What can bring in a revolution in biomedical science

Kuhnian versus Galisonian revolution: Thomas Kuhn published a book in 1962 “The structure of scientific revolution” which became a landmark in the history and philosophy of science. Kuhn says that science does not progress in a continuous smooth curve. There are periodic quantum jumps in the form of paradigm shifts. Rest is “normal science” which expands at the same level without much vertical rise. A paradigm shift is very difficult in science. For multiple reasons people of science do not easily accept the failure of old theories, although there may be quite convincing falsifying evidence. They do not accept alternative theories readily even if they are more logical and evidence based than the earlier ones. Kuhn, of course, illustrates this marvellously with a number of examples.  Perhaps the best examples of paradigm shifts in the history of science are the shift from geocentric to heliocentric view, theory of relativity and beginning of quantum mechanics.

Then in 1997 came another book, “Image and logic” by Peter Galison, which has a different argument, strengthened by equally convincing examples. In the Galisonian view scientific revolutions are triggers by new tools and technologies which open up new horizons to explore.

Many authors later wrote comparative accounts of the two types of revolutions, a notable name being Freeman Dyson. Interestingly while people talk about examples of Kuhnian revolution, they talk mostly about examples in physics. Whenever they talk about revolutions in biology or even chemistry, they mostly argue that these are Galisonian revolutions, not Kuhnian. There have been debatable arguments that even Darwin’s concept of evolution by natural selection was not a truly Kuhnian revolution. While talking about Kuhnian revolution hardly anyone talks about examples in biology, as if biology was not a science, or biology did not have conceptual  revolutions. A layman’s or even an undergraduate student’s perception of biology is generally that biology has a lot of facts but hardly any laws, theorems and the like. It is data-intensive, not concept-intensive, so one hardly expects conceptual revolutions.  Ashutosh Joglekar in a Scientific American article of 2012 argues that physics is a ‘simple’ science and therefore is more theory driven. Chemistry and Biology are more complex and therefore are more empirical, more information driven.  Therefore major scientific achievements in chemistry or mainly biology are Galisonian, not Kuhnian.

Is this really a difference due to complexity? Is physics really so simple? And is biology ‘conceptually’ that more complex, while in its information content it might be? I think more than the nature of the subject it is the culture of the handlers of the subject that really matters. In my experience the culture of physicists and that of biologists are ploes apart. If there is an experimental result which is anomalous to the prevalent theory, physicists appear to debate it. They may or may not reach any agreement, but they certainly engage in fierce debates. As Thomas Kuhn describes, the anomalous findings keep on piling up so that the theory goes on becoming more and more vulnerable, ultimately paving way to a paradigm shift. Building up a burden of anomalies is an essential pre-requisite for a paradigm shift. For building up that burden, it is necessary that the anomalies are recognized by people in the field.

In my experience, the behaviour of biomedicine researchers contrasts that of physicists. They do not debate anomalous results. They simply ignore them. So the burden of anomalies never builds up, the ‘crisis’ situation that precedes a paradigm shift in a Kuhnian process is never felt by researchers in the field. Biologists isolate the anomalies from the main theory and push them under the carpet. Since there is no burden, even wrong theories do not collapse. There are two possible outcomes of this. Either (i) a true paradigm shift does not happen at all in biomedicine even if it is overdue or (ii) it happens eventually without any debate, arguments or fights. Therefore it does not have the typical Kuhnian characters.

Whether the preceding paradigm and the new paradigm are incommensurable (Kuhn’s favourite term meaning that the concepts of the new paradigm just cannot be explained on the platform of the old one) is, in my view, a matter of culture and behaviour of people in the field and not that of science itself. The culture of biologists is that they just don’t worry about logical contradictions, mutual compatibility or commensurability of two theories. They only go on adding more and more data. Inadvertently sometimes the concept changes so dramatically that the older concept is turned completely upside down. But nobody realizes or explicitly says that this has happened. This is one possible outcome. The other is that anything that is not compatible with the prevalent theory is completely ignored and talking about them is a taboo. In Kuhn’s days peer reviews were not followed by all journals. Today, experiments that contradict prevalent theory are most likely to be filtered out in the peer review process itself, but even when they happen to get published, nobody including the authors say that they contradict the theory, that they are anomalous, that they need to be debated or that the theory needs to be re-examined. The authors have to do this otherwise they are unable to publish. It is easier to publish anomalous data if you don’t state that it is anomalous. Me too have experience of publishing 3-4 papers that obviously involved ‘group selection’. In main stream evolutionary biology ‘group selection’ was a taboo for a long time. But by avoiding the words  ‘group selection’, the same results became publishable.

