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The “interstitium”: Interesting science versus PR spin and pseudoscience

Last week, the media were awash with reports of the “interstitium,” which was dramatically described as a hitherto undiscovered “organ,” a narrative that was definitely a triumph of PR over science that went beyond what even the investigators claimed in their paper. Worse, the investigators themselves even speculated that their discovery could “explain” acupuncture and other kinds of alternative medicine, thus providing an opening for quacks to run wild with their discovery, something I expect to see very soon.

If there’s one thing I’ve learned over the years, it’s that quacks are adept at co-opting pretty much any scientific finding in medicine and using it to justify whatever pseudoscientific treatment that they’re offering. Antivaxers are particularly adept at this, having tried to use science such as MTHFR mutations, mitochondrial disorders, and just about every discovery about autism other than genetic links to it to bolster their fixed belief that vaccines cause autism. They are, however, not alone. Quacks of all varieties love to invoke quantum theory, new findings in cancer research (such as the rediscovery of the importance of the Warburg effect), and a variety of new scientific discoveries as “mechanisms” for their woo.

This brings me to a new scientific finding that’s been discussed a lot in the press. Somehow, I didn’t get around to discussing it, even though the study reporting the finding provides several issues, including how eagerly a questionable narrative about the study was accepted by the science press as valid, as grist for Oracian Insolence. Fortunately (or unfortunately), I’ve been informed by readers about a recent episode of Science Friday that is likely to lead to quacks invoking these new scientific findings as a basis for the mechanism of their quackery even faster than I would have predicted. Even worse, the investigators themselves were the first to make the link.

I’m referring to the interstitium, which numerous news reports were portraying as a newly discovered “organ.” There were a number of headlines that made me grit my teeth, like this:

That last one, by the way, is last week’s Science Friday, which featured an interview with Neil Theise, a professor of Pathology at the NYU School of Medicine, and Rebecca Wells, a professor of Medicine and Bioengineering in the Faculty of the Center for Engineering Mechanobiology at UPenn, two of the authors of the study above. In the interview, they imply that the interstitium could explain how acupuncture works, but more on that later. First, let’s look at the study.

I note that study itself was published in Scientific Reports (which is not, as it is sometimes misrepresented, Nature, but rather an open access journal published by Nature Publishing Group). The reason I bring this up is that this is not the first study published in Scientific Reports that I’ve discussed. In fact, a mere two weeks ago, I discussed a particularly dodgy study published in Scientific Reports that claimed to have found that human heart rate variation (HRV) measured by EKG, responds to changes in geomagnetic and solar activity, indicating that the earth’s electromagnetic field controls our autonomic nervous system. Before that, I discussed a study published in Scientific Reports in which mice were tortured in the name of antivaccine pseudoscience. When I last mentioned a Scientific Reports study, the study’s defects led me to make an analogy that was most definitely not flattering to Scientific Reports. Basically, I said that Scientific Reports was Nature’s answer to PLoS but in reality was increasingly striking me as Nature’s answer to Medical Hypotheses, the journal long famous for publishing “speculative” papers on how vaccines cause autism and a number of other scientifically dubious topics.

In fairness, I am not saying that this study on the interstitium is anywhere near that level. Quite the contrary. I find it intriguing, even if the way its findings were communicated to the press were a masterpiece of PR, with the promotion of the narrative that a “new organ” had been found when in fact the study didn’t really show that. I’ll tell you what I mean, and then I’ll discuss the claim that somehow this “new organ” can provide a mechanism by which acupuncture “works.” I also can’t help but wonder why this study was published in Scientific Reports, instead of a pathology, anatomy, or surgery journal, if the discovery is indeed as novel and potentially transformative as the schools’ PR blitz claims. I also note that it appears not to have been the authors who originated the “new organ” narrative.

