Tags

, , , , ,

Posterity. Why do we remember some people and forget others? Are the reasons benign or malicious, banal or coherent? Walking around with Lydia’s story inside my head since 2008, I am no closer to a clear-cut answer today. Unsurprisingly, my story will reveal some usual suspects.

Adjuvant, from the latin word Adjuvare meaning “to aid”, the immunologist’s “dirty little secret”, as the late Charles Janeway said. Today a multi-million dollar “holy grail” for bio-pharma, in 2011, the Nobel Prize in Physiology and Medicine was awarded to Bruce A. Beutler, Jules A. Hoffman and Ralph Steinman for helping us understand how Adjuvants start immune responses (The 2011 Nobel Prize in Physiology or Medicine). In science, it doesn’t get bigger than this. Yet what about Lydia Rabinowitsch-Kempner, the woman who actually discovered Adjuvant activity? Consigned to a foot-note in the history of science.

In the tradition of memorable scientific insights, this too starts with an accidental discovery.  In 2008, working in an intensely academic lab with singular intellectual culture, I spent the months from March to July deep in the history of Adjuvants. Easy access to two of the most wonderful repositories of collective human knowledge, the NIH Library housed inside the National Institutes of Health Clinical Center and the United States National Library of Medicine. Lucky me.

I still recall my shiver as I came across these memorable words written by Jules T. Freund, “As far as we know, it was Rabinovitz, working in the laboratory of Koch, who first thought of the use of adjuvants. He employed Mycobacterium butyricum and other bacteria in butter, and was able to prove that the cellular reaction was evidently identical with that induced by pathological tubercle bacilli”. “…Mycobacterium butyricum injected in experimental animals caused lesions at the sites of injection somewhat resembling tubercles, but when the bacteria were incorporated into butter, they evoked a cellular reaction almost identical with a tubercle caused by pathogenic tubercle bacilli…”. Written in the 1940s, memories of Lydia already so faded, she’d become a he even to Jules Freund, a giant in early 20th century Adjuvant biology?

Who was this Rabinovitz? Why do modern reviews of Adjuvants mention her not at all or fleetingly? A person who had the original insight about Adjuvants, now forgotten by posterity. Like a dog eager on the scent, I was also now on the prowl. Where did this person work? How did they discover Adjuvants? Impatient, I went back to even older papers. Reading century old papers, I had the sudden disconcerting realization that mine were perhaps the first pair of living eyes to read them in years. Living as opposed to electronic eyes.

I discovered Rabinovitz , rather Lydia Rabinowitsch-Kempner in the lab of http://en.wikipedia.org/wiki/Robert_Koch, the discoverer of Mycobacterium tuberculosis. We are talking about a scientific colossus, not a scientific pygmy. Along with Louis Pasteur, Koch brought the Germ Theory of Disease to our collective consciousness. Lydia worked with Robert Koch, one of the fathers of Microbiology! What’s her story? How did her scientific journey start? End?

Born on August 28, 1871 in Kovno, Lithuania. Youngest of nine. Wealthy Jewish family. Laws in her native country discriminated against women and Jews so she studied at the University of Bern, Switzerland, earning a Doctoral degree in medical science in 1894. Since she couldn’t work as a scientist in her native Lithuania, she moved to Germany, working with Robert Koch at the Institute for Infectious Disease in Berlin. Obviously a woman of remarkable strength and fortitude.

How did Lydia discover Adjuvants? She was asking a very interesting question. Why did only pathogenic, and not non-pathogenic, mycobacteria induce tubercle lesions? Did I say she had remarkable strength? How about unbelievably remarkable strength? Here’s how the story unfolded. In 1882, Robert Koch made the dramatic assertion that cow milk harbored tubercle bacilli and could serve as a vehicle for tuberculosis (TB) transmission. Understandably, the fledgling dairy industry was in an uproar. The travesty continued for a full two years. The picture cleared when bacteriologists could confidently assert that yes, milk did contain a tubercle-like bacillus but that it didn’t trigger any disease in animals. This finding induced Robert Koch into an abrupt volte-face, now asserting that human and cow TB were not alike. Apparently he expected his colleagues and the public to go along unquestioningly with his 180-degree turn. That unbelievably remarkable strength of Lydia’s I alluded to? She went against her boss, placing her career in jeopardy, by taking “a radical and unyielding consumer-protection stance” (1). As a result of the brave stance of scientists like Lydia, the attention rightfully turned to the more important issue of milk hygiene. The ensuing Milk War (1) ended up creating a set of rules for milk hygiene, rules that helped shape our modern dairy industry. Not bad for a scientific legacy, eh?

