Tuesday, January 31, 2012

“The Valley of Death” — Behind The Gianormous Fruitfly on ICOC Board

For those who are working in biomedical research, “the valley of death” is nothing unfamiliar. It refers to the difficulty of crossing the gulf between finding a promising new agent and demonstrating its safety and efficacy in humans. For those who do not know what “the valley of death” is, those on ICOC board, those journal editors and reviewers, those grant reviewers, it can be found in the cover story in Newsweek by journalist Sharon Begley titled “Desperately Seeking Cures: How the road from promising scientific breakthrough to real-world remedy has become all but a dead end.” It refers to the status quo of mainstream biomedical research being stuck in the non-human simple model organisms, such as bacteria, drosophila, zebrafish, and mouse, with vast investment to only generate a vast amount of knowledge completely useless for the prevention and treatment of human diseases. It refers to the vast waste land of biomedical research. It refers to all drug development leads but only very few lucky ones have fallen out of clinical trials. It refers to among those few lucky ones, there were not any cures, or even meaningfully effective treatments, for Alzheimer’s disease, lung or pancreatic cancer, Parkinson’s disease, Huntington’s disease, or a host of other afflictions that destroy lives. It is hard for anyone to imagine that it would come up with a cure for cancers, Alzheimer’s disease, Parkinson’s disease, Lou Gehrig’s disease, diabetes, or heart disease by dissecting a fly to molecular levels. However, it has been the status quo of all major universities and institutes. It is still where the vast amount of funding of National Institutes of Health goes, to maintain the status quo of these universities and institutes, despite no return on investment to the American taxpayer for the slightest improvement to human health, despite no return on investment to the American taxpayer judging by the only criterion that matters to patients and taxpayer — not how many interesting discoveries have been made, but how many treatments for diseases the money has bought. The consequence is pounding. To date, after all the biomedical research investment, there is no cure or even meaningfully effective treatment developed for those major health problems that are deadly and affect millions. The extremely toxic chemotherapy, which is based on a simple fact that cancer cells as well as all the normal dividing cells known as stem cells are more sensitive to toxics and radiations, is still the only treatment option for the deadly disease after close to trillion of investment to cancer research, after all those years.


When Prop71 was passed in CA, human embryonic stem cell (hESC) research was a new forefront in human subject research, a unique opportunity to bridge the valley of death, a promising opportunity to turn investment of the California taxpayer into meaningfully effective treatments or cures to relieve the huge burden of those deadly diseases to the CA health care and society we live in. There has been a law for it in CA, a law to ensure hESC research to be funded in CA, a law to ensure stem cell therapy and cures can be developed, a law to ensure return on investment to the California taxpayer. Why could it be that most of the funding has still gone to the valley of death? Why it has been so difficult to fund hESC research?

