I've written a lot about Stanislaw Burzynski and what I consider to be his unethical use and abuse of institutional review boards and clinical trials. Before that, I used to regularly write about Mark and David Geier and their unethical use and abuse of IRBs and clinical trials. In both cases, I lamented how they could use their own IRBs stacked with their own cronies to rubberstamp scientifically and ethically dubious studies. Mark and David Geier got away with it for years. Stanislaw Burzynski got away with it for decades and, apparently, is still getting away with it to some extent. (His IRB is chaired by an old Baylor crony of his from the 1970s, and he has been cited for numerous problems with his IRBs.) I'd like to contrast how their unethical research, in which the Geiers subjected autistic children to chemical castration with Lupron to decrease testosterone levels and allegedly make mercury easier to chelate (to them mercury was bound by testosterone, something that doesn't happen under physiological conditions but requires organic solvents) and Stanislaw Burzynski administered an unproven cancer chemotherapy (antineoplastons) to hundreds of patients over the years and charged them for it, compares to a recent case in the news.
The case has been mentioned by PZ Myers. It happened at t involves the same sort of tumors that Stanislaw Burzynski claims to be able to cure, namely brain tumors. It happened at the University of California Davis (UC Davis) and involved two very prominent neurosurgeons there, a former head of the department Dr. J. Paul Muizelaar and Dr. Rudolph J. Schrot, who were found to have violated university's faculty code of conduct with their experimental work. When you read this part of the story, you'll shiver. At least, I did:
The procedure in question involved three patients described in documents only as Patients 1, 2 and 3 – two middle-aged women and one man who had a common enemy: glioblastoma.
For anyone unlucky enough to be diagnosed with the highly malignant brain tumor, the prognosis is dismal. Median survival is less than 15 months.
Muizelaar and Schrot called their novel approach "probiotic intracranial therapy," or the introduction of live bowel bacteria, Enterobacter aerogenes, directly into their patients' brains or bone flaps. The doctors theorized that an infection might stimulate the patients' immune systems and prolong their lives.
The first patient lived about 5 1/2 weeks. The second survived another year, an outcome that buoyed the doctors and seemed to bolster their theory, they said.
The institutional trouble began in March 2011, when a newly diagnosed third patient developed sepsis, became unresponsive and died two weeks after being deliberately infected. The university's first internal investigation soon followed.
As a cancer scientist and surgeon myself, my first thought here was: Who on earth thought this was a good idea? Let me put it this way. What Muizelaar and Schrot were doing was intentionally causing bacterial meningitis. In cancer patients! You know, patients whose immune systems are often compromised to begin with! To be honest, on the surface, Burzynski's antineoplastons have more biological plausibility than this. Thirty years ago, I could say that they were at least drugs and therefore might have had some activity against cancer.
The concept that inducing an inflammatory reaction might help "prime" the immune system to counter cancer is not a new idea. In general, however, it's not a good idea to use bacteria that could cause potentially life-threatening infections. The CNS is generally viewed to be an immune "privileged" site, meaning that the immune system doesn't function the same way there as it does in the rest of the body. Immune privilege was first observed when it was noted that tissue grafts that would be rapidly rejected if grafted to the skin or other sites would survive a long time when grafted into the CNS. The original thought was that this meant the CNS was somehow cut off from the immune system by the blood-brain barrier, its lack of draining lymphatics, and the apparent inability of cells known as microglia to function as immune cells. However, recently this concept has been reevaluated in light of new data that show that the CNS is neither isolated nor passive in its interactions with the immune system, but that doesn't change the observation that the immune system functions somewhat differently in the CNS. In any case, gut bacteria are in general not expected to be in the CNS, and bacterial meningitis can be really nasty. It's also not that difficult to induce meningitis. Remember the outbreak of fungal meningitis from contaminated steroids injections last year?
Apparently, Muizelaar based his idea on an apparent observation in among neurosurgeons that postoperative infection was associated with better survival in patients with glioblastoma. However, the data supporting this particular association is, to put it kindly, mighty thin, a retrospective study. What Muizelaar apparently did was to place an enteric (gut) bacteria, Enterobacter aerogenes, into the open wound and bone flap after surgery in order to produce a wound infection. E. aerogenes tends not to be pathogenic, except in patients who have compromised immunity, such as the elderly, infants, and, yes, cancer patients.
