Center for a Stateless Society
A Left Market Anarchist Think Tank & Media Center
Cancer Therapy and Barriers to Open Biopharma

Science and innovation are chaotic, stochastic processes that cannot be governed and controlled by desk-bound planners and politicians, whatever their intentions. 

Good scientists are by definition anarchists.

–Theo Wallimann, ETH Zurich


Abstract

Although profitable, cancer therapy has failed to live up to the promises of the War on Cancer waged since 1971. Modern chemotherapy can exceed $100,000 annually for patients prescribed patented medications of dubious long-term benefit. R&D costs, thought to justify high prices, are in fact far less than claimed. The present intellectual “property” regime has impelled researchers like Dr. Isaac Yonemoto to seek crowdsourced funding to develop a promising unpatentable molecule as an open-source cancer drug (9DS, 9-deoxysibiromycin). While fully supportive of this effort, we wish to call attention to longstanding Corporation-State erected barriers to entry for disruptive therapies and funding models.

The Palliative Machine: Medical Monopoly under the Corporation-State by Sebastian A. Stern, is strongly recommended as a prerequisite to this article.

Open Source Drug Development – Rescuing 9DS from Oblivion

The Project Marilyn/indysci.org team should be applauded. As of this writing, they have reached their initial $50,000 goal, and finished about $8,000 over, to fund the project.

We won’t analyze their scientific prospects (though we will say that DNA-alkylating agents are passé and targeting cancer-specific metabolism and cell surface markers is the future of chemotherapy), but sincerely hope that progress is made.

However, as with Wikileaks, Bitcoin, or Anonymous, whether this particular project succeeds is secondary. The truly disruptive event is the model, the idea. Many copycats have replicated cryptocurrency, hacktivism and anonymous leaks and, at times, doing it better.

Should indysci.org or Project Marilyn stumble, let that not be evidence of futility, but a clue for the next iteration of the stigmergic model of science funding. The imperative force to fix the medical system is too great for concerned parties to resign.

The cat is out of the bag. 

Corporation-State Barriers Still to be Overcome

By no means is victory inevitable — quite the contrary. There is a veritable Library of Alexandria of preclinical evidence supporting medicines that never come to market. The problem isn’t curing disease in mice; cancer and other diseases are said to have been cured in mice many times over. The problem is higher up: at the level of the FDA and pharma.

How do we reconcile the irrepressible deluge of preclinical findings for promising drugs with the truly devastating paucity of FDA-approved chemical entities? It’s not that mice and men are so different, but the fatal flaw is in the incentive structure of the centralized, corrupt corporate-regulatory nexus.

There are two major problems faced by Project Marilyn et al and those who will follow in their footsteps: If the drug works too well, it might be tabled by the FDA on behalf of pharma. Secondly, pharma may patent a “me-too” drug analogue, establish it as the standard of care and any doctor deviating from their product will be liable for malpractice. Welcome to patent medicine under corporate capitalism, brought to you by humanitarian John D. Rockefeller and his cartelizing Flexner Report of 1911.

Emerging Alternatives to Centralized Medical Decision-making

The People need a way to conduct clinical trials and distribute medicine that routs around the FDA. For example, quantified self and cheap biomarkers would enable patients to upload their data.

Adverse effect reporting can be conducted by a third party regulator like the Environmental Working Group, which already tests cosmetics and water supplies. This way, desperate patients won’t have to wait 7 years for the FDA to approve a drug showing low toxicity (and regardless of efficacy, after all, “First, Do No Harm” said Hippocrates).

Synthetic biology and distributed biosynthetically-engineered microbial factories (yeast, bacteria, algae) could manufacture the drugs. This is how Genentech makes the recombinant insulin peptide or how Evolva SA makes natural products like resveratrol and vanillin — these can be distributed P2P at low marginal cost per unit.

Forget 3D printer chemistry — evolution has crafted enzymes that are far more efficient than any chemist’s reaction, with no expertise required other than some nutrient broth to culture the cells. The remaining puzzle piece is actually designing the (modified) natural product biosynthetic pathways: it’s not always known which enzymes do which reactions and in what order.

The roadmap to open-source data-driven medicine is coming into view, but we should expect resistance from biopharma and the state going forward.

The Cure: Just Around the Corner Since 1971

Everyone should know that most cancer research is largely a fraud and that the major cancer research organizations are derelict in their duties to the people who support them. –Linus Pauling, PhD, winner of both the Nobel Peace Prize and Nobel Prize in Chemistry, link to original document.

