Media hypes trumpeting the discovery of “new”, “revolutionary” or “breakthrough” treatments for some, or the other, type of cancer are often seen as textbook examples of bad journalism. However, a more detailed look at this phenomena reveals that the researchers, institutions and corporations featured in such articles are every bit as guilty of perpetuating the hype as those who report it. Infact there is very good reason to believe that journalists are, at best, minor beneficiaries of such scams.

Things have gotten so bad today that the majority of “breakthrough” anti-cancer research published in “top-notch” peer-reviewed is no longer reproducible. And let us be clear about one thing- this problem of irreproducibility is not restricted to the discovery of new anti-cancer therapies as potential new therapies for treating conditions as diverse as Depression, Psychosis, Type 2 Diabetes, Alzheimer’s, Coronary Artery Plaques etc have experienced a similar large increase in rates of failure at every step in the process of drug discovery.

There are those who make official-sounding noises about how all the “low hanging fruit” have been discovered. Others make similar noises about how certain diseases (especially cancers) are too complex and tricky to treat. However a closer look at their theories reveal them to be ex post facto rationalizations for explaining their failures. The same people who talk about “low hanging fruits” and “limits of biology” used to sing a very different tune as recently as a decade ago.

So before I go further, let me briefly trash both their arguments. Firstly, it is impossible to determine what is a “low-lying” fruit without the benefit of hindsight or historical revisionism. Similarly, our understanding of biology is still too fragmentary to make any reliable assessments of feasibility- especially in areas where we have few (if any) significant successes. Would you take cooking advice from someone who cannot cook an edible entrée? What about advice on sex from someone who has never done it successfully? Get it?

Consider antimicrobial drugs- especially anti-bacterials, anti-protozoals and anti-fungals. For millenia, infectious diseases were not even considered to be infectious- let alone caused by microscopic life-forms. Even after the discovery and initially reluctant acceptance of the microbial theory of infectious diseases, it was considered almost impossible to specifically target them as earlier attempts (from 1890s to early 1930s) had almost universally ended in failures.

Then a guy working at Bayer discovered anti-bacterial sulfonamides and suddenly everyone started believing that it was not only possible but fairly easy to discover such drugs. Similarly synthetic anti-malarials were a pipe-dream for over 70 years before Chloroquine and Mepacrine were developed in the 1930s. The same is true for many other drug classes as diverse as antihistamines, anticholinergics, natural opiates, synthetic opiates, anti-depressants, anti-epileptics, anti-psychotics, anti-inflammatory, older immunosuppressives, many anti-hypertensives and many others.

Even drugs developed based on some understanding of their mechanism of action such as beta-blockers, ACE inhibitors and even ‘statins’ were developed before we understood their mode of action- which in some cases we still don’t quite understand.

The history of successful drug discovery is therefore mostly about good observation, bold guesses and oodles of good luck.

But what does all of this have to do with our current inability to develop truly effective anti-cancer drugs.. you know the type that can give people almost normal life expectancies. Why have we failed so badly in that area? Why have extremely large amounts of money, “brains” and effort yielded so little? Why do researchers get so excited over some drug that has semi-decent efficacy in one particular variant of an uncommon type of cancer? Why have the largest improvements in cancer therapy come from better diagnostic and imaging technologies rather than drugs? What is going on? Why does throwing ever larger amounts of money, people and resources at the problem not improve the situation?

Some of you might believe that big-pharma is suppressing real cancer cures to keep on making money by selling barely effective or toxic drugs. I believe otherwise and will explain my reasoning in a minute. Now, I am not suggesting that corporations including big-pharma posses anything even vaguely resembling conscience or morals. However believing they are “suppressing cures” implies that they have a grasp on the problem- which they don’t. Let me explain.

Previously, I said something about most breakthrough drugs being discovered before their mode of action was understood. Ever wonder why that was the case? Could it have been that our ability to synthesize hew molecules exceeded our ability to understand their mechanism in the golden era (mid 1930s-early 1990s) of drug discovery? Or is there something about trying to understand the mechanism of drugs or finding new targets for therapeutic intervention that somehow short-circuits the ability to find newer breakthrough drugs? And how is any of all this relevant to our inability to develop truly effective anti-cancer drugs?

Here is the answer.

Drugs discovered before the era of “modern biology methods and techniques” (beginning in the 1980s) were almost always discovered and structurally fine-tuned by testing them in animal models of diseases conditions carefully selected to resemble their human counterparts. But doing so required a very good understanding of functional physiology, pathology and limitations for each animal model. To put it another way, you had to maintain a roster of specialized people who had spent decades developing and studying animal models of human diseases. Their expertise was also pretty hard to transfer and replicate easily. You can see where this is going..

The advent of ‘modern biological methods and techniques’ appeared to herald an era where a completely reductionist approach to biomedical research was within reach. People thought that we would be able to develop drugs against anything and everything of we just cloned every receptor, obtained a crystal structure of every protein and enzyme, made every transgenic mice model possible or made millions of compounds to explore every chemically feasible structure. For a time, from the early 1990s-mid 2000s, it appeared that the new ways would make the older ones look stupid and unproductive.

But then reality intervened and it became obvious that almost every new technique, methodology and ‘paradigm’ introduced since the late 1980s had produced a lot of data but no real or large therapeutic breakthroughs. To make a long story short, the new reductionist ways failed to produce the breakthrough drugs they promised. The area of cancer research was probably the one most affected by this generalized failure of reductionism in drug discovery.

But it was too late. Most scientists recruited in the system since the late 1980s were the product of this reductionist mindset as were the programs that funded the university that “educated” them. Simultaneously, big and medium pharma was overrun by MBA-types who believed that bio-medical research was something amenable to reductionism and cranking out well-understood widgets. It did not help that small pharma also became a get-rich-quick scheme. I have not even touched on the toxic effects of widespread management fads, corporate intrigue, reorganizations, mergers and financialism. Consequently the whole pharma ecosystem detached from reality and became a bizzaro game based on legally acceptable fraud and exaggeration, publishing lots of crap, making cleverly worded claims, selling crappy ideas in nice packages and doing everything except discover truly innovative and efficacious drugs.

It just so happened that the true start of ‘big’ publicly-funded cancer research (early 1980s) coincided with the beginnings of reductionism and MBA-style thinking in pharma research (mid-1980s). This overlap resulted in many unfortunate synergies- from scientists who were indoctrinated in reductionism, public systems that did not fund the older ways and an industry that abandoned what used to work for what sounded and looked good. You get the general idea..

So, the real reason we cannot yet cannot cure most cancers is that we have spent the last 30-odd years trying to do everything but cure common cancers in human beings

Of course, people could admit that they screwed up. They could admit that reductionism is particularly unsuitable for understanding and modulating biological systems. But who will do that? Who is going to expose themselves to ridicule? Who will risk their careers? Who will admit that hundreds of billions and decades was spent on chasing mirages and delusions? Who will admit that they are clueless?

What do you think? Comments?