Time really does fly. It’s hard to believe that it’s been over a week since I gave my big (to me, at least) talk at TAM. It’s equally hard to believe that it’s been more than a week since I had the honor of being kicked out of Penn Jillette’s Private Rock & Roll Bacon & Doughnut Party because back in February I had had the temerity to question whether it was a good idea for Penn & Teller to appear on The Dr. Oz Show. It was a surreal experience, to be sure, to be cussed out publicly (albeit with no mention of my name), kicked out of Penn’s private party, and then to have had Penn sing a song about the whole experience, complete with a liberal sprinkling of f-bombs that I can’t use now that NatGeo runs ScienceBlogs. Maybe I’ll blog about it sometime, along with the reaction to it (which, sadly, was not much). Or maybe not. In the meantime, I want to revisit a frequent topic of this blog, namely Stanislaw Burzynski. Not much has happened since Burzynski’s propagandist Eric Merola released his second movie (reviewed here), but there are leftover issues that I’ve been wanting to cover for a while now. Fortunately, my research for my TAM talk will serve multiple purposes. Since the talk was so brief and required me to cover 40+ years of history in a mere 20 minutes, there was a lot left out. I hate to let all that research go to waste; so I’m going to use it for an intermittent series of blog posts.
While preparing for my TAM talk, I read two books from sources friendly to Burzynski. The first was Galileo’s Lawyer: Courtroom Battles in Alternative Health, Complementary Medicine and Experimental Treatments by Richard A. Jaffe. Jaffe was Burzynski’s lawyer for a long time, and in particular he helped Burzynski beat multiple raps in 1997, when it looked as though Burzynski might well be convicted of insurance fraud, violations of the Food, Drug, and Cosmetic Act, and other charges related to his antineoplaston therapy. Of the two, this book was the most revealing, because Burzynski wasn’t the focus of the book (although his story does take up roughly half of it). Rather, self-aggrandizement on the part of the author clearly is, which perhaps explains why Jaffe would say some things that he says that are particularly unflattering to Burzynski. True, Jaffe clearly thinks they are flattering (to him) and evidence of how clever he was in defending the misunderstood genius that he viewed Burzynski to be and beating the system in the mid- to late-1990s, but what they reveal to me about Burzynski’s current crop of phase 2 clinical trials is appalling. The second book is The Burzynski Breakthrough: The Most Promising Cancer Treatment and the Government’s Campaign to Squelch It by Thomas D. Elias. This book is more pure hagiography, a book designed to portray Burzynski as a Brave Maverick Doctor who can cure cancers that conventional medicine cannot. Amusingly, the latest edition boasts that there are now “clinical trial data” in it, which led me to wonder why Burzynski would provide such data to a columnist writing a hagiography about him rather than, oh, you know, publish it in the peer-reviewed scientific literature. However, Elias provides a bit more detail on certain aspects of Burzynski’s early years, and his account is interesting in that it doesn’t always agree with Jaffe’s account. Elias also provides testimonials from several of Burzynski’s patients who were treated before the Internet era whose stories are hard to find in detail online, for example, Tori Moreno. (For example, nothing in the chapter on Tori Moreno leads me to change my conclusions about how she survived.)
Obviously, given that both of these books are clearly pro-Burzynski, one has to take their claims and accounts with a grain of salt. (Actually, the salt mines under Detroit probably don’t contain enough salt for this purpose.) Even so and even noting that these are pro-Burzynski sources, I was shocked at the sorts of information in the books, there for all to see. To someone who knows cancer research, they contain some pretty damning information. Obviously, the authors didn’t see it that way when writing them, but I do.
