Monday, July 1, 2013

The business of ignorance



Those of you who read this blog regularly may well be waiting on a post on the latest developments in stem cell therapy that I promised recently. I want to reassure you that this is coming, don't fret! However, a story has come to my attention of late that made me reconsider the topic of this post. The story has shocked, saddened, and angered me in equal measure and I felt that it needed sharing with you, dear reader, as it is a prime example of why the public engagement of science is a vitally important task. Given Shaun's heroic efforts last month to bring us the news from the latest  Cosmological Perturbations post-Planck conference, I thought it was fitting to exemplify just why this kind of science reporting is important.

I was first made aware of the story that shocked me so much by an excellent Panorama documentary that aired last month (UK readers can still watch the show online here). For those non-Brits amongst you, Panorama is a highly respected investigative documentary show produced by the BBC, not the kind of programme that bothers with unimportant issues. You can imagine, therefore, that my interest was piqued by the title "Cancer: hope for sale?". I had expected perhaps an exposé on some counterfeit medication ring, or maybe a look at a big pharmaceutical company pushing drugs through ahead of time in countries with lax regulation laws. I could not in my wildest dreams have imagined just how scandalous the actual story turned out to be, nor could I believe that this was the first I was hearing about it.

The main protagonist of this story is a Polish doctor called Stanislaw Burzynski - I had never heard of him before last week but he may be more familiar to those of you from the States. Dr Burzynski has been running a clinic out of Houston, Texas for over 30 years that offers treatment to cancer sufferers and has had thousands of patients through its doors. Burzynski's treatment is based on the notion that there exists a group of peptides (very short proteins) that exist within our bodies and have an immunoprotective effect against the development of cancer and other diseases, which he has given the reassuringly scientific-sounding name 'antineoplastons'. Cancer sufferers, it is claimed, can be treated by oral and intravenous administration of cocktails of various antineoplastons alongside a number of other components of the medication, such as steroids and anti-inflammatories. The antineoplastons used at the Burzynski clinic used to be purified from human urine but are now artificially synthesised from basic chemicals, and, it is claimed, are little short of a miracle weapon in the fight against cancer. The Burzynski clinic proudly asserts that not only do antineoplastons boost the immune response against cancer, but that the correct combination of antineoplastons can be used to generate therapies targeted against specific genes involved in different cancers and so allow for effective, personalised treatment.

This is close enough to real science to sound fairly convincing to the non-specialist. Some peptides are well known to have roles within the immune system (defensins, for example), and gene-targetted therapies represent a huge and promising area of oncology research. It all sounds pretty technical and reassuringly complex. That is enough for desperate individuals looking to cure themselves or loved ones when all else has failed; they're on the first plane to Texas.



Sounds great, but...

The catch with all this is, as I'm sure you've probably guessed, is that there is not a single jot of evidence to suggest that antineoplaston therapy has even the remotest positive effect on cancer progression. Burzynski has never published any peer-reviewed studies that his therapies have any efficacy nor has he made public the precise details of his antineoplaston cocktails so that others could trial them independently. Antineoplaston therapy has therefore unsurprisingly never been cleared for use as a safe treatment, and the Burzynski clinic is only able to admit patients because they exploit a legal loophole allowing them to enrol in 'clinical trials' of unknown design or duration. Nonetheless, this isn't enough to dissuade the hundreds of people who flock there each year. If they have a child, parent, spouse or friend who has been treated with everything medicine can throw at them and things still haven't got any better then really what do they have to lose? Who cares if it's untested, even a tiny chance is better than nothing, right? This was pretty much the belief of everyone who had been to the clinic and then interviewed by Panorama: there's no evidence to support it but there's also no evidence against it because it hasn't been trialled - it's 50:50.

Except it's not. The people who defend the Burzynski clinic as a long but worthwhile shot are neglecting one massively fundamental thing: the odds were not even to start with. What I mean by this is that even though the antineoplastons themselves have never been clinically tested, there is evidence that we can use to assess their validity as a treatment. This is all of the evidence that has ever been collected by any biologist, biochemist, physiologist or doctor - it has been complied, assessed and reorganised into our current understanding of biomedical science. It is the sum total of what we know of human biology and how we think our bodies work. Each and every potential therapy that we develop must stand before this mountain of knowledge and justify its reason for existence. Just because something hasn't been tested doesn't mean that its outcome cannot be reasonably predicted. Nobody  has, as I'm aware, ever tried treating AIDS patients with cough syrup but that doesn't mean its validity as a treatment is uncertain. We understand how HIV infects T cells, and how T cells are integrated into the immune system, and how the immune system combats infection, and how immune depletion causes AIDS. We also understand how cough syrup works. The two don't have anything to do with one another and so there's no need to try testing it.