It's instructive to read some of the PDFs included with the article, such as the report of the UC Davis investigation of Dr. Muizelaar and of Dr. Schrot. It reveals a bit of the complexity of doing investigations like this and, more importantly, why Drs. Muizelaar and Schrot went too far and how they gamed the system. He started with a consultation to the Bioethics Consultation Committee, which, after a lengthy debate, concludes that the practice "may be seen as consistent with the customs and practices of medicine." However, the committee thought that the procedure required more oversight than it could provide, and suggested that the protocol should be reviewed by the IRB. So Dr. Schrot submitted a full application to the IRB in which he admitted that further preclinical work was needed but argued that in this patient the benefit/risk ratio was favorable. On what evidence? Who knows? I don't have the IRB application. Dr. Schrot also discussed the procedure with the Center for Biologics Evaluation and Research at the FDA and was told that "animal studies will be necessary prior to entering into the clinic with your proposed therapy." In addition, he was told that "these animal studies must show not only safety, but also establish a reasonable proof of concept in order for this investigational therapy to be introduced into patients." In other words, the FDA told them to do the preliminary work first.
In the meantime, Drs. Muizelaar and Schrot submitted an NIH grant application for the animal studies. It was not well received by the study section, which characterized it as having "low translational impact with seriously flawed methodology and statistical analysis." The summary statement concluded, "There is absolutely no feasibility evidence in support of this project" and comments that it has a "low translational impact since it is very unlikely that any IRB or the FDA will allow the introduction of Enterobacter aerogenes directly into patients."
Here's where things get interesting. The FDA had told Dr. Muizelaar that he and Dr. Schrot could proceed with their "innovative treatment" if the bacteria were available locally. No doubt this was because the FDA is a federal agency and doesn't have jurisdiction if everything happens within one state. (It's the same issue with Stanislaw Burzynski, actually.) If it was not available locally and had to go through the investigational new drug (IND) process, then more animal work was required, as the CBER stated. It turns out that a graduate student had some Enterobacter aerogenes from ATCC, and that's what was used on these patients.
What follows then is wrangling between Dr. Muizelaar and the university. Dr. Muizelaar went to the Chief Medical Officer Al Siefkin and told him that the IRB had told Dr. Schot that the proposed procedure wouldn't be considered research. In any case, both gave the impression that they were "shopping" for approval, and, although probably not lying, being a bit selective in what they told various parties involved in the approval process. As the news report notes:
Among the university's findings, detailed in reports, email correspondence, interviews and regulatory documents:
- A former top administrator said he believed the doctors went "shopping for approval" and were "doing all they could to get around" the formal approval process. A physician who served on the research oversight board said the surgeons seemed to be "gaming" the system to bypass any institutional rejection or skepticism of their plans.
- Muizelaar and Schrot did not complete a study on rats before they began treating the three human patients, despite an FDA directive in 2008 that "animal studies will be necessary prior to entering into the clinic with your proposed therapy," according to an email to Schrot from an FDA official. When asked by a compliance investigator why animal trials were not done first, Schrot allegedly responded that such testing would take "10 years … his entire career," one internal review states. The investigator found Schrot's "eagerness to proceed" to be concerning and his actions "reckless."
- One university investigator questioned whether the doctors ever would have been able to get federal approval of their concept. According to one report, Schrot's grant application to the National Institutes of Health to study the bacterial treatment was rejected, with NIH commenting in 2009 that "(t)his is a very poorly developed scientific proposal that lacks feasibility." The NIH thought it unlikely that university or federal regulators would allow the introduction of live bacteria directly into patients, the report states.
Ultimately, the procedures were done on three patients. Particularly disturbing is the consent forms that were drawn up, which basically said that there was no evidence that this would work but that the surgeons wanted to do it anyway. While technically that is accurate, one has to wonder how much the patients might have felt coercion and how free they felt to say no. After all, they all had horrible diseases with a median survival of less than 15 months expected. As this editorial points out, patients also weren't told everything:
Despite the absence of any FDA approval or IRB review, the neurosurgeons proposed their treatment, to Terri Bradley. The consent form she and her daughter signed appears straightforward. It made clear that the infection the surgeons were deliberately introducing into Bradley's brain "may be totally ineffective." It then laid out the many serious risks, including "further neurological deterioration … paralysis, coma or death." The women were told the procedure did not have FDA approval.
