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Meeting Ghosts In The Chase For Reality

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Sunrise

Sunrise (via faxpilot @ Flickr CC BY-NC-ND license)

Watching the morning sun beaming through the clouds during today’s morning jog, I was struck by an epiphany. What ultimately transpired was a streak of thoughts, that left me in a overwhelming sense of awe and humility for its profound implications.

Perhaps the rejuvenating air, the moist earth from the previous night’s rains and the scent of the fresh Golden Flamboyant trees lining my path made the sun’s splendor much more obvious to see. Like in a photograph coming to life, when objects elsewhere in the scene enhance the main subject’s impact.

As I gazed in its direction wondering about the sunspots that neither I nor anyone else around me could see (but that I knew were really there, from reading the work of astronomers), I began thinking about my own positional coordinates. So this was the East, I found. But how did I know that? Well as you might have guessed, from the age old phrase: “the sun rises in the East and sets in the West”. Known in Urdu as “سورج مشرق میں نکلتا ہے اور مغرب میں ڈوبتا ہے ” or in Hindi, “सूरज पूरव में निकलता है और पश्चिम में डूबता है” and indeed to be found in many other languages, we observe that man has come to form an interesting model to wrap his mind around this majestic phenomenon. Indeed, many religious scriptures and books of wisdom, from ancient history to the very present, find use of this phrase in their deep moral teachings.

But we’ve come to think that we know this model is not really “correct”, is it? We’ve come to develop this thinking with the benefit of hindsight (a relative term, given Einstein’s famous theory, by the way. One man’s hindsight could actually be another man’s foresight!). We’ve ventured beyond our usual abode and looked at our planet from a different vantage point – that of Space. From the Moon and satellites. The sun doesn’t actually rise or set. That experience occurs because of our peculiar vantage point – of relatively slow or immobile creatures grounded here on Earth. One could say that it is an interesting illusion. Indeed, you could sit on a plane and with the appropriate speed, chase that sliver of sunlight as the Sol (as it’s lovingly called by scientists) appears or disappears in the horizon, never letting it vanish from view and do so essentially indefinitely.

Notes In The Margin About Language

Coming back, for a moment, to this amusing English phrase that helped me gauge my position, I thought about how language itself can shape one’s thinking. A subject matter upon which I’ve reflected before. There really comes a point when our models of the world and the universe get locked within the phraseology of a language that can actually reach the limits of its power of expression fairly unexpectedly. Speak in English and your view is different from somebody who can speak in Math. Even within Math, the coming about of algebra expanded the language’s power of expression incredibly from its meager beginnings. New models get incorporated into the lexicon of a language and because we tend to feed off of such phrases to make sense of ourselves and our universe, there is the potential for an inertia to develop, whereby it becomes easy to stay put with our abstractions of reality and not move on to radically new ones – models that are beyond the power of expression of a language and that haven’t yet been captured in its lexicon. In a way we find that models influence languages and languages themselves influence models and ultimately there is this interesting potential for a peculiar steady state to be reached – which may or may not be such a good thing.

So when it comes to this phenomenon, we’ve moved from one model to another. We began with “primitive” maxims. Perhaps during a time when people used to think of the Earth as flat and stars as pin-point objects too. And then progressed to geocentrism and then heliocentrism, both of which were basically formulated by careful and detailed observations of the sky using telescopes, long before the luxury of satellites and space travel came into being. And now that we see the Earth from this improved vantage point – of Space – our model for understanding reality has been refined. And actually, really shifted in profound ways.

So what does this all mean? It looks like reality is one thing, that exists out there. And we as humans make sense of reality through abstractions or models. How accurate we are with our abstractions really depends on how much information we’ve been able to gather. New information (through ever more detailed experiments or observations and indeed as Godel and Poincare showed, sometimes by mere pontification), drives us to alter our existing models. Sometimes in radically different ways (a classic example is our model of matter: one minute particle, one minute wave). There is this continuous flux about how we make sense of the cosmos, and it will likely go on this way until the day mankind has been fully informed – which may never really happen if pondered upon objectively. There have been moments in the past where man has thought that this precipice had been finally reached, that he was at last fully informed, only to realize with utter embarrassment that this was not the case. Can man ever know, by himself, that he has finally reached such a point? Especially, given that this is like a student judging his performance at an exam without the benefit of an independent evaluator? The truth is that we may never know. Whether we think we will ever reach such a precipice really does depend on a leap of faith. And scientists and explorers who would like to make progress, depend on this faith – that either such a precipice will one day be reached or at least that their next observation or experiment will increase them in information on the path to such a glorious point. When at last, a gestalt vision of all of reality can be attained. It’s hard to stay motivated otherwise, you see. And you thought you heard that faith had nothing to do with science or vice versa!

It is indeed quite remarkable the extent to which we get stuck in this or that model and keep fooling ourselves about reality. No sooner do we realize that we’ve been had and move on from our old abstraction to a new one and one what we think is much better, are we struck with another blow. This actually reminds me of a favorite quote by a stalwart of modern Medicine:

And not only are the reactions themselves variable, but we, the doctors, are so fallible, ever beset with the common and fatal facility of reaching conclusions from superficial observations, and constantly misled by the ease with which our minds fall into the rut of one or two experiences.

