New Insight In Cancer Biology

War Against Cancer

Sthabir Dasgupta

Despite spectacular developments in molecular biology and innovative technology cancer has still remained a largely unresolved issue. This has led many experts and scientists to conclude that the so-called war against cancer has failed so far. The very concept of war against cancer was a brainchild of the then President of the USA, Mr Nixon, ably supported by his favoured scientists and virologist of the time. However, while describing and analysing the anatomy of failure of this war many scientists have said time and again that the war metaphor on cancer was misplaced at the outset. This is primarily because cancer is not like an enemy attacking people from outside, but rather a cellular phenomenon arising from within human bodies. The result of trying to destroy cancer by using more and more sophisticated weapons therefore has been disappointing on the whole. Some have also said that the war on cancer is in fact an American war on cancer akin to war on terror. Why most of the scientists and experts of many other countries chose to look at cancer treatment as a battlefield is an open question, however.

The contentious issue was and still is how should one look at cancer? Is it simply a genetic disease? Is it simply a cellular aberration? Is it a psychosomatic reaction? Is it an environmental disease? Is it destined to occur? Is it hereditary? Each question involves a different therapeutic approach. For instance, if it is a genetic problem then replacement of cancer genes will bring about cure. If it is a cluster of aberrant cells then those cells can be removed by various means. If it is an environmental disease then purification of environment must wither away cancer. If it is a combination of many factors, then a combination of many disciplines will augment a cure. Genetic, out of all these has become the most fashionable culture in cancer research today. First, there were a tidal wave of Oncogenes (genes inducing a cell to become tumorigenic), followed by an eventually comparable wave of Tumour-Suppressor Genes. Although some kind of balance was envisaged in this way, this culture has failed to find out a solid ground to stand upon so far.

Dominant scientists are indeed happily married to fashions. So, they are not ready to yield grounds. In search of uniformity they are still bent upon animal studies followed by human experimentation, known as clinical trial. It is thought that the results of such trials will bring about a uniform protocol and also a uniform conceptual framework. It is claimed that such a framework will help beating cancer. However, in the face of the real-world diversity in biology and therefore, in medicine all these claims and wishful thinking have been reduced to a utopia. Cancers are after all, diverse phenomena of the cellular kingdom with diverse manifestations and prognoses in biologically unique bodies. They ignore the prevailing means and methods of detection, refuse to cause a dis-ease for a fairly long time, even for decades, resulting in so-called delayed diagnoses.

Thus, such an approach has raised more questions than it could answer. For instance, it is impossible to say clearly how early is early, as also what is meant by too late. The conventional teachings on this issue cloud reasoning. Equally confusing are the Gold standard creed in cancer therapy propagated by the American institutions. The average practitioners are now aware that these are merely matters of belief, at variance with the dictates of reason. Cancers refuse to abide by these believes, and patients behave in unique ways with the same disease and same treatment. Thus, the search for uniformity based on reductionism in the field of cancer science has remained an illusion only. Illusions dominate in the other fields of science and society also. The infectious diseases have reappeared in newer forms and vigour, Green revolution has destroyed greeneries. Taming of rivers has increased the propensity of floods. In much similar ways, the dominant cancer science has now created a conceptual chimera one could chase for generations and never capture.

It seems now that cancer studies are basically questions of approach. Should one adhere to reductionism, or holism'? Both the views coexist in medicine and biology. Ideas and models of studying cancer as opposed to the dominant opinions were there in vogue even before the initiation of cancer war. Since reductionism succeeded to a great extent in physics or chemistry, it was thought by the dominant scientists that it would succeed in the field of medicine and biology also. However, it has miserably failed in the chronic diseases, particularly in cancer. Such a state of affairs has compelled the scientists and researchers of newer genre to take another approach, a holistic approach instead of a narrow, reductionist one. The concepts of new physics like chaos and complexity are now gaining grounds in biology and medicine. Thus many biomedical scientists are now busy with the studies in Epigenelics (something above the level of the genes), instead of simple genetics.

Newer Concepts
New insights in biology are based on the holistic approaches which consider that the parts are only conditioned and they are even created by the wholes. Of course, the whole cannot be appreciated in full, but they are of the opinion that a problem should be posed large enough in order to find a solution that fits. That is a better approximation to truth than a reductionist approach which starts with a problem from a narrow angle. However, it is not easy to pose questions big enough, because the very training refuses to help people in this regard. Still, one should start learning afresh. This is, not to mean that a reductionist approach is to be entirely done away with. It must be realised that a holistic approach will not provide people with ready-made or quick-fix solution. It will only enlighten concerned people so that they can understand the problem in its entirety which in turn will pave the way for finding more lasting and unique solutions in future. The reductionist approach on its part will find ingenious solutions to some other questions, albeit trivial.

