discovery by my collaborator and has the potential to result in a great new treatment for not just breast cancer but melanoma as well. It was not the sort of discovery that could have been foretold, and it may never have been noticed if it hadn't been for a basic scientist following curiosity where it led. Although there's no doubt that the NIH can use some improvement, I hope that, whoever the next director of the NIH is, he or she does not succumb to the sort of temptation for quick fixes that Begley seems to think necessary to "fix" the NIH and medical academia.
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As someone who has worked and published (in reputable journals) in nutritional epidemiology for the past 25 years, NO ONE, not even one's own parents (!) pays any attention until it hits the press.
To this day, my dad will send me clippings from the newspaper with notes saying 'you told me this years ago'.
My parents are Mr and Mrs Joe Citizen. They will not listen to the voice of science: 'Me with a PhD from UC Berkeley', until it is on some radio talk show in Australia.
I became so frustrated, that I am now getting a law degree! Maybe I can legally force people to listen - LOL.
With the huge amount of data concerning NIH grants, one can be sure to find a number of instances where funding was initially declined or provided only stintingly for research on treatments that have turned out to be promising.
With the huge amount of data concerning the FDA and drug approvals, one can be sure to find a number of instances where approval was granted for treatments that have turned out to be less efficacious than expected, or whose deleterious effects were more significant than was realized at the time of approval.
So we get treatments from basic research stage to public availability both too slow and too fast. Gosh, what insightful conclusions these lines of reasoning lead to.
Orac
I've just read your blog of July 2008 RE: your precious Echo.
I have an 8 1/2 yo yellow lab named Brandon who is 3 weeks post splenectomy today. Dx: hemangiosarcoma.
I can identify because my husband is a cardiac surgeon and I a former surgical PA. Approx 6 - 7 months ago I noticed Brandon just wasn't himself. He had been "posturing" and his gait was sometimes off. I brought him to the vet who assured me it was arthritis. A CBC showed slightly low RBC's which I was told was nothing to worry about. During this time I took Brandon to 2 other vets who all gave the same opinion.
This is after my telling them that I believed it was something internal.
On May 22, 2009 Brandon got up at 4 am and drank his entire bowl of water which was out of character. He started "posturing" again. I brought him to my vet who took his temp which was below normal did one abdominal xray and told me that he had no idea what was going on and sent me on my way - without blood tests or an exam. Knowing that Brandon needed help stat, I drove across the county to another vet. She did complete bloods as well as many chest and abdominal x-rays. Platelets, RBCs etc... were low and Brandon was taken into surgery.
There was no gross evidence of mets to his heart, liver, omentum, intestines or lung.
I am feeling both anger and guilt. Angry at the vets who wouldn't listen to me as I know my precious little boy better than they - and guilty over the fact that even with my medical training I could do nothing to get this diagnosed sooner.
Brandon is now 3 weeks post-op. His bloods have returned to normal. His appetite is fine and he enjoys swimming in our pool. After speaking with biochemists, university researchers etc... we have decided to try some experimental treatments and can only hope for the best.
Brandon was never ill prior to this and we thought we'd have many more years with him.
Brandon is my best friend who has never left my side since he was 8 weeks old. It's as if we can read each others mind. My love for him is unconditional and I would do anything for him.
People scoff at assigning human qualities to a dog, but Brandon is a gentle creature with a kind heart and soul. I cherish each day with him.
I've always disliked Begley. I think she's a godbot as well (based on her past ridicule of all things rational).
Her articles need to be replaced by Natalie Jeremijenko.
I have been here many times having worked products from academia to market. With the notable exception of Berklky and UC, the issue is almost always red tape, interia and profiteering at the university licensing offices. Pharma and device companies want access to that material, and are generally willing to fund research, thus negating the need fro NIH money in many cases. But the IP barriers are huge at the universities and NIH is a last resort for some mot because big pharma wants to control it, but generally the universities do. Some are getting better, but I live in this world and it sucks.
When trying to get published in a journal with a higher IF, don't many of these studies get published in the annual abstract issue of a publication? There are plenty of studies I have seen that look interesting as abstracts, but are published only as abstracts. Then a few years later, a journal publishes the full study. I do not know if it is generally the same journal that published the abstract that ends up publishing the full study.
