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Address for reprints: Herman Joseph, Board of Directors, National Alliance of Methadone
Advocates (NAMA), 435 2nd Ave. New York, NY 10010, USA
1
National Alliance of Methadone Advocates (NAMA), New York, NY, USA
2
The Rockefeller University, New York, NY, USA
Heroin Addict Relat Clin Probl 2006; 8(4): 9-28 Review
In the Service of Patients: The Legacy of Dr. Dole
Herman Joseph
1,2
and Joycelyn Sue Woods
1
Summary
The underlying theme in Dr. Vincent P. Dole’s work is the effect of metabolism
on behavior. This led to ground breaking investigations at The Rockefeller
University in electrophoresis, lipids, obesity, addiction, and the development
of methadone maintenance in 1964 with his late wife, Dr. Marie E. Nyswander.
Dr. Mary Jeanne Kreek, a research resident in his laboratory in 1964, is now
continuing addiction research as a professor at Rockefeller. Dole developed
methadone detoxification in the New York City jail system and office based
methadone medical maintenance with Nyswander. His major concern was to
resolve the stigma that methadone patients encounter.
Key Words: Development of methadone maintenance -
Dr. Dole legacy
Introduction
With the death of Dr. Vincent P Dole in August of 2006 at the age of 93, the end of
an era has come to pass in 20th century medicine-namely the initial unraveling of heroin
addiction from what was thought to be compulsive immoral behavior to a legitimate
medical disorder that could be treated with medication within clinics and private physi-
cians’ offices
(4,5,8,41)
. Although, known primarily for his work in developing methadone
maintenance treatment for heroin addiction and the promulgation of the metabolic
10
Heroin Addiction and Related Clinical Problems
theory of addiction, his ground breaking accomplishments in this area can only be fully
appreciated in the context of a distinguished career as a research scientist dating back
to the 1940s. His work can be subdivided into two periods, the pre-addiction and the
addiction period which started in the 1960s. However, upon examination it is really
one continuous interconnected arc of metabolic research. His underlying major concern
was the effect of metabolism on human behavior. The range of his work is unique as is
the range of his scientific skills. He made original contributions to the understanding
of electrophoresis, lipid chemistry, the treatment of hypertension and the metabolic
foundations of obesity among other topics
(3,4,31)
. He showed that very obese people
metabolize food differently than others, and that the craving for food was similar to
the craving of a smoker for a cigarette and the craving of a narcotic addict for heroin
although the metabolic pathways resulting in the various cravings differ
(2,4,17,20)
.
His studies in obesity challenged popular belief that obese people lack will-power to
control their food intake. He also noted the tendency for obese people to regain weight
or relapse after dieting and that this relapse had a metabolic basis
(2,4)
.
After finishing his studies in the metabolism of obesity, Dr. Dole embarked on the
study of addiction and the development of methadone maintenance. His partner and
wife in this historical research was Dr. Marie Nyswander, a psychiatrist who died in
1986. In addition to his scientific background, Dr. Nyswander brought to the develop-
ment of methadone treatment a unique insight into the social and personal issues that
heroin addicts and methadone patients face.
Prior to their collaboration, Dr. Nyswander had worked for almost two decades
treating narcotic addicts in various venues including as a Lieutenant in the US Public
Health Hospital in Lexington KY, the Musicians Clinic in NYC, in private psychiatric
practice and with Dr. Beatrice Berle in a storefront in East Harlem that was part of the
addiction program of the East Harlem Protestant Parish. She was a founder of Narcotic
Anonymous (NA) based on the model of Alcoholics Anonymous (AA)
(2,43,50)
.
Dr. Nyswander wrote several papers about her experiences treating addicts includ-
ing the book, The Drug Addict as a Patient in 1956 which was the primary influence
on Dole’s understanding of addicts and addiction. For addicts to be considered patients
was a revolutionary concept in the United States
(43)
. Addiction and heroin addicts were
relegated to the criminal justice system or prison-like hospitals by a series of supreme
court decisions, and national and local laws emanating from the Harrison Act of 1914
which, although only a tax and registration act, was interpreted by the Treasury De-
partment to exclude physicians from treating addiction with maintenance medications
(2)
. However, from her experiences treating addicts as a psychiatrist, Dr. Nyswander
concluded that many addicts need to be maintained on a narcotic to function since
talking therapies of psychiatry and NA were unable to alleviate the craving which for
many was the focal point leading to relapse
(43)
.
It was the complementary knowledge and collaborative efforts of Dole and Nyswander
that shaped both the research and the clinical development of methadone maintenance as
a medical regimen: Dr. Dole was in charge of the laboratory research. Dr. Nyswander
11
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
recruited heroin addicts from the East Harlem for pilot at the Rockefeller University.
From her years of experience she developed clinical protocols both at The Rockefel-
ler University and at The Beth Israel Medical Center where the pilot moved into an
expanded clinical research phase.
