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Review:: This Review Was Written As Part of The Cel
Review:: This Review Was Written As Part of The Cel
BACKGROUND: This review was written as part of the cel- To write this review we have delved into the ar-
ebration of the International Year of Chemistry 2011. chives of clinical chemistry to provide a guide to refer-
ence materials, with a focus on North America, to help
CONTENT: In this review we provide a chronicle of the those interested in the history of clinical chemistry.
history of clinical chemistry, with a focus on North These archival materials provide a map of how this
America. We outline major methodological advances medical subspecialty arrived at its present state, infor-
and trace the development of professional societies and mation that will undoubtedly help visionaries to deter-
journals dedicated to clinical chemistry. This review mine the direction in which clinical chemistry will
also serves as a guide to reference materials for those move in the future.
interested in the history of clinical chemistry. The var- Clinical chemistry is the term most commonly
ious resources available, in sound recordings, videos, used around the world to define the field, although
moving images, image and document archives, muse- clinical biochemistry and chemical pathology are also
ums, and websites dedicated to diagnostic company widely used. Because chemistry is the foundation of the
timelines, are surveyed. science that underlies biochemistry and pathophysiol-
ogy, it is appropriate to use the term clinical chemistry.
SUMMARY: These resources provide a map of how the
To reach the level of sophistication that defines present
medical subspecialty of clinical chemistry arrived at its
day clinical chemistry, major advances in analytical
present state. This information will undoubtedly help
visionaries to determine in which direction clinical chemistry, biochemistry, and pathophysiology have
chemistry will move in the future. been necessary. Clinical chemistry is that branch of
© 2011 American Association for Clinical Chemistry
medical science that involves the analysis of biological
materials, usually body fluids, to provide diagnostic in-
formation on the state of the human body. Veterinary
clinical chemistry is a branch of clinical chemistry ap-
The International Year of Chemistry 2011, designated plied to animals. The production of accurate, precise,
by the United Nations General Assembly, has the goal and timely results, and the interpretation of these re-
of increasing public awareness of chemistry in meeting sults and assessment of margins of error, are key ele-
world needs, increasing the interest of young people in ments in clinical chemistry and are the most important
chemistry, generating enthusiasm for the creative fu- skills of the clinical chemist.
ture of chemistry, and celebrating the 100th anniver-
sary of Madam Curie’s Nobel Prize. Clinical chemistry Chronicle of the History of Clinical Chemistry
most certainly must be featured in such an initiative
because it plays a key role in the diagnosis and treat- This discipline, which could originally be practiced in
ment of the sick and in the maintenance of health
small laboratories in which relatively few manual tests
through preventative medicine. Clinical chemistry also
were performed, now requires highly automated and in-
has a direct link to the contributions of Marie Curie
tegrated laboratories that perform millions of tests each
through the development of the technique of RIA
year (Fig. 1). There is a body of literature, albeit not exten-
(which led to Roslyn Yalow’s Nobel Prize). This tech-
sive, in which the history of clinical chemistry is chroni-
nique has revolutionized endocrinology and has led to
cled. Table 1 lists the most significant general reviews of
remarkable contributions to other subspecialties (such
the field, most of which chronicle the development of
as toxicology and cardiology).
clinical chemistry from its beginnings in antiquity (1–11 ).
Johannes Büttner has contributed several articles
and books based on research of the roots of clinical
1
Department of Pathology and Laboratory Medicine, University of Pennsylvania chemistry, with a primary focus on clinical chemistry
Medical Center, Philadelphia, PA; 2 Department of Pathology, University of
Virginia, Charlottesville, VA.
in Germany (3– 6 ). These texts include History of Clin-
* Address correspondence to this author at: Department of Pathology and ical Chemistry (5 ), edited by Büttner, which explores
Laboratory Medicine, 3400 Spruce St., Philadelphia, PA 19104-4283. Fax 215- the origins of clinical chemistry. The most ambitious
662-7529; e-mail kricka@mail.med.upenn.edu.