Similarly, all the facets of different cancers are not yet fully understood, and nor is all of the wondrous machinery that is our immune system, but I can tell you definitively now, as a biochemist, immunologist, and soon-to-be husband of an oncologist, that there is no logical reason why antineoplaston therapy should work.

Alchemy - 21st century style

The notion that cancer sufferers somehow lack the correct balance of peptides to offer them the protection afforded by healthy people is just gibberish no different from the ancient notions of misbalanced humours or miasma causing disease. The idea that peptide treatments could target specific genes in different cancers and turn them on or off is even more fanciful, if that is indeed possible! The mechanisms by which genes are regulated are well-studied and understood (see my post here for more) - many do indeed recognise different proteins that influence their activity in a number of ways. However, these proteins are made within the cells themselves and then targeted to the cell nucleus, where the DNA is kept. Random proteins from the bloodstream don't just get scooped up and transported into the cell, much less directly transported to the nucleus, and any peptides that get taken orally will just be broken down in the stomach!

Even if we were to say, for sake of argument, that antineoplastons could get into the nucleus, there is no reason whatsoever to suspect that they might affect gene activity. Burzynski's peptides are far to small to recognise specific DNA sequences and are highly unlikely to bind to any DNA at all, no matter how non-specifically. Specific protein-DNA interactions require complex structures within the proteins that allow them to select between different DNA sequences, as well as separate structures that work to actually affect gene activity. Such structures are made of basically the same stuff that are in antineoplastons, but the complexity of antineoplastons is far, far too low to have the same effect. It's the same reason why a lone electron can't do as much as a whole molecule, or why a single brake pad doesn't do the same job as a whole car.

On top of that - even if antineoplastons did manage to mysteriously work their way into the cell nucleus, and then, bizarrely, were able to bind to and affect specific genes - there is then no good reason why they would have any effect on cancer! The genes involved in cancer number in the thousands, and simply turning one off or on is not enough to sort out the whole, massively complex disease. Cancer cells are tough bastards, and if you knock out one gene that they need, they often just compensate with another. Some cancers have been shown to rely predominantly on activity from a single gene (their so-called 'Achilles heel') but they are very rare and not variable in their reliance on the genes in question. Also, the genes involved in cancer don't have anything in common with each other - they don't all contain, for example, a single DNA sequence that could be targeted across all of them as a group. Randomly turning genes on and off in an unknown number of cells in your body and then hoping that exactly the right ones get affected to cause cancer remission is a bit like randomly firing a shot gun into a crowd and hoping only to hit people born in November.

The nearest I can come to finding a potentially beneficial outcome from antineoplaston therapy is that it may act on cell surface receptors (see another post of mine here) which in turn regulate intracellular signalling that affects gene expression. However, this is no more likely to have an anti-cancer effect than just randomly messing with gene expression, and is massively unlikely anyway because cancers can arise from any tissue whereas any one receptor is only found in a handful of different tissue types.

So, long story short, it's just nonsense. Not untested but possible; just pure imagination. Back in the day, when nobody really knew anything about how the body works on a molecular level, ideas like this were bandied about all the time because they didn't have the means to test any of them so had to rely on pure guesswork. In that academic setting, antineoplaston theory would have been just as likely to be right as any of the others, but we've moved on a bit since then. Burzynski can dress up his notion with all the science-y sounding words he likes, it doesn't change the fact that his idea is based an a massively flawed understanding of biology. The fact that this is not immediately apparent to everyone who hears about his treatment is in part due to the way in which science is reported in the popular mainstream - people think that science works in the way Burzynski does it: you just try and and see. This is not true, modern scientific progress is the product of tiny advancements, each building on the conclusions of the last. Burzynski represents a out-dated and flawed way of doing science. He is the modern day alchemist - blindly trying to turn lead into gold in sheer ignorance of its absolute impossibility.

Lead into gold

Although, perhaps that's being unduly kind to Dr. Burzynski, as ignorance on his part would in this case be a mildly redeeming feature. The reality of antineoplaston treatment is actually that it has managed to do the impossible and turn lead into gold, although not the gold of an effective cancer treatment, but the gold of dollar signs for the Burzynski Clinic and its shareholders. Antineoplaston therapy costs between $7000 and $9500 a month and can last years, potentially raking in hundreds of thousands of dollars for each patient seen. This is money wasted on a pointless treatment that could otherwise go towards funding genuine research that may one day help save lives. Worse still, because some of the antineoplaston components are highly toxic, and patients undergoing antineoplaston therapy cannot simultaneously receive conventional treatment, this is actually money spent on potentially making a very sick person much more ill. The BBC documentary that brought this story to my attention interviewed a harried doctor in the nearby Houston General Hospital who is tasked with treating the remnants of patients leaving the Burzynski Clinic: she has never known one to survive. Even if they would not have survived anyway, that money could have gone towards making their final days memorable and happy rather than painful and terrifying.