Although the pilot did not begin officially at The Rockefeller University until
February of 1964, Dole and Nyswander were meeting during 1962/63 planning the
research, the need for a maintenance medication and discussing the theories of addic-
tion. Notwithstanding her psychiatric orientation, Nyswander accepted Dole’s concept
that, like extreme obesity, heroin addiction was a metabolic disease
(8)
.
Dr. Mary Jeanne Kreek, a first year medical resident at New York Hospital –Cornell
Medical Center in internal medicine and neuroendocrinology was recruited towards
the end of 1963 to assist in the research pilot that began in February of 1964. Her duties
included bone marrow biopsies and tests of narcotic tolerance. She worked with Dole
and Nyswander on the seminal paper, Narcotic Blockade
(7)
. However, Kreek had to
leave the project temporarily to finish her residency at Cornell. Upon returning to the
Dole Laboratory she embarked on a landmark series of studies concerning the medical
safety and side effects of methadone, how methadone functions in a stabilized patient,
the biological basis of addictive disease: opiate, cocaine, and nicotine addiction and
alcoholism
(14,16,19,37)
. She is now Professor and Head of the Laboratory of the Biology
of Addictive Diseases at The Rockefeller University. A summary of the extent of her
work and a list of her publications are available at the website of The Rockefeller
University.
For the clinical phase at The Beth Israel Medical Center Dr. Nyswander recruited
Dr. Joyce Lowinson in 1964, a second year psychiatric resident at New York Medical
College who had shown an interest in the treatment of addicts on the detoxification ward
at Metropolitan Hospital. Dr. Lowinson subsequently became a professor of psychiatry
at the Albert Einstein College of Medicine (AECOM), developed the first methadone
program associated with a medical school at AECOM and became the senior editor of
Substance Abuse: A comprehensive textbook.
Dole also enlisted Dr. Norman Gordon, a psychologist to administer and analyze
reaction time, coordination and related studies on methadone patients. Dr. Gordon’s
research demonstrated that stabilized patients were not impaired from methadone and
could perform in all jobs for which they were trained or qualified
(28)
.
Other researchers, administrators, and physicians who were affiliated with Dr. Dole
during the program’s development include Dr. Enoch Gordiss who subsequently became
the head of NIAAA, Dr. Ann Ho who worked on various laboratory studies with Dr.
Dole and then with Dr. Kreek, Dr. Jerome Jaffe who became head of President Nixon’s
drug programs in the Special Action Office of Drug Abuse Prevention and from 1971
to 1973 developed a network of methadone programs in the United States, Dr. Robert
Newman who made the initial major expansion of methadone treatment in N.Y., Dr.
Ray Trussell who transferred the original pilot to Beth Israel Medical Center, Dr. Harold
Trigg who was the first medical director at Beth Israel; Dr. Melissa Freeman of Beth
12
Heroin Addiction and Related Clinical Problems
Israel Medical Center who treated the first female methadone patients; Dr. Elizabeth
Khuri and Dr. Robert Millman who developed the first adolescent methadone program;
and this author who worked with Dr. Dole on topics related to the criminal justice
system, the adjustments of patients during and after treatment, and the establishment
of office based prescribing of methadone.
Modern Theory of Addiction
Possibly Dole and Nyswander’s greatest achievement was to shift the paradigm
of addictive behavior from a moral stigmatizing psychological failing to a chronic
metabolic disease
(8)
. The metabolic theory evolved from a seminal paper published
in 1966, Heroin addiction: A metabolic disease. Dole and Nyswander suggested the
adaptation of a metabolic theory of addiction. Factors were introduced such a neurologi-
cal susceptibility, an altered biological response to narcotics that results in continued
use, a protracted abstinence syndrome and metabolic narcotic craving which precipitate
relapse. According to Dole at the time the specific narcotic hunger leading to relapse
was symptomatic of a metabolic alteration within the central nervous system irrespec-
tive of the addict’s psychological profile, social class or emotional state
(8)
.
In 1970 Dr. Dole published The Biochemistry of Addiction. In this article he predicted
the existence of opiate receptors in the brain, their location, density and the technology
needed to isolate them
(9)
. The complexity of the endogenous opioid receptor system was
discovered, and is being currently mapped out and studied
(16,48)
. According to Dole,
the metabolic alteration responsible for the specific narcotic craving described earlier
in his work, appears now to be associated with as yet an undiscovered impairment or
deficit in the function of the opioid receptor system
(16)
.
In his paper written for the Lasker Award for Clinical Medical Research in 1988,
Dole discussed methadone maintenance and its implications for theories of addiction
and stressed the following
(16)
:
1) The high rate of relapse of addicts after withdrawal is due to a persistent dis-
order or defect within the endogenous opiate narcotic ligand system caused
by long use of powerful narcotics such as heroin.
2) Methadone administered orally in daily adequate doses with blood levels
in a range of 150ng/ml and 600ng/ml can compensate for this defect with
continuous and stable occupancy of the narcotic receptors.
3) Methadone normalizes the neurological and endocrinologic processes in
patients with this disorder.
4) The major purpose of long term research is to identify the derangement or
defect within the endogenous opiate narcotic ligand system and correct it.