Journals with higher IFs sometimes publish abstracts of studies published in journals with lower IFs, in order to get information out to a broader audience.
What I find odd is that, if I had to pick a way that academic research slows down progress, publications wouldn't be it; after all, if you're in the field, you've already 'heard' the paper months before publication.
This is a classic example of the "hindsight is 20/20" fallacy. It is trivial to look backwards at scientific progress and identify infinity fucktillion examples of people either going in wrong directions or failing to go in correct directions, based on what we know now. None of this helps us assess contemporaneous decision-making processes.
Begley. . . Begley. . . where have I heard that name? Oh, yes, from Steve Novella:
Self-fulfilling prophecy or frank self-appraisal?
"A stark example is the work of Donald Stein, now at Emory University, who in the 1960s noticed that female rats recovered from head and brain injuries more quickly and completely than male rats. He hypothesized that the pregnancy hormone progesterone might be the reason."
The female rats recover more quickly from head injury because female is Yin and male is Yang. The stronger Yin of the female heals the head faster than the weaker Yin of the male.
I do not agree or disagree with the suggestion that progesterone is involved. It very well could be. What I am saying is that there is another way of describing why female rats recover from brain injury faster than male rats.
Why would a health worker resist that information? If the information could help a patient isn't it the job of the medical worker to investigate the information?
It is valid to describe what is going on in western science terms or in terms of Yin Yang Theory. The only difference is in the words and concepts that different people from different cultures developed to label the same physical phenomenon.
Progesterone and Yin Yang Theory in this situation would be like the human arm and atoms. You could describe the movement of every single atom in the arm to describe the overall movement of the arm. But why? It is easier to say "The arm moved here".
Instead of dealing with microscopic progesterone, why not work with Yin Yang Theory which employs words that encompass large scale phenomenon over large areas of the body?
You can still work with progesterone if you want, but since that is complex and Yin Yang Theory is easy, you can learn Yin Yang Theory and give your patients relief with Yin Yang Theory based treatment now, while you wait for the years or decades it will take to figure out the complex progesterone stuff.
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There are no coincidences. It is not a coincidence you are writing about Begley and his predicament while I and Happeh Theory are circulating around the blog. Begley's situation applies to me.
In 40 years someone will realize what I was trying to do and begin work on it. Why not take your outrage at the Begley situation and make up for what happened to Begley, by seeing if you are able to understand what I talk about? You can cut out 40 years of wasted time.
I promise you what is talked about by Happeh Theory will have an immeasurable impact on your type of medicine. I keep telling people they will be world famous and win prizes if they can figure out what I am talking about.
If you don't want fame and prizes, what if I told you that some of the material of Happeh Theory will tell you what it really means to be a human being? You would learn that this life is mostly a game to keep ignorant people occupied, like a video game keeps children occupied until they become adults.
Aren't you the least bit curious of why you are really here on the planet earth and what your adult form really is?
DNFTEC, everyone! Thank you.
Thanks Happeh. I just lost a little more hope for humanity.
Thank you. I read that article and was pretty sure it was off the mark, but didn't have enough background to know why.
Happeh the insane woo-addled conspiracy theorist:
Do you have the slightest speck of evidence to support this claim? Including a way to acutally define and measure "yin" and "yang" and an explanation of why they behave as you claim? Didn't think so.
Happeh the mad again:
Because there is not the slightest speck of evidence that "yin yang theory" is acutally accurate or useful.
Why not just describe everything in terms of Blurdiggeldyflorp? Because blurdiggeldyflorp is a made-up word that has no bearing on reality!
Happeh, reality denier:
Again, do you have the slightest speck of evidence to support this claim? No, of course not, the very idea of evidence is anathema to you, you've just declared all reality nothing more than a video game!
Congratulations, Happeh, you are so completely wrapped up in your delusions that no fact will ever penetrate as long as you live! You could set yourself on fire and burn to death, all while believing you were cold, you're that out of touch with reality.
I will instead speculate that 'the force' is stronger in women. Can you prove me wrong?
Got distracted by Happeh there.
Doesn't that sound like something waiting to be exploited somehow by Mark and David Geier?
