Posts Tagged ‘translational research’
The astronomer, Carl Sagan once said:
It has been said that astronomy is a humbling and character-building experience. There is perhaps no better demonstration of the folly of human conceits than this distant image of our tiny world. To me, it underscores our responsibility to deal more kindly with one another, and to preserve and cherish the pale blue dot, the only home we’ve ever known.
— in the Pale Blue Dot
And likewise Frank Borman, astronaut and Commander of Apollo 8, the first mission to fly around the Moon said:
When you’re finally up on the moon, looking back at the earth, all these differences and nationalistic traits are pretty well going to blend and you’re going to get a concept that maybe this is really one world and why the hell can’t we learn to live together like decent people?
Why is it I wonder, that we the human race, have the tendency to reach such profound truths only when placed in an extraordinary environment? Do we have to train and become astronomers or cosmonauts to appreciate our place in the universe? To find respect for and to cherish what we’ve been bestowed with? To care about each other, our environment and this place that we are loath to remember is the one home for all of life as we know it?
There is much to be learned by reflecting upon this idea. Our capacity to gain wisdom and feel impressed really does depend on the level to which our experiences deviate from the banal, doesn’t it? Ask what a grain of food means to somebody who has never had the luxury of a mediocre middle-class life. Ask a lost child what it must be like to have finally found his mother. Or question the rejoicing farmer who has just felt rain-drops on his cheeks, bringing hope after a painful drought.
I’m sure you can think of other examples that speak volumes about the way we, consciously or not, program ourselves to look at things.
The other day, I was just re-reading an old article about the work of biomathematician, Steven Strogatz. He mentioned how as a high-school student studying science, he was asked to drop down on his knees and measure the dimensions of floors, graph the time periods of pendulums and figure out the speed of sound from resonating air columns in hollow tubes partly filled with water, etc. Each time, the initial reaction was that of dreariness and insipidity. But he would then soon realize how these mundane experiments would in reality act as windows to profound discoveries – such as the idea that resonance is something without which atoms wouldn’t come together to form material objects or how a pendulum’s time period when graphed reflects a specific mathematical equation.
There he was – peering into the abstruse and finding elegance in the mundane. The phenomenon reminded me of a favorite quote:
The real voyage of discovery consists not in seeking new landscapes, but in having new eyes.
For that’s what Strogatz, like Sagan and Borman was essentially experiencing. A new vision about things. But with an important difference – he was doing it by looking at the ordinary. Not by gazing at extra-ordinary galaxies and stars through a telescope. Commonplace stuff, that when examined closely, suddenly was ordinary no more. Something that had just as much potential to change man’s perspective of himself and his place in the universe.
I think it’s important to realize this. The universe doesn’t just exist out there among the celestial bodies that lie beyond normal reach. It exists everywhere. Here; on this earth. Within yourself and your environment and much closer to home.
Perhaps, that’s why we’ve made much scientific progress by this kind of exploration. By looking at ordinary stuff using ordinary means. But with extra-ordinary vision. And successful scientists have proven again and again, the value of doing things this way.
The concept of hand-washing to prevent the spread of disease for instance, wasn’t born out of a sophisticated randomized-clinical trial. But by a mediocre accounting of mortality rates using a much less developed epidemiologic study. The obstetrician who stumbled upon this profound discovery, long before Pasteur later postulated the germ theory of disease, was called Ignaz Semmelweis, later to be known as the “savior of mothers”. His new vision led to the discovery of something so radical, that the medical community of his day rejected it and his results were never seriously looked at during his lifetime (So much for peer-review, eh?). The doctor struggled with this till his last breath, suffering at an insane asylum and ultimately dying at the young age of 47.
That smoking is tied with lung cancer was first conclusively learned by an important prospective cohort study that was largely done by mailing a series of questionnaires out to smoking and non-smoking physicians over a period of time, asking how they were doing. Yes, even questionnaires, when used intelligently, could be more than just unremarkable pieces of paper; they could be gateways that open our eyes to our magnificent universe!
From the polymath and physician, Copernicus’s seemingly pointless calculations on the positions of planets to the dreary routine of looking at microbial growth in petri-dishes by physician Koch, to physicist and polymath, Young‘s proposal of a working theory for color vision, to the physician, John Snow’s phenomenal work on preventing cholera by studying water wells long before the microbe was even identified, time and time again we have learned about the enormous implications of science on the cheap. And science of the mundane. There’s wisdom in applying the KISS (Keep It Simple Stupid) principle to science after all! Even in the more advanced technologically replete scientific studies.