Based on an observation while investigating a patient’s bile duct for signs of cancer in which Mount Sinai Beth Israel Medical Center medics Dr David Carr-Locke and Dr Petros Benias noted cavities that did not appear to match any previously known human anatomy. They therefore approached New York University pathologist Dr Neil Theise to ask for his expertise. Together they used a technique known as confocal laser endomicroscopy (pCLE) to examine extrahepatic (outside the liver) bile ducts. This technique can provide real-time histologic imaging of human tissues at a depth of 60–70 μm during endoscopy. using this technique, the investigators examined extrahepatic bile duct tissue taken at endoscopic biopsies looking for pancreatic or bile duct cancer after injection of fluorescein, a fluorescent dye commonly used in medicine. They noted a reticular pattern within fluid-filled sinuses that, according to them, had no anatomic correlate. Freezing the biopsy tissue before fixation preserved this structure, demonstrating that it was part of the submucosa. (The submucosa is a thin layer of tissue in various organs of the gastrointestinal, respiratory, and urinary tract underlying the mucosa, the layer containing the epithelial cells and the membrane upon which they sit, to the smooth muscle surrounding the tubular structures of the organ). In addition, specimens were obtained from twelve pancreatico-biliary surgeries, with the patient being injected with fluorescein a few minutes before the blood vessels to the organ were tied off and divided to resect the organ, and the tissue subjected to various immunohistochemical studies.

The discovery process is illustrated in Figure 1 of the paper:

How the “interstitium” was discovered

The authors started recognizing this structure in other organs as well:

The characteristic histological features of this bile duct submucosa structure (spaces filled with fluid and with collagen bundles lined asymmetrically by flat cells) are readily visualized in other tissues. The structure was recognized consistently in the dermis in clinical resection specimens of skin (Fig. 3A), and pCLE applied to thin regions of skin in vivo after fluorescein injection showed the same reticular pattern in the dermis as in the bile duct. Fluid-filled spaces and collagen bundles lined by cells staining for CD34 are seen on histology in multiple organs and tissues, including in the submucosa of the entire digestive tract, the urinary bladder, peribronchial tissue, fascia, and stroma of arteries and veins of all sizes (Fig. 3B and Supplemental Fig. 1).

The existence and nature of these spaces have implications for medicine, as they could potentially better explain the phenomenon of “third spacing,” in which fluid moves from the vascular space to the interstitial “third space,” resulting in edema, too little intravascular fluid, and decreased cardiac output. It might also explain why gastrointestinal tumors are much more likely to metastasize to regional lymph nodes once they reach the submucosa, particularly given that the interstitium appears to be connected to the lymphatic system.

Now here’s the interesting thing. Nowhere in the paper do the authors propose that this new network of spaces is actually a new organ. For instance, here is the conclusion:

In sum, while typical descriptions of the interstitium suggest spaces between cells, we describe macroscopically visible spaces within tissues – dynamically compressible and distensible sinuses through which interstitial fluid flows around the body. Our findings necessitate reconsideration of many of the normal functional activities of different organs and of disordered fluid dynamics in the setting of disease, including fibrosis and metastasis. A submucosa subjected to directional, peristaltic flow is not the previously envisaged wall of dense connective tissue, but a potential conduit for movement of injurious agents, pro-fibrogenic signaling molecules, and tumor cells. This raises the possibility that direct sampling of the interstitial fluid could be a diagnostic tool. Finally, our study demonstrates the power of in vivo microscopy to generate fresh insights into the anatomy and physiology of normal and diseased tissues.

That is basically a fairly conservative view of the finding. It’s interesting. It suggests further areas for research. It validates the usefulness of their technique. It contributes to our knowledge. But identify a new organ? I’m with Anirban Maitra, a pathologist at the University of Texas MD Anderson Cancer Center, who observed:

News reports have suggested that this interstitium could represent a widespread organ in the body, whose connections with the lymphatic system might be involved in cancer metastasis. While researchers not involved in the study agree that the interstitium likely plays diverse roles in the human body, they are reticent to call it a new organ.

“It is fair to say that histologists [and] pathologists have long known that there is an interstitial space and that it contains fluid,” Anirban Maitra, a pathologist at the University of Texas MD Anderson Cancer Center who did not participate in the work, writes in an email to The Scientist. “The claim that it is a hitherto undiscovered organ, and the largest one ever at that, seems a stretch,” he cautions.

“Most biologists would be reticent to put the moniker of an ‘organ’ on microscopic uneven spaces between tissues that contain fluid. By this definition, the abdominal cavity and pleural spaces should be discrete organs” too, says Maitra.