The early years: Childhood
In many ways, Stanislaw Burzynski’s story is a prototypical immigrant rags-to-riches story. Stanislaw Burzynski was born in Nazi-occupied Poland in the city of Lublin on January 23, 1943, right as the Holocaust in Poland was gearing up in earnest. The previous year, mass killings had begun at Auschwitz-Birkenau, and mere months before Burzynski’s birth, the Sobibor and Treblinka camps had opened. So had the Belzen camp, to which the Jews of Lublin were deported soon after its opening. Other notable events in the year before Burzynski was born include the beginning of Operation Reinhard (the mass deportation of Polish Jews to concentration camps), the beginning of the liquidation of the Warsaw Ghetto, and many other atrocities. In 1943, the Jews of the Warsaw Ghetto mounted their uprising, and later Himmler ordered the liquidation of the remaining Jews in Poland.
Little is known about Burzynski’s early childhood and youth aside from what Burzynski himself has told sympathetic sources like Thomas Elias, from whose book I gleaned most of this account. Despite the devastation going on all over Poland, Stanislaw Burzynski was largely sheltered from the grim reality of Nazi-occupied Poland in his early years. His mother’s family was well-off and owned an ornate family house in the old part of Lublin built around three inner courtyards that had served as the local Roman Catholic bishop’s palace in the 1800s. It was designed in a Baroque Renaissance style, and its three-story facade bore elaborate sculptures around all the windows. Before the war, Elias reports, Burzynski’s grandmother used its large spaces to operate a private high school for girls. In the early 1940s, she gave her daughter and her husband an apartment in the building.
There was also a country house at the edge of the great Stary Las Forest outside of Lublin where the Burzynskis spent a lot of their time as well. Burzynski’s father, a teacher who was the son of a blacksmith, was apparently not well-regarded by his mother’s side of the family because he came from poverty and Poland was a very class-conscious society at that time. His father was also imprisoned by the Nazis because he kept teaching Jewish children, and the local Nazis did not like that. Interestingly, after the war, the Communists imprisoned Burzynski’s father for giving underground lessons that were apparently not politically acceptable. His father sounds as though he were quite the man. The son, on the other hand, was pugnacious and described himself as getting into fights almost every day, a situation that persisted until the fourth grade.
After the war, the Communist government confiscated the Burzynski house in Lublin and turned it into apartments, which were distributed to whoever needed them, although the Burzynskis got to keep their apartment. Elias also informs us that Burzynski’s brother Zygmunt was an anti-Communist fighter who was shot fighting the government in 1948 and died of meningitis as a result of his wound. In Elias’ book, Burzynski recounts these stories and uses his childhood pugnaciousness and belief that one should never duck a fight as a rationalization for not having moved his clinic to Tijuana years ago, saying:
So, the idea of fighting a government was nothing new to me when I began having troubles with the Food & Drug Administration.
And, based on the death of Zygmunt:
The idea of fighting people in authority became natural to me. I learned that you must never let them defeat you in your own core.
In some ways, these can be most admirable traits. Virtually all highly successful people who make a difference in the world possess some measure of this sort of determination and willingness to fight for what one believes. If only Burzynski had found a good cause to which he could yoke them. Unfortunately, he found antineoplastons.
The early years: The dawn of antineoplastons
Despite his tendency to fight, Stanislaw Burzynski was, unlike his brother, academically inclined. He did very well in secondary school and entered medical school straight from there, which was how it was done in Poland at that time. Somehow, he became intensely interested in amino acids and peptides. Working for chemistry professor Irana Krzeczkowski and biochemist Janina Blaut, the young Burzynski studied peptides in wild mushrooms that grew in the Stary Las Forest because his mentor wanted to find uses for them in agriculture. By the time he graduated from medical school in 1967, he had published fourteen scientific papers, which, as we say, ain’t too shabby.
In 1967, Burzynski was ready to work on his doctoral thesis. He had become interested in differences in the amount and types of peptides found in the blood and urine of renal failure patients and cancer patients. He reported that some of these chemicals were found at high levels in the blood of renal failure patients. He also found that cancer patients had a low level of some of these substances, which were not, it turned out, peptides. Ultimately, his work in this area resulted in a thesis entitled “Investigations on amino acids and peptides in blood serum of healthy people and patients with chronic renal insufficiency.” Of note, according to Elias, Burzynski finished his thesis in 1968, which makes one wonder how he could have possibly gotten a PhD based on it in such a short period of time. However, my purpose here is not to worry about whether his PhD is legitimate, as Saul Green has done. I don’t really care if Burzynski’s PhD is legitimate or not. What I care about is what Burzynski has done with his medical education over the last 46 years.