William Osler in Counsels and Ideals

The World According To Anaximander

The World According To Anaximander (c. 610-546 BCE)

The phenomenon is really quite pervasive. The early cartographers who divided the world into various regions thought funny stuff by today’s standards. But you’ve got to understand that that’s how our forefathers modeled reality! And whether you like it or not someday many generations after our time, we will be looked upon with similar eyes.

Watching two interesting Royal Society lectures by Paul Nurse (The Great Ideas of Biology) and Eric Lander (Beyond The Human Genome Project: Medicine In The 21st Century) the other day, this thought kept coming back to me. Speaking about the advent of Genomic Medicine, Eric Lander (who trained as a mathematician, by the way) talked about the discovery of the EGFR gene and the realization that its mutations strongly increase the risk for a type of lung cancer called Adenocarcinoma. He mentioned how clinical trials of the drug Iressa – a drug whose mechanism of action scientists weren’t sure of yet but was nevertheless proposed as a viable option for lung adenocarcinomas – failed to show statistically significant differences from standard therapy. Well, that was because the trial’s subjects were members of the broad population of all lung adenocarcinoma cases. Many doctors realizing the lack of conclusive evidence of a greater benefit, felt no reason to choose Iressa over standard therapy and drastically shift their practice. Which is what Evidence-Based-Medical practice would have led them to do, really. But soon after the discovery of the EGFR gene, scientists decided to do a subgroup analysis using patients with EGFR mutations, and it was rapidly learned that Iressa did have a statistically significant effect in decreasing tumor progression and improving survival in this particular subgroup. A significant section of patients could now have hope for cure! And doctors suddenly began to prescribe Iressa as the therapy of choice for them.

As I was thinking about what Lander had said, I remembered that Probability Theory as a science, which forms the bedrock of such things as clinical trials and indeed many other scientific studies, had not even developed until the Middle Ages. At least, so far as we know. And modern probability theory really began much later, in the early 1900s.

Front page of "Doctrine of Chance – a method for calculating the probabilities of events in plays" by Abraham de Moivre, London, 1718

Abraham de Moivre's "Doctrine of Chances" published in 1718, was the first textbook on Probability Theory

You begin to realize what a quantum leap this was in our history. We now think of patterns and randomness very differently from ancient times. Which is pretty significant, given that for some reason our minds are drawn to looking for patterns even where there might not be any. Over the years, we’ve developed the understanding that clusters (patterns) of events or cases could occur in a random system just as in a non-random one. Indeed, such clusters (patterns) would be a fundamental defining characteristic of a random process. Absence of clusters would indicate that a process wasn’t truly random. Whether such clusters (patterns) would fit with a random process as opposed to a non-random one would depend on whether or not we find an even greater pattern of how these clusters are distributed. A cluster of cases (such as an epidemic of cholera) would be considered non-random if by hypothesis testing we found that the probability of such a cluster coming about by random chance was so small as to be negligible. And even when thinking about randomness, we’ve learned to ask ourselves if a random process could be pseudo-random as opposed to truly random – which can sometimes be a difficult thing to establish. So unlike our forefathers, we don’t immediately jump to conclusions about what look to our eyes as patterns. It’s all quite marvelous to think about, really. What’s even more fascinating, is that Probability Theory is in a state of flux and continues to evolve to this day, as mathematicians gather new information. So what does this mean for the validity of our models that depend on Probability Theory? If a model could be thought of as a chain, it is obvious that such a model would be as strong as the links with which it is made! So we find that statisticians keep finding errors in how old epidemiologic studies were conducted and interpreted. And the science of Epidemiology itself improves as Probability Theory is continuously polished. This goes to show the fact that the validity of our abstractions keeps shifting as the foundations upon which they are based themselves continue to transform. A truly intriguing idea when one thinks about it.

Some other examples of the shifting of abstractions with the gathering of new information come to mind.

Image from Andreas Vesalius's De humani corporis fabrica (1543), page 190.

An image from Vesalius's "De Humani Corporis Fabrica" (1543)

Like early cartographers, anatomists never really understood human anatomy very well back in the days of cutting open animals and extrapolating their findings to humans. There were these weird ideas that diseases were caused by a disturbance in the four humors. And then Vesalius came along and by stressing on the importance of dissecting cadavers, revolutionized how anatomy came to be understood and taught. But even then, our models for the human body were until recently plagued by ideas such as the concept that the seat of the soul lay in the pineal gland and some of the other stuff now popularly characterized as folk-medicine. In our models for disease causation, we’ve progressed over the years from looking at pure environmental factors to pure DNA factors and now to a multifactorial model that stresses on the idea that many diseases are caused by a mix of the two.

