RESCUING FERSTER AND DEMYER'S BEHAVIORAL PHARMACOLOGY RESEARCH IN AUTISM FROM OBLIVION
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EUROPEAN JOURNAL OF BEHAVIOR ANALYSIS 2009, 10, 5 - 18 NUMBER 1 (SUMMER 2009)
5
Rescuing Ferster and DeMyer’s
behavioral pharmacology research in autism
from oblivion
Edward K. Morris
University of Kansas
and
Charryse M. Fouquette
University of Kansas and The Lovaas Institute for Early Intervention, Midwest Headquarters
In 1961, Charles B. Ferster and Marian K. DeMyer published a one-page report in the Journal of the
Experimental Analysis of Behavior titled, “Increased Performances of an Autistic Child with Prochlor-
perazine Administration.” It may be the first and only report of basic behavioral pharmacology research
using both operant apparatus and measures and a within-individual replication design to analyze the
behavior of a child with autism. However, it is now lost in history. In this article, we rescue the report
by providing historical context (e.g., a literature review, the setting), describing and elaborating on the
report (e.g., the participant, method), and relating the report to the research of its day and afterward.
We also discuss the grounds on which the report warrants being rescued and, in a postscript, summarize
Ferster’s later work in autism.
Keywords: Ferster, DeMyer, history, autism, behavior analysis, behavioral pharmacology
In 1961, Charles B. Ferster and Marian K. only report of basic behavioral pharmacology
DeMyer (1961b) published a one-page report research using operant apparatus and measures
in the Journal of the Experimental Analysis of and a within-individual replication design to
Behavior (JEAB) titled, “Increased Performances analyze the behavior of a child with autism.
of an Autistic Child with Prochlorperazine However, it is now lost in history – in the his-
Administration.” It was perhaps the first and tory of autism, behavior analysis, and behavioral
pharmacology. It is lost in what historians call
This article is dedicated to Joseph V. Brady for his funda- oblivion.1
mental contributions to behavioral pharmacology, strong ad-
vocacy for behavior analysis, and gentle encouragement of the Using primary source publications, citation
first author. We thank Mike Aman, Len Green, Joe Hingtgen, analyses, personal communications, and archival
Vic Laties, Al Poling, Steve Schroeder, Alan Silberberg, Travis
Thompson, Steve Warren, and Stan Weiss for assisting our review records, we rescue Ferster and DeMyer’s report
of the literature for this manuscript and, in some cases, for com- by placing it in historical context, describing the
menting on earlier drafts. We thank the Archives for the History
of American Psychology, the Harvard University Archives, and research in greater detail, and offering evidence
the American University Archives for granting us access to their that supports our observations about its priority
collections. And, we thank the manuscript’s several legions of
reviewers for their suggestions. Correspondence may be sent to and uniqueness. The evidence notwithstanding,
the first author at the Department of Applied Behavioral Science, the report is weak in several regards, leading us
Dole Human Development Center, University of Kansas, 1000
Sunnyside Avenue, Lawrence, KS 66045. Phone: 785.864.4840; to discuss whether it warrants being rescued in
fax: 785.864.5202; email: ekm@ku.edu. the first place. After weighing arguments for and
56 Edward K. Morris and Charryse M. Fouquette
against this, we conclude that it does because it Medicine (est. 1903), located at the university’s
represents an as-yet developed area of research Medical Center in Indianapolis, IN. He was,
that has important clinical implications. At the in addition, appointed as a Principal Investiga-
very least, we will have added depth and detail tor in Experimental Psychology at the medical
to the early modern history of autism, behav- school’s Institute of Psychiatric Research (est.
ior analysis, and behavioral pharmacology. We 1956), whose mission was to foster multidisci-
begin with some background. plinary research in basic and applied biological
psychiatry. At the Institute, Ferster conducted
Background basic nonhuman research on, for instance,
schedules of reinforcement and aversive control
Charles B. Ferster (e.g., Ferster, 1960a; Zimmerman & Ferster,
Charles B. Ferster (1922-1981) is renowned 1964) and conducted or consulted on applied
in the history of behavior analysis. After receiv- research on obesity (Ferster, Nurnberger, &
ing his undergraduate degree from Rutgers Levitt, 1962), stuttering (see J. P. Brady, 1990),
University in 1947, he entered the graduate and teaching (Ferster, 1960b).