Ultimately, in 1970, Burzynski decided that he couldn’t stay in Poland anymore. What hadn’t been clear to me from all the reports and retellings of his decision to come to the US is why he chose to leave Poland in 1970. Whatever happened between 1968 and 1970, Elias reports that in 1970 Burzynski was being recruited to join the Communist Party but refused to join. This was perhaps the first case, but definitely not the only case, where his stubbornness caused him serious problems. Burzynski learned he was going to be drafted into the Polish Army, where he would be sent to wherever the Soviet Union needed him, but, thanks to the intervention of a prominent scientist, managed to get a passport and get out of Poland before his draft notice was delivered in early September. He arrived, as he has said so many times, at JFK Airport with only $20 in his pocket. Later he learned that his position at the university had been terminated.
Burzynski stayed with an uncle in The Bronx but soon managed to get a job at the Baylor College of Medicine in the Department of Anesthesia, then headed by Georges Ungar, a Hungarian refugee with whom he hit it off. Ungar was famous for proposing that memory resided in peptides made by the brain, and he tried to “transfer” memory by transferring those peptides from one mouse brain to another. It’s a hypothesis that seemed to be supported by his experiments at the time but faded from favor as more research failed to support it. Burzynski split his time between working on Ungar’s project and working on his own peptides, which he had finally dubbed “antineoplastons. He even managed, with the help of an investigator at M.D. Anderson, to secure an NIH grant in 1974. These years were productive for Burzynski, and he and Ungar published a lot of papers. Burzynski apparently killed a lot of rats in his time at Baylor doing Ungar’s research, which is something I can totally relate to, having dispatched hundreds of mice myself while doing angiogenesis research in the 1990s. Basically, rats were trained at tasks by the hundreds, after which they were killed and the peptides from their brains isolated. These peptides were then injected into the brains of other rats in order to see if the “knowledge” could be transferred with the peptides. Fun times!
The long, slow ethical slide
It was in Stanislaw Burzynski’s later years at Baylor that, arguably, the seeds of what he has become today were planted. In 1973, after three years of study, Burzynski had managed to pass the medical board examinations and obtain his Texas medical license. However, as I’ve pointed out before multiple times, he had no U.S. specialty training in oncology. In fact, he doesn’t appear to have had any specialty training even in internal medicine, and an internal medicine residency is a prerequisite to doing an oncology fellowship and becoming a fully-trained oncologist. One thing I couldn’t figure out from either book or any of my other reading is how Burzynski got a license to practice medicine in Texas. Usually, getting such a license requires at least a year of postgraduate medical training (usually an internship) in addition to medical school and passing the national medical board examinations. I can only speculate that whatever postgraduate clinical training Burzynski might have done in Poland must have counted, because I can’t find any reference to him doing any clinical training after arriving at Baylor. That’s not really the most important issue here, but it is a curiosity to me as a physician.
It’s also indicative of the extreme arrogance that Burzynski exhibited at the time. Elias recounts how in 1976 Burzynski thought that because he had obtained his medical license in 1973 he was then qualified to be the principal investigator for the first clinical trial of antineoplastons. He didn’t want to let anyone else be in charge of such a trial, even though it is obvious to me that at the time Burzynski was completely unqualified to run even a small phase I oncology trial. It’s rather instructive to look at what happened here from three different perspectives, the narrative in Elias’ book, the narrative in Jaffe’s book, and the description in Gary Null’s Penthouse article. Oddly enough, for being nearly contemporaneous, Null’s article mentions very little about Burzynski’s time at Baylor and why he ultimately left, at least nothing more than I discussed when I originally considered this article.
