In science, we typically dwell on the “what,” “who,” and “when” of discovery much more than the “how.” There are several obvious reasons for this. Of these four types of facts, the “how” is usually the first to go obsolete. It is the first to become buried in dated jargon that will puzzle those curious in the future. And in the wake of technological advance, it is often the first to be taken for granted. No wonder we look at past “hows” and wonder what the fuss was about, because, well, didn’t they just have iPhones?

The Beckman pH meter, Model G. Built in 1937, refurbsished in 1958. Photo provided by the author

It occurs to me that many instruments in the modern laboratory might suffer the same detached bemusement. And these, of course, are the ones that survived obsolescence (for now). There must be hundreds, if not thousands, more “hows” that we’ve long forgotten, the ones thrown out with each upgrade or perhaps occasionally encased in a museum display. On the one hand, one could see that as a victory: the technology did its job purposefully, enough to warrant a better device. Still, on the other, are all the things we forget with many instruments and technologies, such as the creative passions of their makers or what discoveries they opened up. In short, we lose sight of how they made the world a richer place, and perhaps more generally, a better one.

Thankfully, this university has a large repository of the “hows” of yesteryear. Tucked in the belly of Caspary has been a little known but remarkable exhibit of scientific instruments from the historic instrument collection. In this series, I’ll be profiling an instrument per month where we’ll explore what it was used for and why it was important. And we’ll start with the Beckman Model G pH meter, made in the late 1930s and used in the laboratory of Oswald T. Avery (accession no. 33).

In the era before insulin, diabetes was a tough disease to manage. If you were a clinical chemist in the early twentieth century, it was both tough and frustrating. The most feared complication of diabetes was (and still is) ketoacidosis, an often fatal increase in blood acidity due to the buildup of ketone bodies. As a clinical chemist, you reason that a suitable treatment would be to reduce blood acidity to normal levels, that is, to supply an alkali (a base). But how do you know how much to administer? Too little and it won’t have an effect; too much and you might cause alkalosis (also bad). The ideal would be to have a machine that could quickly and sensitively measure the acidity or basicity, in other words the pH, directly from a small amount of blood to guide treatment.

For clinical chemist Donald van Slyke in the Rockefeller Institute hospital in the 1910-1920s, defining the acid/base balance in diabetes was a laborious but ultimately solvable problem, heroically without a pH meter. Only in the mid-1930s when van Slyke’s colleague Duncan MacInnes, a Rockefeller electrochemist, invented a suitable glass electrode for measuring hydrogen ions directly, was even the idea of a simple meter for small volumes possible.

Such a machine had remained a dream for van Slyke, but it hadn’t for Arnold Beckman, who ran into a similar problem in the mid-1930s as van Slyke had a few decades earlier. Beckman was a chemist at Caltech at the time, and was approached by an old classmate in the fruit industry who needed a better method of measuring pH in citrus fruit. The glass electrode was in use by then, but it was typically hooked up to a galvanometer, and as a result, required ever-thinner (and extremely breakable) glass electrodes. Beckman used the more durable MacInnes electrodes and substituted the galvanometer with a newer and more rugged invention: a vacuum tube voltmeter. It worked.

The story of Arnold Beckman’s subsequent entrepreneurial venture to market the pH meter is the stuff of biotechnology legend. Rockefeller scientists were early adopters of the Beckman instrument and it soon became as ubiquitous as thermometers in laboratories all over the world (over 350,000 Beckman meters were sold over 50 years). The Model G pH meter on view in Caspary was purchased by Oswald Avery for use in the laboratory in 1938 for a little over $200, an expensive sum for the time. This machine remained in service well after Avery’s retirement in 1945, but it is notable for having been used by Avery and McCarty during their DNA work. Crucial too, in hindsight, for had the pH been slightly acidic in McCarty’s DNA preps, the usually stable DNA molecule would’ve been hydrolyzed at glycosidic bonds on purines. The resulting apurinic DNA is super fragile, and easily breaks (an aside: I learned this the hard way last month, when I added the wrong and slightly acidic buffer to some cDNA samples. The subsequent PCR reactions were not pretty!) It’s perfectly conceivable that had McCarty been unaware of the pH, the transforming activity of DNA might not have been observed. Thankfully, this trusty and commercially available pH meter was on hand to ensure that this critical parameter was not an issue. And the molecular biology revolution began.