Faced with the alternatives presented and the near certainty of death, not surprisingly, the Bradleys signed.
Here's what the Bradleys weren't told. They were not told that the FDA hadn't just failed to approve the procedure their physicians were pushing, federal officials had told the doctors specifically not to perform the procedure until they had conducted animal studies. The Bradleys were not told that the doctors had bypassed the university's IRB process or that the IRB had previously told the doctors not to perform their "experimental" procedures on human patients.
In other words, the "informed consent" provided was every bit as much misinformed consent as what antivaccinationists advocate.
The end result was one patient living less than six weeks, another surviving two weeks, and the second patient, the "success story" living over a year. However, the family of that patient, Terri Bradley, didn't view it as a "success." Indeed, Mrs. Bradley required at least one operation to "clean out" her infected head wound and directly administer antibiotics. Indeed, her daughters report that the infected wound had begun to smell bad. True, this patient did apparently have some tumor shrinkage. As I read about the tumor shrinkage, thoughts of Stanislaw Burzynski came to mind, as did the observation that three patients are too few to say anything and that one sees longer-than-expected survival in cancer patients with homeopathy (i.e., treatment with nothing but water). In any case, despite the doctors' thinking that Ms. Bradley had benefited, she did not:
"Patient 2 did not experience significant functional benefit," investigators concluded, "and upon her death … recurrences of the tumors and chronic infection of the brain were identified."
Shockingly, even after this almost certainly treatment-related death, Drs. Muizelaar and Schrott convened an ad hoc ethics committee and presented them with a proposal to proceed with five additional patients. According to this report, the ad hoc committee concurred with the proposal and recommended continuing clinical activities with the understanding that they would develop an IRB-approved protocol as soon as possible.
In the end, this case demonstrates just how much oversight is needed on human subjects research and just how disturbing what "brave maverick doctors" like Stanislaw Burzynski, Mark Geier, and, yes, Drs. Muizelaar and Schrot do can be. The problem, of course, is that the line between research and trying something "innovative" (or truly innovative without the scare quotes) is not always clear, nor is the line between research and making a "last ditch" effort to save a patient's life. It also speaks to the inherent conflict between the desire of a doctor to save lives and the need to do rigorous research in order to determine whether what the doctor does actually does save lives. As a physician, it's very easy to develop a tunnel vision and believe that your latest idea is something that will work, that will save lives, if only those unimaginative clods would see what you see. Also, in the service of the goal of saving lives, it becomes progressively easier to justify cutting ethical corners, as Drs. Muizelaar and Schrot appear to have done. It's very easy to start to view the system designed to protect human subjects as obstacles to be overcome rather than the patients' advocate.
You know how they say that the road to hell is paved with good intentions? I can't think of a better example in medicine than a case like this.
This leads one to wonder if Drs S and M themselves have s**t for brains?
Sounds like the drive for glory and money took over. Coley had already evolved away from live bacteria generations before, even without the added CNS exposure. Seeming paranoia over being scooped can create this kind of stampede amongst gloryhounds, the hungry, and the innovatively impotent.
I say seeming paranoia because a silicon valley buddy recently mentioned a high school student scooping UC medical researchers. To their chagrin, once posed a problem, the kid showed up with a basic patent six months later...
People use orthotopic xenografts as well as genetically engineered models to make mice have brain tumors, which you then try your tricks on. PMID:23618720 reviews several. The literature is huge. These guys have no excuses that I see. The institution should look at how their system failed.
NB. at six months, it was a patent filing.
I could go up to any six year old and ask if this was a good idea, scratch that, I could ask my goldfish Nigel if she thought it was a good idea, and she'd probably jump out of the tank and slap me.
Ethics? Anyone? Is medicine particularly attractive to sociopaths?
This brings us back to the days of lobotomies. That's how unethical, immoral and illegal what these two doctors did.
Running to human trials without animal trials on something like this is mind-boggling. It's not like it is something that would not work for mice (if it worked).
Wow, sauerkraut and yogurt may cure autism! Probiotics are the new panacea, apparently. Regards, OOE
@ Old One Eye:
At anti-vax and alt med sites ( AoA, TMR, PRN, Natural News etc), fermentation-as-pancaea has been on the rise for a while**.