program in psychology at Columbia University, Most notably, though, he and DeMyer
from which he earned an M.A. in 1948 and a began perhaps the earliest program of behavior-
Ph.D. in 1950. His mentors were Fred Keller analytic research on children with autism. This
and Nat Schoenfeld (on the Columbia program, included a behavioral interpretation of autism
see Dinsmoor, 1990; Keller, 1986). In 1950, (Ferster, 1961); human operant research on
he became a research fellow with B. F. Skinner children with autism, funded by the National
(1904-1990) in the Pigeon Lab at Harvard Uni- Association for Mental Health (NAMH) 2 and
versity, the main result of which was, of course, Smith, Kline, & French (Fester & DeMyer,
their text, Schedules of Reinforcement (Ferster & 1961a, 1962; see Ferster, 1962); an application
Skinner, 1957; see Ferster, 1970; Skinner, 1981; of operant conditioning to autism, also funded
on the lab at that time, see Gollub, 2002). In by NAMH (DeMyer & Ferster, 1962); and their
1955, Ferster took a position as a research as- behavioral pharmacology research, for which no
sociate at the Yerkes Laboratories of Primate funding source was listed.
Biology in Orange Park, FL, where he, Roger At the time, DeMyer was an assistant profes-
Kelleher, and John Falk conducted operant sor in the Department of Psychiatry, a clinical
research with chimpanzees (Dewsbury, 2003; consultant and research collaborator at the In-
see, e.g., Ferster, 1957). At Yerkes, Ferster also stitute, and the Director of Children’s Services
drew up plans for JEAB, which was founded in at the Larue D. Carter Memorial Hospital. This
1957 (Kelleher & Morse, 1987; Laties, 1987). was a state hospital for inpatient mental health
He was its first editor -- 1958-1960. treatment and research, as well as a training site
In 1957, Ferster took a position as an assis- for the medical school’s psychiatric residents and
tant professor in the Department of Psychiatry the site for her research with Ferster.
(est. 1940) at Indiana University’s School of
1
The report is available on-line through the Society for the Ferster and DeMyer (1961b)
Experimental Analysis of Behavior (http://seab.envmed.rochester. When Ferster and DeMyer (1961b) pub-
edu/) by searching for “Ferster DeMyer” (not “autism”), but its
three paragraphs are condensed into one and its figure, footnotes, lished their report, behavioral pharmacology
and references are missing. An October 25, 2008, Pub Med was still in its infancy. Although Skinner had
author search for “ferster cb demyer mk” yielded Ferster and
DeMyer (1961a, 1962), but not Ferster and DeMyer (1961b). conducted related research in the 1930s (see
The full report, however, is accessible through the PubMed Heron & Skinner, 1937; Skinner & Heron,
Central Archives link to Administrative Content (i.e., http://
www.Pubmedcentral.nih.gov/picrender.fcgi?artid=1403980&b 1937), the field was not founded until the
lobtype=pdf ). Ferster and DeMyer (1961b), the way, is not the
only report of behavioral pharmacology research in develop- 2
The NAMH was founded in 1950, but its roots lie in the
mental disabilities lost in history. See, for example, McConahey, National Committee for Mental Hygiene (est. 1909). In 2006,
Thompson, and Zimmerman’s (1977) chapter, “A Token System the NAMH became Mental Health America, “the country’s oldest
for Retarded Women: Behavior Therapy, Drug Administration, and largest nonprofit organization addressing all aspects of mental
and Their Combination.” health and mental illness” (http://www.nmha.org/go/history).Rescuing Ferster and Demyer 7
mid-1950s (e.g., Dews, 1955; see Laties, The Report
2003; Pickens, 1977; Poling, 2000), with hu-
man behavioral pharmacology emerging soon The Participant
thereafter (e.g., Dews & Morse, 1958; see Ferster and DeMyer’s (1961b) participant
Poling, 1986, pp. 3-20). Both were a melding was a 10-year-old boy who had been an inpatient
of the experimental analysis of behavior with at the Larue D. Carter Memorial Hospital for
pharmacology, a melding pursued in three the preceding three years and who, during the
settings -- departments of psychology and 16 months prior to their pharmacology study,
pharmacology, and the pharmaceutical industry had participated in their program of human
(Laties, 2003). operant research (Ferster & DeMyer, 1961a,
Although published early in the field’s 1962). In this research, children learned to press
founding, Ferster and DeMeyer (1961b) is a key on a dispenser for “coins” that could be
not cited in the histories of behavioral phar- used to operate “reinforcing devices” that lined
macology (e.g., Laties, 2003; Pickens, 1977); the walls of a research room. Among the devices
in biographies of the field’s founders, for were vending machines that dispensed food and
instance, those of Joe Brady (Barrett, 2008), trinkets, a television, an electric train set, and
Peter Dews (Barrett, 2006), or Roger Kelleher a three-window matching-to-sample (MTS)
(Branch, 2006); or in recent reviews of behav- apparatus. With the coin dispenser and the de-
ioral pharmacology in autism (e.g., Handen & vices, Ferster and DeMyer analyzed the effects of
Lubetsky, 2005; Schaal & Hackenberg, 1994; reinforcement schedules (e.g., fixed-ratios) and
Tsai, 2005). It is also not cited in the histories stimulus control (e.g., light-signaled reinforcer
of applied behavior analysis (e.g., Kazdin, 1978, availability, matching-to-sample).
