Doing Science....?

Sthabir Dasgupta

The size of the elderly population in India is increasing, resulting in the increase in the incidences of intrinsic diseases like Cancer and Cardiac Attack.

If we believe that the economic, political and judicial infrastructures constitute the foundation of a stable and secured society and therefore, health care, then we must agree that the foundation is very weak indeed. Such a weak foundation is ill-matched with the achievements of the modern biomedical sciences. Thus, while the increase in life expectancy is considered as a scientific gains, has turned out to be a loss.

This state of affairs raises a basic question: what is the very purpose of scientific researches? It is interesting to note that this question is being raised by none other than the authors and experts from various field of scientific activities today. Despite the fact that spectacular discoveries have taken place in the fields of genetic and molecular science during the last few decades, it is being asked, what kind of public good is being served by these researches? Not only that, it is also being said that the propagation of scientific information should further the public's interest in the specific issues. Debates also should be raised about the transparency of the researchers and the source of their funding.

The issues of transparency and funding are important because it is held by certain quarters that science as such is free of bias, it is neutral in nature and therefore, immune to public response. What is to be remembered here is that even if it is held as true, the scientists as human beings are not free of bias and cannot remain neutral and therefore, cannot remain immune to public criticism. That is why the scientists, after the nuclear holocaust at the end of WW-II, spoke against nuclear arms race, criticised pesticides in the 1950s and some of them indeed raised their voices against the so-called cancer war in the 1970s, chemical warfare, and turned their attention towards climate issues.

ln the modern world, the citizenry has the right to know what is really happening behind the closed doors of the labs. So, the public media around the world have become pro-active. In our country however, instead of informed debates and discussion, we are being fed. with oversimplified interpretation of the scientific studies.

Most of us would agree that scientific studies may not always translate into immediate benefit of the people. Knowledge of science essentially means knowing the fundamental principles and laws of nature so that one can use it for further benefit, today or tomorrow. It should also create greater opportunities for our future generations, and it should help a responsible government to serve the best interest of its people. But knowing science does not mean doing science.

Genomic research, particularly in cancer science is a case in point. Cancer research during the last five decades or so has been buffeted by successive tidal waves of fashion. Genes are the dominant fashion today. The lay and the learned alike now think that the ultimate answer to cancer lies in the secret and sacred zones of the 'double helix'. Obsessed scientists have poured their entire energy and brilliance into genome and molecular researches in order to manufacture powerful weapons to kill cancers and banish them from the face of earth. Thus, newer weapons are indeed being manufactured almost every year, but with dubious teeth. Such exercises have certainly increased our knowledge, but they have failed to satisfy our needs.

Misadentures
No wonder therefore that the medical journals are now full with colourful armamentarium of genes and molecules waiting for a devastating fight against an abnormal entity, e.g. cancer. However, it was shown and proven long back that cancer is a normal stage of a dividing cell that has a cancer genome. That means, if a cell is endowed with the cancer genome it will be pushed into a cancerous state, only in time. In order to kill one cancer cell, you have to kill thousand normal cells, because the only sustainable difference between a normal and a cancer cell is in its behavioural pattern. Thus, the fundamental principles that govern our life dictate us to keep away from such genetic misadventures.

Such misadventures have already proved disastrous in the field of agriculture. It has been warned by the experts in that field of research that gene manipulations sow the seeds of destruction. The same is true in human life also. While the gene researchers are out for hunting mutated genes in our body, there is strong evidence that the onset of cancer is determined by quite different mechanisms. That is why despite the triumphalist claims of modern medical science the basic problem of cancer has remained untouched. As the revered geneticist, Professor Steve Jones observed that decades of the mountain of genetic research produced not more than a mouse. So, the practical therapeutic benefits of this vast enterprise are scarcely detectable.

Still, the Governments insist and private enterprises sponsor these research programmes and the researchers in their turn steadfastly promise great benefits for the patients tomorrow. It is interesting to note that the promises are always for tomorrow which never comes and so, the promises never materialise. It is true that the genome researches have yielded insightful surprises one after another, because the cellular world is an eternal mystery, but the primary goal to ferret out the genetic roots of diseases like cancer has remained elusive. This has compelled Harold Varmus, a Nobel laureate scientist who was once the president of the Memorial Sloan-Kettering Cancer Centre in New York, to say that genomics is a way to do science, not medicine.

Rather than being interested in the details of dynamic pattern of every single gene, we must learn how the whole genetic output combines to produce the functional reality of living organisms. One may wonder, does this mean that such a vast empire of molecular biology is simply useless? The answer is that doing rain dances in the desert may be tremendously laborious and also brilliant in terms of art, but will not fulfil our desire. So, doing science for the sake of science is one thing, but doing it for the sake of mankind or medicine is quite another.

Failure Of Science?
This is not the failure of science as such. Rather, this is a failure of the way of doing science. These scientists never realise that their views and outlook, from patients' perspectives are mislaid. Or else, why with such a huge treasure of knowledge, the scientists fail to deliver sustainable goods to the patients? War against cancer was officially declared in the USA almost 50 years ago by Nixon. Cancer Moonshot was launched by Obama, in 2016, being faithfully followed by Donald Trump with his usual rhetoric of breakthroughs. Thanks to all these efforts the impact of the molecular biology bandwagon has been so sound that the real goal of improving patients' life has been forgotten. The war has largely, failed.

Failure essentially means that neither the incidence of cancer, nor its mortality has improved. Meanwhile, the war has produced some basic science discoveries. But a study revealed that despite tall claims of delivering profound clinical benefit, only 1% of them could sustain the test of the time after a period of two decades. It is no surprise that some researchers have pointed out in highly respectable journal like Clinical and Translational Medicine that cancer chemotherapy and immunotherapy have produced outcome failure-rates of 90% (±5) according to governmental agencies and industry. Major scientific reasons for such repeated failures are attributed to wrong and reductionist approaches of modern science. Thus, it seems now that these researches are building bridges to nowhere.