Cancer is big business. It is the second leading cause of death in the U.S. (576,961 in 2010, after heart disease) and War on Cancer is worth over $125 Billion annually according to the National Cancer Institute. Biopharma elites consider illness a cash cow rather than a blight to be eradicated. This is illustrated most recently by Memorial Sloan-Kettering Cancer Center whistleblower Ralph Moss, PhD in the documentary “Second Opinion” (2014).

The goal of the industry is to indefinitely “manage” disease — curing it would destroy the market. (Talk about a perverse incentive structure.) Recall how the “defense” industry seeks to initiate armed conflict, Gen. Smedley Butler’s “war is a racket” and Gen. President Eisenhower’s military-industrial complex.

The prime directive of any individual or institution is self-preservation (and corporations seek indefinite expansion at all externalized costs).

The economic idea behind this suppression is akin to reverse planned-obsolescence: call it planned-permanence, a form of retarding progress in order to extract economic rents.

The same dynamic prevails with new energy, transport, finance, and less violent forms of governance. (Government-imposed invention secrecy is on the rise, and applies especially to high efficiency energy systems).

The legal magic that keeps disruptive technology under-wraps is called intellectual “property.” (See “Against Intellectual Monopoly” PDF by Boldrin and Levine 2008).

There are many examples of government-pharma suppression of disruptive therapy (a few are discussed in The Palliative Machine: Medical Monopoly under the Corporation-State).

Regardless of whether any one of them works: shouldn’t free individuals be allowed to chose their own therapy, especially when the standard of “care” has failed them? Shouldn’t the same logic apply to the consumption of any chemical? Or any behavior that doesn’t violate the negative rights of others?

For those skeptical that the politburo would conspire to conceal any medically relevant information: Never forget that, for half a century, Big Tobacco and the State successfully convinced doctors and the public that cigarettes were not harmful. (The film “Thank You For Smoking” (2005), executive producer Elon Musk, is a witty modern take on tobacco lobbying).

Today, we recognize cigarettes as the world’s leading cause of preventable death.

Next we’ll be hearing about how sugar and non-ionizing electromagnetic radiation (cell phones, wi-fi) cause cancer, or some such quackery that threatens profits. There is little financial incentive to uncover the causes of illness, because discovering hexavalent chromium 6 (see Erin Brockovich and PG&E) in the water supply doesn’t make money for shareholders (and that the development of cancer does generate new business).

Furthermore, many plant-derived natural products (like curcumenoids, compounds found in turmeric) show high efficacy against cancer with low toxicity (in addition to a litany of other benefits, including augmenting adult neurogenesis). Natural products don’t interest pharma because they cannot be patented without modification. Furthermore, most modern disease, including cancer, arises due to improper diet, lifestyle and the scourge of biological aging.

Creative Accounting and Overstated R&D Costs by Big Pharma

It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor of The New England Journal of Medicine. –Marcia Angell, M.D.

Pharma attempts to justify its exorbitant drug prices by claiming high R&D and regulatory costs. This is a huge lie: Pharma spends double on marketing than R&Dhalf the price tag is an estimate of the profits a drug company might have made, over the course of bringing a product to market, if it had, instead, invested its capital elsewhere; and they include the cost of failed research on other drug candidates (which simply reflects the inefficiency and bloat of a cartelized industry). GAAP accounting is not a great concern for pharma’s PR department.

Take the example of the canonical 21st century wonderdrug: imatinib (Gleevec). It allegedly works well for highly specific mutations (targeting the tyrosine kinase fusion protein Brc-Abl, a.k.a. the Philadelphia chromosome of chronic myelogenous leukemia), but pharma extorts over $100,000 per year for the treatment, despite protests like the recent letter in Blood (the leading hematology journal) from dozens of the physicians who actually ran the clinical trials for Novartis in the first place. The more advanced “me too” iterations of imatinib cost even more.

Nearly all research is funded by taxation via the NIH. It costed Novartis relatively little to develop imatinib, but the company knows they can literally extort patients for their lives (and by proxy tax cattle).

Genentech attempted the same tactic with Avastin, declaring that it would charge whatever the market would bear (until being recalled because it was shown to be ineffective — serves Genentech right for stealing the plasmid for recombinant insulin from UC San Francisco, culminating in a $200M settlement in which Genentech admits no wrongdoing).

Pharma claims about $1B costs per drug. This meme is extremely pervasive in medicine, apparently justifying their exorbitant drug prices despite very low marginal costs per unit. (Pharma is historically among the most profitable business sectors). Anyone familiar with the cost of automated drug assays, animal studies and clinical trials must question this astronomical figure. FDA user fees are in the $5-10M range. Where is this money going? The funny thing is, these costs are not itemized, even by studies claiming these inflated numbers.