Raphael Kellman has been a starter in the mix for years.
Yoghurt has been up woo-meisters' ... er.. 'alley' as well.
** however they hate alcoholic beverages and usually, bread.
If fermentation is a panacea, I think I'll have another beer.
What. The. Hell. How do you obtain a medical degree, or graduate highschool for that matter, when you are so clueless as to think that introducing bacteria into the brain is going to help anyone? I don't have the words to express my disgust.
I have to really compliment you on this article. It's the best Orac entry I've ever seen. It's really a model of how to write about this sort of thing.
Good God! I mean . . .
When I was four years old, I got meningitis. I nearly *died*. I was very healthy before, and I spent two weeks in the hospital (though I don't remember much of the first week, as I was barely conscious).
Deliberately giving bacterial meningitis to patients, seeing all three develop horrible infections, one directly dying of theirs in just two weeks, and then wanting to do this to *more* people????
If I met these alleged "doctors", I'd have to work very hard not to actually punch them in the face. This is totally abhorrent.
WTF? If a researcher insists on putting bacteria in a patient's brain in the hope it might stimulate their immune systems, is it too much to hope they might kill the bacteria first? Unbelievable.
Add my voice to the Whiskey Tango Foxtrot chorus. If I read that right, these dudes didn't have IRB approval to attempt this experimental treatment (I use that last word very loosely here). "[N]ot considered research?" Pull the other one, it has bells on.
Does this further dispell the 'like cures like' theory?
I kept a list, for a while, of things I didn't need to try to know they were bad ideas (basically I got tired of the phrase "don't knock it 'til you try it). This list included things like heroin, sexual practices involving lightbulb insertion, and walking into a spinning propeller.
This article makes me think I need to start keeping that list again because it must be woefully incomplete.
@ Krebiozen-- WTF? If a researcher insists on putting bacteria in a patient’s brain in the hope it might stimulate their immune systems, is it too much to hope they might kill the bacteria first? Unbelievable..
If you killed the bacteria first, then it would be a vaccine of sorts, which would have meant all that silly safety testing, because, of course, killed bacteria are so much more dangerous than iatrogenic meningitis. (sarcasm off)
PZ Myers links to a UCDavies blog, which in turn links to further research into the remission-from-brain-infection idea; there's a general failure to replicate Coley's observations.
The blogger also points out that there is genetic diversity across strains of Enterobacter aerogenes, some more pathogenic than others, so to pick one random strain just because it was available without FDA approval is about as uncontrolled as using fresh feces.
This was all happening three years ago. Inquiries started two years ago.
This lacks a probable mechanism on so many levels (besides being unethical and stupid).
1) If you do cause an infection, the immune system will be busy dealing with the infection, not wandering off to look for cancers.
2) If the immune system (innate and adaptive) clears the infection, nothing about the infection would induce it to attack the tumors it had been ignoring. Is there some hidden epitope overlap between brain tumors and gut bacteria?
3) Even if there *were* a probable mechanism, you still need an IRB!!! Duh!
These surgons seem to have a bit of a god-complex.
From what I read, shit is injected into the brain or meninges and that is supposed to cure.
Did I read this incorrectly?
Not sh*t per se, but rather a bacteria that lives in that sh*t.
But same difference, since it's the bacteria in feces that wreak havoc on us when they find their way into areas of the body outside of the GI tract.
I have an hypothesis that doctors perform dangerous act sometime (especially to the untrained eyes) and that time, they carried it too far and given the comments here, I have to wonder if there isn't something else at play beside my hypothesis.
Alain (ever cautious).
According to this report, the ad hoc committee concurred with the proposal
It appears from the report that the pair received permission from the IRB to treat one or two patients (under the understanding that it was 'innovative' or 'compassionate' treatment rather than research), having misled the IRB about the source of the bacteria procured from
ATCC of Virginia specified as “not intended for human use.” .
They then went back to the ad-hoc ethics committee saying "all three patients are dead but the non-results of our non-research are very promising, let's non-research on another 5 subjects"; and they actually received permission to do so. The only reason we are reading this now is that a pharmacist from the med school queried their use of a particular drug in a non-approved way... the pharmacist persisted, and then the actual source of the bacteria came to light, and suddenly everyone was scrambling to be on the other side of the room from Muizelaar and Schrot.