Those over-optimists who celebrate over postponing patient's death-sentence for a few months of remission from disease conveniently forget to mention tremendous economic burden to the society. Moreover, these irresponsible decision makers either abandon data on failed outcomes or ignore the serious consequences of treatment. Another study held a few years back by a group of doctors who examined 363 articles published in a coveted medical journal revealed that not more than 38% of the current standard medical practice are truly efficacious. John Ioannidis, the famour physician-scientist proved that about 89% of the published medical information that doctors rely on were not reproducible and therefore, scientifically flawed. One may ask therefore, are the vandals how ruling at the gates of medicine?

This question cannot be ignored, because there was indeed a golden age of medicine that began after the WW II. It gave us life-saving antibiotics, vaccines, many other truly effective drugs. Newer surgical innovations and improved anaesthetics could save thousands of patients. Patients were grateful and doctors were much conscious of their responsibilities. However, this scenario could not last beyond the seventies of the last century. It seems, Golden ages are always in the past or the future and never now!

Triumphs
Still, some people tend to think that the gold is rather more glittering now, with unthinkable and astonishing progress in modern medicine. They insist that medicine has now achieved much desired speed and valour. Key-hole surgery, Microsurgery, Robotics and organ transplantation have become familiar today. Biomedical research is rapidly reaching its peak and is supposed to deliver goods that we have never dreamt of. Therefore, they propagate that instead of attacking science, we must have a moral obligation to offer it more support, pursue it and should actively participate in this progress.

It is true that this is an age of evidence-based medicine (EBM). However, the claim that EBM is good for the patients is only half-true. The other half of the truth is that evidence-biased medicine (EbM) is dangerous for us. The new paradigm of EBM was announced in the nineties of the last century. Three decades thereafter, it was pointed out in the Journal of Evaluation in Medical Practice that it has largely failed to achieve population-level health gains. This is particularly true in cancer and heart diseases where there is known paucity of high-quality evidence in support of current practice. This paucity is inevitable, because we are looking for a black hat in a dark room on a dark night.

We have also forgotten that mere citing evidences in support of some medical decision does not suffice. It is imperative to appreciate the presence of counter-evidences and to explain them in their perspectives. If we ignore the negative results out of the medical researches and fail to give them equal weight, it only means that what we practice is, EbM, rather than EBM. EBM is failing and this failure is due to the bias in the choice of hypotheses tested, manipulation of study design and results, data massaging and selective publication. Most of these flaws are clearly found in those studies that are industry—funded. Since these flaws are ignored, the clinical decisions remain flawed, less effective and sometimes even harmful.

Of course, it goes without saying that the results of the reductioninst approach in modern biomedical research and practice has been wonderous some times, for some things; but such an approach fails and fumbles while dealing with chronic, degenerative and senescent diseases. Medicine took this path for analysing and evaluating the natural world, since Descartes and the Renaissance. But this approach is something like divide and conquer, for it assumes that complex biological phenomena can be solved by dividing them into smaller and simpler-units. This assumption is incomplete and has its inherent limitation. Conversely, Sir William Osler argued that while treating the disease in the body, the physician must attend the human being, the person, who has the disease.

But Oslerian teaching has no currency in modem medical industry. Thus, a flawed outlook made us believe that there is a pill for every ill, and even if there is no ill there must be a pill to prevent its emergence.

Epistemic Break?
However, looking at the nature of medical science today, we believe that skepticism is welcome. This is because there are hordes of counter-evidences to suggest that the conventional rules governing the cardiac sciences, for instance are riddled with loopholes. It has been repeatedly asserted that coronary interventions neither benefit in reducing symptoms nor improve the quality of life, when compared with a placebo procedure. This is why the unconventional wisdom says that the grammar of the intrinsic diseases may ever remain a will-o'-the-wisp. Much talked about cancer mutation is still under scrutiny: we do not know if mutation begets cancer, or cancer begets mutation. Similarly, the arterial blocks may not produce cardiac dysfunctions; it may be the other way around.

So, Oslerian wisdom dictates us to remain less aggressive unless warranted. However, the reductionist belief has become so calcified that one refuses to reconsider the aggressive approach towards any doubtful symptom. Thus, it seems now that an epistemic break with the conventional stance of modern medicine is required, for it has become an industrial culture of excess.

It is to be understood that the rising costs of treatment that we are perturbed with, are driven primarily by new advances in research. Every new advance in medicine needs new avenues for its application. In the absence of suitable avenue, it must invent disease. In this way, modern medical research medicalises our life and death; it reduces the patients to mere consumers. The empire of medical industry does not encourage values; so, everyone here seems to be so busy that patients have to struggle hard to find a chance to put forward his urgent question. It is not difficult to understand that it is much easier to order another scan than to meddle with difficult conversation with the patients.

Thus, instead of becoming oasis for the distressed, modem medical research has become a major threat to public health. It innovates new drugs almost on a routine basis, claiming that those will improve survival of cancer patients. It has been estimated however, that out of 48 drugs approved between 2009 and 2013, just 10% benefit the quality of life of our patients. Between 1992and 2017, only 19 of 93 new cancer drugs showed same survival advantage. An article in New Scientist just a few days back has shown very clearly that most of the newer cancer drugs are not only exorbitantly costly, they do not let people live longer, and on the top of this' they have very serious side-effects.

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Frontier
Vol. 52, No. 35, Mar 1 - 7, 2020