Comments by Mitchell Roitman (February 2022).

To truly appreciate a ‘classic’ work of art, one needs to understand the period during which it was produced – the state of the art at the time, the artist’s influences, and the influences that the work went on to have. Ilene L. Bernstein’s 1978 classic “Learned taste aversions in children receiving chemotherapy” was published on the heels of revolutionary work by John Garcia and colleagues – that changed the way we think about learning. Building on earlier work on toxin-induced “bait shyness” in rats (Rzóska, 1953), Garcia found that rats avoid a taste that had previously been made available during illness-inducing radiation (Garcia et al., 1955) – a phenomenon that we now refer to as conditioned taste aversion (CTA), in which a specific taste becomes a conditioned stimulus (CS) that predicts unconditioned (US) illness. Tastes, in contrast to other stimuli (e.g. auditory or visual stimuli), were especially suited for strong conditioning with illness (see the ‘tasty, bright and noisy water’ experiments of Garcia and colleagues - which are very well discussed by Davidson and Riley [2015]). In addition, and as highlighted by Alan Spector in Ingestive Classic #20, Jim Smith demonstrated that CTA differed from other learning paradigms in part because it tolerated very long CS-US intervals (Smith and Roll, 1967). Using retrospective self-report, Garb and Stunkard (1974) found that humans also formed learned taste aversions following gastrointestinal (GI) illness, supporting a highly conserved form of learning that we now know is exhibited in a wide range of organisms from C. elegans and drosophila to humans.

What makes the Bernstein, 1978 paper an Ingestive Classic is that it was the first to experimentally manipulate taste and illness experiences in humans to establish CTA. In so doing, Bernstein truly translated pioneering rodent work to human subjects – greatly impacting the care of cancer patients by awakening a more holistic approach integrating oncology and nutrition.

Bernstein recruited outpatients receiving chemotherapies that induced nausea or emesis. They were randomly assigned to different experiences prior to chemotherapy treatment: some played with a toy (control) while others (experimental group) were offered an unusual ice cream called Mapletoff – (flavored with maple and black walnut extracts). While Mapletoff would not be my selection (in summer, give me blackberry all day), control patients were happy to wolf it down weeks later when offered it for the first time. In contrast, those who had Mapletoff prior to GI illness-inducing chemotherapy, weeks later opted for time with a toy instead. A hallmark of Bernstein’s work that I’ve always admired is her use of careful controls. Additional control groups of patients received Mapletoff before a type of chemotherapy that did not induce GI illness, and they enthusiastically consumed Mapletoff again weeks later. In a follow-up experiment, patients in all groups were offered a choice between Mapletoff and another unusual ice cream – Hawaiian Delight. Patients in the experimental group ate just as much ice cream as those in the control groups but avoided Mapletoff relative to controls – months after the initial and sole pairing – supporting the formation of a learned taste aversion. The reader is encouraged to review equally interesting follow-up studies in both rodent and human subjects (e.g. Bernstein and Sigmundi, 1980; Bernstein and Webster, 1980). Bernstein’s work is perhaps best appreciated in its contribution to the clinic, as we search to understand the impact of circulating factors released by tumors on appetite and body weight, and for therapeutics, particularly in cancer treatments, that can irradicate the cancer without causing devastating appetite and weight loss.

On a personal note, Ilene supervised my dissertation studies – and shaped my growth as a scientist. She is equal parts tough-as-nails New Yorker and nature-loving, laid back Pacific Northwesterner. Research ideas brought to her had better be well thought out and well-controlled, lest they be laid to waste. And yet Ilene had this amazing ability to soften and measure her voice when her trainees were most strained – her lab was equal parts crucible and forge.

Our society members continue to study CTA to understand mechanisms for learning in ingestive behavior (e.g., Schier and Spector, 2019), for its utility in screening specific, potentially physiological versus non-specific inhibitions of ingestion (a method originally proposed by Jim Gibbs and Gerry Smith [Gibbs et al., 1973], as described in Ingestive Classic #7) as well as for mechanisms underlying cancer- and cancer treatment-induced anorexia. Ilene’s classic study put a human face on this work.

References

Bernstein, IL. (1978) Learned taste aversions in children receiving chemotherapy. Science 200: 1302-1303.

Bernstein, I.L., & Sigmundi, R.A. (1980) Tumor anorexia: a learned food aversion? Science 209: 416-418.

Bernstein, I.L., & Webster, M.M. (1980) Learned taste aversions in humans. Physiol Behav 25: 363-366.

Davidson, T.L., & Riley, A.L. (2015) Taste, sickness and learning. Am Scientist 103: 204. https://www.americanscientist.org/article/taste-sickness-and-learning

Garb, J.L., & Stunkard, A.J. (1974) Taste aversions in man. Am J Psychiatry 131: 1204-1207. Garcia, J., Kimeldorf, D.J., & Koelling, R.A. (1955) Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122: 157-158.

Gibbs J., R.C. Young, R.C., & Smith, G.P. (1973). Cholecystokinin decreases food intake in rats. J. Comp. Physiol. Psychol. 84: 488-495.

Schier, L.A., & Spector, A.C. (2019) The functional and neurobiological properties of bad taste. Physiol Rev 99: 605–663.

Smith, J.C., & Roll, D.L. (1967) Trace conditioning with x-rays as an aversive stimulus. Psychon Sci 9: 11-12.