Knew I'd read about something similar. Apparently a doctor championed similar therapy back near the turn of the 20th century:
"Coley spent the next decade hoping to replicate Stein’s extraordinary recovery. In “A Commotion in the Blood,” published in 1997, Stephen S. Hall describes how Coley inoculated cancer patients, first with extracts of streptococcal abscesses, termed “laudable pus,” and later with purer cultures of the microbes. He claimed several successes, but the medical establishment did not embrace his approach, because his results could not be reliably reproduced."
Article is a bit heavy on the "persecution" angle, but does go on to talk about MODERN immunotherapy, which is no picnic - talk about curing the disease but killing the patient.
I've heard that some awful bowel conditions can apparently be cured by introducing other people's bacteria into the patient's bowels, but ... hey, the gut is where bacteria are SUPPOSED to live.
I should know more about this given my background, but wouldn't a bacterial immune response be entirely inappropriate for inducing anti-cancer immune responses? You'd get lots of cytokines generated, but the wrong kind of immune cells would be showing up...
Of course I neglected to carefully read through all the comments, like HDB's comment #21 with the mention of Coley and the link to the UCDavies blog. Far more inclusive (and damning) than a lame New Yorker article.
But I'll just say UGGGH again anyway.
Between these guys and creationist Mike Egnor and anti-vax loony Russell Blaylock, the expression "brain surgery" to refer to something brilliant doesn't really fit.
The Safety/Quality manager in me is dumbstruck at this, especially knowing the red tape and hoops to be negotiated in the public system I work in with regards to new medical procedures, let alone human experimentation.
Those poor patients. Good grief, those poor families.
I echo everyone's questions on here. There's some 'splainin to do by the hospital too, one would think.
And I'd like to meet Elburto's goldfish Nigel
You're describing a process called a fecal transplant. There are absolutely nauseating, disgusting instructions on how to do it at home on some "wellness" websites (you start by collecting a week's worth of feces in a bucket... A funnel and gastro tube are involved. I'll leave the rest to your imagination.) I kid you not. It was one of the first things I encountered when I entered this wonderful world of woo. I think it might even have been mentioned on some autism self-help websites.
I know the procedure is legitimately administered in a hospital setting as a last-ditch attempt to treat some bacterial infections like c. diff. But they're not using a bucket and funnel.
Yup, it's been touted as a cure for autism. Click on any of these Google links at your own risk:
(you start by collecting a week’s worth of feces in a bucket…
I could be wrong on this, but when a medically supervised "fecal transplant" is done (usually to treat a recalcitrant clostridium difficile GI tract infection), I don't believe the donor stool is allowed to sit around for a week. That would probably result in way too much bacterial overgrowth--which is something you can see in people who suffer from poor/slow bowel transit.
Of course, I have a dog who sometimes eats poop (both her own and "donor" doggie doo--but she only eats the fresh stuff), with various theories about on the internet (such as she's not getting enough to eat--which isn't true--she's an mildly obese beagle). And since we're dwelling on stool, one of the most dreaded patient calls I get is the infant or toddler who just "ate something" out of the litter box. Ugh. Not much to do except get the littler box off the floor and call me if you child becomes ill.
Hey, don't worry! when your brain swells up and you die in agony and delirium, it won't be the tumor, it'll be the Fucking Cerebral Meningitis!
Holy Shit !
Seriously nuclear safety alert levels of burning stupid.
Whisky F-in Foxtrot Tango you stupid vacuumheads!
@palindrom - As half of a couple of IBD sufferers* I can't begin to tell you about the number of discussions we've had about faecal transplants in this house!
The consensus though? They've been touted as possibly therapeutic in Crohns Disease, and we would have our arses in the air before you could say "Sh¡t in my pocket and call me Derek!" if we were offered the procedure. Hell, we'd chug it in a milkshake if it meant no more (literally) crapping our insides out, bleeding so much that transfusions are necessary**, and being in agony because you're fulfilling that most basic of drives - eating.
*That's why I've been uncharacteristically quiet recently, Other Mrs elburto had a flare so bad that she was bleeding, looked 40 weeks pregnant, and has oesophageal spasms so strong that only her GTN spray would relieve them. She lost 14lbs in eight days.
**A few years ago she haemorrhaged so badly that she needed three units of blood, a week in hospital, and four months leave from work. She lost 25% of her body weight, the steroid treatment caused her teeth to dissolve, and she developed cardiac issues from the rapid weight cycling.