1982; Krasner, 1982) or in texts on applied When Ferster and DeMyer prepared their
behavior analysis in autism (e.g., Ghezzi, Wil- 1962 human operant manuscript for publica-
liams, & Carr, 1999; Luiselli, Russo, Christian, tion, not when they began that program of
& Wilczynski, 2008; Volkmar, Paul, Klin, & research, their participants were an 11-year-old
Cohen, 2005). girl and two boys, ages 3½ and 10. The older
In a search of the Web of Science (April 27, boy was thus the likely participant in their
2008), we did find nine citations to Ferster pharmacology research. In their manuscript,
and DeMyer’s (1961b) article, but they were, they described him this way:
on average, over 35 years old and published in Thomas, aged 10 and hospitalized 3 years, has
journals outside mainstream behavior analysis. been studied for 12 months. He had a normal
Three of the citations appeared in introductions motor and speech development, speaking short
to studies in basic and applied human behav- sentences until he was 2½, when he developed se-
ioral pharmacology, two of them conducted at vere rage reactions, wandering away from home,
the Institute (i.e., J. P. Brady, Levitt, & Baydan, gradual loss of speech, an excessive reaction to
1962; Zimmerman & Baydan, 1963; see also changes in his daily routine, and withdrawing
Davis, 1971). The other six appeared in reviews to a corner where he would remain for weeks.
of childhood autism (i.e., Ornitz, 1973), drug (p. 90)
effects on learning (i.e., Freeman, 1966) and on In their pharmacology report, they noted
clinical outcome (i.e., Aman & Singh, 1986), that he had no speech, few interactions with
behavior modification in childhood psychosis people or toys, and “frequent severe temper tan-
(i.e., Leff, 1968), and the integration of drug trums and atavistic performances” (p. 84). Over
interventions with behavioral and psychologi- the course of their human operant research,
cal treatments (i.e., Sevin, Bowers-Stephens, Ferster and DeMyer (1962) observed that the
Hamilton, & Ford, 2001; Willner & Gordon, children’s “tantrums declined continuously”
1969). With this background, we turn to Fer- (p. 93) and, in their pharmacology report,
ster and DeMyer’s report. noted that their participant’s performance had
“developed continuously and come under the8 Edward K. Morris and Charryse M. Fouquette
control of the automatic devices” in the human behavioral neuroscience that was consistent
operant research. with these interests (see Aprison, 2001). Over
luncheons at the Institute, Ferster, DeMyer, and
The Drug Aprison discussed conducting and collaborating
The drug Ferster and DeMyer (1961b) used on research (J. Hingtgen, personal communica-
in their pharmacology research was prochlorper- tion, October 14, 2008). With DeMyer, Ferster
azine, which belongs to the phenothiazine class conducted research on autism; with Aprison,
of “typical” or first-generation antipsychotic he collaborated on behavioral neuroscience re-
drugs, of which chlorpromazine (Thorazine) is search (Aprison & Ferster, 1960, 1961a, 1961b,
the best known. In the early 1950s, chlorpro- 1961c; see also Ferster & Aprison, 1960).3
mazine was found to improve the emotional
and cognitive functioning of adult psychiatric The Apparatus
patients and, in 1954, was approved by the The apparatus Ferster and DeMyer (1961b)
US Food and Drug Administration as the used in their research was a three-window MTS
first antipsychotic drug for this population. device. What they described of it was that
Before then, patients were sedated, received sample stimuli – colored dots -- were presented
electroconvulsive or insulin shock therapy, or in the lighted center window, while the side win-
underwent psychosurgery. Chlorpromazine was dows remained dark. When the child touched
so effective that tens of thousands of psychiatric the sample, the center window went dark and
residents were released from institutions over the side windows were lighted – a successive,
the next decade (Swazey, 1974). It was also used but not delayed MTS procedure. A colored
to treat temper tantrums and hyperactivity in dot corresponding to the sample appeared in
children with mental retardation and emotional one of the side windows, while a different col-
disturbances (e.g., Bair & Herold, 1955; Freed 3
Ferster and Aprison came to collaborate in the following
& Peifer, 1956). By the late 1960s, however, way. On arriving at the Institute, Ferster set up a display in its
chlorpromazine was discontinued for long- lobby of a pigeon in an operant chamber and a sign that said that
the pigeon would “work for food” if a penny were dropped into a
term psychiatric treatment because it eventually slot (Aprison, 2001, p. 12). The pigeon “worked” on a multiple
produced debilitating side-effects (e.g., tardive FR-50/FI-10’ schedule of reinforcement. At the time, Aprison
was looking for an animal model of depression and, when he saw
dyskinesia). Today, it is only prescibed for the the pigeon’s steady-state performances, he became “ecstatic” (p.