Received March 18, 2011; accepted March 29, 2011. publication on the history of clinical chemistry is a
Previously published online at DOI: 10.1373/clinchem.2011.165233 book by Louis Rosenfeld, Four Centuries of Clinical
1118
History of Clinical Chemistry
Review
International Year of Chemistry 2011
Chemistry (9 ), which describes the development of tions and impact of Donald Dexter Van Slyke, Stanley
knowledge of analytical chemistry and biochemistry Benedict, and Otto Folin are prominently featured, as
and the emergence of clinical chemistry. Contributions is the introduction of analysis by color comparison and
beginning in the 16th century and leading to more re- the Duboscq colorimeter, invented by Jules Duboscq in
cent times are covered. Specific assays that formed the 1870. Rosenfeld’s extensive publication was preceded
cornerstone of the clinical chemistry laboratory in the in 1973 by an article by Wendell Caraway, a practicing
1960s are described, such as glucose, urea, creatinine, clinical chemist in Michigan who graced the clinical
electrolytes, cholesterol, some basic enzymes, total pro- chemistry scene in the post–World War II era. Caraway
tein, and albumin/globulin. Of course, the contribu- was the president of AACC from 1965 to 1966 and was
a pioneer in chronicling the history of clinical chemis- to the development of trade and accumulation of
try. His landmark papers (1, 2 ) are concise and present wealth. Spectrophotometry, a development that dates
a fascinating exploration of the origins of the field. back more than a century, has, in all of its forms, cer-
Major technological milestones that have contrib- tainly contributed the most to the process of perform-
uted to the present day clinical chemistry laboratory ing basic measurements in the routine clinical chemis-
are listed in Table 2 (2, 12–23 ). The analytical balance try laboratory. Previously known as colorimetry, this
has been known since antiquity because the accurate method was used for most of the early clinical chemis-
weighing of gold and other precious materials was vi- try assays such as urea, creatinine, uric acid, glucose,
tally important in ancient civilizations and contributed total protein, and albumin. Chemical reactions be-
Fig. 2. (A), William Pepper Laboratory of Clinical Medicine, Hospital of the University of Pennsylvania, circa 1925,
(built 1894 –1897, Cope and Stewardson, architects, demolished in 1928) (©courtesy of the University of Pennsyl-
vania Archives); (B), the terra cotta frieze from the north face of the William Pepper Laboratory of Clinical Medicine
now displayed on the seventh floor of the Maloney building at the Hospital of the University of Pennsylvania.
One of the most fascinating aspects of the study of chemistry in many countries (e.g., the Association for
the history of clinical chemistry is the lives of those who Clinical Biochemistry in the UK in 1953) (50 ) and also
founded the field. Otto Folin was one of the pillars of an international body, initially known as the Interna-
the field of clinical chemistry, and his life and work are tional Association of Clinical Biochemists (1952) that
captured in Samuel Meites’ biography of Folin (46 ). subsequently became the IFCC (International Federa-
Biographies of other key figures include those of Henry tion of Clinical Chemistry) in 1953 (51 ).
Bence Jones (47 ) and Joachim Kohn (developer of cel-
luose acetate electrophoresis) (48 ). Museums of Clinical Chemistry
The first professional organizations dedicated to
clinical chemistry sprang up in the 1940s, beginning The size and weight of some of the larger clinical chem-
with the AACC in the US in 1948 (49 ). This was fol- istry analyzers has no doubt posed a barrier to their
lowed by the founding of national societies for clinical retention for exhibition in museum collections. Never-
theless, several museums have exhibits related to the Royal Hospital Sheffield (Sheffield, UK) (65 ). It shows a
history of clinical chemistry that contain analyzers of clinical chemist performing a glucose test. This image
different types. The Chemical Heritage Foundation provides a graphic illustration of the changes in labora-
(CHF) (52 ) has a number of clinical chemistry analyz- tory safety standards between now and then: he is mouth-
ers on display, such as a Technicon AutoAnalyzer Sam- pipetting and not wearing gloves! (Fig. 3). Despite the
pler Unit, in their permanent exhibition in Philadel- long and concurrent histories of the clinical laboratory
phia, “Making Modernity.” The AACC also has a small and movie/video cameras, there are relatively few other
exhibit of historic instruments at its office in Washing- examples of movies or videos showing the content and
ton, DC, which includes a Klett Photoelectric Color- workings of early clinical laboratories. Another notable
imeter, a Folin-Wu Sugar Tube, a Technicon Auto- example is the movie taken by Peter Wilding in 1966 at the
Analyzer System, and a Beckman Model DU clinical chemistry laboratory of the Los Angeles General
Spectrophotometer (53 ). The Beckman Coulter Heri- Hospital, California (66 ). This archive also has video re-
tage Center and Caltech’s Science Museum’s Beckman cordings of lectures on RIA by John Landon at the Uni-
Room Exhibit (54 ) feature exhibits relating to the work versity of London in 1972.
of Arnold O. Beckman and the analyzers produced by In addition, the Nobel Prize website contains links
the Beckman company. In addition, several companies to a video lecture (“RIA: Tool for Biomedical Investi-
have virtual museums in the form of illustrated online gation and Clinical Medicine”) presented by Rosalyn
interactive timelines and histories, e.g., Beckman Yalow (1977 Nobel Prize in Physiology or Medicine) at
Coulter (55 ), Ortho Clinical Diagnostics (56 ), Abbott the 1978 Nobel Laureate Meeting in Lindau, Austria
Laboratories (57 ), Roche (58 ), Instrumentation Labo- (67 ). There are now available numerous grand rounds
ratory (59 ), and Olympus (60 ). video archives and live audio and synchronized Pow-
erPoint presentations of more recent lectures by fa-
Sound Recording, Video, Movie, Image, and mous clinical chemists, and these provide a historical
Document Archives
record of the state of knowledge and thinking at a par-
ticular point in time.