The Monty Hall paradox, about which I’ve written before is another good example. You’re presented with new information midway in the game and you use this new information to re-adjust the old model of reality that you had in your mind. The use of decision trees in genetic counseling, is yet another example. Given new information about a patient’s relatives and their genotype, your model for what is real and its accuracy improves. You become better at diagnosis with each bit of new information.

The phenomenon can often be found in how people understand Scripture too. Mathematician, Gary Miller has an interesting article that describes how some scholars examining the word Iram have gradually transformed their thinking based on new information gathered by archeological excavations.

So we see how abstractions play a fundamental role in our perceptions of reality.

One other peculiar thing to note is that sometimes, as we try to re-shape our abstractions to better congrue with any new information we get, there is the tendency to stick with the old as much as possible. A nick here or a nudge there is acceptable but at its heart we are usually loath to discard our old model entirely. There is a potential danger in this. Because it could be that we inherit flaws from our old model without even realizing it, thus constraining the new one in ways yet to be understood. Especially when we are unaware of what these flaws could be. A good example of abstractions feeding off of each other are the space-time fabric of relativity theory and the jitteriness of quantum mechanics. In our quest for a new model – a unified theory or abstraction – we are trying to mash these two abstractions together in curious ways, such that a serene space-time fabric exists when zoomed out, but when zoomed in we should expect to see it behave erratically with jitters all over the place. Our manner of dealing with such inertia when it comes to building new abstractions is basically to see if these mash-ups agree with experiments or observations much better than our old models. Which is an interesting way to go about doing things and could be something to think about.

Making Sense Of Reality Through The Looking Glass

Making Sense Of Reality Through The Looking Glass (via Jose @ Flickr, CC BY-SA-NC license)

Listening to Paul Nurse’s lecture I also learned how Mendel chose Pea plants for his studies on inheritance rather than other complicated vegetation because of the simplicity and clarity with which one could distinguish their phenotypes, making the experiment much easier to carry out. Depending on how one crossed them, one could trace the inheritance of traits – of color of fruit, height of plant, etc. very quickly and very accurately. It actually reminded me of something I learned a long time ago about the various kinds of data in statistics. That these data could be categorized into various types based on the amount of information they contain. The highest amount of information is seen in Ratio data. The lowest is seen in Nominal data. The implication of this is that the more your experiment or scientific study uses Ratio data rather than Nominal data, the more accurate will your inferences about reality be. The more information you throw out, the weaker will your model be. So we see that there is quite an important caveat when we build abstractions based on keeping it simple and stripping away intricacy. When we are stuck with having to use an ape thumb with a fine instrument. It’s primitive, but it often gets us ahead in understanding reality much faster. The cost we pay though, is that our abstraction congrues better with a simpler and more artificial version of the reality that we seek to understand. And reality usually is quite complex. So when we limit ourselves to examining a bunch of variables in say for example the clinical trial of a drug, and find that it has a treatment benefit, we can be a lot more certain that this would be the case in the real world too provided that we prescribe the drug to as similar a patient pool as in our experiment. Which rarely happens as you might have guessed! And that’s why you find so many cases of treatment failure and unpredictable disease outcomes. How the validity of an abstraction is influenced by the KISS principle is something to think about. Epidemiologists get sleepless nights when pondering over it sometimes. And a lot of time is spent in trying to eliminate selection bias (i.e. when errors of inference creep in because the pool of patients in the study doesn’t match to an acceptable degree, the kinds of patients doctors would interact with out in the real world). The goal is to make an abstraction agree with as much of reality as possible, but in doing so not to make it so far removed from the KISS principle that carrying out the experiment would be impractical or impossible. It’s such a delicate and fuzzy balance!

So again and again we find that abstractions define our experiences. Some people get so immersed and attached with their models of reality that they make them their lifeblood, refusing to move on. And some people actually wonder if life as we know it, is itself an abstraction :-D ! I was struck by this when I came upon the idea of the Holographic principle in physics – that in reality we and our universe are bound by an enveloping surface and that our real existence is on this plane. That what we see, touch or smell in our common experience is simply a projection of what is actually happening on that surface. That these everyday experiences are essentially holograms :-D ! Talk about getting wild, eh :-D ?!

The thought that I ultimately came with at the end of my jog was that of maintaining humility in knowledge. For those of us in science, we find that it is very common for arrogance to creep in. When the fact is that there is so much about reality that we don’t know anything about and that our abstractions may never agree with it to full accuracy, ever! When pondered upon deeply this is a very profound and humbling thing to realize.

Even the arrogance in Newton melted away for a moment when he proclaimed:

If I have seen a little further it is by standing on the shoulders of Giants.

Isaac Newton in a letter to rival Robert Hooke

Here’s to Isaac Newton for that spark of humility, even if it was rather fleeting :-) . I’m guessing there must have been times when he might have had stray thoughts of cursing at himself for having said that :-) ! Oh well, that’s how they all are …


Copyright Firas MR. All Rights Reserved.

“A mote of dust, suspended in a sunbeam.”



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Filed under: Medical Science, My Best Posts, Nature, Research, Science, Statistics Tagged: history, medicine, nature, Probability, Research, Science, Statistics

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