short-term treatment of aggression, anxiety, 13) about the preparation and convinced Ferster to collaborate
with him. As Aprison related later:
nausea, and vomiting. Prochlorperazine (Com- The first step in this program was a specification of the
pazine) is a derivative of chlorpromazine, yet 10 behavior of the animal for which the biochemical correlate
was sought. Because the Skinnerian psychologists had already
to 20 times more potent, but is also no longer developed techniques that could provide predictable baselines
prescribed for long-term treatment for the same in a systematic account of animal behavior and because the
reproducibility of the behavioral baseline was comparable
reasons. It is used mainly for the short-term to that obtained in pharmacological bioassay techniques, we
treatment of nausea and vomiting caused by believed that such advances made it possible to quantitatively
measure the behavior of an animal objectively. (Aprison,
chemotherapy and radiation therapy. 2001, p. 14).
Ferster and DeMyer may have been in- Their collaboration yielded among the earliest studies on the
neurochemical correlates of behavior (Aprison & Ferster, 1960,
terested in prochlorperazine because of chlo- 1961a, 1961b, 1961c; see Ferster & Aprison, 1960). It also fore-
rpromazine’s effectiveness with children who told the value now placed on interdisciplinary research. In 1959,
Aprison and Ferster submitted a three-year grant proposal to the
had behavior problems similar to those of the National Institute of Mental Health (est. 1949), titled “Neuro-
participants in their human operant research logical Correlates of Behavior.” Later that year, Aprison reported:
I received a call from the [NIMH] study section secretary…
(e.g., tantrums; Ferster & DeMyer, 1961a, who informed me that the grant was approved, and that the
1962). Ferster was already conducting research committee had recommended that it be extended for 2 ad-
ditional years. I quickly accepted the report and asked how
on chlorpromazine with pigeons at the Institute the decision had been made. He told me that the committee
(e.g., Ferster, Appel, & Hiss, 1962). In addition, had not only thought the experiments were important but
also they were pleased that two young and proven inves-
Morris Aprison (1923-2007), a Principal Inves- tigators from different fields of study had chosen to work
tigator in Biochemistry at the Institute (1956- together in an overlapping area of research that should be
supported. (p. 15)
1997), had launched a program of research inRescuing Ferster and Demyer 9
ored dot appeared in the other. Correct color tions were higher on the FR-4 schedule (range:
matches produced coins on a fixed-ratio (FR) 145-210) than on the FR-2 schedule (range:
schedule that could be used to obtain “a variety 90-135). Given the schedule parameters, this
of reinforcers such as food or toys, a view of a would have been expected (Ferster & Skinner,
trained monkey, a television set, or an electric 1957), but its replication with children with
train set.” Incorrect matches produced 2-sec autism could not have been assumed. Within
time outs. This was likely the same MTS device the experiments, prochlorperazine increased
Ferster and DeMyer (1962) used in their hu- the number of responses per condition rela-
man operant research, but it was programmed tive to the placebo control. In Experiment I,
differently there: It used a simultaneous MTS the increases were between 50% and 125%;
procedure; the stimuli became progressively in Experiment 2, they were between 9% and
more complex (e.g., from colored dots to geo- 45%. Although the ranges overlapped in both
metric figures); and incorrect matches produced experiments, the differences became statistically
6-sec time outs. significant. Finally, the participant erred on only
Ferster and DeMyer’s (1961b) use of the 5% of the MTS trials. In their human operant
MTS apparatus in their pharmacology research research, Ferster and DeMyer (1962) presented
was likely influenced by its use in their human cumulative records of his correct and incorrect
operant research. In both cases, they might have MTS performances, showing how clearly dif-
been influenced by Ferster’s ongoing research ferentiated they became.
on the MTS performances of pigeons, in which
he was studying the effects of intermittently The Discussion
reinforcing correct matches and of time-out Ferster and DeMyer (1961b) did not sum-
on errors (e.g., Ferster, 1960a; Ferster & Ap- marize their results, discuss any limitations of
pel, 1961; Zimmerman & Ferster, 1963). Joe their methods, integrate their findings with
Zimmerman was replicating this research at the the literature, or suggest future research. They
Institute with college students (Zimmerman & did, though, include Dews (1958) and Kelle-
Baydan, 1963). her, Riddle, and Cook (1960) among their
references, but without citing them in the text.