When Prop71 was passed in CA, as a controversial human subject research that can still be sued, hESC research virtually did not exist in all the universities and institutes in CA. Unlike every other scientific field where the director has demonstrated record of achievement in the field they direct, in order to get a piece of the stem cell pie, all the universities have appointed professors, mostly very prestigious in their own research field but no hESC research experience at all, as stem cell center directors overnight. However, research is not community charity or communism. It has research data ownership, research facility ownership, authorship, and intellectual properties. It has competition, recognition, prize, and award to outstanding individuals for the achievement. Those directors, created solely for the money purpose, have no demonstrated record of achievement in the areas of pluripotent stem cell and progenitor cell biology and medicine that the law requires to deliver the real goods, but have strong connections in the scientific community, such as on, affiliated, or connected to many advisory boards of companys and foundations, many editorial boards, review boards, committee boards, meeting committee boards. In order for multi-millions of stem cell bond to come their ways, they have used their muscles to compart the research community, to block their competitors, in the name of collaboration. Some of those directors are also on CIRM advisory board, with majority of the board members are from the same universities and institutes, it would not be too difficult for them to sneak in multi-millions initiatives that can bypass the law, multi-millions initiatives that have nothing to do with Prop71 but bore the criteria of their resume so that only qualify themselves and disqualify their competitors. To make things even easier for them, there were hand-shakings and undocumented internal meetings with CIRM behind the public eyes. Finding one stem cell professor in UC was difficult, where did the 100 stem cell professors, publicly known as stem cell experts, come from? Finding one stem cell professor in UC was difficult, but finding 100 fly-dissecting professors in UC was no problem. Larry Goldstein sent a mass email to 100 fly-dissecting professors in UC to promise everyone a guaranteed spot on Sanford Consortium for Regenerative Medicine and easily got $40M come his way, so did every other appointed stem cell center directors. Craig Venture and Ellen Feigal only needed 50 of them to sneak through another round $40M of genomic initiative for Catriona Jamieson despite that there already are many companys that can provide the same or even better genomic services. You could not believe your ear to hear some stem cell director or professor, who really is a virus professor or a fly-dissecting molecular biologist without slightest care for or knowledge of hESC research, saying things like “I just got $5M from CIRM, I do not even know what I am going to do with it”, while those stem cell research facilities do have the demonstrated record of achievement that the law requires, such as ACT, had to close their facility because they could not get that $5M to keep their facility open and some meaningful stem cell research going. With 100 of those fly-dissecting professors awarded $M by CIRM without any record of achievement that the law requires and without having to do anything to advance stem cell research, those really qualified applicants would only feel shocked their stem cell therapy development grants blocked by CIRM’s pre-application with critiques saying things like that the PI did not have drug development experience or did not address immunogenicity issue. When did California stem cell research and cure bond act become drug development for big Pharms? Do we all know Ellen Feigal from drug development company, has drug development experience, was there any connection, was that why most of CIRM disease teams went for drug development? You would wonder why there was the immunogenicity initiative while hESCs are already less immunogenic than anything else, why the stem cell research leadership initiative excludes anyone in CA, why there is only iPS cell bank, not hESC bank initiative. Why would Catriona Jamieson need another $40M from CIRM while she already got $20M CIRM disease team award not for a stem cell therapy but a conventional drug development in her drug development company, is it because her connection with Stanford, with those Harvard reviewers on CIRM board, or her drug development company’s close connection with CIRM board member and UC Connect Duane Roth, you go figure.

To ensure fairness, in a democratic capitalism country, all the federal and state contracts usually need to have at least 2 bidders. However CIRM has no competition, therefore, can do whatever they want, their job is to dole out the money, to dole out someone else’s money not single one of those on CIRM board and staff would really care, and whoever receives the money and what happens to someone else’s investment would not really matter to any of them. To believe the fairness of CIRM is just like to believe the idea of communism. Do you think it is a bit of odd that 8 years after passing Prop71, there is still only stem cell center, but no stem cell faculty for stem cell research in all the universities and institutes? Do you think it is a bit of odd that CIRM’s stem cell research leadership awards have never listed those leaders’ achievement in stem cell research and leadership activity as any leader should have. If take a look at ICOC board, there was not any one advocate for hESC research considering it is a stem cell agency, Bob Klein probably was the only one who is a strong supporter for hESC research. Whoever wrote Prop71, whoever voted for it, must feel ill to see a gianomous fruitfly on ICOC board qualified for a piece of stem cell pie, while the same group behind the gianomous fruitfly on stem cell pie was also plotting to sue the remaining of the hESC research labs that have struggled hard to open to develop crucial stem cell therapy to the patients that CIRM really cares about, to force them to close, to shut them down for good. What makes those big universities and institutes so ruthless? NIH’s new iPS cell center director Mahendra Rao was mentioned at the ICOC board to implicate that NIH might be part of the conspiracy too. We all know Mahendra Rao was from Buck, has close connection with Sanford Burnham and my mentors. Subconsciously, the gianomous fruitfly might be little bit too odd to the picture of the CIRM ICOC board, so one of the board member asked CIRM staff about the grants criteria in the law to make sure, and the CIRM staff could not give a full account either. The ICOC board meeting definitely was an eye opening experience. Without total transparency, without competition for the job that CIRM is doing, whoever thinks their grant will get a fair review by CIRM, judging by the demonstrated record of achievement in the areas of pluripotent stem cell and progenitor cell biology and medicine, judging by the scientific merits written into the law, judging by the return on investment to the California taxpayer, is just as naïve as I was.

The result of CIRM’s strategy to fund the valley of death is the valley of death. The consequence is pounding. To date, after having doled out $1.3B investment of the California taxpayer on stem cell research by CIRM, there is no return no stem cell therapy no cure developed for those major health problems that remain a huge burden to the CA health care and the society we live in.

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