Orac, you nailed it on that analysis. I can only add the view from a pharma company: If the effect is robust, even if the compound is not patentable, some pharma somewhere will develop it. The company gets 3 years "data exclusivity" which in some ways is more secure than a patent. Additionally you could put the progesterone in an extended-release pill and patent the release characteristic (then generics and other immediate release forms couldn't be substituted). Lots of ways for a pharma company to be successful by developing new indications for old drugs. The requirement is that the market has to be big enough to recoup development costs within a short time period. For some recent examples, look up fampridine or ampligen (first publications mid-80s), both under present development.
Because the absence of firebenders from daily life suggests that we are not, after all, living in the world of Avatar.
Taking a moment to extract my face from my palm over Happeh's Yin/Yang crap...
Anyway, sometime I should write up a Doggerel post that addresses the perception of research being like Sid Meier's Civilization: "You can find it! You just need to devote enough beaker icons towards it!"
Harsh truth: You can devote generations of study to a problem only to find out it's been for nothing.
Anyway, speaking of Doggerel, I was thinking of asking you, Orac, if you'd be interested in covering "Toxins" for me. I think it's a topic that needs a finer polish than I can give it.
@Bronze Dog: Heh, I like the Civilization analogy.
I've used a similar analogy to explain the progression of technology, and I think the same analogy works for science: A lot of people think of the pursuit of new technology like a person climbing a mountain. You see the peak you want to get to, and you walk towards it until you are there. But really, the progression of technology is more water flowing down a mountainside. It seems like it's going one way, but then there's a boulder that diverts its course, or some bumpy ground makes it break off into little rivulets, etc. You can kinda look down the mountain and maybe make some rough predictions about where the water is going to flow, but you're probably going to get it wrong.
Regarding Happeh, folks, the more he writes the more it reminds me of a guy I knew who had a couple of psychotic episodes, one of which culminated in him jumping from a second story window and shattering his ankles, and the other which ended with him getting dragged out of his apartment in his underwear by ten cops. Scary shit. We should not be ridiculing him; we should be trying to figure out how to get him help.
Oh damn, I forgot the most important part of the analogy: The terrain of the mountainside represents as-yet-undiscovered information about the nature of reality itself. It's not just that the development of technology is random and unpredictable, because it's actually not random at all (though it is unpredictable). It is determined by what is actually possible, by what turns out to be easy, by what turns out to be hard.
We just can't actually know any of that with any certainty in advance.
Okay, then, how do you apply Yin Yang Theory in order to enhance recovery from head injuries? What exactly do you do to a patient's body in order to enhance their Yin?
@Happeh:
Is the treatment you claim can enhance a person's Yin a part of Traditional Chinese Medicine (TCM), or is it an improvement of TCM which you came up with yourself? Or is it not a part of TCM at all?
Happeh,
A Great Sage, Equal of Heaven, a renowned martial artist who was born from a stone egg on a mountaintop once declaimed:
"In the worlds before Monkey, primal chaos reigned. Heaven sought order. But the phoenix can fly only when its feathers are grown. The four worlds formed again and yet again, as endless aeons wheeled and passed. Time and the pure essences of Heaven, the moisture of the Earth, the powers of the Sun and the Moon all worked upon a certain rock, old as creation. And it became magically fertile. That first egg was named "Thought". Tathagata Buddha, the Father Buddha, said, "With our thoughts, we make the World". Elemental forces caused the egg to hatch. From it then came a stone monkey. The nature of Monkey was irrepressible!"
This is proof indeed that the Apollo moon landings were not indeed on the moon but on the satellite of a planet in another galaxy.
Oh baby, somebody spiked my drink with woo again. . .
But progesterone is not easily patentable. Nature already owns the patent, as it were, so industry took a pass. "Pharma didn't see a profit potential, so our only hope was to get NIH to fund the large-scale clinical trials," says Stein.
Does Dr. Stein realize that birth control pills are still highly profitable even decades after generics became available? Wyeth, Schering-Plough, Barr, J&J all sell hormones that were once patented formulations and, although currently off-patent, still make big $$$.
The formulation would likely be different for stroke patients anyway (birth control pills require more of a steady release, while in a stroke you'd want it to hit the bloodstream right away), and formulations for particular indications are definitely highly patentable.