5) Methadone treatment is corrective not curative since most patients but not all
relapse after withdrawal.
6) The return of specific narcotic craving after withdrawal is symptomatic of the
defect within the endogenous opiate narcotic ligand system.
In 1994 Dole summarized the metabolic theory of addiction that has evolved over
the past 40 years.
13
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
“A modern theory of narcotic addiction is that the compulsive and quite specific
craving for narcotic drugs is a symptom of a deficiency in function of the natural opi-
ate-like substances in the brain. To be sure, sociological and psychological forces
enter into the making of an addict, but these factors determine exposure—whether or
not addictive drugs are available in the environment and whether a person chooses to
experiment with them. In any person with repeated exposure to a narcotic drug, the
brain adapts and becomes pharmacologically dependent on a continuing input. In
some susceptible persons —fortunately a minority of the population—the adaptation
becomes fixed and with repeated use a regular input of narcotic becomes a necessity.
The experimenter has become an addict. From this perspective methadone maintenance
is replacement treatment, compensating for impairment in function of natural opiate-
like substances”
(21)
.
With this statement of the modern theory of addiction, social, psychological and
biological components are incorporated, each with a defined and interrelated role.
Eventually biological forces take over irrespective of the psychosocial elements that
may be responsible for experimentation or initial use. The continued craving, relapse
and tolerance associated with addiction have biological component, which are independ-
ent of will power and a person’s psychological profile. The basic characteristics of a
continued addiction are therefore biologically influenced. The resolution of personal
problems does not mean that the majority of addicted individuals can subsequently
resolve drug craving or other biological components of an addiction. A minority of
addicted individuals can resolve their cravings but studies have shown that addiction
in a majority of the persons can continue indefinitely irrespective of a person’s emo-
tional or intellectual characteristics
(39)
. Most important, methadone treatment is not a
substitution of one addiction for another (methadone for heroin) but is compensation
or replacement for the body’s impaired natural opioids
(7,8,14,16,17,20,36)
.
The Role of Adjunct Services in Methadone Maintenance Treatment
In reviewing the early papers produced by Dole, Nyswander and colleagues the reverber-
ating theme is that although methadone is essential to relieve craving no one medication
is able to address the many social, personal, and medical issues that patients present to
methadone programs, and social services are essential for rehabilitation
(6,43)
. In 1988
when he received the Lasker Award for Clinical Medical Research, Dole reiterated the
need for social services as follows:
“When somatic functioning has been normalized (by methadone), the ex-addict
supported by counseling and social services can begin the long process of social re-
habilitation”
(16)
.
The issues of homeless and unemployment were recognized from the beginning
of the program. In the 1960s these social ills were more readily addressed than today.
Furnished rooms for the homeless and jobs requiring minimal skills were available.
Although at program entry most of the patients were unemployed in need of housing
14
Heroin Addiction and Related Clinical Problems
and estranged from families within a few months after entering the program most
were productively engaged in employment, enrolled in school, housed, reunited with
families and where applicable, functioning as homemakers. This dramatic turnaround
within a period of 6 months to one year was a testimony to the efficacy of adequate
doses of methadone, the resources in the community and the reality oriented counseling
offered in the clinics which may have included legal help to address old warrants and
court cases
(17,23,32)
.
To assist in rehabilitation, Dole and Nyswander created a position in the clinics
known as research or patient assistants. Successfully stabilized methadone patients
were hired as a link to resolve issues between mistrustful patients and the professional
clinic staffs
(44)
. Although the position no longer exists, eligible patients were hired and
eventually absorbed into the clinics as counselors and administrators. McLellan et al
showed that outcomes of methadone patients in a Veteran’s Medical Center methadone
program improved with enhanced on site services to patients which included a psy-
chiatrist responsible for medical and psychiatric issues, a vocational counselor, and a
family therapist over patients who received standard counseling in the study. Patients
who only received methadone did less well than patients who received standard coun-
seling. About 69% of the subjects who received only methadone had to be transferred
to standard counseling since their adjustments were poor in regard to continuing use
of opioids and cocaine
(38)
. However, these onsite services are expensive and may not
be available to all programs unless they are located within large medical institutions
such as the Veterans Administration which offer a panoply of medical, psychiatric and
social services to veterans.
However, beginning in the 1970s a confluence of social changes and medical epi-
demics converged on the patient and addicted population. Economic downturns and
the changing nature of work from manufacturing jobs to employment in the emerging
information age which demanded a degree of computer skills and literacy adversely
affected the employability of patients except for those with the skills and educations
applicable in the new job market. Affordable housing for lower middle class and the
poor began to disappear, and social benefits were reduced.
These social changes produced a new era of destitution, homeless and hunger af-
fecting many cities and rural areas in the United States
(49)
. By the 1980s and 1990s
improvised dwellings constructed from cartons and discarded materials were seen on
the streets. Lack of affordable housing and chronic unemployment produced a mod-
ern form of destitution across the country and impacted negatively on the methadone
patient population into the 21st century
(49)
. HIV and hepatitis C emerged within the
population starting in the 1970s and possibly earlier for hepatitis C
(30,42)
.
