Reports of the Death of the Microscope Have Been Greatly Exaggerated

As developments in medical science progress at breathtaking speed, and continue to accelerate, predictions of the death of the microscope's pivotal role in diagnosis and research abound.1,2 The central arguments predicting the demise of microscopy are outlined in an essay that won the 2014 British Society for Haematology essay competition. In his winning essay entitled “Does the 21st Century Haematologist Need a Microscope?” Handley thoughtfully outlines the main evidence that newer technologies have the “potential to render the microscope's place as a primary diagnostic tool obsolete.” 2 He points out that clinicians and scientists of the 20th century began to “employ diagnostic techniques that did not require imaging of the cells, but were based on molecular signals too small and complex to be detected by the microscope.” He professes the power of molecular and personalized medicine and tells us genomics is “symbolic of the movement in the medical field, which is no longer so focused on a morphological relationship between form and function, but rather has adapted a ‘black box' methodology.” Handley predicts doctors of the future “may take a sample from a patient and present the sample to a machine” and “this machine then runs a number of tests on the sample designed to detect minute differences between cells, and generate a (usually quantitative) response.” (Of course, this is already happening). Handley does cautiously point out that microscopic technology is evolving but concludes that “a new exclusively molecular, branch of medicine may appear in the place of the discipline we currently call haematology.”Taking the opposite point of view in an equally thoughtful essay, Rosai presents the case that “morphologic analysis by skilled observers, that is, well-trained pathologists, will be with us for many years to come.” 1 (Like me, Rosai could not resist appropriating the commonly modified version of the quote from Mark Twain responding to newspapers reports of him being either ill or dead.) Rosai tells us “it is my opinion that there is no available technique that provides so much information so abundantly, so quickly, and as inexpensively as conventional microscopy.” He asserts that advances in molecular biology rely heavily on a “symbiosis of pathologists and molecular pathologists” and expects this symbiosis to continue. Rosai also argues that our forays into understanding the molecular pathogenesis of many cancers make it “painfully obvious that unraveling the molecular features of cancer will take many years, probably decades, and that the crucial role microscopy will continue to play during this period will provide irreplaceable data if properly integrated with newer techniques.”In the end, both authors strike a somewhat cautious note, with Rosai1 limiting his prediction for the continued utility of the microscope for “years, probably decades,” and Handley2 concedes the microscope may continue to “work alongside” newer technologies. Nevertheless, the authors are making antithetical predictions based on sober arguments for and against a future role for microscopy in medicine.So, who's more likely to be correct? What is the prognosis for microscopy? Is there another way to approach these questions? While the arguments made by Rosai1 and Handley2 appear to share nothing in common they, in fact, do—and at first glance it's easy to miss. Both authors present evidence selected exclusively from what decision scientists refer to as the “inside view.”Two thoroughly different approaches to prediction exist, which have been termed the inside view and the outside view.3 The inside view examines “specific circumstances” to address a particular problem such as predicting the future utility of the microscope. In contrast, the outside view steps away from investigating the specific circumstances and asks if there are similar situations from the past that can guide our prediction. Mauboussin4 cleverly illustrates the differences between these 2 approaches with an illuminating example from the world of thoroughbred horse racing. In assessing Big Brown's likelihood of winning the Belmont Stakes to capture the Triple Crown in 2008 after having successfully won the Kentucky Derby and the Preakness Stakes, one could focus on the inside view. The inside view was that Big Brown seemed to be running faster as the season progressed and looked strong during training sessions. The competition did not seem as strong and one of Big Brown's strongest rivals was forced to drop out of the race.4 The outside view ignores the specific circumstances of the race and takes a statistical approach, asking the simple question: How many horses win the Belmont Stakes to capture the Triple Crown after having won the first 2 events? It turns out that only 3 of 20 horses with a chance of capturing the Triple Crown after winning the first 2 events had done so between 1950 and 2007.If you focused on the inside view—and apparently most bettors did—you'd hardly be surprised when Big Brown left the gates as the 3 to 10 (betting odds) favorite. In fact, Big Brown finished ninth in a field of 9 horses (dead last). It's important to emphasize that the outside view is not infallible. After all, horses do win the Triple Crown as American Pharoah did in 2015. And in some circumstances it might even be advisable to overweight the inside view, perhaps even ignore the outside view altogether. Applying the outside view to a horse of rare talent such as Secretariat, who won the Belmont stakes by 31 lengths to capture the Triple Crown in 1973, might be misguided. Overall, however, it seems to be a characteristic of human nature to consistently overestimate the importance of the inside view and underestimate, or totally ignore, the outside view—to our detriment.5 Kahneman states “this is a common pattern: people who have information about an individual case rarely feel the need to know the statistics of the class to which the case belongs.” 3 We seem to be easily deceived by immediately available information about specific circumstances and situations. The hard and boring statistics of the outside view seem so much less compelling than the seductive power of the immediate and the anecdotal. Kahneman points out “pallid statistical information is routinely discarded when it is incompatible with one's personal impression of the case.” 3Returning to the arguments presented by Handley2 and Rosai1 regarding the future of microscopy, we can see that both authors have drawn evidence exclusively from inside view. Rosai1 presents powerful examples of how the microscope quickly and inexpensively arrives at a diagnosis, provides important prognostic information, and makes the case that morphologic and molecular genetic classification are dependent on each other, while Handley2 focuses on developments in molecular biology that have the ability to classify pathologies in ways that are impossible for the microscope.What then is the outside view with regard to the microscope's future utility? Is there a guide that can help predict the future longevity of other examples that belong to the same reference class as the microscope, namely, technology? It turns out there is, and the implications of this guide, termed the Lindy effect, are surprising and counterintuitive. The outside view that the Lindy effect provides us with takes advantage of the observation that “every year that a technology remains in use increases its life expectancy by another year.” 6It is rather natural, particularly for a pathologist who studies disease, to think of life expectancy as we do for fellow humans, our pets, toasters, and cars. These are all perishable objects: as they age they march closer to their demise. Paradoxically, when it comes to inanimate things (nonperishable objects), the older the age at which we encounter them, the longer it will take them to meet their end.7 At first glance this may seem hard to believe until you consider some examples. A book (the content, not the physical book) that has been in print for 100 years is much more likely to be in print 25 or 50 years from now than the latest thriller. Religions that are thousands of years old are much more likely to be around in hundreds of years, compared to recently founded cults.7 The Lindy effect is thought to apply to scientific theories as well.7 And, for our purposes, the Lindy effect applies to technologies, such as the microscope, as well.6,7 Technologies, in other words, seem to “age in reverse.” 7The Lindy effect has its limitations and critics, and certainly does not have universal predictive power.8 The statistical basis of the Lindy effect, the delta t argument, only gives us a probabilistic estimate about the future longevity of a technology and does not provide an expiration date for the microscope or even guarantee that the microscope will be around in, say, 10 years.9,10 But since the microscope has been around for roughly 425 years, the delta t argument tells us there is a 75% chance the microscope will be alive and kicking in 144 years.9,10Sure, the microscope could be displaced by newer molecular technologies or future technologies we can't even conceive of, but I am going to bet on the outside view and renew the service maintenance contract on my beat-up 20-year-old microscope and doubt very much it will be a waste of money—because I'm worried about my microscope, and because I am not worried about the future of microscopy.