"...those horrible basic scientists, with their insistence on knowing molecular mechanisms that keep clinical research in the ghetto of lower tier journals, are somehow keeping teh curez from teh sick babiez!!!!"
As a basic scientist, I apologize to all the sick babiez out there. Damn me. (And damn me even more because I wish one of my studies was clogging up the works in Science, Nature or Cell!). ;o)
Matthew Cline - "Okay, then, how do you apply Yin Yang Theory in order to enhance recovery from head injuries? What exactly do you do to a patient's body in order to enhance their Yin?"
Any therapy which strengthens the Yin of the body. Physical therapies, herbal or chemical therapies, or energy therapies.
The therapies are not limited to Asian developed therapies because Yin Yang Theory was developed in Asia. Other human cultures developed therapies that operate on the same principles and have the same effect.
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Because people are so resistant to the words Yin and Yang, maybe if I present a different approach to the ideas it will help.
What if I told you that the Yin of the body was like a balloon that completely enclosed the body when it was fully inflated? Sickness would be a loss of pressure in the balloon that left part of the body with less pressure than it should have, or no pressure at all.
Everyone knows how pressure behaves from inflating car tires or balloons or other objects holding pressure, so that analogy should be familiar.
The head injury problem would be described as a loss of Yin pressure which made the Yin balloon collapse so it no longer covered the head. The answer to Matthew Cline's question of "what therapies would be used to fix the Yin?" is easy if you use the pressure analogy.
If something has lower pressure than it should, you do whatever it takes to make the pressure go back up.
Any therapy which increased the pressure of the Yin of the body would cause the Yin balloon to reinflate until it was big enough to properly cover the head again. The reason the body of the female is better at recovery from a head injury in this study is that their Yin pressure is stronger, or using the air pump analogy, their air pump is operating at a higher pressure.
The stronger Yin of the female can fill the Yin balloon that surrounds the human body back up so it covers the head faster, just like a high pressure air hose fills a tire up faster than a low pressure air hose.
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The pressure analogy is a very good one to talk about the health of a human being. We all know that an object with high pressure bulges, and an object with low pressure looks crumpled up and collapsed.
Doesn't a healthy human being look like they are bulging or expanding or filled up with pressure? Like a filled up balloon?
Doesn't a sick human being look like they are crumpled up or collapsed from a lack of pressure? Like a flat tire?
Interesting fantasy work on how big pharma works, Orac. However, here is the reality from a Bloomberg article this week (BELOW). This deals with Zyprexa and the shady dealings of Eli Lilly.
(By the way, I'm not going to take the giant leap that all research and articles on drugs and vaccines are shady like this one, but if you are wondering why people don't believe medical research, big pharma, doctors, the CDC, the stuff on your blog, this article kinda shows why. Safe to say big pharma may have some credibility problems going forward. Enjoy!)
From Bloomberg:
"Eli Lilly & Co. officials wrote medical journal studies about the antipsychotic Zyprexa and then asked doctors to put their names on the articles, a practice called ''ghostwriting,'' according to unsealed company files.
Lilly employees also compiled a guide to hiring scientists to write favorable articles, complained to journal editors when publication was delayed and submitted rejected articles to other outlets, according to documents filed in drug-overpricing suits against the Indianapolis-based company, the largest manufacturer of psychiatric medicines.
Drugmakers' use of ghostwriters has created ''a huge body of medical literature that society can't trust,'' said Carl Elliott, a University of Minnesota bioethicist who has written about the practice.
Lilly sought to make Zyprexa ''the number one selling psychotropic in history,'' according to a 2000 plan distributed to its product team. The memo was among more than 10,000 pages of internal documents unsealed last month in lawsuits by insurers and pension funds seeking to recoup money spent on the drug. They allege Lilly exaggerated Zyprexa's effectiveness."
"If something has lower pressure than it should, you do whatever it takes to make the pressure go back up."
So in order to make someone healthy again, we should do things that make them healthier.
Wow, why didn't I think of that.
"Doesn't a healthy human being look like they are bulging or expanding or filled up with pressure? Like a filled up balloon?"
No.
"Doesn't a sick human being look like they are crumpled up or collapsed from a lack of pressure? Like a flat tire?"