More on the topic of finding extraordinary ideas in ordinary things, I was reminded recently of a couple of enchanting papers and lectures. One was about finding musical patterns in the sequence of our DNA. And the second was an old but interesting paper1 that proposes a radical model for the biology of the cell and that seeks to reconcile the paradoxes that we observe in biological experiments. That there could be some deep logical underpinning to the maxim, “biology is a science of exceptions”, is really quite an exciting idea:
Surprise is a sign of failed expectations. Expectations are always derived from some basic assumptions. Therefore, any surprising or paradoxical data challenges either the logical chain leading from assumptions to a failed expectation or the very assumptions on which failed expectations are based. When surprises are sporadic, it is more likely that a particular logical chain is faulty, rather than basic assumptions. However, when surprises and paradoxes in experimental data become systematic and overwhelming, and remain unresolved for decades despite intense research efforts, it is time to reconsider basic assumptions.
One of the basic assumptions that make proteomics data appear surprising is the conventional deterministic image of the cell. The cell is commonly perceived and traditionally presented in textbooks and research publications as a pre-defined molecular system organized and functioning in accord with the mechanisms and programs perfected by billions years of biological evolution, where every part has its role, structure, and localization, which are specified by the evolutionary design that researchers aim to crack by reverse engineering. When considered alone, surprising findings of proteomics studies are not, of course, convincing enough to challenge this image. What makes such a deterministic perception of the cell untenable today is the massive onslaught of paradoxical observations and surprising discoveries being generated with the help of advanced technologies in practically every specialized field of molecular and cell biology [12–17].
One of the aims of this article is to show that, when reconsidered within an alternative framework of new basic assumptions, virtually all recent surprising discoveries as well as old unresolved paradoxes fit together neatly, like pieces of a jigsaw puzzle, revealing a new image of the cell–and of biological organization in general–that is drastically different from the conventional one. Magically, what appears as paradoxical and surprising within the old image becomes natural and expected within the new one. Conceptually, the transition from the old image of biological organization to a new one resembles a gestalt switch in visual perception, meaning that the vast majority of existing data is not challenged or discarded but rather reinterpreted and rearranged into an alternative systemic perception of reality.— (CC BY license)
Inveigled yet ? Well then, go ahead and give it a look!
And as mentioned earlier in the post, one could extend this concept of seeking out phenomenal truths in everyday things to many other fields. As a photography buff, I can tell you that ordinary and boring objects can really start to get interesting when viewed up close and magnified. A traveler who takes the time to immerse himself in the communities he’s exploring, much like Xuan Zang or Wilfred Thesiger or Ibn Battuta, suddenly finds that what is to be learned is vast and all the more enjoyable.
The potential to find and learn things with this new way to envision our universe can be truly revolutionary. If you’re good at it, it soon becomes hard to ever get bored!
- Kurakin, A. (2009). Scale-free flow of life: on the biology, economics, and physics of the cell. Theoretical Biology and Medical Modelling, 6(1), 6. doi:10.1186/1742-4682-6-6
Copyright Firas MR. All Rights Reserved.
“A mote of dust, suspended in a sunbeam.”
I’ve always been struck by how nerds can act differently in different fields.
An art nerd is very different from a tech nerd. Whereas the former could go on and on about brush strokes, lighting patterns, mixtures of paint, which drawing belongs to which artist, etc. the latter can engage in ad-infinitum discussions about the architecture of the internet, how operating systems work, whose grip on Assembly is better, why their code works better, etc.
And what about math and physics nerds? They tend to show their feathers off by displaying their understanding of chaos theory, why imaginary numbers matter, and how we are all governed by “laws of nature”, etc.
How about physicians and med students? Well, like most biologists, they’ll compete with each other by showing off how much of anatomy, physiology or biochemistry or drug properties they can remember, who’s uptodate on the most recent clinical trial statistics (sort of like a fan of cricket/baseball statistics), and why their technique of proctoscopy is better than somebody else’s, the latest morbidity/mortality rates following a given procedure, etc.
And you could actually go on about nerds in other fields too – historians (who remembers what date or event), political analysts (who understands the Thai royal family better), farmers (who knows the latest in pesticides), etc.
