Molecular Stamp Collecting

Senior physician at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School in Boston, MA

The great experimental physicist Ernest Rutherford (1871-1937) provocatively claimed, “All science is either physics … or stamp collecting.”

Lord Rutherford intended his cocky quip as a jab at the geologists, chemists, and biologists of his era – especially zoologists and botanists, with their endless species descriptions and taxonomies, but lack of a coherent narrative about the relationships among organisms, or their functions. Physicists, by contrast, value deductive reasoning and reduction to first principles. The biologists Lord Rutherford knew seemed happy to wallow in clutter, while his physicist friends craved the seductive power of simple, elegant explanations for complex phenomena.

Behind Lord Rutherford’s arrogant bluster, there is truth: Physics (and its supporting mathematical constructs) is, in a real sense, the mother of all science. Physics is fundamental to everything else. All other scientific disciplines can be considered “special cases” of physics (e.g., chemistry is essentially the physics of electrons and nuclear interactions).

Still, while most geologists and zoologists of Lord Rutherford’s age were concerned with filling the dusty cases of natural history museums with exotic trophies, a few were genuinely trying to deduce patterns from the pandemonium of those collections. For example, useful theories such as plate tectonics and the gene-chromosome model of heredity arose from those efforts, and he was wrong to dismiss them as a silly hobby. The tension between these two approaches to understanding the world is as old as the debate between Platonic rationalism and Aristotelian empiricism.

As a lifelong stamp collector, I also think Lord Rutherford was selling philately short.

In the internet era, postage stamps are seen by many (especially those of my children’s generation, who have never known an era without wi-fi) as useless bits of old paper. Stamp collecting was once the king of hobbies, enjoyed by literal kings (George V) and presidents (Franklin Delano Roosevelt), but today the ranks of collectors are dwindling and aging. At some recent stamp shows, I was the youngest person there. Yet stamps still have plenty of stories to tell. If you know how to look, stamps also have tremendous explanatory power, and that is their enduring magic.

Figure 1

Argentina’s Perón-era Scott #594 stamp (FIGURE 1), for instance, looks like a simple map of the republic … until you notice that the shaded areas include the Falkland Islands/Islas Malvinas (claimed by the United Kingdom), Tierra del Fuego and portions of the Andes (claimed by Chile), and a large wedge of Antarctica (neutral ground by treaty). This stamp is pure political propaganda, a philatelic land grab, and Chilean or British authorities who saw these provocative stamps on incoming letters likely marked them “return to sender.”

The German definitive stamps of late 1923 (FIGURE 2) have no pictures, yet poignantly illustrate the hyperinflation that plagued the Weimar Republic and the looming economic disaster that paved the way for the rise of National Socialism in the 1930s. Similarly, hematologist/oncologist Yamil Kouri, MD, recent vice president of the American Philatelic Society and one of the leading philatelists of our era, has created show exhibits in which a single envelope illuminates multiple dimensions of Spanish-American colonial politics and trade economics.

Figure 2

How is this relevant to hematology? There is a parallel of sorts between stamps and genetics. We are living in an era of molecular biology in which report after report describes mutations and gene polymorphisms in samples with hematologic diseases and other conditions.

These days, anyone can sequence anything. For example, a family friend who studies plankton took a recent trip to the Southern Ocean in an oceanographic vessel that had an Illumina sequencer on board, eliminating the risk of sample degradation during the trek from Antarctica back to New England. If it is possible to sequence water samples in the extremes of the Southern Ocean – where the weather is so treacherous that mariners say, “Below 40 degrees south there is no law; below 50 degrees south there is no God” – then any neophyte can sequence archival blood or tumor tissue back in Portsmouth or Portland.

It is easy to get lost in the deluge of genetic information resulting from this Easy-Bake Oven sequencing. Authors of many recently published papers have not helped us sift through the debris. As important as it is to collect molecular “stamps” to look for patterns, we do the community a disservice by torturing sequencing data with esoteric statistical techniques to find associations that are unlikely to be real, or meaningful, in order to publish a paper.

What matters most is transforming the functional insights we gain from genetics into better diagnostic tests and treatments. Drug companies cannot design new medications by computation alone; they need experiments. Similarly, although we need to “collect stamps” and look for patterns, we also need to try to understand the stories behind them.

It seems unlikely that anyone will stumble across a boyhood stamp album belonging to Ernest Rutherford but, with time, he may have come to appreciate that his views were overly reductionist. When he won a Nobel Prize in 1908, it was not the prize in physics – it was in chemistry.