How is it proposed to set the biological problems in a larger perspective? One can take the relationship between muscles and bones in body, for an example. Conventional teachings are that bones lend their surfaces so that the muscles and tendons get themselves attached there. It is held therefore that had it not been so the muscles and tendons would only float without an anchor. It means that the bones prepare themselves to receive the muscles and tendons as their guests. In human ontogeny on the contrary, bones arrive long after the nerve tissues, muscle tissues and other organs form an ocean of collagen in human body. Bones appear thereafter, like some islands of ossification, an island here, an island there, in a designed fashion in the oceanic continuum of tissues. This means that the bones are not attached to anything, and neither the muscles are attached to any bone. Bones are independent structures, like the air in tubeless tyres. They give rigidity and shape to the tyre, and in return take the shape of the tyres. They are so independent by nature that a femur bone, in an average person, can easily withstand a compression load of as much as 3600 pounds.

Although the clinical significance of such a newer anatomical concept is unknown at the moment, but it surely illuminates concerned people, for such an anatomical formation is comparable to the universe. The visible part of the universe as people know is constituted by all the visible stars and planets and galaxies. Modern physics has it that this visible part is no more than 10% of the material universe. The remaining 90% or more is in the form of invisible plasma. Similarly, the bones of the human body are comparable to the visible parts of the universe. Take an X-ray of the human body, and you see the visible parts of it, the skeleton. The ocean of collagen remains largely invisible. It is true that newer technological developments have helped science view the ocean of collagen to some extent. Thanks to technology, more and more invisible plasma may become more and more visible in future.

However, viewing the human body in terms of the universe will also raise some fundamental questions in evolutionary biology. For instance, how, when and why cancer evolves, and for what purpose? Developmental biology tries out to answer these unanswered questions of medicine. The arswers are not always clear and loud, but there are certain Laws of Nature that must be taken into account in the entire endeavour to understand medicine.

Laws of Nature and Cellular Laws
Laws of Nature are some principles. Science includes these principles. In other words, these principles appear to have a central role in scientific practice. There are many such laws, for example. Newton's law of gravitation, Mendel's laws, the laws of motion, the laws of supply and demand, and so on. It is believed that these laws are indispensible, for they can describe reality. However, there are debates and confusion on this score. Still, setting aside those philosophical debates it can be safely said that Laws of Nature are to be distinguished both from Scientific Laws and from Natural Laws. It is held that Scientific Laws/ Physical Laws, with few exceptions - are inaccurate, are at best approximations of the truth, and are of limited range of application. In contrast, Laws of Nature are more complex, which are accurate, and are not approximation to the truth but are literally true.

Man starts as a featureless zygotic cell and ends up as a formed individual comprising of 50 to 100 trillions of cells. This has become possible because of exponential multiplication of cells, given adequate nutrition and desirable environment. This happens as a consequence of evolution or in other words, as law of evolution. This law also suggests that under normal circumstances the cells will not multiply indefinitely, without any rhyme or reason. They are restrained by a process called differentiation. Differentiation signifies that a given cell makes itself different from the primitive cell and the other cells around in terms of structure as well as function. Once it differentiates it will multiply only when needed, according to the physiological needs. Therefore, it is clear that differentiation is a strictly limited exercise, being more functional than structural. Thus differentiation is also a law. Although it remains a riddle why should a cell differentiate, numerous studies indicate today that this is because of a unique relationship between the cytoplasm and the nucleus of a cell.

Holistic approach in biology takes these cellular laws into consideration and views cytoplasm, ignored so far and so long, in its proper perspective. Such an approach demands considering cancer cell from a different angle. It is said today that a cancer cell is not an abnormal cell indeed. It is a normal cell with the same property of exponential multiplication, with discontinuity and pauses. The period of its pause and rest is known as dormant phase. This is possible because a cancer cell also is a differentiated cell. However, it is unique in two terms : First it is not only differentiated, it is in fact super-differentiated; and second, it differs from its so-called normal counterpart not in structure basically, but in behaviour essentially. Its super-differentiation and behaviour pattern are enigma with the people. Dominant biology regards a cancer cell merely as a faulty and renegade one. It tries to find the cause of its fault in the nucleus of the cell, and fails. New insights in biology on the other hand, consider that cancer cells develop not out of some fault, but as a result of some cellular laws. They explain that these laws are ingrained in the cytoplasm of human cells. It is the cytoplasm that calls the tune and nucleus simply responds to that tune, as the gene expressions also. Thus, as a law of nature, i.e. as a part of cellular law there must be a loss in the ability to execute the differentiation programme in order to develop a cancer. This loss in the ability occurs in one out of five human beings, as a whole.

However, the differentiation programme of a cell has still remained a riddle. Dominant biologists are biased with nucleism and therefore, continue to dig into the nucleus in order to unravel the cellular mysteries. As long as they will continue to do so the mechanism of cancer will remain a riddle as also its therapeutics. It is time that they start searching the cytoplasm. The mystery, if any lies there only. It is true that the new insights so far have not produced earth-breaking news but they have surely drawn people’s attention to dig into the darker aspects. Or else, all this endless search of the coin under the street lamp while the coin was lost in the darkness around will make everybody tired, frustrated and exasperated only. And who does not know that damages to the humanity are not done always out of design; they are done out of exasperation, also.

Frontier, Autumn Number
Vol. 46, No. 13-16, Oct 6 - Nov 2, 2013

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