Method Without the citations, we are unsure of their
Ferster and DeMyer’s dependent variable was function. They might have been a basis for their
the median number of correct MTS responses in research or have been research with which their
each condition of two experiments. In Experi- findings could be integrated.
ment I, correct matches were reinforced on an Dews (1958) was a JEAB article reporting
FR-2 schedule. The independent variable was that pigeons’ food-reinforced key pecking in-
three 0.5mg doses of prochlorperazine admin- creased on the FI component of a mixed FR-FI
istered at 8:00am, 2:00pm, and 8:00pm daily. schedule at high, but not low doses of chlorpro-
The research design was an A-B-A (placebo- mazine. The higher doses attenuated pauses in
drug-placebo) withdrawal design across 14, 7, responding between the FR and FI components.
and 20 sessions, respectively. In Experiment II, Perhaps Ferster and DeMyer sought to replicate
correct matches were reinforced on an FR-4 this rate-altering effect with prochlorperazine
schedule. The independent variable was three and a child with autism.
10mg doses of prochlorperazine, administered Kelleher et al. (1960) was an abstract from
at the same times of day. The research design the Federation Proceedings reporting that both
was a B-A-B-A withdrawal design across 13, 11, chlorpromazine and prochlorperazine increased
3, and 11 sessions, respectively. pigeons’ rates of pecking an observation key
which made food available for pecking a sec-
The Results ond key. This replicated Dews’s (1958) results
In both experiments, the participant’s MTS with chlorpromazine, so perhaps Ferster and
responding in the drug and the placebo condi- DeMyer sought to replicate this with the MTS10 Edward K. Morris and Charryse M. Fouquette
performance of a child with autism, but we do discrimination learning on a “computer-con-
not know. trolled operant conditioning apparatus” (e.g.,
discriminated lever-pressing to auditory-visual
Discussion stimuli). In this context, discrimination learning
was a means for assessing drug effects, not for
In our introduction, we observed that Ferster analyzing them. Her research program was thus
and DeMyer’s (1961b) report may be the first more applied than basic (see, e.g., Anderson,
and only one of its kind. This can be supported Campbell, Adams, Small, Perry, & Shell, 1989;
by several lines of evidence. First, in the nine Anderson, Campbell, Grega, Perry, Small, &
Web of Science citations, Ferster and DeMyer Green, 1984; Campbell, M. et al., 1978, 1988;
(1961b) was sometimes the only (i.e., Leff, Campbell, Anderson, Small, Perry, Green, &
1968), but always the earliest citation to basic Caplan 1982; Cohen, Campbell, Posner, Small,
or applied behavioral pharmacology research Triebel, & Anderson, 1980).
with children with autism (e.g., Aman & Singh, On the methodological count, Campbell
1986; Sevin, Bowers-Stephens, Hamilton, & randomly assigned the children to one of two
Ford, 2001). Second, over the next decade, experimental groups – an A-B-A withdrawal
behavioral pharmacology research with chil- design group and a B-A-B withdrawal design
dren with developmental disabilities addressed group (A = placebo, B = drug) – for two to ten
clinically relevant behavior (e.g., body rocking), sessions per condition. Her results were that
which made it applied, not basic, research (e.g., haloperidol reduced the symptoms and facili-
Davis, 1971; Hollis, 1968; Hollis & St. Omer, tated discrimination learning (i.e., changes in
1972). In addition, the participants in these discrimination indexes), while fenfluramine
studies were drawn from undifferentiated popu- had little effect on the symptoms and hindered
lations of children with developmental disabili- discrimination learning (e.g., Anderson et al.,
ties (e.g., autism, retardation, hyperactivity), 1984; Campbell et al., 1982, 1988). Although
and thus may not have included any children Campbell used within-subject withdrawal de-
with autism. Third, only one of the other 28 signs, she grouped the children by condition;
behavioral pharmacology studies published in no individual data were reported. Thus, her
JEAB in the three years before and after Ferster research was a within-group, not a within-
and DeMyer’s publication used human partici- individual, experimental analysis of behavior.
pants. This was Dews and Morse (1958), who For the record, Campbell neither cited nor ref-
used medical students. Outside of JEAB, basic erenced Ferster and DeMyer (1961b) in this or
human behavioral pharmacological research was any related research (e.g., Anderson et al., 1989;
generally conducted with adult volunteers (e.g., Cohen et al., 1980) or in her major review of the
J. P. Brady et al., 1962) or hospitalized adult pharmacotherapy research in autism (Campbell,
psychiatric patients (e.g., Lindsley, 1956). Cohen, & Anderson, 1981).