The methadone clinics were usually the patient’s only point of contact with medical
and social services. As conditions deteriorated for marginal populations, the needs of
patients became more complex, diversified and more difficult to obtain and deliver.
Clinics located in facilities without services would have to develop linkages with com-
munity agencies in order to address the issues that patients presented. This may entail
15
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
obtaining funds through grant applications.
Within the past two decades, services were developed in methadone programs
to meet women’s issues including partner violence
(24)
. In her evaluations of the
methadone program in the mid 1960s thorough the early 1970s, Dr. Gearing noted
decreasing retention rates over the course of time and in the 1970s, patients were
entering treatment with life threatening medical conditions including pneumonias. She
recommended that to obtain needed medical services, methadone treatment should be
affiliated with medical centers
(23)
. Dole and Joseph also noted decreasing retention
rates in treatment in cohorts that entered methadone treatment in the early 1970s. There
existed a group of transient, chronically unemployed, ill patients who were cycling
in and out of treatment and getting arrested on petty charges. There are no adequate
services available to help stabilize these patients other than the methadone programs
which had limited facilities to address their problems
(13)
. Problems related to social
issues such as homelessness, chronic unemployment and polydrug abuse continue in
methadone programs to the present day. While Dole advocated counseling, he was con-
cerned about the philosophy of counseling with the primary goal of removing patients
from methadone. Dole’s premise was that the primary goal of counseling should be
productive functioning in the community while the patient is enrolled in treatment. He
believed that patients should be assisted in solving serious problems before attempting
withdrawal, considering the serious risks that are involved such as high probabilities
of relapse and death
(39)
. Also, Dole was against overly intrusive counseling that may
threaten a patient’s job or education because of the time that counseling was scheduled
and the hours spent in counseling activities which may detract from employment and
educational opportunities and family obligations.
Dole and the Criminal Justice System
In 1972 at the invitation of the New York City Department of Corrections Com-
missioner, Benjamin J. Malcolm, Dr. Dole, as a non-compensated volunteer, set up the
first detoxification service in the New York City jails to withdraw arrested addicts from
heroin using methadone. This was the first service of its kind in the United States. Dole
was also responsible for enlisting the services of a major hospital, Montefiore Medi-
cal Center, to provide the ongoing detoxification services and primary medical care to
prisoners in New York City Rikers Island Jail
(10,11)
. Dole established the jail medical
services as a non-compensated volunteer. In 1972 he received a “Citation by the City
of New York for Extraordinary Voluntary Service for Establishing the Methadone
Detoxification Program- Volunteer of the Year”.
In 1987, the service was developed into KEEP (Key Extended Entry Program)
by the New York State Office of Alcoholism and Substance Abuse Services and the
Department of Corrections. Heroin addicts were not only withdrawn from heroin but
if they chose, they could be maintained on methadone and referred for treatment in
the community upon their release. Arrested methadone patients could also be main-
tained on methadone in the jails and, when released, referred back to their programs
for continued treatment. KEEP became a model worldwide for methadone treatment
16
Heroin Addiction and Related Clinical Problems
in jails and prisons.
Adolescent Program
In 1968 Dole and Nyswander began research into the needs of addicted adolescents
between the ages of 14 and 18 who were unable to enter methadone treatment because of
their age. This was the first such research undertaken on an adolescent group. Linkages
were made between a local high school located near The Rockefeller University, Dr.
Dole’s laboratory at the university and the Department of Public Health and Pediatrics
Divisions of the New York /Cornell Medical Center now known as the Weill Cornell
Medical Center
(35)
.
In 1971 an ambulatory adolescent clinic to house the program was opened near
the high school, the university, and the hospital. Applicants had to present a well
documented history of heroin addiction of at least two years with at least one failure
in treatment program. Parental consent was required and students had to be registered
in the local high school. The students reported daily to the clinic and were eventually
stabilized on average doses of 35 mg/dy with a maximum of 50/mg/dy. Emphasis was
on rehabilitation although detoxification was available when the social situation war-
ranted it. A panoply of supportive services were available: medical services either at
the clinic or the hospital, counseling to continue education with tutoring if indicated,
vocational referrals and job placements, legal services and recreational activities
within NYC through an organization called Hospital Audiences. Over a three year
period with 85 admissions there was an overall retention rate of 83%, 22 adolescents
had been detoxified although two had to be restabilized because of relapses
(35)
. The
physicians assigned to the program were Drs. Elizabeth Khuri, a pediatrician and Dr.
Robert Millman, a psychiatrist. Both physicians had joint appointments at Cornell and
in the Dole laboratory at The Rockefeller University.