If Burzynski genuinely believes in his therapies then I consider him merely to be a dangerously incompetent doctor and a failure as a scientist. However I find this difficult to believe. I am more inclined to think that he knows very well that he is peddling nonsense to fund his own lifestyle and that of his backers. If that is actually the case then Stanislaw Burzynski is a hatefully abhorrent human being who thinks nothing of exploiting the desperation and death of vulnerable individuals to satisfy his own sickening greed. He has taken the purity of scientific endeavour and distorted it into a money-making machine that not only does not advance science, but actively seeks to promote ignorance and fear for its own ends. How he has managed to keep this charade up for so long is beyond me, but the virtual cult-like reverence that his followers have for him is, I'm sure, in no small part responsible for the survival of the clinic thus far.

But my disgust at this grotesque spectacle is not what really matters. Burzynski has never harmed me or my loved ones with his antineoplastons so my abhorrence is somewhat irrelevant. What does matter is the suffering and torment of thousands of individuals who risk bankruptcy to line the pockets of a charlatan. All that I want to achieve in writing this is to highlight just how important the public understanding of science really it. Engaging laypeople in current scientific understanding is often talked about in nondescript terms of how it would be beneficial to society and to the individual, but this is a clear case in point of how a lack of scientific understanding can be fatal when mixed with the right combination of desperation and fear. Burzynski and his ilk not only profit from this misery, but they also actively encourage poor understanding of, and confidence in, science.

To anyone out there who may ever be in the desperate situation faced by the thousands who have turned to Burzynski's treatments, and I sincerely hope that none of you ever is, I implore you not to even consider for a minute getting on that plane to Texas and wasting huge amounts of money on false hope. Do not give in to Burzynski's sophisticated mis-information or the testimony of any of his of magically 'cured' patients. I know what it is like to feel the helplessness of watching a loved one succumb to cancer and I understand just how desperate the situation does, inevitably, become. But there is nothing that would persuade me to give in to Burzynski's propaganda and spend thousands on that one last shot in the dark.

I put my faith in evidence-based medicine, and I will readily risk my life for that faith by opting for treatments that are scientifically sound and clinically proven. I very much doubt that Stanislaw Burzynski would do the same for the treatments that he sells.

6 comments:

  1. Obviously I'm kind of already convinced by all of this, what with me being a science blogger and all too. However...

    This is something I agree with strongly. Recently in New Zealand we had our own version of this guy. He claimed he could predict earthquakes based on the lunar cycle. Again, there's a sort of hint of genuine science because his arguments talked about gravity and tectonic plates, etc. But it just wasn't true. He even named specific dates when earthquakes would happen and some Christchurch residents would flee the city.

    Also, the council in Hamiltion recently decided to de-flouridate their water.

    I don't think that better education into scientific *knowledge* is the answer though. You're never going to teach me enough biochemistry such that I can tell, based on the science, who is a crackpot and who isn't. But I understand the process of science and that allows me to tell genuine, honest, trying to determine the actual reality scientists apart from those with something to sell, or who are just deluded.

    I would go as far as to say that I think the process of science should be a compulsory subject at high-school. If it was, stuff like this would presumably be much less common.

    The Hamilton thing is very recent and very annoying as it affects people who do understand the science as well. Everyone's water is going to be de-fluoridated.

    In fact, the UK has its anti-vaccination people as well and if I recall correctly there have been some measles outbreaks recently over there.

    Gah!

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  2. You're spot on - it's as much about making the scientific process understood to the general public as the science itself. I also think, though, that the public can be aware of what is known without actually having to understand it. I don't understand physics in any substantial detail, but I feel that I could fairly accurately guess the broad strokes of what is actually known by others. One of the Burzynski patients interviewed in the Panorama show retorted to a comment by an interviewer that antineoplastons were untested with the question, "Well what evidence is there that radiotherapy works?". I don't think people should be expected to understand things like radiotherapy in great detail, but I would hope they might know that others do. I guess this comes down to an issue of trust in the scientific process - a trust that gets eroded by frauds like Burzynski.