The main challenge to our observation that Other than Campbell’s studies, behavioral
Ferster and DeMyer (1961b) was the earliest pharmacology research in autism has mainly as-
and only report of its kind is, perhaps, Magda sessed the effects of drugs on clinically relevant
Campbell’s program of research in the late 1970s behavior within individuals (e.g., aggression;
and the 1980s, but the challenge fails on two Burgio, Page, & Capriotti, 1985) or across
counts, one substantive, the other methodologi- them in clinical trials (see Barnard, Young,
cal. On the substantive count, Campbell and Pearson, Geddes, & O’Brien, 2002; Kennedy &
her colleagues studied the effects of haloperidol Meyer, 1998). As a result, Ferster and DeMyer’s
and fenfluramine on (a) the behavioral “symp- (1961b) report is likely the earliest and only
toms” of children with autism (e.g., attention basic behavioral pharmacology research using
span, hyperactivity, object relations, stereotypy) both operant apparatus and measures and a
measured via direct observation, automated within-individual replication design to analyze
detectors, and rating scales and (b) the children’s the behavior of a child with autism (or of anyRescuing Ferster and Demyer 11
children at all). If so, then it is, arguably, a land- develop. During the past two decades, autism
mark report in the history of autism, behavior has become recognized as a problem of such
analysis, and behavioral pharmacology. profound individual and social importance that
behavioral neuroscience research has begun to
Warranting a Rescue address it (e.g., Sparks et al., 2002; see Amaral,
Notwithstanding the evidence supporting Schumann, & Wu Nordahl, 2008; Minshew &
our observation regarding the priority and Williams, 2007). Basic behavioral pharmacolo-
uniqueness of Ferster and DeMyer’s (1961b) gy research with children with autism, thus, may
report, the report is deficient in several regards, follow (see J. V. Brady, 1991). In fact, it should
which leads us to consider whether it warrants follow for an important reason: Drugs are be-
our having rescued it. Several arguments may ing prescribed for children whose effects and
be made for and against this. utility have only been studied and established
Arguments against. Ferster and DeMyer’s with adults (Brown & Sammons, 2002). This
report was deficient in three ways. First, the is both a clinical and ethical concern (Ameri-
research was conducted with just one partici- can Psychological Association, 2006; Vitiello,
pant, perhaps an idiosyncratic one, and was not 2003). Should a program of basic behavioral
replicated across any others. It was also not pharmacology research emerge in autism, then
obviously informed by the behavioral pharma- Ferster and DeMyer’s report will have proved,
cology literature of the day, for instance, about at least, prescient.
prochlorperazine or what the drug might have These arguments for rescuing Ferster and
revealed about children with autism or their DeMyer’s (1961b) report from history still beg
MTS performances. And, it did not analyze the question of why their report has not been
which aspects of the child’s performance were generative. Among the reasons may be that,
differentially sensitive to the drug, that is, the first, researchers have had ethical qualms about
drug’s mechanism of action. Second, their re- conducting such research with children because
port did not discuss the basis for the research their developmental course might be adversely
or any limitations in its methods, integrate its affected by the drugs and because they can not
findings with the extant literature, or suggest voluntarily consent to participate in research.
any future research. It also listed articles in the Moreover, children with autism should be in
reference section that were not cited in the text, treatment or, at least, participating in applied,
which might have clarified these matters. Third, not basic research.4 Their parents may not even
although the report may be a landmark in some consent to the latter. Second, typical adult
respects, it neither influenced other research of
its day nor was generative for subsequent lines 4
Whatever the reason for the lack of such research at the
time, it was not due to professionally prescribed ethics or gov-
of research. It is, perhaps, as one reviewer put ernment policies in the United Sates. As for ethics, although the
it, just “an historical curiosity.” Nuremberg Code of 1947 required informed voluntary consent
for medical research with humans (see Annas & Grodin, 1992),
Arguments for. The deficiencies notwith- at the time Ferster and DeMyer published their report, the
standing, Ferster and DeMyer’s (1961b) report American Psychological Association’s (1959) ethical standards
required consent only “when the possibility of serious aftereffects”
warrants being rescued for two reasons. First, existed (p. 282). The ethical principles of the American Medi-
the interplay between basic behavioral phar- cal Association (1958) did not address consent at all, although
obtaining it was consistent with the Hippocratic oath, as well as
macology research and childhood autism were with the dictum attributed to Hippocrates -- Primum non nocere
