In the quest for knowledge, Elmer McCollum cooks up some synthetic rodent food.
This is Part 3 of a blogged essay “Steampunk Data Science.” A table of contents is here.
Shortly after Elmer McCollum was hired as a young faculty in agricultural chemistry at the University of Wisconsin, Edwin Hart recruited him to work on the single-grain experiment. Being a junior faculty member susceptible to the pressure from those more senior, McCollum reluctantly agreed to join the project. But McCollum knew from the get-go that the Single Grain Experiment was probably hopeless. How could they hope to isolate the differences between the grains if every experiment would require the half-decade needed to raise their herd of cows to maturity?
McCollum was trained as an organic chemist, and his limited experience in nutrition had been gleaned during his postdoctoral fellowship at Yale. As a go-getting young faculty member, he hit the books, purchasing all 37 volumes of the German “Yearbook on the Progress of Animal Chemistry.” There, he found numerous nutrition studies done in Germany on mice. McCollim had an epiphany. Clearly, the Wisconsin investigations into nutrition could be accelerated by switching from cows to smaller animals, thereby converting studies that were taking years to complete into ones that could be finished in a few months. But which animals would be most appropriate?
McCollum decided upon rats. Rats certainly grew much faster than cows. Rats were also much smaller. A researcher could keep dozens of cages in the same space required to house a cow. Also, for better or for worse, rats would eat almost anything you put in front of them. And few have sympathy for rodents being sacrificed for the sake of human knowledge.
For McCollum, it was settled: the Wisconsin Agricultural Experiment Station must immediately begin investigations on rats. He presented his plan to the Dean of the Agriculture School in 1907, shortly after the Single Grain Experiment had begun. McCollum’s lobbying met the same fate as Stephen Babcock’s earlier pleas for the single-grain experiment. The dean emphatically denied his request. He told McCollum he couldn’t imagine the trouble he’d be in had the citizens of Wisconsin discovered that he had allowed vermin to be grown at his field station on the government dime.
Undeterred, and with the encouragement of now emeritus faculty Babcock, McCollum decided to covertly run rat experiments anyway. He had grown up on a farm in Kansas, and his parents had paid him and his brother a bounty of a penny for each rat they could catch. So he put his farmboy skills to the test. Despite the dean’s denial, the Madison campus’ sprawling array of barns was already swimming with rats. McCollum trapped some of the locals and set up a clandestine animal laboratory. After several unfortunate encounters, McCollum determined that the wild rats were far too feral to keep in a lab.
McCollum needed nicer rats. He journeyed south to Chicago and bought a dozen tame white rats from a pet store. The pet rats proved far more manageable than the barn rats. From this initial dozen, McCollum bred a large rat colony with some combination of his research discretionary funds and his personal salary.
Now ready to experiment, McCollum returned to the European literature to find the best initial foray into nutrition science. Data visualization in nutrition was still in its infancy, but by the early 1900s, growth curves had become standard tools for understanding diet. An influential paper by Watson and Hunter analyzed various food diets for rats, feeding them restricted diets of either bread and milk, porridge and milk, rice, horse flesh, or ox flesh. In Figure 1, they plotted the average growth of the rats fed bread and milk and those fed porridge (oats cooked in boiled skim milk and water with a pinch of salt).
The thin line is the average weight in grams of the rats fed the bread and milk diet, while the thick line is the average weight in grams of the rats fed the porridge diet. The arrows denote the deaths of the rats. Watson and Hunter observed that the bread-and-milk diet resulted in uniformly healthy adolescent rats. In contrast, for whatever reason, young rats couldn’t live on only porridge, and all died in under 22 weeks.
Watson and Hunter never specify exactly what they mean by “bread.” Indeed, not every bread recipe is the same, and British bread likely differed from French or German bread in its grains, seeds, and other ingredients. From the experimental protocol in the paper, we can’t determine what exactly the bread contained that was lacking in the porridge. Whatever was in the bread and not in the oatmeal seemed essential for sustaining the growth of rats.
McCollum realized he needed a more fine-grained approach to isolating the nutrients necessary for rat growth. Using his skills as a chemist, he created “synthetic diets” that built food up from its basic building blocks. McCollum’s synthetic foods could be titrated to find the bare essentials required to sustain rats.
In his first paper on his rat colony, McCollum compared the nutritional value of some of his synthetic diets. He recorded the results in tables like these:
He fed some rats a diet based on some organic compounds and some inorganic phosphorus. He compared this synthetic diet to one with added hydrolyzed beef fat to make it tastier for the rats. McCollum’s assessment of the experiment was somewhat surprising: he concluded that palatability, that is, the tastiness of the diet, was the most essential factor in nutrition. In fact, he went as far as ruling out the possibility that poor growth could be attributed to the “lack of certain organic complexes in the food given, which the body was not able to supply through its synthetic power from the materials at hand.” This conclusion was astonishingly wrong.
I’ll tell you why in the next installment of this series, but let’s first try to understand how McCollum could have been so confused by his experiment. His data presentations certainly didn’t help. Though growth curves were commonplace by the time he had published this work, McCollum’s paper contained no plots. All the data are collected in unruly tables listing the weights of different rats under different diets. Even his experimental protocols were confusing. He decided to change the diet of Rat VII on day 53. McCollum describes that he made this dietary change for Rat VII because the animal ate more aggressively than the others, and wanted to find out whether the phosphorus was necessary for continued growth.
It’s possible that plotting the data may have revealed to McCollum the tenuousness of his conclusions. For example, in Figure 3, I plotted McCollum’s data (from Figure 2) in the style of Watson and Hunter, having each point denote the average weight of each rat in the lot.
In McCollum’s experiment, the control group was fed a combination of oats, corn, and wheat, like in the single-grain experiment. It is clear here that the two lots fed synthetic foods are doing much worse than rats fed normal food mixtures. Perhaps the differences between Lots 1 and 2 were due to unrelated traits of the individual rats in the study. With the data we have, it’s impossible to know.
Even though it wasn’t particularly convincing, McCollum still managed to find a journal to accept his first attempts at systematic experimental nutrition. Though we now know the results were not reproducible and the conclusions were way off, the publication got the ball rolling in American nutrition science. Within a few years, it would lead to a revolution in our understanding of food.
Endnote: Though I heard many variants of McCollum’s legend when I was a professor at Wisconsin, I’ve based my account here mostly on McCollum’s autobiography, which paints the most favorable account of him. McCollum was a prickly guy, and his bucking the trend of the cow experiment did not make him many friends in Madison. Whereas Babcock and Harry Steenbock have buildings and streets and ice cream shops named after them, McCollum’s legacy is the Sprague-Dawley rat, developed at Wisconsin after McCollum had moved to Johns Hopkins, but still one of the most popular strains of laboratory rat in biology.