    The debacle with the MMR vaccine her is almost entirely the fault of sensationalist reporting in the tabloid media, which is sadly quite powerful in the UK. Clearly there's some blame with the guy who published the original, flawed, analysis that MMR is linked to autism, but plenty of honest scientists make errors - that's why peer review is so important. For the media to seize on a sensationalist report that is pretty much universally panned by the scientific community is irresponsible, but to do it to the extent that they did is just outrageous. And because of such reporting, MMR uptake rates in the UK crashed to less than 70%, which meant that there were millions of children walking around without protection against debilitating disease. Moreover, even children who had been vaccinated were now at risk because mass-vaccination depends heavily on population immunity. Unsurprisingly we now have measles outbreaks and deaths in several areas of the country, which means the people responsible for inflating the story to the extent that it was now have blood on their hands.

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  3. After watching the movies Burzynski 1 and 2 (especially 2) I'm a bit confused how you can say all of your comments. They show a girl with brain stem glioma being cured of her tumors on the Burzynski treatment. The first patient in history to survive. And she was doing more than just surviving, she was thriving and it was 10 years later. We are all entitlted to our opinions, and I appreciate that you have yours. Your blog post was well written and somewhat respectful, so thank you for that. I believe that Burzynski is curing about 30% of his patients with cancer and that the American FDA is trying to block, discredit, suppress, and smear him at every turn because it would cause the conventional cancer industry to lose billions. When there's that much money involved it's not hard to imagine that big pharma wants time to come up with their own antineoplaston treatment or time to steal it from Burzynski. I appreciate your warnings but what should bother you is that the American FDA and big pharma are very corrupt, and don't care if we live or die. If I ever had cancer I would want the opportunity to try his antineoplaston and gene targeted therapy first. What is important to me is that I have a choice. I want to choose my treatment, not have it chosen for me. My college roommate, Ryn Cline Quast was diagnosed with a brain tumor, I think it was called oogliodendroma, in 2003. She went through radiation treatments which were $90,000 US dollars a month and very toxic. Burzynski's treatments are $9,000 US a month and non toxic. She died in 2009 at age 44 leaving 2 children and a husband behind. She didn't die from the cancer, she died from the harsh radiation treatments, which weakened her brain blood vessels and she had stroke after stroke. I WISH we had heard of Dr Burzynski's treatment back then. It exisited, we just didn't know about it. I think she would be alive today if she had gone to see Dr Burzynski. That's my opinion. I appreciate your warning, but I wish you would warn everyone how much corruption is in the FDA and big pharma instead.
    Leigh Anderson
    Chicago

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    1. Many thanks for your comment, Leigh.

      My first response to this is to ask you to please not base your views on antineoplaston therapy on the Burzynski movies, which are nothing more than transparent propaganda produced by the Burzynski clinic. I question the veracity of many of the claims made regarding patients in these films, but even if they were true they are not in themselves evidence of the efficacy of antineoplastons. These movies exploit the perfectly natural human instinct of mistaking association with causation, i.e. believing that because two things occurred simultaneously or sequentially they must be causally linked. This is a very difficult instinct to overcome, and the scientific process has been established with the principal aim of getting around this and allowing objective, quantitative assessment of such information. It is important to remember that conventional cancer treatments are not 'cures', they simply improve the odds of survival and clearance compared to remaining untreated. In some cases the odds are, sadly, not in your favour and no amount of treatment will help. In others, you may be lucky and spontaneously clear the tumour without any medical intervention at all. It is these cases that Burzynski depends on for his propaganda, as any single case in isolation can appear miraculous. It is only when you consider the general efficacy of treatment on large numbers of people that it can be objectively assessed. The claim of a 30% success rate given in the Burzynski movies has never been subject to peer review as it has never been published. There are so many ways that data can be dressed up to make it seem like 30% of patients are cured that the value is meaningless until it has been properly scrutinised, as all other therapies have been. For example: how are they defining ‘cured’? Does that correlate with recognised medical standards of ‘cured’? Are all potential patients accepted or just those most likely to recover? Which specific therapies contribute to this 30% success rate? There are just so many variables that the claim is baseless without peer review. The case you give of the girl with brain stem glioma is a classic example, how is she being defined as ‘cured’? You’re right that BSG is among the most aggressive cancers with a mortality rate of nearly 100%, but conventional treatment does allow some patients to live for years with the condition. Moreover, who diagnosed her with BSG? If it was the Burzynski clinic itself then I would be highly concerned about over-diagnosis to allow fantastical claims in the future.