I will give examples of both types of outcomes of the biomedicine culture. Prior to the elucidation of DNA structure, the nucleus of a cell and the chromosomes in particular were thought to be the decision makers. They were believed to regulate and coordinate all activities in the cell. After a few decades, people started talking about ‘gene regulation’. This was a complete somersault. The regulator became the regulated, but hardly anyone seems to have realized that the paradigm is completely turned upside down. Such paradigm shifts in biology have been silent because biologists avoid debating on any apparent or even true contradictions.

Examples of the other extreme are even more dramatic. Some of the theories in biology or medicine are simply illogical or mathematically incompatible. For example, in a prediabetic state, they say the body becomes insulin resistant, and then in order to compensate insulin resistance, the body produces more insulin. Exactly how does the compensatory insulin response happen? The textbooks say that when insulin action is subnormal, glucose levels increase. Glucose stimulates more insulin production, thereby insulin levels are raised. The higher levels of insulin bring back glucose to normal and you get a hyperinsulinemic normoglycemic (i.e. high insulin but normal glucose) state. A simple unanswered question is that after bringing back glucose to normal, how does insulin remain high? Insulin has a short half-life of 5 minutes. So when glucose is back to normal, insulin should be back to normal quite quickly. But in a prediabetic state we typically get normal fasting glucose but 5 to 10 fold higher fasting insulin. Such a condition can never be obtained in a mathematical model based on the textbook assumptions. The interesting thing is that in biomedicine, nobody has pointed out this paradox, there is no debate, no discussion, it is not considered an anomaly that needs to be addressed. Even when the flaw is obvious, it is simply ignored.

Several dozen such anomalies have actually accumulated in the field of type 2 diabetes. But nobody talks about them. Treatment to bring back sugar levels to normal has failed to reduce diabetic complications in all large scale clinical trials. There is absolutely no evidence that there is any health benefit of bringing the sugar back to normal. But entire diabetes treatment revolves around sugar normalization and this important contradiction remains unrecognized. Almost everything that was believed to happen in type 2 diabetes has been challenged and even falsified by reproducible experiments. There is no sound explanation for these anomalies in the current paradigm. The pre-paradigm-shift ‘crisis’ state described by Kuhn actually exists on ground. Still nobody is upset. No research focuses on addressing the anomalies. Instead people are busy using new tools to generate new data. Now we have genomic, epigenomic, proteomic, metabolomic profiles of diabetics and controls. So much data are generated that nobody knows what to do with it. Is this a revolution? All signs of Galisonian processes are there, but revolution is not on the horizon. Nobody even feels that the classical theory stands challenged.

In a typical Galisonian process the rate at which data grow is not at all matched by the rate at which insights grow. Genomic information is growing exponentially today. Initially people hoped that they will get major insights into complex diseases after having genomic information on human populations. But hardly any insights were obtained about the origins of disorders like diabetes. Then they argued that if it is not genetic, it must be epigenetic. Again epigenetics of obesity and diabetes is adding to the data pool exponentially. Any major insights? No luck.  Any chance of appropriately addressing the anomalies? Zero. But flashy publications? Yes. Promotions, awards, funds? Almost certain. Is this the revolution?

This is the culture of researchers in biomedicine. Addressing an anomaly is simply not in the culture. A paper exposing anomalies and raising difficult questions faces hard times getting published. But a paper giving lots of new data using latest tools with zero insightful impact will get readily published in high “impact” journals. Everyone is happy generating new data using new tools, while patients keep on spending money on useless medicines and still keep suffering from complications. So Galisonian revolution is not sufficient for biomedicine. It needs to be realized that Kuhnian ones are as essential in biology as in physics.

Kuhn correctly points out that a paradigm shift would happen only if a better alternative paradigm is available. Evidence falsifying the preceding paradigm is not enough. But there is a hen and egg problem here. Unless the preceding paradigm is perceived as inappropriate, they won’t feel the need for an alternative. Research based on any alternative way of thinking will be neither funded nor published. Even an existing sound alternative will remain ignored if the need for a change is not felt. So although there is plenty of evidence for a ‘crisis’ state and the need for a paradigm shift in type 2 diabetes research, as long as the cultural practice of playing ostrich does not change, the actual shift will never happen.

The biomedicine researcher is an anomaly for the Kuhn’s paradigm itself.

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