How ironic then that her unyielding stance was also the ingredient necessary for her Adjuvant discovery. After all, isn’t it curious Lydia was incorporating bacteria in butter in the first place? Why did she do so? At the height of this so-called Milk War and while working in Robert Koch’s lab in 1895, at the request of the Bolle dairy farm, Lydia began experiments on butter being sold in Berlin. Carl Bolle was then Berlin’s largest milk and butter dealer, and was apparently interested in using the “war on microbes” as a weapon in his battle for territory in Berlin’s milk market. Immunological surprise at the intersection of science and capitalism.

Later still in 1895. We now find Lydia inexplicably all the way across the ocean on another continent, in Philadelphia, at the Women’s Medical College (WMC) of Pennsylvania (2) to be precise. Now called the Medical College of Pennsylvania, we find Lydia in the vortex of another battle. The older, more established Pathology Department opposes the creation of a Bacteriology Department at the WMC. Opposition or not, the Bacteriology Department opens, offering its first course in March 1896. Lydia has been appointed its First Director, out-competing the other two applicants, both men, both Americans, Dr. Arthur A. Stevens and Dr. M.V. Ball. The college alumni had apparently supported her candidacy. Choosing a Ph.D. rather than the traditional choice of a physician for such a position? Another first in Lydia’s cap. Even the official announcement of her appointment is remarkable for one detail, namely, “at the same salary paid the other professors, $1150 for the year 1898 and ‘9” (2). Same salary when even today women earn 77 cents for every dollar a man earns! Our progress in contrast seems more an oxymoron, no? Soon, Lydia became “Dr. Rabby” to her students, fondly remembered even years later.

1899. Lydia is back in Koch’s lab. Married to Dr. Walter Kempner, a colleague, she remains with Koch until his death in 1910. Obviously her brave stance didn’t burn bridges. First female professor at the Institute of Bacteriological Research in Berlin, her key research on the BCG vaccine showed it was non-virulent in guinea pig and rabbits. Working until almost the end of her life, Lydia died at the age of 64 in Berlin on August 3, 1935.

Even today the long shadow of Lydia Rabinowitsch-Kempner looms large in Adjuvant research. MF59 is the first modern Adjuvant approved for human use in almost 70 years. Its principal component? Squalene, a natural precursor to cholesterol. An unmistakable direct thread leads us from squalene to the mineral oil in Freund’s Adjuvant to the butter Lydia Rabinowitsch-Kempner used in 1895, the butter that started us on our Adjuvant journey.

Back to Lydia and posterity. Why did we forget Lydia? Lithuanian Jewish woman scientist in Weimar Germany or more simply apathy? Politics of gender, of ethnicity, of expediency? The reasons appear lost in the mists of time. We can pick and choose to the dictates of our proclivity. When it comes to Adjuvants, however, and disregarding the lamentable inaccuracy of modern curators of scientific history, the record is quite clear. Lydia Rabinowitsch-Kempner is the woman who discovered Adjuvants.

  1. Barbara Orland. Cow’s Milk and Human Disease. Bovine Tuberculosis and the Difficulties Involved in Combating Animal Diseases.Food and History, 2003, 1 (1): S. 179-202 (and references therein).
  2. Lori R. Walsh, James A. Poupard. Lydia Rabinowitsch, PhD, and the Emergence of Clinical Pathology in Late 19th-Century America. Archives of Pathology and Laboratory Medicine, November 1989, Volume 112: 1303-1308.

Post by Tirumalai Kamala:

Lydia Rabinowitsch-Kempner: Homage to the forgotten First Lady of Adjuvants.

Lydia Rabinowitsch-Kempner: Homage to the forgotten First Lady of Adjuvants.

Advertisements