So what did happen? From what I can gather from Elias and Jaffe, a confluence of events conspired to push Burzynski towards his fate. Yes, I’m exaggerating a little, but not much. As I discussed before, Burzynski successfully got an NIH grant in 1974, but was unable to renew it in 1976; it expired in 1977. In 1976, apparently internal politics led to Ungar’s ouster from the Department of Anesthesia. According to Elias, the new “boss of anesthesiology” (as Burzynski was quoted as putting it) was Lawrence Schumacher, who wasn’t interested in peptide research and didn’t think much of Burzynski. He also, arguably quite appropriately, didn’t think that Burzynski’s research was the sort of research that was appropriate to a department of anesthesia. So Ungar ended up taking a job at the University of Tennessee, and Burzynski had trouble renewing his grant. Apparently, if Burzynski is to be believed, the new cancer research center at Baylor wanted to hire him and even offered him a $30,000 start-up package (respectable at the time), but it also imposed two conditions that were unacceptable to him. First, it wanted the rights to his antineoplaston discovery. This has been common practice at universities for a long time. If an investigator discovers something patentable while working for a university, usually the university will patent it and share a significant cut with the inventor. Burzynski, however, didn’t want to share. Similarly, although Ungar offered Burzynski a position in Tennessee, Burzynski did not want to follow his friend there because he was afraid that the University of Tennessee would want his antineoplastons, too.
There was another condition, too, and it’s a problem that tells me that from a very early time in Burzynski’s career he didn’t “play by the rules.” However, it was more than that. Not only did he not “play by the rules,” but he didn’t much care for those pesky regulations and ethical codes designed to protect human subjects. Here’s where Elias and Jaffe diverge. According to Jaffe, shortly after he got his medical license Burzynski started a private practice on the side, and that practice became fairly lucrative. According to Jaffe, Burzynski joined someone else’s practice part time. Actually, Elias is inconsistent on this issue, at one point implying that it was Burzynski’s private practice and at another point saying that Burzynski worked for someone named Dr. Walker. Whatever the case was, both agree that before he even tried to undertake clinical trials of antineoplastons at Baylor, Burzynski had been giving ANPs to patients at his private practice. Just how long he had been doing that was not clear from either account, but it was clear that he did it before undertaking clinical trials. Indeed, that was why Baylor’s requirement as a precondition for his taking a position at the cancer research center that Burzynski give up his private practice that was such a sticking point to Burzynski, as Elias describes:
Despite the enhanced prestige, secure salary and tenure that could have been his had he gone along with the proposed changes, Burzynski hesitated. He didn’t like the idea of subjecting himself to the authority of an institution. As long as he had a private practice, he believed he could use whatever medications he thought most effective, subject only to the consent of his patients.
In any case, in late 1976, Burzynski applied to the Baylor Institutional Review Board to be able to begin a clinical trial of antineoplastons but was turned down. Both Elias and Jaffe claim (no doubt because Burzynski told them this) that the reason Baylor’s IRB turned Burzynski down is because he didn’t have an IND. An IND is an “investigational new drug” application, which the FDA requires before it will approve a clinical trial of an experimental drug. In both accounts, Burzynski laments that Baylor turned him down and that he couldn’t get an IND because, according to him, IRB approval was required to get an IND, leading to what he referred to as a circular process that dogged him for several years. Reading these accounts, I can’t help but think that there must have been more going on. For example, I’m not sure how much different it was in 1976, but in general the FDA requires the following information for an IND:
The IND application must contain information in three broad areas:
- Animal Pharmacology and Toxicology Studies – Preclinical data to permit an assessment as to whether the product is reasonably safe for initial testing in humans. Also included are any previous experience with the drug in humans (often foreign use).
- Manufacturing Information – Information pertaining to the composition, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product. This information is assessed to ensure that the company can adequately produce and supply consistent batches of the drug.
- Clinical Protocols and Investigator Information – Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose subjects to unnecessary risks. Also, information on the qualifications of clinical investigators–professionals (generally physicians) who oversee the administration of the experimental compound–to assess whether they are qualified to fulfill their clinical trial duties. Finally, commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.
