Things that used to be on a blog.

Burzynski's "research" – Part 2

July 21, 2012

Another piece of published research thrown in everyone's faces by Burzynski supporters multiple times over the last fortnight was a paper titled "Phenylacetylglutaminate and Phenylacetate in Combination Upregulate VDUP1, Cause Cell Cycle Blockade and Apoptosis in U87 Glioblastoma Cells". This appeared in the Journal of Cancer Therapy. Here's the abstract:

Phenylacetylglutaminate (PG) and Phenylacetate (PN) are metabolites of Phenylbutyrate (PB) and are constituents of antineoplaston AS2-1. These are sodium salts of amino acid derivative and carboxylic acid that inhibit the growth of neoplastic cells without growth inhibitory effect in normal cells. The aim of this study was to identify molecular pathways involved in the anti-proliferative effect of antineoplastons. Using a total human genome microarray we have found that 1) Vitamin D3 upregulated protein (VDUP1) is significantly upregulated in response to PG and PN in the U87 glioblastoma cells; 2) Isobologram analysis shows that PG and PN act in an additive or synergistic manner to effectively suppress proliferation of U87 cells; 3) PG and PN cause cell cycle arrest, changes in expression of several cell cycle genes and suppress expression and activity of the G2/M checkpoint kinase, CHK1. The multiple cellular targets possibly make these compounds effective anti-proliferative agents. We propose that PG and PN in combination target important cellular pathways and upregulate VDUP1 leading to detachment-induced apoptosis in cancer cells.

Now that's a very sciency set of words. Let's do some evaluation.

• The Journal of Cancer Therapy is indeed a peer-reviewed publication. Unlike most reputable journals, however, you can pick your own referees. Try telling Nature who the peer reviewers are to be and expect a very frosty reception, if they bothered to answer at all. It simply isn't done.
• Publication in the journal costs $600. As you can select your own reviewers it is difficult to imagine how anything can be rejected, so it is probably safe to assume that anything that gets submitted will be published as soon as possible after the cheque clears.
• Remember Impact Factor? This journal does not appear to have one. That means that almost nobody references it in their papers.
• Among the billions of web pages indexed by Google, 113 of them contain the word "Phenylacetylglutaminate". A quick scan of the first couple of pages of the Google results shows mainly references to this paper and other things written by or for Burzynski. Perhaps antineoplastons aren't the only chemicals he has invented.
• It says "[t]he aim of this study was to identify molecular pathways" but it seems that what was being observed was the effect, not the process that produced that effect.
• It goes on to say that maybe molecular pathways have something to do with what they saw but they don't know.
• I looked at the full paper to see what controls were used. The tests were not blinded and it appears that the controls were cell cultures that were simply left alone.
• As the chemicals used have a high sodium content (recognised in the preparation of test samples) and it is known that sodium salts can damage cells in high enough concentrations it might have been a good idea to test some samples with a saline solution of the approriate concentration as a control.

So, in summary, it was found that an in vitro test of chemicals which when dissolved produce a significant concentration of sodium ions (enough to cause concern when preparing reagents) damaged cancer cells more than doing nothing to the cells did. No attempt was made to see if the effect could have just been due to the high level of sodium salts, but the ability of salt to inhibit cell division and kill cells has only been known since the first woman discovered salt as a meat preservative so why would the scientists need to worry about it in this experiment? Lots of things kill cancer cells in vitro, but I'm not about to start letting anyone inject bleach into me. The results were then published in a pay-for-publication journal that uses a meaningless "peer review" process.

This "experiment" proves nothing that couldn't have been predicted by a thought experiment and some knowledge of basic chemistry and biology. All the supposed science and graphs and statistics in the published paper are window-dressing to hide the fact that nothing new has been discovered and to provide yet another advertising tool for Burzynski and his supporters to use to snare more victims. Non-scientists referred to the paper will see all the big words and graphs and have no idea that it is all a smokescreen. There is no way this paper could get published in a reputable journal where proper peer review was conducted. It is a junior high school science project dressed up to look like grown-up science.

But here's the real question – if Burzynski has been researching antineoplastons for 45 years, why has he waited until now to see if they kill cancer cells in vitro? Surely that would be the first thing you do before you ever go near a human patient. Like I said, this is a smokescreen to hide the fact that Burzynski has no science to back up his claims. It's like the homeopaths that offer experiments purporting to demonstrate that water has a memory. It doesn't matter if antineoplastons kill cancer cells in a petri dish, what matters is whether they are an effective treatment for cancer. Until Burzynski starts doing real clinical trials, with adequate subject numbers and proper controls and blinding, running the trials through to their conclusion and publishing the results we are entitled to  treat him according to the image he presents. The image of a charlatan who lies about science in order to steal the life savings of desperate, sick people. The image of a calculating crook who will do or say anything to get what he wants.