Quite right. What appears to have happened is that the NYU Langone medical center press release described the finding as a “new organ,” and that characterization stuck in every news report I’ve seen about this finding. The authors are not blameless, though. The press release states that the “current study is the first to define the interstitium as an organ in its own right, and as one of the largest of the body, say the authors.” Whether they said that or not to the university PR person who composed the press release, I don’t know, but I do know that they’re cited as having said this.

The authors are also far from blameless when it comes to their Science Friday appearance. In it, they didn’t really push back against Ira Flatow’s use of the narrative that the interstitium is a new “organ,” although I must admit that most of the conversation about the finding (at least the first half) was pretty interesting, including the unanswered questions about this space.

As is often the case in live radio, things started to go south when Flatow started taking phone calls. The first call was from an osteopath, who started pontificating about how, for over a hundred years, osteopaths have had literature about the importance of the lymphatics and fascia in health and disease and how osteopathic manipulation can impact both. Dr. Theise, unfortunately, fed into this narrative by saying that the fascia really is this space (something that I as a surgeon, having actually seen these dense bands of fascian in vivo during operations, have a hard time believing) and basically buttered up the osteopath regarding how he had hoped that the osteopathic community would look at his study and go, “Aha!”

Then, near the end of the interview, Flatow asked whether this discovery lends any sort of explanation for how acupuncture or acupressure works. I groaned. I groaned even more as Rebecca Wells went off the rails by agreeing that, yes, she thought that it could explain acupuncture. She asserted that acupuncture definitely does work. (No, it does not. It is a theatrical placebo.) Theise then joined in, citing work that claims that, when you stick a needle into the skin, sound waves go 1 cm in all directions detectable on ultrasound but that if you put it in an acupuncture point it travels all the way up the meridian. Yes, he went there. He speculated that these interstitial fluid channels could be explain acupuncture meridians and provide a way for messages to travel along them. Wells then speculated about the electrical properties of collagen and how their discovery could suggest ways for signals to be transmitted. I dearly wanted to find the specific study to which Theise referred, but there wasn’t enough information for me to do so, other than that it’s probably at least ten to fifteen years old and one of its coauthors is named Yang. Given that there is such a thing called Yang acupuncture points, trying to narrow down the many hits on searches was taking way more time than I was willing to devote to the task.

Elsewhere, in another interview published in The Science of Us:

“Acupuncture has no anatomical correlate,” says Theise. “There’s no vein; there’s no artery; there’s no nerve corresponding to the meridian [the map of acupuncture points on the body].” Without any anatomical correlate, it’s been difficult for researchers to explain why a localized therapy like acupuncture could have such far-reaching effects. Knowing that the interstitium is filled with fluid could change that. “This is the layer of skin the acupuncture needle goes into,” says Theise. “There’s fluid in there. When you put the needle [into an accu-point], maybe the collagen bundles are arranged into a channel through which fluid can flow.” Studies show that “sham” acupuncture, or acupuncture in which needles are placed a centimeter off the meridian, doesn’t provide the same kind of pain relief that true acupuncture does: Sham accu-points may reduce pain in the immediate, local vicinity, but won’t have the widespread effects that true accu-points do. If accessing true accu-points allows interstitial fluids to travel throughout the body, that might account for the difference.

Not surprisingly, “integrative medicine” specialists are all over this finding too:

Dr. Shaista Malik, director of the Susan Samueli Center for Integrative Medicine at UC Irvine, says that in the cardiovascular world, specialists have long been aware of this “third space” (the circulatory system being the first, and the lymphatic the second), but agrees that the new research provides a deeper understanding of what it looks like, and what it does. “[The third space] was very elegantly described in this paper, because it’s showing that there’s organization and structure to this, while previously it was considered unstructured,” says Malik. “This is a really interesting finding that could go a long way in explaining why local therapy, stimulating only certain acupuncture points, could produce systemic effects.

We’ve met Dr. Malik before in my discussion of the quackery promoted by the Samueli Center at UC-Irvine and how the $200 million gift to the university will transform it into a center for quackademic medicine. You can see from her quote the direction that we’ll hear apologists for quackery taking this research and how they will use it.