In other words, an investigator doesn’t need to get IRB approval before applying for an IND. The investigator has to promise he will have the study that ultimately derives from an IND will be reviewed by an IRB, obtain informed consent from patients, and adhere to the FDA’s IND regulations. I can, however, see many reasons why an IRB might be reluctant to give its approval for a study using a treatment like ANPs. For one thing, in 1976 Burzynski had no animal data to speak of. In fact, the question of animal studies is an interesting one. Both Elias and Jaffe recount a story in which ANPs didn’t work in animal tumors, and Burzynski has been quoted in multiple places as claiming that ANPs are species-specific and that ANPs derived from human blood and urine don’t work in animal tumor models. This is in contrast to what Null reports in his near-contemporaneous account, in which he stated that in tissue culture and animal models Burzynski’s ANPs worked “specifically against certain types of cancer,” all with “no toxic side effects.” It makes one wonder whether the “species specificity” was an excuse developed later to explain the lack of animal data.
Whatever the case, it’s not surprising that an IRB would balk. From what I can tell from every account I’ve read, in 1977 there just wasn’t enough preclinical data to justify a clinical trial, nor was it even clear yet exactly what ANPs were, as Burzynski hadn’t yet identified all the constituent chemical compounds were that made them up. Worse, ANPs were derived from urine, which opened up the possibility of infectious agents being transmitted from ANP preparations made from human urine. Moreover, in 1977, as far as I can tell, Burzynski didn’t have the capability to isolate sufficient quantities of ANPs to treat patients, having told Elias that he required 30 L of urine per day per patient. It wasn’t until the early 1980s that Burzynski learned how to synthesize ANPs, and that was after he had left Baylor.
After Baylor’s IRB rejected his application, Burzynski tried the Park Plaza Hospital, which was affiliated with Baylor. Park Plaza turned him down. Ultimately, the IRB at Twelve Oaks Hospital, which is where he treated his first patients with ANPs, approved his application. At this stage, Jaffe’s account is more illuminating, because it demonstrates just how scheming Burzynski was at the time. He had lawyers investigate whether he could give ANPs to patients at his clinic and how he could avoid getting into trouble. Their advice to him was that, because Texas at the time didn’t have a “mini-FDA” act, in which only FDA-approved drugs could be given to patients, the only way he might get in trouble with the law administering ANPs was if he were to ship them across state lines and thereby fall under the federal Food, Drug, and Cosmetic Act and the FDA’s authority. Basically he was told that, as long as he was making ANPs in his own laboratory and giving them only to his own patients, it should be legal under Texas law.
Jaffe also recounts some amusing anecdotes of Burzynski’s early years after leaving Baylor. Back then, he really did isolate ANPs from blood and urine. Apparently before he left Baylor, he got ANPs mainly from blood:
For the previous few years, he had been obtaining antineoplastons from human blood in an unusual way. He got his raw material from the blood of his friends and acquaintances. He would go to parties and public gatherings with IV lines and bottles and beg and cajole his friends and colleagues to donate blood for his research.
After a while, he noticed he was getting fewer and fewer invitations to parties, and, when his friends would see him on campus or the street, they would turn and walk away quickly, pretending they didn’t see him.
This sounds a lot like Andrew Wakefield and his “experiments,” doesn’t it?
After he went into practice for himself, Burzynski’s need for raw materials skyrocketed, and the only feasible way to get them was from urine. To get it, Burzynski arranged to install urine collectors in public parks and the state penitentiary system. Most amusingly of all, apparently Burzynski collected urine from Gilley’s Bar, where Urban Cowboy was filmed. One wonders whether John Travolta contributed to some of those early antineoplaston batches.