“The US$802-million figure was based on the research-and-development costs of 68 drugs at 10 companies. The data, however, were not made available to other researchers, and drug-industry watchdogs say this lack of transparency is typical. …[I]t is in the best interests of drug companies — who often lobby governments to loosen price regulations and increase patent protection — to overstate costs.”

“These high estimates are all from industry-supported studies done by industry-supported economists who, as far as I can tell, compete to see who can come up with the higher number.” Donald Light, professor of comparative health care at the University of Medicine and Dentistry of New Jersey and coauthor of an article challenging the validity of the 2003 study (J Health Econ2005;24[5]:1030-3).

…Another criticism of studies that produce numbers in the billion-dollar range is that large portions of those estimates aren’t out-of-pocket expenses. About half of the 10-figure price tag is an estimate of the profits a drug company might have made, over the course of bringing a product to market, if it had instead invested its capital elsewhere. Calculating forgone profits is, according to Light, a reasonable way for a company to determine if it should go ahead with a project. “What is not reasonable,” he says, “is to then take that estimate, which is a calculation of investment, and claim it as a cost against society.”

The cost estimate of successful drug development also includes the cost of research that fails to net new products. Again, this is a common practice. But critics claim the pharmaceutical industry misleads the public by claiming it costs more than a billion dollars to overcome the 1-in-5000 odds of a new chemical compound making it to market. About two-thirds of true research and development costs, Light says, are incurred in phase III trials, where the odds of success are about 3 in 5. Earlier trials are relatively inexpensive, and most compounds don’t even make it to the trial stage. –Collier, R. 2009. “Drug development cost estimate hard to swallow.” CMAJ.

We have had some insight into the expenditures of the companies overall. Lo and behold, pharma spends roughly double on marketing what it does on R&D.

A Minefield of Patents Driving Up The Costs of Basic Research

Although drug development costs are far lower than claimed, biomedical R&D is indeed too expensive. Not because labor is expensive — God knows there is a gross oversupply of grad students and PhDs, fomenting the Postdoc-opalypse. (NIH finding is only $30B annually and funds almost all the medical research in the U.S. Meanwhile, DARPA’s official budget is $90B and the DoD is $600B. The problem is not too many scientists, but not enough funding, and most of it paying rents on instruments and reagents).

Scientists, of course, are not stupid like economists. They know full well that half their grant is being eaten by inflated costs (and academics don’t even bear the full brunt of IP because of the Safe Harbor Clause).

In a survey published in Nature Biotechnology, biologists overwhelmingly felt that IP restricted their progress.

“[B]iologists’ accounts of recent instances of delayed or blocked access to research tools recognize this negative net effect of the proliferation of university IP protection after the Bayh-Dole Act of 1980.” –Lei et al. (2009) Patents versus patenting: implications of intellectual property protection for biological research. Nature Biotechnology.

Invitrogen almost succeeded in patenting the antibody — a fundamental tool in molecular biology. The whole field of antibody-based therapeutics would not exist if everyone had to license the very idea of an antibody — produced by all higher organisms — from Invitrogen. Similarly, 70% of the human genome has patent claims by industry. They charge thousands of dollars to conduct very cheap tests for genetic variants. Scams like these are why the U.S. medical system is the most expensive yet broken medical system in the developed world.

The reason basic research is so expensive is due to IP, which leads to high capital costs, a barrier to entry protecting the cartelized market. Small biopharma companies almost always sell out to a bigger fish — they’re the ones who can afford the next steps to commercialization. Thus, rarely does a drug come to market without big pharma sponsorship.

Case Study on Trusting the Government: The Food and Drug Administration

“The thing that bugs me is that the people think the FDA is protecting them. It isn’t. What the FDA is doing and what the public thinks its doing are as different as day and night.” –Dr. Herbert Ley, former commissioner of the FDA (1968-9).

The current head of the Food Divison of the FDA is Michael R. Taylor, former Vice President of Public Policy for Monsanto. Monsanto is that corporation that is trying to monopolize global seed reserves via genetic modification, sells BT corn, Round-Up (highly toxic glyphosate herbicide poisoning the food and water), aspartame and MSG, and is best known for suing farmers when their GMO pollen fertilizes crops by blowing many miles down the road. Notable alumni include Hillary Clinton and Clarence Thomas. It has been this way since the very beginning, as the FDA began as the Division of Chemistry of the Department of Agriculture at the turn of the 20th century, ushering in the new era of patent medicine (and pushing out unpatentable plant extracts as the dominant form of medicine).