Each type has its own traits, that reflect the predominant mindset (at the highest of intellectual levels) when it comes to approaching their respective subject matter. And nerds, being who they are, can tend to take it all to their heads and think they’ve found that place — of ultimate truth, peace and solace. That they are at last, “masters” of their subjects.
I’ve always found this phenomenon to be rather intriguing. Because in reality, things are rarely that simple – at least when it comes to “mastery”.
In medicine for instance, the nerdiest of most nerds out there will be proud and rather content with the vast statistics, nomenclature, and learn-by-rote information that he has finally been able to contain within his head. Agreed, being able to keep such information at the tip of one’s tongue is an achievement considering the bounds of average human memory. But what about the fact that he has no clue as to what fundamentally drives those statistics, why one drug works for a condition whereas another drug with the same properties (i.e. properties that medical science knows of) fails or has lower success rates, etc.? A physicist nerd would approach this matter as something that lies at the crux of an issue — so much so that he would get sleepless nights without being able to find some model or theory that explains it mathematically, in a way that seems logical. But a medical nerd? He’s very different. His geekiness just refuses to go there, because of the discomforting feeling that he has no idea whatsoever! More stats and names to rote please, thank you!
I think one of the biggest lessons we learn from the really great stalwarts in human history is that, they refused to let such stuff get to their heads. The constant struggle to find and maintain humility in knowledge was central to how they saw themselves.
… I can live with doubt and uncertainty and not knowing. I think it’s much more interesting to live not knowing than to have answers which might be wrong. I have approximate answers and possible beliefs and different degrees of certainty about different things, but I’m not absolutely sure of anything and there are many things I don’t know anything about, such as whether it means anything to ask why we’re here, and what the question might mean. I might think about it a little bit and if I can’t figure it out, then I go on to something else, but I don’t have to know and answer, I don’t feel frightened by not knowing things, by being lost in a mysterious universe without having any purpose, which is the way it really is so far as I can tell. It doesn’t frighten me.
— Richard Feynman speaking with Horizon, BBC (1981)
The scientist has a lot of experience with ignorance and doubt and uncertainty, and this experience is of great importance, I think. When a scientist doesn’t know the answer to a problem, he is ignorant. When he has a hunch as to what the result is, he is uncertain. And when he is pretty darn sure of what the result is going to be, he is in some doubt. We have found it of paramount importance that in order to progress we must recognize the ignorance and leave room for doubt. Scientific knowledge is a body of statements of varying degrees of certainty – some most unsure, some nearly sure, none absolutely certain.
Now, we scientists are used to this, and we take it for granted that it is perfectly consistent to be unsure – that it is possible to live and not know. But I don’t know everybody realizes that this is true. Our freedom to doubt was born of a struggle against authority in the early days of science. It was a very deep and very strong struggle. Permit us to question – to doubt, that’s all – not to be sure. And I think it is important that we do not forget the importance of this struggle and thus perhaps lose what we have gained.
Besides being an important aspect for high-school students to consider when deciding what career path to pursue, I think that these nerd-personality-traits also illustrate the role that interdisciplinary thinking can play in our lives and how it can add tremendous value in the way we think. The more one diversifies, the more his or her thinking expands — for the better, usually.
Just imagine a nerd who’s cool about art, physics, math or medicine, etc. — all put together, in varying degrees. What would his perspective of his subject matter and of himself be like? Would he make the ultimate translational research nerd? It’s not just the knowledge one could potentially piece together, but the mindset that one would begin to gradually develop. After all, we live in an enchanting web of a universe, where everything intersects everything!
Copyright Firas MR. All Rights Reserved.
“A mote of dust, suspended in a sunbeam.”
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Have developing countries actually been active in EBM (Evidence Based Medicine)? This was a question that kept ringing in my head during a discussion I had with some of my buds recently. Speak to a Joe medic in any of the medical establishments in a country like India, and you can’t help feeling that developing countries for the most part have become consumers of research that cannot be applied to them. These medics are not only being taught but are also being tested on guidelines developed by a plethora of alien organizations such as NICE (National Institute of Clinical Excellence-UK), SIGNS (Scottish Intercollegiate Guidelines Network-UK), Cochrane (UK), ACP (American College of Physicians-US), CDC (Centers for Disease Control-US), NIH (National Institutes of Health-US) and many others in their curricula. Most of these guidelines have been produced for patient populations that are entirely foreign to them.