Faecal transplant? In a heartbeat.
This is a pretty great post. Nicely done.
As half of a couple of IBD sufferers
It has occurred to me, elburto, that it would be a serious mismatch -- a medical miracle, even -- if some part of you were not irritable.
WTF. I'm an Infectious Diseases physician with a research interest in meningoencephalitis, including working with mouse models of bacterial & fungal meningitis I've also treated several cases of Enterobacter meningitis in trauma & immunosuppressed post-surgical patients - usually without much success. Enterobacter spp. are colony sensing organisms with the capacity to form biofilms and modify the colony microenvironment to resist dedicated phagocytic cells (which do not exist in the unbreached blood-brain barrier).
That these arrogant f*ckwits even contemplated doing this in humans in the face of extant data from mouse models of Gram negative meningitis is inexcusable. How the hell can they still be practicing, let alone subject to code of conduct violations? Doesn't California have Medical Disciplinary Boards? This is as bad as Wakefield.
OMG - I am a monitor for clinical research studies in oncology. This is horrifying! These people should lose their licenses, their degrees, hell - they should lose everything! They killed these people faster than glioblastoma ever could.
More likely the road to hell is paved with scams.
BRI-IRB and the Geiers are novices and outclassed by the chelationists' Great Lakes College of Clinical Medicine IRB (GLCCM) - 4 TACT investigators where members of this nightmarish IRB. The astounding FDA warning letter, EIR, and follow up correspondence is here: http://www.circare.org/foia2/docs.htm
The letters between FDA and the IRB are hilarious and terrifying by turns.
The chelationist who set up the GLCCM IRB also set up the American College for Advancement in Medicine IRB. The two IRBs even had similar (useless, non-compliant) documents: http://www.circare.org/tact/tactindex.htm#acam
Not to be outdone, proponents of IV hydrogen peroxide also had an IRB, though apparently it consisted of one chiropractor and virtually no records or SOPs: http://www.circare.org/fdawls/ibomfirb_19970602.pdf
Clueless louts in NV created the Nevada IRB to promote alleged medical tourism, which was expected to result from passing legislation allowing homeopaths to provide stem cell therapy. Fortunately it seems like FDA scared them off: http://www.circare.org/fdawls/nirb_20070711.pdf
More recently we have electrocuted acupuncturists IRB or some such: http://www.circare.org/fdawls/aaabemirb_20081113.pdf
Second warning letter: http://www.circare.org/fdawls/aaabemirb_fdawl_20110324.pdf
Muizelaar and Schrot: UC Davis vigorously defended them in the institution's response to the findings of non-compliance by CMS. Perhaps worse UC Davis didn't report the docs to the medical board. Hopefully not many medical centers would condone failure to disclose your intended surgical procedure to the OR manager or waltzing into the OR with an unidentified bucket of foul smelling liquid in which you soak the patient's skull bone flap & reattach it.
There are a few more but I'm becoming nauseated & must stop.
So if you get a terminal glioblastoma and there is a possible untested treatment with no alternative, you prefer that a government committee decide your fate? Not me.
If I have a terminal glioblastoma, these are the three possible outcomes, listed in descending order of desirability:
1) That some amazing new treatment will cure the "terminal" part of the glioblastoma and let me live close to what my normal life expectancy should have been.
2) That palliative care will let me avoid the worst pain and discomfort of the disease until the end.
3) That neglect, either by not giving me care or by giving me treatments that have no value, will maximize my pain and distress until the end.
Now, here's a really important thing. I know which of those three outcomes I want. That doesn't mean I know how to choose the treatment that will give it to me. Necromancer Steve talks about letting "a government committee decide your fate," but if I lack any training in oncology, and that so-called "government committee" includes at least one oncologist, it seems that they are better qualified to make the decisions that might bring me the fate I want, than I am.
So if you get a terminal glioblastoma and there is a possible untested treatment with no alternative, you prefer that a government committee decide your fate? Not me.
If the socalled untested treatment is tested for many years, without any publication of possitive results and still is sold as being a possible treatment, I prefer to spend my money on things to make the remaining part of my life worthwhile. And I prefer having a government commitee, which includes real experts to prevent quacks from selling hope, without any proof.