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Tuesday, April 10, 2012

"We Re-Measured" Honesty

In my study of the Cargo Cults of Biotech I have seen first hand the curious deceptions that humans employ to get around the rigors of the scientific method. We had a drug to prevent angiogenesis, for example, that was to stop tumor cells from growing. In a study using mice, the Rituxan control group stopped tumor growth entirely. The PBS group all sprouted various sized tumors. Some mice, with smaller tumors, had to be euthanized sooner than those with bigger tumors. The group of mice receiving our drug were no different than the PBS control group. Without any trickery, Rituxan was an obviously efficacious treatment for mice being injected with cancer cells. Our drug was not working.

We were sent back to the lab with a grad student who showed us how to "properly" measure the tumors. She got the desired results by squeezing the caliper a little tighter around our drug group, and less so around the PBS control group. When I handed her a mouse that she had already tested, she wanted to know what her first measurement was. I refused to tell her even what group the mouse was in. Should she measure tight or loose with the caliper?

Why not simply take out a new data sheet and change the numbers? Because that would be misconduct. By re-measuring the tumors we were being, by Cargo Cult standards, more honest. The ceremony of re-measuring made us feel better about fudging the data. It somehow took us out of the realm of flat out fraud.

This experience shaped my view of early stage cancer research. The measurements are meaningless because cancer doesn't work in a manner that would make our research easier. Tumor size is an end point that the human beings conducting research can handle. The reality of explaining the "leaves blowing in the wind" chaos of cancer cells in the body would be too hard to follow. Using the "Drunk Under the Streetlight" logic we now have a place to look for efficacy. Using the "Beer and Pizza Diet" we then have a way of dealing with the nonsense we find.

Our anti-angiogenesis drug used in the cancer study described above, was picked up by a company called Cancervax. Their product was an attenuated cancer cell that expressed 26 antigens on its surface. It failed clinical trials in 2005 and the drug development ended. The anti-angiogenesis drug faded away, last heard from in 2007. While these two anti-cancer products were discontinued, the methodology remains much the same. Cargo Cults may have many iterations of their airports but the thing that is missing is always missing.

Two news items came up this week to exemplify the Cargo Cult science as usual approach. Presage Biosciences make the claim that they can separate the winning compounds from the losers early in development. According to Xconomy, Presage has partners who, "are hoping to improve the odds of success in clinical trials, where only about one out of every 10 cancer drugs that enters clinical trials ever makes it through the hoops necessary to become an FDA-approved product." The leaders are right ten percent of the time? Well anyway, Presage will help them increase their hit rate. "One of the operative words in cancer research today is “combinations,” which Olson (Presage founder) said people are buzzing about this week at the American Association for Cancer Research meeting in Chicago. Companies are becoming more interested in finding those instances in which a single drug doesn’t work on its own, but can show a potent effect when given synergistically with another compound that works in a different way." 

In 2012 folks at the AACR are buzzing about combinations? Perhaps science needs historians to keep the research in a scientific perspective. In addition to CancerVax's 26 antigens, I think  the Anil Potti story is germaine to this company. The Presage approach assumes that maybe we are only off by a few targets. Instead of grandma taking one or two pills for her cancer, she might need ten. Twenty? A thousand? No, that couldn't be because we can't make grandma take that many pills. The bloggosphere is buzzing too. Here is a comment on the AACR from In the Pipeline:
Take a look at the 6000+ abstracts from the 2012 AACR national meeting last week. Wishful thinking is a mild description for that carnival sideshow. Maybe 3% of the work was worthwhile. Four darts and a genome map would provide a better chance of hitting a cancer response biomarker.
I added that because it cleanses the palette after Jim Olsons gung-ho attitude towards the AACR meeting. And it's funny. 

The second news item this week comes from Oncothyreon.  They are marching forward with a Beer and Pizza Diet approach to their original stinker. According to Xconomy:
There are some very interesting scientific and business reasons why Oncothyreon wants to test the second-generation product, called ONT-10. It is attached to a more potent immune-boosting compound than the original, and the new drug is designed to stimulate a sort of two-pronged immune response, instead of just the T-cell reaction sparked by the original.
Why not start with the more potent immune booster? Why did they need to improve something on which they had already placed a huge bet. The company and their investors have us thinking that the clinical trials of their original product won't be much to talk about. But the new and improved product... now that's... well it's just going to be better... that first thing we did wasn't well thought out and... is it getting hot in here?

My message is that we are not really changing the way in which we approach cancer research. At the end of the sciencey meetings and the millions of dollars, a low paid BS Biology major, in her early 20s will be given a caliper and told to go measure the tumors on the backs of nude mice. Whatever the method, whoever makes the measurement, some things will remain the same. All of the promises will be backed up by the same "we-remeasured" honesty. We have not worked out a method to prevent it. It is a human issue involving psychology, not a laboratory issue, business model or funding issue.

Of course we hope that Presage and Oncothyreon are telling the truth. We want to believe them. We want them to be honest and not just "we re-measured" honest.

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