The only international body with a modicum of relevance to their lives and that of their patients and one which cuts across all geographical and cultural lines is the WHO (World Health Organization). Some might argue that such an enormous and overarching agency as the WHO is intrinsically incapable of producing practice guidelines that might be sufficiently context-centric to be of any use. The WHO sure has a lot of responsibility on its hands and it really is difficult to produce guidelines that apply to all geo-cultural contexts. Indeed, the WHO has produced only a handful of guidelines to date.
India and developing countries like it, desperately need indigenous agencies to construct and regulate guidelines that are appropriate to their peoples’ resources and needs. It is extremely common, for example, to see how guidelines by some agency are taken lightly solely because of resource constraints (transportation problems, lack of appropriate instruments, etc.). Actions that a clinician needs to make given these constraints, need to be backed by evidence. The whole idea of EBM is that actions need to be based on the ‘best available’ collective body of scientific evidence pertaining to a problem – pathological, economic, whatever. Doesn’t it make sense then, to look for ‘evidence’ backing a given course of action to our problems?
We do have bodies like the ICMR (Indian Council of Medical Research) making progress, but honestly we aren’t doing enough. Over the course of my undergrad career, perhaps the only ICMR guidelines we came across were a handful of appendices at the back of a pediatrics textbook. I mean, come on! We can do better than that, right? The arguments linking this appalling void to decreased government funding are no doubt valid. Budgets allocated to healthcare are grossly below the minimum ‘5% of Gross Domestic Product’ standard set by the WHO and quite surprisingly have kept declining. Amidst this budget-strapping, public healthcare establishments are overwhelmed by the demand for clinicians whose focus is on the manual delivery of healthcare services rather than research. In the ‘medical automobile’, these clinicians are just too busy being passengers in their back seats to care about driving. This unbalanced emphasis has had a profound impact on the very nature of our medical society. Its effects are visible right from the very beginning, as medical students enroll into institutes. Students are not even remotely exposed to the tenets underlying academic medicine and there is absolutely no mentorship mechanism in place at any level, all the way up to post-graduation and beyond. Departmental research is obscenely underfunded and students lack motivation to get involved in the absence of a nurturing environment. To make matters worse, owing to the abject lack of any academic medical component whatsoever in their curricula, students find it near impossible to take time out to engage in any form of academic activity at all. Even if they do manage it, their efforts often receive no curricular credit. Post-graduate students take the thesis requirement casually and often resort to a trial-and-error hodgepodge approach in the absence of necessary guidance. The situation finally spirals down to a vicious cycle where the blind lead the blind. End result: Institutes in chaos whose sole purpose is to produce en masse, semi-literate manual clinicians of low-innovative-potential who can’t even search or appraise medical literature, let alone use it properly.
Let’s just try to understand why this is the need of the hour. It not only paralyzes our education system but also our fragile economy. How does it degrade our economy? Well, without national guidelines there can’t be a just audit system in healthcare establishments. Without audits, resources are squandered and quality of care declines. When quality declines, the disease burden in a population rises and that in turn leads to an economic vicious cycle as national productivity declines.
How do we solve this?
- Government funding on healthcare ought to increase. Clearly, providing concessions and subsidies to private establishments hasn’t and most definitely isn’t going to produce results. Private establishments only care about making money – from the public or the government, and that’s all. Unless incentives are provided to them to engage in academic medicine or research, they aren’t going to bear the torch. In a developing country like India, the sheer demand for manual services forms a competing interest for these entities.
- Even if public funding is lacking, it might be possible to develop meaningful research. Some of the most groundbreaking research comes out of very small undertakings. It didn’t take a million dollars for us to realize the benefits of surgical asepsis.
- Hierarchical translational research bodies ought to be created – private or public or a possible mix of the two. Guidelines need to be produced and taught at medical schools. Students should no longer need to put up with the arbitrary whims of their superiors in the face of inapplicable guidelines in their textbooks.
- Audit systems should be enforced at all healthcare establishments. Students and practitioners should be taught how to audit their departments or practices.
- An academic component should be incorporated into the medical curriculum at all career grades – whether optional or otherwise. Mentorship mechanisms should be brought into place and could be incentive driven. Sources of funding and grants should be made more accessible and greater in number.
I hope readers have found this post interesting . Do care to leave behind your comments.
Readability grades for this post:
Flesch Index: 49.1/100
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Lix: 50.3 = school year 9
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