Methadone Medical Maintenance
Methadone medical maintenance, the prescribing of methadone by a private physi-
cian in an office based practice was originally developed in 1983 at The Rockefeller
University by Dole, Nyswander, Kreek and Joseph. The purpose of this program is
to enable socially stable patients to be treated in the offices of private physicians or
other venues of medical practice such as primary care centers instead of the traditional
methadone clinics with rigid reporting regulations. The program gives patients the
opportunity to further improve their social adjustments, job and educational opportuni-
ties. In this program patients report once month to their physicians who prescribe the
methadone and receive a month’s supply of methadone in a convenient tablet form in
one or two vials rather than individual daily liquid formulations in vials which may
spill and are difficult to store. Patients submit a urine sample at the time of their visit
(41,46)
. It was Dole’s idea to transfer socially rehabilitated patients into the practices of
physicians who had never worked in a methadone clinic to determine whether the doc-
tors could treat the disease of addiction within their practices as they would treat other
conditions. At the time of its initial expansion from The Rockefeller University, the
17
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
program was transferred to the office-based practices of internists Drs. David Novick,
a hepatologist and Edwin A. Salsitz, a pulmonologist. While Dr. Novick did work with
Dr. Kreek at The Rockefeller University on research projects, and Dr. Salsitz worked
on the detoxification wards at Beth Israel, neither physician ever worked in a traditional
clinic. Dr Salsitz harbored negative opinions about methadone as a maintenance medi-
cation since his only experience was on the detoxification wards with dysfunctional
methadone patients who were poly drug abusers, alcoholics, chronically unemployed
and some, destitute and homeless. He was unprepared, psychologically, for the first
office patients in medical maintenance who were employed, well dressed, and well
behaved. He advised this author that he never met or treated successful methadone
patients. When he started to treat stable patients his attitudes changed, and he made
“a 180 degree turn.” Salsitz realized that his previous negative perceptions about the
ineffectiveness of methadone treatment were really about the effects of poverty, chronic
unemployment and destitution on human behavior and not about the success or failure
of methadone treatment as a medical regimen.
Different models of medical maintenance have been developed in NY State by
this author while employed at the N.Y. State Office of Alcoholism and Substance
Abuse Services prior to 2003. They are still in existence and are being monitored by
the agency.
During the past two years in Albany, NY methadone maintenance treatment for
socially stable patients was added to an existing primary care center which has a phar-
macy on the premises. At present 25 socially stable methadone patients have been
integrated into medical care at the center with a physician who prescribes methadone.
The patients receive their monthly methadone at the center pharmacy without observed
ingestion. They are seen by the methadone prescribing physician and other specialists
in the center, and if needed, the social service counseling staff. Patients are employed
and most are married with families. This primary care center has proven to be success-
ful for the delivery of multi-services without taxing the limited financing and space
of a traditional methadone clinic. The use of primary care centers to offer methadone
treatment is as yet an untapped resource for the expansion of the program and integra-
tion of methadone patients into mainstream medical practice.
The physician/commercial pharmacy model was developed at Weill Cornell Hospital
with the medical director of the clinic assuming responsibility for care of 14 patients
who receive their methadone in a neighborhood pharmacy upon presenting a photo ID
card. The patients also receive psychiatric care if indicated, in this program since the
medical director is a psychiatrist and will prescribe needed medications for anxiety
and depression. The patients in this program are employed and report once per month.
However, if there are any problems of a psycho-social nature, then the patients may
see the psychiatrist more often.
The pharmacy and the primary care center had to be brought into compliance with
the regulations of Federal Drug Enforcement Administration, the Federal Center for
Substance Abuse Treatment, and the NY State Office of Alcoholism and Substance
18
Heroin Addiction and Related Clinical Problems
Abuse Treatment as Narcotic Treatment programs with the installation of alarm systems
and special safes to store the methadone.
Although the network of seven methadone medical maintenance programs in New
York State has been successful according to records maintained at OASAS, the pro-
gram has not been duplicated on a large scale in the United States. This may be due
to the regulations for setting up programs and the expenses involved. Nevertheless,
the successful implementation of a few medical maintenance projects in the United
States did serve as a model for the introduction of buprenorphine treatment in office-
based practices.
The Need for Evaluation
Inherent in Dr. Dole’s work was his insistence on objective evaluation of the metha-
done program. When the pilot project of six patients moved to Beth Israel Medical
Center in late 1964 a major evaluation was planned with the Columbia School of
Public Health under the direction of Professor Frances Rowe Gearing. Patient reten-
tion in treatment, reasons for discharges, duration of treatment, employment status and
patient demographics were among the variables studied. In addition a committee was
formed to oversee the evaluation, make recommendations concerning the direction
of the evaluation and the expansion of the program. No other treatment for addiction
was subject to such a continuous investigation for a period of six years. The major
findings were that the majority of the patients improved made favorable adjustments
with reductions in or elimination of heroin abuse and crime, and increases in produc-
tive behavior such as employment, school and child care. However, because of the
changes in social conditions patients were entering into treatment in the 1970s with
life threatening major medical illnesses, chronic unemployment, and homelessness. It
was recommended that methadone treatment be developed in conjunction with medical
centers
(23)
. Also, in the 1970s the federal government introduced regulatory measures
which Dole considered excessively intrusive into patient care. Paper work increased
in the clinics and the perception of the program became one of control rather than
treatment. Patients perceived a strong social stigma targeted to methadone and were
ambivalent about entering and remaining in treatment
(39,40)
.