Dr. Theise is also wrong on so many levels, and his contributing to the narrative that quacks will use to justify acupuncture is infuriating. As I like to say, it doesn’t matter where the needles are placed. It doesn’t even matter if the needles are placed. Indeed, twirling toothpicks against the skin produces the same effect. Basically, acupuncture is nothing more than a theatrical placebo. It does not work any more than placebo. The author of the article Katie Heaney asks Do We Finally Understand How Acupuncture Works? The answer is most definitely no, because acupuncture doesn’t work. Steve Novella recently reviewed why again while discussing Theise’s and Wells’ study, noting:

We have had over 40 years and thousands of studies, and still researchers are unable to show that acupuncture is a real thing. The simplest explanation for this fact is that acupuncture is not a real thing. This also conforms nicely to everything we know about biology and physiology – magical meridian lines do not exist.

Unfortunately, thanks to an overeager PR department at NYU, coupled with investigators who mistakenly believe that acupuncture works and have been willing to shoehorn their discovery into the narrative promoted by quacks, I foresee a whole lot of “interstitium” quackery and use of Theise’s and Wells’ discovery by quacks to “explain” their quackery coming. It won’t just be acupuncture, either. Indeed, Malik went beyond acupuncture to claim that this discovery suggests how Tai Chi and yoga supposedly “work,” too. Chiropractors will soon be all over the interstitium because anything involving fascia and the lymphatics is catnip to them. Soon we’ll see regimens designed to “detox” your interstitium or to use your interstitium to “detox.”” We’ll learn from antivaxers that vaccines are so harmful because the evil “toxins” get into the interstitium. I guarantee it. (I’m guessing some antivaxer somewhere has already done this.)

This is the harm that poor science communication can cause. Not only did PR department spin vastly overinflate the importance of a study with an interesting finding beyond what that finding warrants, but the investigators themselves have provided a narrative custom-made to promote quackery.

By Orac

Orac is the nom de blog of a humble surgeon/scientist who has an ego just big enough to delude himself that someone, somewhere might actually give a rodent's posterior about his copious verbal meanderings, but just barely small enough to admit to himself that few probably will. That surgeon is otherwise known as David Gorski.

That this particular surgeon has chosen his nom de blog based on a rather cranky and arrogant computer shaped like a clear box of blinking lights that he originally encountered when he became a fan of a 35 year old British SF television show whose special effects were renowned for their BBC/Doctor Who-style low budget look, but whose stories nonetheless resulted in some of the best, most innovative science fiction ever televised, should tell you nearly all that you need to know about Orac. (That, and the length of the preceding sentence.)

DISCLAIMER:: The various written meanderings here are the opinions of Orac and Orac alone, written on his own time. They should never be construed as representing the opinions of any other person or entity, especially Orac's cancer center, department of surgery, medical school, or university. Also note that Orac is nonpartisan; he is more than willing to criticize the statements of anyone, regardless of of political leanings, if that anyone advocates pseudoscience or quackery. Finally, medical commentary is not to be construed in any way as medical advice.

To contact Orac: [email protected]

36 replies on “The “interstitium”: Interesting science versus PR spin and pseudoscience”

The Alkaline Diet grifters are going to claim vindication as well, because Young and his medscam acolytes include something called the “Schade Organ ” in their “New Biology”:

8) During heavy exercise, if the the resulting lactic acid was not adsorbed by the collagen fibers, the specific acid catchers of the body, the organism would die. The total collection of these fibers is the largest organ of the body called SCHADE, the colloidal connective tissue organ. NO liquid exchange occurs between the blood and the parenchyma cells, or in reverse, unless it passes through this connective tissue organ. This organ connects and holds everything in our bodies in place. This organ is composed of ligaments, tendons, sinew, and the finer fibers that become the scaffolding that holds every single cell in our bodies in place.

This appears to be Young hearing of some papers by an anatomist called Schade, and in his dumbfuck incomprehension, thinking that Schade must be the name of the tissue. He connects it to “Psihinger’s space”:

The blood eliminates this increase in gastrointestinal acid by throwing it off into the Pishinger’s spaces.