(and are) important and interesting enough in (i.e., “First, not to harm”; see Smith, 2005). As for government
policies, the U. S. Public Health Service (est. 1798/1912) did not
themselves that the report should have influ- have any policies for the independent review of human subjects
enced and been generative for other research. research until 1966 (e.g., reviews by institutional review boards
at, for instance, universities and medical schools). Moreover, no
The historical curiosity may not be their report, reviews were actually required until the passage of the National
but that it was not influential or generative. Research Act in 1974, followed later that year by regulations
for establishing internal review boards -- Regulations for the
Second, although no subsequent research Protection of Human Subjects of Biomedical and Behavioral
was generated by the report, basic behavioral Research (Code of Federal Regulations, Title 45, Public Welfare,
Department of Health and Human Services, Part 46, Protection
pharmacology research in autism may still of Human Subjects).12 Edward K. Morris and Charryse M. Fouquette
participants might be easier to recruit and have ological note (Levison, Ferster, Niemann, &
more useful collateral behavior (e.g., verbal Findley, 1964). Indeed, at the time, Travis
reports). Third, the developmental course of Thompson reported that Ferster “expressed no
atypically developing adults may be less likely to interest in pharmacology or anything remotely
be affected by drugs. In addition, basic research neurobiological” (personal communication,
with adults from whom treatments have failed May 3, 2008). Even at Indiana, Ferster may
may be more ethically acceptable. In any event, not have been fully engaged in behavioral
why Ferster and DeMyer’s research has not been neuroscience. In his research with Aprison, for
replicated or extended awaits further analysis. instance, he humorously (or humorlessly) re-
ferred to 5-hydroxytryptophan, a serotonin-like
Postscript neurotransmitter, as “5-hydroxy-chicken-fat” (J.
Hingtgen, personal communication, October 4,
Although Ferster was promoted to associate 2008). Thus, the impetus for his pharmacology
professor in psychiatry in 1961, he left Indiana research with DeMyer may have been more
in 1962 to become the Executive Director of hers than his. She was interested in “develop-
the Institute for Behavioral Research (IBR) in ing an integrated neurobiological approach to
Silver Spring, MD.5 He remained in that and psychiatric disorders” (see, e.g., DeMyer, 1975a,
related positions until 1968, when he was hired 1975b). Ferster was not (T. Thompson, personal
as a professor in the Department of Psychology communication, May 3, 2008).
at Georgetown University. In 1969, he moved This point notwithstanding, Ferster had
to American University, where he remained evinced some interest in behavioral neurosci-
until his death in 1981 (Boren, 1981; Keller, ence prior to moving to Indiana. As he was
1981).6 completing his work with Skinner, Skinner
Between 1962 and 1981, Ferster published (1983) noted:
both basic and applied behavioral research (e.g., For a time, he had planned to work with Walter
Ferster, 1968b; Ferster & Hammer, 1965) and Rosenblith at MIT on the operant condition-
developed an interest in psychotherapy (e.g., ing of nerve impulses from the brain of various
Ferster, 1979), especially for depression (e.g., preparations, allowing efferent impulses to
Ferster, 1973), but published no more research operate the programming equipment normally
in behavioral pharmacology, only a method- operated by pecking a key or pressing a lever. (p.
5
When Ferster left Indiana, Joseph N. Hingtgen took his 111; see also Skinner, 1987)
place, both with Aprison and DeMyer. With Aprison, he collabo- Moreover, the Archives for the History
rated on animal model research on the neurochemical correlates
of depression (Aprison & Hingtgen, 1970, 1993). With DeMyer, of American Psychology houses two boxes of
he conducted behavior-analytic research with children with Ferster’s papers, one of which contains a folder
autism (e.g., Hingtgen & Coulter, 1967; Hingtgen, Coulter, &
Churchill, 1967; Hingtgen, Sanders, & DeMyer, 1965; Hingtgen labeled “Interpreting Drug-Behavior Effects
& Trost, 1966). with a Functional Analysis of Behavior” (Box
6
Aprison remained at Indiana, where he had a distinguished
career in behavioral neuroscience, discovering, for instance, gly- M93, Folder 1). Its contents are (a) a near-final
cine’s role as a neurotransmitter inhibitor (Aprison & Werman, draft of a co-authored paper with James Appel
1965; see Aprison, 1990). In 1975, he received the Gold Medal
Award from the Society of Biological Psychiatry and, in 1978, (not DeMyer) by the same title as the folder;
was named Indiana University’s first Distinguished Professor of (b) an independent abstract, rough draft, and
Neurobiology and Biochemistry. He retired in 1997 as profes-
sor emeritus and passed away in 2007. DeMyer also remained draft of a presentation of the paper; and (c) some
at Indiana, directing the Research Center for Early Childhood original data from the summer of 1960. Writ-
Schizophrenia in a Children’s Services wing of the Larue D.