In addition Dole and this author completed a major follow-up study of patients
who were discharged from the program in good standing, against medical advice or
death. Post treatment outcomes were studied including death rates both in treatment
and during the post treatment period
(13)
. Taking the lead from the Gearing, Dole-Joseph
studies, other investigators began to evaluate their programs including follow-up
data. A mega analysis by Magura and Rosenblum showed a consistency of trends in
all follow up studies: high relapse rates after leaving treatment, post- treatment death
rates were at least twice the in-treatment rates with the excess of deaths in the post
treatment period associated with heroin use. They recommended that care should be
taken in recommending termination from treatment because of the high risks such as
relapse rates and deaths
(39)
.
However, evaluation was not confined to the overall clinical management of the
19
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
program but also to medical safety of methadone as studied by Kreek. Pregnancy
and neonatal development were extensively studied in numerous investigations and
methadone was found to be safe for use in pregnancy
(22)
. Most important are studies
that showed methadone can stop the transmission of HIV if patients receive adequate
doses
(34)
.
Both this author and Dole indicated that claims about the success or failure of
a program without evaluation was only propaganda irrespective of what a program
is capable of achieving. Another factor about evaluation is the study not only of the
successes but also of failures in treatment which will define the limits inherent in the
program and/or the need for further services
(32)
.
Interim Methadone Maintenance
Interim Methadone Maintenance although controversial, is a needed service in
cities and countries where limited funding is available, and a heroin epidemic exists
with the presence of HIV, hepatitis C, high mortality rates and drug related criminality
among the addicted population. The concept has the support of Dr. Dole who wrote
an editorial favoring this approach when there is limited access to comprehensive
treatment
(18)
. Interim methadone maintenance provides patients with adequate doses
of methadone to eliminate heroin use and counseling on an emergency basis. It is an
alternative to traditional waiting lists where patients do not receive medication and
continue to inject heroin. It is not an alternative for comprehensive treatment which
must be developed. Evaluations of two interim clinic programs in New York City and
Baltimore showed that: 1) heroin use and crime were reduced as compared to applicants
on the traditional waiting lists, 2) an increase in the likelihood of patients in the interim
program entering comprehensive treatment and 3) in New York City a higher rate of
interim patients retained in treatment at 16 months than those on traditional waiting
lists (72% vs. 56%)
(47,51)
.
While an interim program is not a traditional clinical service, it is a service to the
community by helping to reduce crime and to heroin addicts by reducing or possibly
eliminating the transmission of HIV and hepatitis C until they enter a comprehensive
program
(18)
. Notwithstanding favorable research the interim methadone maintenance
concept has been rejected by the treatment community, the US Public Health Working
Group on Methadone and state authorities such as the NY State Office of Alcoholism
and Substance Abuse Services since the interim clinic is not a full service program with
many of the social services that patients may require. It is now up to communities to
evaluate the need for such a program which does have the ability to reduce heroin use,
crime and the transmission of HIV and hepatitis until the patient enters a full service
program. The National Alliance of Methadone Advocates supported the development
of interim methadone maintenance to assist addicts on waiting lists until they entered
regular treatment.
20
Heroin Addiction and Related Clinical Problems
Awards
Dole received numerous distinguished awards throughout his career. Among these
are the following:
- The Stouffer Award (1972) for his original work in isolating free fatty acids
from plasma, demonstrating their origin in body fat stores and their inter-
relationships with insulin and carbohydrate metabolism.
- The Albert Lasker Award for Clinical Medical Research (1988) for hypothesiz-
ing the physiological basis of addiction and developing methadone maintenance
treatment for heroin addiction.
- The Fourth annual New York City Mayor’s Awards of Honor for Science and
Technology (1988) for the development of methadone maintenance to treat
heroin addiction.
- Prince Mahidol Award in Public Health (1996) for research into addiction and
the development of methadone maintenance for heroin addiction
Stigma: the most destructive social force that methadone patients face.
The social stigma that methadone patients face appears to be pervasive throughout
society although some progress is being made through education and advocacy. Patients
are especially concerned about their treatment in the criminal justice system where they
can be ordered to withdraw from methadone by probation and parole officers and judges
irrespective of the adjustments they are making. It appears that physicians’ judgments
about the applicability of methadone treatment for a particular patient before the court
is secondary to the judgments of non medically trained personnel in the court system.
Also, methadone treatment for withdrawal or maintenance is not widespread in the
jails and prisons. The New York City Rikers Island Jail addiction treatment programs
have as yet not been widely accepted in the United States. There is now a campaign
spearheaded by enlightened lawyers, judges and advocates to implement nationwide
programs and changes in court practices. However, at the last AATOD meeting in
2005, Kathy Coughlin, the Assistant Commissioner of the New York City Department
of Corrections reported that few if any referrals were made to methadone treatment in
the Drug Courts of New York City.