6) The space enclosed by these finer and finer fibers is called the Pishinger’s space, or the extracellular space that contains the fluids that bath and feed each and every cell while carrying away the acidic waste from those same cells. There is no mention of this organ in American physiology text books. There is mention of the extracellular space but not of any organ that stores acids from metabolism and diet, like the kidney. I call this organ the “pre-kidney” because it stores metabolic and gastrointestinal acids until they can be buffered and eliminated via the skin, urinary tract, or bowels.

I realize that acupuncture can seem more plausible than other modalities to scientists – even you pointed out that you had thoughts on that, and most people would not have done what you did – but it seems a very strange leap for two legitimate scientists to make so confidently. I mean, it sounds like they come in from an assumption that acupuncture really works. I wonder why.

Because it has been so widely promoted by so many–including credulous MD’s, who haven’t bothered to look into the claims, and who buy all the “ancient Chinese” mumbo jumbo.

It’s also that doctors may not be aware of the experimental data that shows that acupuncture is bunk.

Some forms of woo involve mechanisms that on their face violate basic principles of physics or chemistry. Homeopathy and theraputic touch are two of the more notorious examples of that category. Other forms of woo involve mechanisms that are at least superficially plausible, until you do the clinical trial to show that the mechanism doesn’t exist. Acupuncture is in that category: even though proponents have always been vague in their definitions of “meridians” and “qi”, the notion that sticking needles in a patient might produce some effect in that patient isn’t ridiculous on its face. The problem with acupuncture is rather that the effect produced is indistinguishable from a placebo treatment.

The experiments which showed that acupuncture is a placebo have only been published in the last decade or so. Fifteen years ago, I might have been willing to try acupuncture as an alternative to things like high-risk back surgery, knowing that if the acupuncture didn’t work, I could fall back on the surgery. Now that I know that acupuncture is no more effective than a placebo, I would not do that. I gather that Orac has had a similar evolution in his thinking on the subject of acupuncture. But most doctors, especially the ones who completed medical school before those papers were published, have not seen those papers. They only see the claims of the pro-acupuncture crowd (which I grant you are a persistent bunch). To be fair, it is hard for even a specialist (let alone a GP) to keep up with the medical literature, as so many papers are published every week.

I knew Neil when I was a resident. He’s a bright guy, but, just like almost every pathologist, he probably has never been taught how to evaluate quackery in a rigorous way. In fact, it was probably never on his radar given how steeped we are all in basic science. I mostly learned that stuff here and over at Science-Based Medicine. I never had a work-related reason to interact with it.

I’m not making excuses for him. Neil should have done his homework before he opened his mouth (or allowed the PR guys to open it for him). I just wanted the background out there.

He might have been naive about PR people. Or maybe he never saw the press release before it was released, and by the time he did it was too late; so he just went along. Or maybe he liked all the attention and requests for interviews and didn’t want to jeopardize that. I can understand this latter potential motivation. I discovered after journalists started contacting me for interviews that it is kind of seductive and flattering to have reporters interested in interviewing you and radio shows and podcasters interested in having you on their shows. I say that even though I’ve probably never faced anywhere near the number of press requests from major press outlets that these investigators did. In any event, I highly doubt that these two realize the potential consequences of endorsing their finding as a potential explanation for “fascial manipulation” and acupuncture or their going long with the NYU PR department’s overblown narrative that this study shows that the interstitium is a new, previously undiscovered organ. I’m not sure which aspect of this study irritates me more.

Slate is now reporting that Theise is into New Age stuff, supports alternative medical practices, and has collaborated with Deepak Chopra. Also–this paper was rejected eight times before being published.

So reading those excerpts up there, I found myself thinking this:

Someone had cancer.
They found some intestinal mucosa that had deteriorated to the point where cancer was “leaking” out of the mucosa and spreading to other areas through the mucosa.
No one had documented that sort of deterioration before.
Deterioration of mucosa could explain some other disease phenomena.
It could even be a normal variant, not a pathology, would could also explain some interesting stuff.

Is this more or less a correct reading? The media spin on this one has been extreme.

The best answer is perhaps. This is now a physiological plausible way for a cancer to spread regionally. The next question, does it actually happen, has yet to be answered.

This paper does present some interesting new findings that need to be investigated further. I think it’s a little too soon to get really excited about it.