No.
Happeh, as one of the least educated people here, I HOPE that perhaps my words can reach you, because they won't discuss science, per se, or research, but, rather, plain, old rational thinking.
The reason your yin and yang contribution is so useless is because you are applying it backwards. Science noticed the same thing that your yin and yang proponents did - that women recovered more quickly and better from head trauma than men did. Rather than describing it with mystical, invisible forces, Science asked, "Why?"
In Science asking why and investigating, they found a way to address it and make it possible for both genders to recover, rather than ascribing it to "decreased yin in the male."
You taking your mystical observations and applying them AFTER THE FACT to medical research makes them no more applicable than they were before. Science has no problem with observation. It is, however, in everyone's best interest if the observations are explained and quantified so everyone may benefit. Mythical observation improves no one's life.
Oh, and on the "flat tire" thing - I have an "invisible" chronic pain condition that affects every part of my life. Like most pain patients, one of the biggest frustrations are the well-meaning people who tell me I "don't look sick."
Illness does not always "deflate" its patients.
You probably have inflamed Yang or something.
Of course, if one takes the 'inflated' claim literally, then one must assume people with any form of oedema or swelling must logically be well.
If one takes it as a metaphor, that is, 'ill' people look less active and full of life than 'non-ill' people, then the statement that is effectively being made "Ill people look ill" is totally true, but utterly irrelevant unless you're proposing that we can diagnose the illness from the presentation.
Lisa - "Rather than describing it with mystical, invisible forces, Science asked, "Why?"
I truly do not understand how people claiming to be scientists can talk like this. The words Yin and Yang are terms developed by the people of a foreign culture to describe certain physical phenomenon.
Where does your idea that they are mystical forces come from? Maybe you need to educate yourself about Yin and Yang more? Yin is commonly defined as soft and Yang is commonly defined as hard.
Are you saying that the english words "hard" and "soft" are mystical words? Could you point out that definition to me? I have never heard that before.
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Lisa - "Illness does not always "deflate" its patients."
Are you certain? You should let someone with skill determine that. Your comments indicate you have no skill. Post a picture of yourself and I will tell you what I see. I bet you 10 american dollars I can point out where your health problem has deflated your body, and offer some insight into your health situation you have never thought of before.
If you are so confident that I am wrong that you would publicly denounce me and what I say, then you must also be confident enough to take up my challenge. It will be your chance to show everyone I don't know what I am talking about and shut me up.
Don't be chicken. Put your reputation on the line and let's do battle.
Let me offer something to the thinking people.
I say that women have more of what could be called Yin pressure. This Yin pressure would cure a head injury faster because the higher pressure of the woman's Yin would push the Yin up into the head faster, than the lower pressure Yin of the man would push his Yin back up into his head to repair his head.
What do women do that men cannot do? Woman can have babies. How does a woman have a baby? The woman puts pressure on her lower body to force the baby out of the vagina.
It is plain common sense that women have more pressure than men. The biggest thing a man might have to push out of his body is a large fece. A woman is pushing an 8 inch diameter by a foot long maybe 8 pound solid mass of baby out of her lower body.
How can any of you scientists deny that woman have higher pressure than men?
Happeh,
Save your ten dollars to hire some better comedy writers.
Wee, something I'm competent to comment on! Huzzah!
This is pretty much exactly right, which makes me go "holy crap" because way too many publishers/editors, even of high-end journals, don't. The IF is actually calculated like this: a journal's 2008 IF is equal to the number of citations made in 2008 to items published by the journal in 2006/2007, divided by the number of items published in 2006 and 2007.
One common flawed assumption is that items which appear in high-impact journals are better than items in low-impact journals. This is wrong, because IF says nothing about any individual item, only about how much a journal influence the scientific conversation. And, as you said, comparing the IF of a journal in the general science category to one of a journal in, say, neuroscience, is not valid and shows nothing of value. Even in-category comparisons can be misleading for a variety of reasons.
Uh, all views expressed do not represent ThomsonReuters etc etc, whatever. I'm just an intern for them, but still, might as well cover my bases.