Carter Memorial Hospital. In 1962, she received a grant from the ten while Ferster et al. (1962) was both in press
National Institute of Mental Health that for many years funded and just published, the unpublished paper was,
her research on autism’s diagnosis (DeMyer, Churchill, Pontius, &
Gilkey, 1971), prognosis (e.g., DeMyer, Barton, DeMyer, Norton, as its title suggests, a behavioral interpretation
Allen, & Steele, 1973), and biological basis (e.g., DeMyer, 1975a, of drug-behavior interactions, supported by a
1975b). She also wrote a major review of the autism literature
(e.g., DeMyer, Hingtgen, & Jackson, 1981) and books on parents review of the basic behavioral pharmacology
and their children with autism (DeMyer, 1979). Today, she is a research of the day (1955-1962) and illustrated
professor emerita of psychiatry at the Indiana University School
of Medicine. with original data, presumably the same data asRescuing Ferster and Demyer 13
(or similar to) those in the folder. The research References
was funded by a grant from the National Sci-
ence Foundation (G-7617), the same grant Aman, M. G., & Singh, N. N. (1986). A critical
that supported Ferster and Appel (1961) and appraisal of recent drug research in mental
Ferster et al. (1962). Ferster was presumably the retardation: The Coldwater studies. Journal
principal investigator. of Mental Deficiency Research, 30, 203-216.
Although he conducted no more pharma- Amaral, D. G., Schumann, C. M., & Wu Nor-
cology research after leaving Indiana, Ferster dahl, C. (2008). Neuroanatomy of autism.
did retain an interest in autism, publishing Trends in Neuroscience, 31, 137-145.
articles and chapters on its analysis and treat- American Medical Association (1958). Prin-
ment (e.g., Ferster, 1966, 1967, 1968a; Ferster ciples of medical ethics. The Journal of the
& Simons, 1966). He also consulted with the American Medical Association (Special Edi-
Linwood Children’s Center in Ellicott City, tion). Chicago, IL: AMA Press.
MD. Founded in 1955 by Jeanne Simons American Psychological Association (1959).
(1909-2005), the Center became known for its Ethical standards of psychologists. American
“Linwood Method” of treating children with Psychologist, 14, 279-282.
autism (Simons & Oishi, 1987). The method American Psychological Association (2006).
appears similar to today’s Developmental, In- Report of the Working Group on Psychotropic
dividual Difference, Relationship (DIR) model Medications for Children and Adolescents:
known as “Floor Time” (Greenspan & Wieder, Pharmacological, psychosocial, and combined
2006). Although neither the Linwood Method interventions for childhood disorders: Evidence
nor DIR is based on a science of behavior or base, contextual factors, and future directions.
is evidence-based, they appear to involve the Washington, DC: Author. (see http://www.
intensive free-operant differential reinforcement apa.org/releases/PsychotropicMedication-
of clinically-relevant behavior (e.g., parent-child sReport.pdf )
interactions) through successive approxima- Anderson, L. T., Campbell, M., Adams, P.,
tions (i.e., shaping), along with some incidental Small, A. M., Perry, R., & Shell, J. (1989).
teaching. The effects of haloperidol on discrimination
At Linwood, Ferster observed the method, learning and behavioral symptoms in autistic
interpreted it behaviorally, described its similari- children. Journal of Autism and Developmen-
ties with operant conditioning (e.g., reinforce- tal Disorders, 19, 227-239.
ment, extinction, shaping), and vouched for its Anderson, L. T., Campbell, M., Grega, D. M.,
effectiveness (Ferster & Simons, 1966). He also Perry, R., Small, A. M., & Green, M. D.
assisted Simons in operationalizing it, which (1984). Haloperidol in the treatment of
reportedly improved staff training and treat- infantile autism: Effects on learning and
ment fidelity (Ferster, 1967). This work was sup- behavior. American Journal of Psychiatry,
ported by a $220,000 grant to Ferster through 141, 1195-1202.
IBR from the Bureau of Research at the Office Annas, G. J., & Grodin, M. A. (Eds.). (1992).
of Education in the U.S. Department of Health, The Nazi doctors and the Nuremberg Code:
Education, and Welfare, titled “Treatment and Human rights in human experimentation.
Education of Autistic Children: Combined Ap- New York: Oxford University Press.
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(1965-1968). After the grant’s completion, neurotransmitter role of glycine. In O. P.
Ferster’s interests turned more to psychotherapy. Otterson & J. Storm-Mathesen (Eds.),
However, just prior to his death, he accepted an Glycine neurotransmission (pp. 1-23). New
appointment to serve on the Advisory Board of York: Wiley.
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