This whole mess is going to pop up as real “science” that will be touted to the patients in the brand new and very fancy Acupunture Pain Clinic that is under construction near me. I am pretty sure that this is the result of Medicare and Medicaid now covering acupunture–for PAIN. It is now so widely held that it “works” for pain and nassau, that I fear the ship has sailed in spite of our collective efforts. Sadly, too many scientists, doctors, and policy makers haven’t bothered to look beyond the type of PR hype that is so well demonstrated in this post.

Interstitial fluid as putative pathways for meridians is nothing new. I’ve not come across the sound waves stuff before. There’s lots of claims for evidence of the physical reality of meridians. That’s all – just claims. Fame awaits the person who can do more than claim to have revealed the fabled channels. Time will reveal what scientific experts make of the detailed anatomical claims of Theise and Wells, but they’ve haven’t helped their scientific credibility by claiming to provide evidence for meridians. Acupuncture does not work. They clearly know nothing about it. Or else they are happy to gain some cheap publicity.

I have become only occasional listener to Science Friday, although I used to listen fairly regularly when it was only on radio. My impression is that it (or is it Ira Flatow?) are not as good as I remember.

Given that there is such a thing called Yang acupuncture points, trying to narrow down the many hits on searches was taking way more time than I was willing to devote to the task.

I’m pretty sure it’s this, given that Theise cited it in this paper (open access).

Yeah. a friend made me aware of that paper—and much more about Dr. Theise. I’m probably going to blog about what I found out about him tomorrow. Please don’t reveal too many spoilers before then 🙂

Not surprising that Theise is impressed by physiological needle-dabble given his penchant for quantum complementarity babble.

I was listening to Science Friday last night and started thinking the calls were going to start discussing manipulation (DO or DC).
So fascia and lymphatics and 3rd space fluid is there that is far from proof manipulation can affect it.

Not sure where to put this ( I didn’t want to OT the current thread but I think Orac & company would like to know )

Yesterday, Mike Adams called for a tweet storm directed at You Tube because of its censorship of his crap

THEN a shooter appeared at their San Bruno campus which he reported.

Today he continues.

Sceptics should observe just how he presents his story.
Remember that he and the loon at prn are attempting to coopt mainstream news.

Not sure if it was a coincidence or contributing factor.

According to the NY Times, she was upset because YouTube was censoring some of her videos and cutting into her revenue.

I had heard it was a domestic dispute. I heard that last night from friends reporting “safe” but I wonder why such different reports?

First, apologies to Dr. Malik if I have the pronunciation of her name wrong, but hers reminds me of this quote from the movie “S.O.B.”:
“I could sue you for calling me that, Polly! A shyster is a disreputable lawyer. I’M a QUACK!”

Next, Narad: “I’ll simply note that ‘acupuncture’ is not “Latin for needle prick.”” Correct. “Acupuncturist” is English for “needle prick”. Assuming a male acupuncturist, of course.

I’m 77.When I was 48 I learnt Qi Gung and Wing Chun Kung Fu.(I even had the honour of practicing with Yip Chun the son of Yip Man,the”father” of KUNG Fu,and who was also the teacher of Bruce Lee).I saw many demonstrations as to how ENERGY could be channeled.I saw much use of the words “meridians“ and Qi in explaining “things” that I witnessed.One example:
Other than the word “Quackery” how do you explain my teacher being able to “push over” from a distance of 15 feet ,eleven COMPLETE STRANGERS,both men and women, with their backs to the teacher, using the Qi he had built up in his body from “doing” his Qi exercises earlier in the day?THEY WERE IN A LARGE HALL IN FRONT OF 200 people,and had no idea what was going to be attempted and they had their backs to him so they couldn’t see him! They ALL FELL FOREWARD WITHIN 30 seconds!

I don’t need to explain it. You made the claim. If you want anyone to believe in it, you have to show your evidence.
A single-take unedited video would be nice and even better if it were to stand up to all kinds of expert analysis.
If you can’t supply the evidence, your account isn’t worth the bandwidth it takes to read it.

Just by the way, upper-case emphasis does not make your unsupported claim more believable. It just reinforces the impression that you’re a crank.

Gee, how do we explain eleven “COMPLETE STRANGERS” mysteriously falling. There is no possible way they could be in on the trick right?,,,,,

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