[NOTE: reposted minus Wikipedia links in order to escape the spam trap; Orac, please just delete the previous version of this comment from the moderation queue]
@Happeh:
So then, Yin (the force/energy/whatever, not the particular parts of the body which are Yin) is something that is pulled down by gravity, and thus has to be pushed up against gravity in order to reach the head? Would you recommend that people with a head injury spend as much time laying down as possible so that the Yin doesn't have to work against gravity in order to reach the head? Maybe elevate their legs as well, so the force of the gravity pulling down on the Yin in the legs will push more Yin into the head?
Also, I recall you saying that Yin is just a shorthand for complex biochemical mechanisms. But a woman having higher concentrations of progesterone in her blood isn't going to generate a pressure which pushes progesterone upwards against the force of gravity (that's not how concentration gradients work); it's the blood that carries the progesterone, and the heart which pushes the blood up against gravity into the head. So would that mean that either progesterone isn't a part of Yin, or that it's a part of Yin, but not the part of Yin which is responsible for accelerating the healing of head injuries? Or maybe higher Yin makes the heart better able to pump blood against the force of gravity?
That pressure is generated by the contraction of muscles. The immediate energy source for the contractions is ATP (adenosine triphosphate). ATP is generated via the citric acid cycle (a.k.a. the Krebs cycle) within the mitochondria. The mitochondria oxidate pyruvate (pyruvic acid), producing carbon dioxide and water as a byproduct. Pyruvate is the breakdown product of glucose (blood sugar).
To the extent that the pressure exists within a woman's body before being converted into uterine muscle contractions, it exists as potential energy within the ATP and glucose in the woman's body (and the other molecules within her body which can be converted into glucose). You might hypothesize that Yin facilitates the above mentioned biochemical pathways (facilitate the delivery of oxygen and glucose to the cells of the uterine muscles, facilitate the removal of carbon dioxide, etc), but it's not at all obvious that Yin facilitates such things in the uterine muscles more than in other muscles in the body; indeed, it's not obvious that Yin facilitates such things at all.
And as an aside, I'd like to note that it seems that you've done no research into the things I mentioned above before you talked about the pressure needed to give birth. However, when I (supposedly) did no research into asthma before speaking about it, you castigated me for it. Why is okay for you to speak on things without first researching them, but not okay for me to do the same?
Matthew Cline - "So then, Yin (the force/energy/whatever, not the particular parts of the body which are Yin) is something that is pulled down by gravity, and thus has to be pushed up against gravity in order to reach the head?"
I really can't figure out where you are going with this. I want to say no to what you have written. But then I think that everything on the planet is subject to gravity, so maybe I should say yes?
Matthew Cline - "Also, I recall you saying that Yin is just a shorthand for complex biochemical mechanisms."
I want to disagree with this. There must be biochemical reactions that take place when the Yin part of the body does it's thing, but I would not say "Yin = biochemical reactions".
Matthew Cline - "So would that mean that either progesterone isn't a part of Yin, or that it's a part of Yin, but not the part of Yin which is responsible for accelerating the healing of head injuries?"
Individual chemicals have nothing to do with the word Yin as I am using it in this situation.
Matthew Cline - "Or maybe higher Yin makes the heart better able to pump blood against the force of gravity?"
I think you are trying to fixate on combining the two ideas. Yin and progesterone I guess both help the injury. I do not want to talk about progesterone at all. It is my position that while progesterone may have an influence, it would be relatively minor in comparison to the very large influence that the Yin part of the body would have on the head injury.
Matthew Cline - "Why is okay for you to speak on things without first researching them, but not okay for me to do the same?"
Because all of those things you came up with have no bearing on the issue. Knowing about the Yin part of the body, diagnosing it, or treating it, have nothing to do with any of those chemical reactions you have listed.
Regarding the muscle contraction comments, I would not want to discuss individual muscle contractions with you. For this discussion, I would want to treat the Yin part of the body as a big blob like a piece of bubble gum. That blob of bubble gum that is the Yin part of the body can deform in any way like a blob of bubble gum can. That blob is what is pushing the baby out of the woman.
I agree there would be muscle contractions, the ATP chemical reactions, etc that you describe when the baby was pushed out, but those things can be disregarded when talking about the Yin part of the body.