Patients are also concerned about their treatment in hospitals if their enrollment
in methadone maintenance is discovered by medical staff. They are concerned that
they may not receive proper pain management or they may be withdrawn from their
medication. Most of all they are concerned about the biased attitudes of physicians,
nurses, and other health personnel.
The fear of social stigma pervades the patients’ lives in the workforce if it is discovered
that they are enrolled in methadone treatment. Patients may lose jobs or be placed under
unusual surveillance. Furthermore if there should be a theft in an office, methadone
patients feel that they would be the first to be suspected. Dr. Norman Gordon reported
that in the workforce stable methadone patients are more stigmatized than alcoholics
21
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
who may have relapsed. He indicated that “methadone patients are very conscious
of the fact that employers and potential employers frequently view their employment
with a jaundiced eye”
(29)
. If a stable methadone patient is in the “closet” and never
revealed on an application that he is in the program and urine tests are implemented in
the firm, the patient faces indecision, panic about the tests and fear of possibly losing
his job. A prime activity for patients therefore is to act consciously in a manner to
avoid detection or bring attention to themselves especially at work. Patients therefore
develop behaviors to conceal their enrollment in methadone treatment
(26,27,40)
.
Dr. Dole was always at the service of patients and advocacy groups such as the
National Alliance of Methadone Advocates to help resolve issues of stigma and mis-
directed policies that came to his attention. For him, his greatest legacy would be the
elimination or reduction of the stigma that is directed to methadone patients, programs,
and the medication itself. He communicated with patients through letters, email, phone
contacts and personal interviews. Both Dole and Nyswander were concerned about
the way methadone is perceived. In an article published on the tenth anniversary of
methadone treatment they expressed their misgivings as follows:
“What was not anticipated at the onset was the nearly universal reaction against
substituting one drug for another, even when the second drug enabled the addict to
function normally. ...... The analogous long term use of other medications such as insulin
and digitalis in medical practice has not been considered relevant”
(12)
.
Kosten and George indicate in the following statements that Dole’s metabolic theory
can lessen the stigma associated with addiction and methadone treatment if patients
understand their condition.
“Brain abnormalities resulting from chronic use of heroin, oxycodone and other
morphine-derived drugs are underlying causes of opioid dependence (the need to keep
taking drugs to avoid withdrawal syndrome) and addiction (intense drug craving and
compulsive use)”
(36)
.
“...patients who are informed about the brain origins of addiction can benefit from
understanding that their illness has a biological basis and does not mean they are ‘bad’
people”
(36)
.
Dr. Edwin A Salsitz who treats employed patients in his medical maintenance private
office based practice at the Beth Israel Medical Center in New York City and this author
found that stigma directed towards methadone treatment is the most destructive force
that methadone patients face. They are concerned that revealing their status to family,
employers and friends will lead to social alienation and possible job loss. Salsitz indicated
that almost all of the patients and families have little or no conception of the nature of
addiction and the role of methadone. Methadone is regarded as a heroin substitute, and
therefore the patients are not considered cured since they do not have will power and
are substituting one drug for another. The term opioid substitution therapy adds to the
stigma. Salsitz advised that he must schedule sessions with patients and their families
to explain that addiction is a metabolic disorder, and that methadone is a legitimate
medication and not a heroin substitute. The conception of methadone maintenance as
22
Heroin Addiction and Related Clinical Problems
a legitimate medical regimen is sometimes difficult to impart since the patients and
their families harbor entrenched beliefs and misinformation received from the media,
the general public and unfortunately from the medical profession itself
(46)
.
In a speech to the 1997 AATOD conference Dr. Avram Goldstein, professor emeritus
of pharmacology at Stanford University, stated that it is wrong to consider methadone
a heroin substitute. He reported that the continuous occupancy of methadone on the
mu receptor is the stabilizing factor that allows patients to stop the abuse of heroin and
normalize their behavior.
“It is therefore not correct to think of methadone as a “substitute” for heroin; its
totally different pharmacokinetic properties make it, in effect, a completely different
drug. It is true that both heroin (morphine) and methadone can occupy the mu opioid
receptors. But the steady, stable occupancy by methadone contrasts sharply with the
repeated excessive “highs” followed by excessive “lows” with heroin”
(25)
.
In a December 9, 1998 New York Times article “Report backs methadone for addicts”,
Dr. Alan Leshner, the then director of the National Institute on Drug Abuse, stated that
“... probably the biggest disservice that has been done to getting effective treatment to
heroin addicts is the inaccurate statement that methadone is a heroin substitute.”
A major source of stigma and rejection for methadone patients comes from absti-
nence oriented therapeutic communities and 12 step programs based on the Alcoholics
Anonymous model. What is not widely known is that Dr. Dole was on the board of
AA and was a friend of its founder Bill Wilson. Wilson had a great deal of respect for
Dole’s development of methadone treatment for heroin addiction.