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    2. I appreciate your concerns about big pharma and the FDA. I am of the opinion that medicine should never be a for-profit industry as that can never be in the interest of the patient (Burzynski is a classic case in point). I also don’t trust big pharma, I think that they often time patent applications in order to maximise profit rather than improving patient outcomes, and also that the association of money with medicine can have a profound impact on the clinical choices made at the bedside, particularly in the US. Nonetheless, I would say that the conventional treatments of chemotherapy and radiotherapy basically don’t turn a profit for the big pharma companies. They are too simple and too easily manufactured to allow the large patents that turn huge profits. Pharmaceutical companies have spent decades and billions of dollars trying to come up with more targetted treatments that do not require chemo- or radiotherapy. This is done with the expressed intention of overcoming the toxic side-effects of these conventional treatments, but in reality they are fully aware that such therapies would be massively profitable. In many cases they have succeeded, take Herceptin for instance, and have raked in huge amounts of money as a result. If Burzynski’s treatments were really effective, it would make far more sense to simply try and buy the company and patent the antineoplastons rather than partake in some shadowy conspiracy to keep Burzynski out of the mainstream. It is important to remember that Burzynski is very skilled at making himself appear victimised – people are inherently more likely to distrust large, faceless industries and regulators than the charming, chubby, harmless doctor who’s being pilloried for just trying to help people.

      However, let’s say for sake of argument that big pharma and the FDA do, for whatever reason, want to suppress antineoplaston therapy – there’s still no reason why Burzynski couldn’t just publish his findings and let the scientific community judge it objectively. The reviewers of peer-reviewed articles are academics with no vested interests in the therapy. Journal editors would be falling over themselves to be the first to publish evidence of an effective, non-toxic, targetted cancer treatment, if it existed. Scientists will believe anything, literally anything, that there is sufficient evidence for. Take quantum mechanics or general relativity, they’re absolutely bat-crap crazy concepts to normal human thinking, but we believe them because of the evidence that backs them up. The same would be true of antineoplaston therapy. Even though there is literally no biological reason whatsoever that it would work (as expanded on in my original post) if it were shown to be effective under peer-reviewed clinical trial then people would believe it. There is nothing big pharma can do to stop that; they can’t prevent publication, and once an effective treatment is in the scientific arena the weight to opinion is far, far too much for big pharma to silence or ignore.

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    3. Your concerns about the FDA are more puzzling. If they’re such a big problem then why wouldn’t Burzynski just move to another country? The FDA only has jurisdiction in the US, bear in mind. He could move to any number of places where science is equally or more advanced than in the States – pretty much anywhere in Western Europe, or even his native Poland. Regardless, I don’t see how the FDA could prevent his treatments, if effective, from becoming widely acknowledged. They can’t stop publication any more than the big pharma can, and in fact have been pressing him to perform proper clinical trials for years. Burzynski has rather cleverly misportrayed the FDA’s insistence on rigorous, objective clinical assessment as some kind of vendetta against him. He seems to think he should just be free to pump whatever he wants into patients with no need to justify it to the regulators. However, as I say, this is all somewhat moot as he could just take his research elsewhere – any country would be very happy to take someone who possesses a viable cancer treatment and can show it works.

      My final point is to ask you not to lose faith in conventional therapy. I’m very sorry to hear about your friend who died following radiotherapy. Oligodendroglioma is an awful condition that is difficult to treat, but there is a lot of evidence that chemotherapy and radiotherapy have profoundly beneficial effects on the prognosis of patients with this cancer (e.g. http://thejns.org/doi/pdf/10.3171/foc.2005.19.5.16). That your friend lived for 6 years with the condition is probably only because she was being treated, otherwise she would have succumbed far sooner. It is no secret that both radio- and chemotherapy are toxic, but they’re the best we have at the minute. My mother died because of a leukaemia that was, in my mind, probably partly due to chemotherapy that she had undergone for breast cancer 3 years previously. Nonetheless, if she had not had that therapy she would have died years earlier and we would have lost more time together. The treatments she underwent and that other cancer patients undergo simply give the best odds that we are currently able to achieve, but that isn’t to say it doesn’t come with risks attached. To not use them simply because there are risks is far more dangerous. Like you I cherish the right of an individual to chose, but an informed decision is always better than an uninformed one. The main aim of my post was to highlight the necessity for effective public education in the scientific process, and the importance of the demystification of science in general so everyone can see through the fog of pseudo-science used by businessmen like Burzynski. I sense I won’t convince you that antineoplaston therapy is nonsense as you’ve already read my post and don’t seem fazed by the evidence therein (NB. this evidence is quite separate from my own opinions regarding Burzynski himself), but I hope that I have encouraged you not to take at face value to sob story that Burzynski touts as the reason why antineoplastons are not in every hospital. If they truly worked there would be no way of suppressing it and no reason for Burzynski not to publish his findings.

      James

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