@Happeh:
Previously you wrote:
Why exactly does the Yin need to be pushed? Is it pushed outwards from the center of the body to all extremities? Is the Yin you're talking about some sort of energy or force? The energy I'm familiar with from physics doesn't need to be pushed to get from one place to another (unless it's energy which is being carried by matter and the matter is being pushed), and fields of force (like electromagnetic fields) don't need to be pushed either. If Yin is an energy/force that's pushed from one part of the body to another, then it's very, very different than any energy/force modern physics has ever encountered.
Do you mean that biochemical reactions and Yin are two different ways of looking at the same thing? Two different models for the same thing? Or do you mean that biochemical reactions and Yin are two different things going on simultaneously at the same place, that the biochemical model and the Yin model are each incomplete on their own, and that a full model of what was going on would consider both of them at once?
Why is regarding the Yin part of the body as a blob a better way at looking at the mechanism of a baby being pushed out of the uterus than looking at it as the uterine muscles contracting, with those contractions being what generates the pressure which pushes the baby out? I am currently not convinced of the existence of Yin energy (or Yin force). Does the "baby is pushed out of a uterus via the contraction of muscles" model have some hole in it that necessitates bringing in the idea of Yin? If that model has no hole in it, and on its own adequately explains the process of birth, then how is it "common sense" that women have a higher internal pressure than men?
On the other hand, if neither the Yin model nor the muscular contraction model is better than the other, and the Yin model requires a great pressure within women, yet the muscle model doesn't, then how does one decide if women have this great pressure?
When reading about the genetic research in European Jews, who else thought that showing the mechanism that the mutation works through was a good idea?
I was thinking "well done!" when I read that, but according to the journalist it was a bad thing to do. The quote even implies that it is unethical!
Obviously she has not heard about the number of non-replicated genetic association studies that are published!
Matthew Cline - "Why exactly does the Yin need to be pushed? Is it pushed outwards from the center of the body to all extremities?"
FINALLY! Now you are being a scientist. Whew. I thought it would never happen.
Yes the Yin is pushed outwards from the center of the body to the rest of the body.
Matthew Cline - "Is the Yin you're talking about some sort of energy or force? "
Yes.
Matthew Cline - "The energy I'm familiar with from physics doesn't need to be pushed to get from one place to another (unless it's energy which is being carried by matter and the matter is being pushed),"
I want to spell out what I am thinking. I want to use a garden hose as an analogy. A garden hose is like a hose of force. If you direct the hose onto something, the force of the water has an effect. The force flows from the garden hose to whatever object it is directed at.
The force is carried by the water or matter in the way you describe. Why talk about the water though? The water is there and we can see it's effect, but in science terms, if we were in physics class, we can say that a garden hose is a force projector or force transferrer. We can ignore the water. In Yin Yang and the human body, you can talk about Yin and ignore what is happening with the muscles etc.
Matthew Cline - "Do you mean that biochemical reactions and Yin are two different ways of looking at the same thing?"
Yes. Yin could be a large grouping word that could cover many different muscle actions or chemical actions or hormones or enzymes or whatever.
Matthew Cline - "Or do you mean that biochemical reactions and Yin are two different things going on simultaneously at the same place,"
Yes.
Matthew Cline - "that the biochemical model and the Yin model are each incomplete on their own, and that a full model of what was going on would consider both of them at once?"
The biochemical model is incomplete in my opinion because no one has a complete biochemical model of the entire human body. They are still working on it. The Yin model is complete because it only deals with large scale things that are easily described and well known.
I would agree that a complete model of the health of a human body would contain both Yin Yang Theory and conventional science knowledge for the conventional scientists. For the Yin Yang practitioner, there is no reason to learn the conventional view of medicine. Knowing about microscopic chemical reactions will not help a Yin Yang practitioner with their work.
Matthew Cline - "Why is regarding the Yin part of the body as a blob a better way at looking at the mechanism of a baby being pushed out of the uterus than looking at it as the uterine muscles contracting, with those contractions being what generates the pressure which pushes the baby out?"
Because it is a large scale concept that includes uterine contractions and anything else you can think of. Because thinking of the Yin as a blob means that anyone, not just people fortunate to have higher education, will be able to understand what is being said. People with no education have no idea what you mean when you start talking about muscle contractions and chemical reactions.