Back to the future
In my next installment in this series (which probably won’t be next week), I’ll discuss some of Burzynski’s legal battles, up to and including his epic battle in the 1990s that led to his indictment in late 1995 on insurance fraud and violation of the Food, Drug, and Cosmetic Act and his ultimate acquittal based on a hung jury in early 1997, as well as how the Burzynski Patient Group was formed and used to bring pressure on the FDA and Texas Medical Board to rule in Burzynski’s favor, all with the help of some very powerful politicians, such as Representative Joe Barton of Texas. At some point, I’ll also look at the “clinical trial statistics” that Elias promised on the cover of his book. However, I will conclude by pointing out exactly what it is that Jaffe said that he really shouldn’t have. It’s of a piece with Burzynski’s history in that shows how, 20 years later, Burzynski wasn’t really interested in doing clinical trials. They are and always have been a means to an end: To let him give ANPs to patients unmolested by the authorities.
Jaffe in essence boasts about this in his book. Because Rep. Joe Barton had put such enormous pressure on the FDA through his Congressional hearings and bad publicity replete with crying cancer patients lamenting how they would die if Burzynski were shut down, in 1997-1998 the FDA was going to relent and let Burzynski apply to undertake clinical trials. In response, Burzynski put together a clinical trial known as CAN-1, which was basically a retrospective study of all the patients Burzynski had treated with ANPs up to that point in 1997. Listen to how Jaffe described it:
So we decided to hit the FDA with everything at the same time. All of his current patients would be covered in a single clinical trial which Burzynski called “CAN-1.” As far as clinical trials go, it was a joke. Clinical trials are supposed to be designed to test the safety or efficacy of a drug for a disease. It is almost always the case that clinical trials treat one disease.
The CAN-1 protocol had almost two hundred patients in it and there were at least a dozen different types of cancers being treated. And since all the patients were already on treatment, there could not be any possibility of meaningful data coming out of the so-called clinical trial. It was all an artifice, a vehicle we and the FDA created to legally give the patients Burzynski’s treatment. The FDA wanted all of Burzynski’s patients to be on an IND, so that’s what we did.
This is Burzynski’s lawyer writing here. I thank him for his candor, particularly since he describes how the dozens of other clinical trials, 61 of which still show up on the ClinicalTrials.gov website, came into existence. According to Jaffe, it was not because Burzynski was so interested in knowledge and finding out whether ANPs work. It was because he already believed they worked and wanted to keep treating patients without interference:
CAN-1 allowed Burzynski to treat all his existing patients. That solved the patients’ problems, but not the clinic’s. A cancer clinic cannot survive on existing patients. It needs a constant flow of new patients. So in addition to getting the CAN-1 trial approved, we had to make sure Burzynski could treat new patients. Mindful that he would likely only get one chance to get them approved, Burzynski personally put together seventy-two protocols to treat every type of cancer the clinic had treated and everything Burzynski wanted to treat in the future…Miracle of miracles, all of Burzynski’s patients were now on FDA-approved clinical trials, and he would be able to treat almost any patient he would want to treat!
And for patients who didn’t fit into one of these seventy-three clinical trial protocols (CAN-1 plus the other seventy-two), there were always single-patient INDs, otherwise known as compassionate use protocols. I also can’t help but wonder what the alt-med believers who support Burzynski would say if I were to say about my cancer center something like, “A cancer center cannot survive on existing patients. It needs a constant flow of new patients.”
Yes, from a very early time in the late 1970s to twenty years later in the 1990s to this very day, for Stanislaw Burzynski, clinical trials are but a means to an end, and that end is not scientific knowledge or to determine whether or not they work against cancer. The end is to allow Burzynski to treat cancer patients with ANPs. He is, after all, the Brave Maverick Doctor fighting the system, as he thought of himself as fighting the system in Communist Poland. From what I’ve been able to discern, to him government laws and regulations are not designed to protect patients but to keep him from curing them. So getting around them by any means necessary is not only justified but mandatory. The question becomes: Does Burzynski still believe himself to be the man who has cured several forms of cancer, or does he now know that ANPs almost certainly don’t work and are definitely not some sort of “miracle cure”?
To be continued…