Wilson was not against the use of effective medications such as methadone to treat
people with addiction. He realized that many alcoholics did not respond to AA, dropped
out or did not enter the program only to disintegrate or die from the disease. He asked
Dole to create a methadone for alcoholism. This encouraged Dole towards the end of
his career to conduct alcoholism studies in his laboratory. However, he was unable to
find an analogue of alcohol which could be used as a medication
(19)
.
That the founder of AA, Bill Wilson, accepted methadone as a legitimate medication
is in direct contrast to the philosophy of 12 step programs based on AA concepts such
as therapeutic communities, Narcotics Anonymous, and local AA groups. Methadone
patients have never been allowed to fully participate in 12 step programs or until re-
cently to enter treatment in therapeutic communities since methadone is considered a
mood altering drug akin to heroin. Methadone patients, therefore, formed their own
MA groups (Methadone Awareness and Methadone Anonymous).
Patients are now beginning to organize and confront the media about biased
presentations of methadone treatment. Recently a film maker who did not understand
methadone produced a documentary, “Methadonia.” By interviewing dysfunctional
patients, some enrolled in methadone programs and some not, who were attending an
abstinence-based group therapy program. It was a misguided effort. Methadone treat-
ment was portrayed in a negative light adding to the stigmatization of patients. The title
itself is stigmatizing derived from the term ‘methadonians’ which stable patients reject
23
H. Joseph & J.S. Woods: In the service of patients: the legacy of Dr. Dole
as a subhuman description of themselves. This perception of the term, methadonians,
by patients conforms to the observation of Goffman, the sociologist, that stigmatized
individuals are regarded as “not quite human,” and subjected to bias and discrimination
which reduces their chances for life advancement
(27,28)
.
Patients from the National Alliance of Methadone Advocates (NAMA) and the
Committee of Methadone Program Administrators (COMPA) of New York State met
with the producer. The representatives from NAMA were the first methadone patients
he met who were not living in the streets, who were employed and socially stable. He
was educated about methadone and agreed to add a 10 minute segment to the docu-
mentary by interviewing two patients: a married female lawyer with two children and a
businessman who now devotees himself full time to advocacy work. A highly respected
physician from a major medical school was enlisted to participate in the segment to
explain methadone maintenance. Nevertheless, the damage was already done since
the film was aired on nationwide television before patients were aware of it, and the
segment was included in the documentary.
In the summer of 2005, NAMA posted an informal survey on its website with the
following question: In Europe methadone treatment is called “Substitution Therapy.”
Do you think this term is positive, negative, not good for the US, or can’t decide? Of the
389 respondents, only 26% thought the term was positive, 54% thought the term was
negative, 11% thought that it was not a good term for use in the United States, and 8%
could not decide. One patient indicated that when she hears the term substitution therapy
all of the shame of heroin addiction returns. Gordis observed that the term substitution
implies for the public and policy makers that there is little difference between heroin as
used in addiction and methadone treatment
(26)
. Several patients were angered by the
term since they felt it added to their stigmatization. The Center for Substance Abuse
Treatment (CSAT) in the United States has now adopted the term Medical Assisted
Treatment (MAT) to describe methadone and buprenorphine treatment.
Patients and applicants may incorporate the biases of society and enter methadone
with great ambivalence including mythologies about methadone (e.g., it rots the
teeth and bones) and self negation thereby potentially affecting their progress and the
duration of treatment
(39)
. Education is needed if patients are to understand addiction,
methadone treatment and confront the many aspects of stigma in their families, the
media and the community.
Recently, NAMA and the methadone program of the Albert Einstein College of
Medicine received a four year grant from CSAT to develop educational materials
and new patient advocates to address addiction, treatment, stigma, the semantics of
vocabulary, legal and medical issues. This is the first grant awarded to a methadone
patient organization which will allow a systematic development of materials for patients
and professionals to improve treatment, promote advocacy and to destroy myths and
stigma by creating a scientific base of accessible knowledge for patients and others to
disseminate. It is almost a throw back to the 1960s when Dole and Nyswander created
the patient assistants in the original methadone clinics to educate the professional staffs
24
Heroin Addiction and Related Clinical Problems
about addiction, methadone treatment and the patients.
Summary and Conclusion
Throughout his lifetime in research, Dr. Dole’s insights transformed whatever topic
he investigated. In a sense he planted the seeds and set the direction for further research
and clinical development. However, Dr. Dole was always at the service of patients and
advocacy groups such as NAMA to help resolve issues of stigma and misdirected poli-
cies that came to his attention. For him, his greatest legacy would be the elimination
of stigma that is directed to methadone patients, programs, and the medication itself.
He communicated with patients through letters, email, phone contacts and personal
interviews. Dr. Dole always regarded methadone as a legitimate medication to normal-
ize aberrant metabolism and thus behavior in the chronic disease of opioid addiction.
Neither he nor Dr. Nyswander used the term “substitution therapy” in speech or in
writing to describe methadone maintenance treatment. When one examines addiction
research and the development of treatment today with all of its advances and set backs,
the ideas of Dr. Dole seem to pervade those leading the good fight.
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Received and Accepted October 2, 2006
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