Sunday, June 14, 2015

Can A Biologist Fix A Radio? A Look Into Process

Worth a read. I like this part:
" I started to contemplate how biologists would determine why my radio does not work and how they would attempt to repair it. Because a majority of biologists pay little attention to physics, I had to assume that all we would know about the radio is that it is a box that is supposed to play music.

How would we begin? First, we would secure funds to obtain a large supply of identical functioning radios in order to dissect and compare them to the one that is broken. We would eventually find how to open the radios and will find objects of various shape, color, and size (Figure 2). We would describe and classify them into families according to their appearance. We would describe a family of square metal objects, a family of round brightly colored objects with two legs, round-shaped objects with three legs and so on. Because the objects would vary in color, we would investigate whether changing the colors affects the radio's performance. Although changing the colors would have only attenuating effects (the music is still playing but a trained ear of some can discern some distortion) this approach will produce many publications and result in a lively debate.

A more successful approach will be to remove components one at a time or to use a variation of the method, in which a radio is shot at a close range with metal particles. In the latter case radios that malfunction (have a “phenotype”) are selected to identify the component whose damage causes the phenotype. Although removing some components will have only an attenuating effect, a lucky postdoc will accidentally find a wire whose deficiency will stop the music completely. The jubilant fellow will name the wire Serendipitously Recovered Component (Src) and then find that Src is required because it is the only link between a long extendable object and the rest of the radio. The object will be appropriately named the Most Important Component (Mic) of the radio. A series of studies will definitively establish that Mic should be made of metal and the longer the object is the better, which would provide an evolutionary explanation for the finding that the object is extendable.

However, a persistent graduate student from another laboratory will discover another object that is required for the radio to work. To the delight of the discoverer, and the incredulity of the flourishing Mic field, the object will be made of graphite and changing its length will not affect the quality of the sound significantly. Moreover, the graduate student would convincingly demonstrate that Mic is not required for the radio to work, and will suitably name his object the Really Important Component (Ric). The heated controversy, as to whether Mic or Ric is more important, will be fueled by the accumulating evidence that some radios require Mic while other, apparently identical ones, need Ric. The fight will continue until a smart postdoctoral fellow will discover a switch, whose state determines whether Mic or Ric is required for playing music. Naturally, the switch will become the Undoubtedly Most Important Component (U-Mic). Inspired by these findings, an army of biologists will apply the knockout approach to investigate the role of each and every component. Another army will crush the radios into small pieces to identify components that are on each of the pieces, thus providing evidence for interaction between these components. The idea that one can investigate a component by cutting its connections to other components one at a time or in a combination (“alanine scan mutagenesis”) will produce a wealth of information on the role of the connections.

Eventually, all components will be cataloged, connections between them will be described, and the consequences of removing each component or their combinations will be documented. This will be the time when the question, previously obscured by the excitement of productive research, would have to be asked: Can the information that we accumulated help us to repair the radio? It will turn out that sometimes it can, such as if a cylindrical object that is red in a working radio is black and smells like burnt paint in the broken radio (Figure 2, inset, a component indicated as a target). Replacing the burned object with a red object will likely repair the radio.

The success of this approach explains the pharmaceutical industry's mantra: “Give me a target!” This mantra reflects the belief in a miracle drug and assumes that there is a miracle target whose malfunction is solely responsible for the disease that needs to be cured.

However, if the radio has tunable components, such as those found in my old radio (indicated by yellow arrows in Figure 2, inset) and in all live cells and organisms, the outcome will not be so promising. Indeed, the radio may not work because several components are not tuned properly, which is not reflected in their appearance or their connections. What is the probability that this radio will be fixed by our biologists? I might be overly pessimistic, but a textbook example of the monkey that can, in principle, type a Burns poem comes to mind. In other words, the radio will not play music unless that lucky chance meets a prepared mind.

Yet, we know with near certainty that an engineer, or even a trained repairman could fix the radio. What makes the difference? I think it is the languages that these two groups use (Figure 3). Biologists summarize their results with the help of all-too-well recognizable diagrams, in which a favorite protein is placed in the middle and connected to everything else with two-way arrows. Even if a diagram makes overall sense (Figure 3A), it is usually useless for a quantitative analysis, which limits its predictive or investigative value to a very narrow range. The language used by biologists for verbal communications is not better and is not unlike that used by stock market analysts. Both are vague."
Yep. And evolution is even worse, because there is no hope of any hypothetico-deductive empirical testing or language which even could be applied. The type of science being described is not just unsettled, it is completely unsettleable.

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