Rest assured, the FDA, just like the SEC, Federal Reserve, EPA, NLRB, FCC, CIA, NSA (and whatever agency put over 100,000 innocent Japanese Americans in concentration camps) have your best interests at heart. They mean well, they really do. It’s just that the executives are revolving-door psychopaths. Salt-of-the-earth types, frankly.

“[A]s a chemist trained to interpret data, it is incomprehensible to me that physicians can ignore the clear evidence that chemotherapy does much, much more harm than good.” –Alan C Nixon, PhD, former president of the American Chemical Society.

“In regard to surgery, no relationship between intensity of surgical treatment and duration of survival has been found in verified malignancies [for breast cancer]. […] Although there is a dearth of untreated cases for statistical comparison with the treated, it is surprising that the death risks of the two groups remain so similar. […]

The evidence for greater survival of treated groups in comparison with untreated is biased by the method of defining the groups. All reported studies pick up cases at the time of origin of the disease and follow them to death or end of the study interval. If persons in the untreated or central group die at any time in the study interval, they are reported as deaths in the control group.

In the treated group, however, deaths which occur before completion of the treatment are rejected from the data, since these patients do not then meet the criteria established by definition of the term “treated.” The longer it takes for completion of the treatment, as in multiple step therapy, for example, the worse the error…. With this effect stripped out, the common malignancies show a remarkably similar rate of demise, whether treated or untreated.

The apparent life expectancy of untreated cases of cancer after such adjustment in the table seems to be greater than that of the treated cases.

–Hardin B. Jones, Ph.D., professor emeritus of medical physics and physiology at the University of California at Berkeley. “A Report on Cancer,” paper delivered to the ACS’s 11th Annual Science Writers Conference, New Orleans, Mar. 7, 1969

Today, there is a revolving door of public policy, lobbying, academia and corporate influence. The FDA was once funded entirely by the federal government (perhaps a time when corporate co-optation was less blatant).

In 1992, George H.W. Bush changed the rules, and the FDA now derives over 40% of revenue from fees charged to pharmaceutical companies. Britain’s version of the FDA derives 70% of revenues from drug companies, thanks to Margaret Thatcher’s earlier reforms in the ’80s. The FDA having a monopoly on regulation is bad enough, and the aforementioned mercantilist conservatives simply required bold-faced bribery.

There are a of myriad methods employed to misrepresent the research. Not all of it is published—only about 40% of research finds its way to a journal. Of those that do, there is a “publication bias,” where studies that find positive results (that the drugs work) are more often published than those that show the drugs don’t work or are toxic.

Another technique is “Salami slicing”—Big Pharma will cite the same data multiple times in numerous studies. There is no profit motive for independently funded research that seeks to take dangerous drugs off the market. Further, independent research is not published in the major journals like The Lancet or NEJM. Finally, standard cooking of the books, or fun with numbers: anyone along the chain of command can, with a keystroke, corrupt the data. Industry-supported research must be taken with colossal, hypertension-inducing grains of salt.

See the documentary “The War on Health” (2012) for more on the FDA.

The Emperor of All Maladies? Cancer as a Discrete, Tractable Metabolic Cellular Dysfunction

Let us end with some good news.

A common refrain in medicine is that cancer is many diseases, each tissue-type of cancer being distinct. As such, they each require a different drug! Fortunately, over 60% of cancerous cells share the same phenotype: a form of fermentation known as aerobic glycolysis, or the Warburg Effect.

Discovered by Nobelist Otto Warburg in the 1920s, this common metabolic feature makes cancer tractable broadly. Cancer cells burn a lot of sugar and without using oxygen, even when oxygen is present. This is why tumors are hotter on thermograms. It is hypothesized that the effect occurs because tumor microenvironments are oxygen-poor because cells form a dense ball into which oxygen cannot diffuse.

The drug 3-bromopyruvate, developed by Peter Pedersen at Johns Hopkins, and others like it under development, take advantage of the Warburg effect as “metabolic poisons.” Whether they see the light of the open market remains to be seen.

A sincere wish for the best of luck to Project Marilyn, but I am more hopeful about medical research elsewhere in the world, further from the reach of the US medical establishment.

Further reading:

The Cancer Industry by Ralph Moss, PhD

“Dying to Have Known” (2006), “The Beautiful Truth” (2008), “Cut, Poison, Burn” (2010); documentaries covering suppressed therapy and the overhyped safety and efficacy of conventional cancer treatment.

This excerpt in UTNE from book “Malignant,” on the cancer industry.

Here is the perspective of a cancer survivor who dug into big pharma corruption.

Bad Pharma by Ben Goldacre.

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