Matthew Cline - "Does the "baby is pushed out of a uterus via the contraction of muscles" model have some hole in it that necessitates bringing in the idea of Yin?"
Yes. You are only describing one small part of what is going on with the birth of a baby. Do you honestly believe that only the uterine muscles push a baby out of the woman's body?
That is silly.
The woman's entire body pushes the baby out. The woman clenches her entire body, not just the uterine muscles. Talking about the Yin part of the body includes all of those other muscles that help the uterine muscles push the baby out.
Matthew Cline - "On the other hand, if neither the Yin model nor the muscular contraction model is better than the other, and the Yin model requires a great pressure within women, yet the muscle model doesn't, then how does one decide if women have this great pressure?"
By looking for corroborating evidence. Aren't women usually soft and blubbery and expanding looking, while men are hard, leathery, and contracting looking?
High pressure expands. The female human being looks expanding compared to the male human being. Low pressure contracts. The male human being looks contracted compared to the female human being.
@Happeh:
Then does it make a round trip, like the blood which is pushed out of the heart does? Or is it pushed out to the rest of the body and stay there? If the latter, in the physical systems I'm familiar with, with the body acting as a container for the Yin, the pressure will quickly reach an equilibrium over all parts of the body, and the extremities no longer having less pressure than the center of the body, so unless there's holes at the extremities out of which the Yin is pushed into the outside world no movement of Yin will take place.
Also, is the Yin and Yang generated by a particular organ in the torso? If it's not a particular organ, and just the torso in general, then why isn't it generated all around the body?
That's not how it works, unless you're using the word "force" as a synonym for energy. The water carries kinetic energy and momentum. Assuming the hose is spraying water at a constant rate and velocity, once the water is out of the hose and still in the air the water is in free fall, and the only forces acting on it are the friction of the air and the pull of gravity (with the water exerting an equal-and-opposite friction on the air, and an equal-and-opposite gravitational force on the Earth). While in the air, any particular piece of water isn't pushing on the water in front of it or being pushed by the water behind it (though the hydrogen bonds between the water molecules keeps the water together in a cohesive whole). When the water hits a solid object force transfers kinetic energy and momentum from the water to the solid object.
They wouldn't have any idea about chemical reactions, but no idea about muscular contractions? Anyone who has lifted and carried something heavy has felt their arm muscles contract. If you give someone with no education a squishy ball and have them squeeze, then tell them "you're squeezing it by contracting the muscles in your hand", they'll understand. It doesn't need to be simplified to "the Yin/Yang pressure in your body is squeezing the ball".
Okay, every muscles in her body clenches, and that squeezes the baby out of the uterus. That fully explains the mechanism of the baby being pushed out of the uterus without having to invoke the concept of Yin.
First, hard vs soft and soft vs leathery don't have anything to do with pressure. Second, I don't perceive women as being expansive and men as being contractile, unless you mean personality (bubbly vs taciturn), and even then that's only how I perceive men and women in fiction, not in real life. Third, pressure is something that I associate with hardness, not softness.
Matthew Cline - "Also, is the Yin and Yang generated by a particular organ in the torso?"
That sounds like a common sense belief.
Everything else is you proving you know facts or being argumentative. Let me demonstrate you being argumentative.
Matthew Cline - "Okay, every muscles in her body clenches, and that squeezes the baby out of the uterus. That fully explains the mechanism of the baby being pushed out of the uterus without having to invoke the concept of Yin."
I agree with what you say mostly. But if I want to use the word "Yin" to replace the phrase "every muscle in a woman's body pushes the baby out", why would you argue with me? You know I am using the word "Yin" as a shortcut. You know that science uses shortcut words all of the time. "Circulatory system" for "All of the arteries, veins, and capillaries within the human body".
Why do you want to argue over the use of the shortcut word "Yin"?
The question that nobody has asked here is why bother to calculate an IF? It conveys no scientific information whatsoever. It contributes nothing - zero - zip - nada to science. So what purpose does it serve? Only to create a pecking order. Capable researchers don't need it - they can tell which articles are important on their own. But bean counters must love IF's as justification for denying tenure, promotion, or funding.