Various archives of surviving photographs, moving
Notably, the Smithsonian Institution Archives
images and oral histories, and collections of artifacts
(Oral Histories in Medicine and the Health Sciences)
and memorabilia, make it possible to trace the growth
has a number of oral and video histories of relevance to
of clinical chemistry from its origins in small one-room
clinical chemistry, including histories of DNA se-
laboratories with a few staff performing a very limited
quencing and PCR (68 ).
menu of manual tests to large modern laboratories
with large staffs overseeing an extensive menu of highly A more extensive collection of interviews with
automated tests. prominent clinical chemists is to be found on the
The Science Museum in London, UK, has a web- Oral Histories section of the CHF website (69 ). In
site, Brought to Life, which explores the history of medi- addition the CHF website includes images of clinical
cine. It includes images of early instrumentation (e.g., a analyzers such as the circa 1975 YSI (Yellow Springs
ureometer from the 1800s), urine test kits (e.g., the Instrument) Blood Glucose Analyzer, Model 23A
Clearblue One Step Pregnancy test kit, England, 1988), (70 ), and the Photovolt Hemoglobin and Glucose
and biographies of famous clinical chemists [e.g., Meter (71 ).
Leonard Skeggs (1918 –2002)] (61 ). Getty Images (62 ) The Images from the History of Medicine website pro-
also provides numerous images relating to home test- vides access to images in the collections of the History of
ing (e.g., pregnancy and diabetes testing). Medicine Division of the US National Library of Medi-
The Wellcome Images: 2000 Years of Human cine (72 ). This collection contains images of clinical
Culture archive at the Wellcome Library, also lo- chemists (e.g., Donald S. Fredrickson), chemistry labora-
cated in London (63 ), contains numerous images tories of various military and university hospitals (e.g.,
relating to test strips (e.g., pregnancy tests, urine University of Virginia Hospital in 1929, the chemistry lab-
tests) and glucose meters. A detailed and illustrated oratory in the laboratory of pathology at St. Elizabeth’s
history of pregnancy testing can be found on the Hospital Blackburn, UK, circa 1910), and posters for cho-
NIH archive (64 ). This source contains images of lesterol testing and for the National Medical Laboratory
test devices and early advertisements for over-the- Week. One of the latest image archive initiatives has been
counter pregnancy tests. the AACC History Division Analyzer Archive. The objec-
The Wellcome Moving Image and Sound Collection tive of this project is to collect images of the full scope of
(a collection of moving images on 20th-century health- clinical laboratory analyzers (including chemistry, immu-
care and medicine) contains what may be the earliest noassay, hematology, and other areas) and associated au-
movie of a hospital laboratory, shot around 1932 at the tomation equipment (73 ).
Fig. 3. A hospital biochemist performing a blood glucose test at the Royal Hospital Sheffield, UK, circa 1932 [frame
grabbed from Hospital Laboratory, Skinner and Watson (65)].
©Reproduced with permission from the Wellcome Library, London.
The advent of YouTube in 1985 has provided a of the future. Now, some 27 years later, these predictions
source for numerous contemporary videos of clinical lab- have come to pass.
oratories, commercial diagnostic tests, and the testing that As we conclude this present history we are cau-
is performed. These films will provide future historians tiously offering our predictions for the next quarter
with a wealth of historical data on clinical chemistry from century. We expect that as the cost of healthcare con-
the end of the second millennium onwards. A notable tinues to spiral almost out of control, major develop-
entry on YouTube is the introductory video for the 45th ments in technology related to clinical chemistry will
annual meeting of the AACC in New York, NY, in 1993, be made to reduce these costs. More point-of-care test-
which documents the contribution of the Northeastern ing linked to telemedicine will be introduced to de-
US to the development of clinical chemistry (74 ). crease the number of hospital visits for patients with
chronic conditions and hence reduce overall healthcare
Whither Clinical Chemistry?
costs. We will mimic the electronics industry and see
At the AACC National Meeting in 1984, one of us (J.S.) more technology convergence and cost reduction for
presented the National Lectureship Lecture, which was handheld devices. Emphasis will continue to be placed
entitled “On Such a Full Sea Are We Now Afloat,” a quo- on more specific markers for disease and testing for a
tation from Shakespeare’s Julius Caesar. The year, 1984, patient’s vulnerability to acquiring an illness. Cancer
was a time of some despondency by clinical chemists be- and heart disease will continue to be targeted, but there
cause the exciting early times of method development in will be an intense initiative to develop early markers for
the hospital laboratory had been virtually taken over by neurodegenerative disorders. Despite a great deal of
commercial manufacturers of instruments and reagents. research into the pathogenesis of Alzheimer and Par-
The purpose of the lecture was to point out the golden kinson disease, little progress at the early detection and
future of the field, with the introduction of molecular di- treatment has been made. This will change and we an-
agnostics, the applications of robotics, and the routine use ticipate that the clinical chemistry laboratory will play
of mass spectrometry in the clinical chemistry laboratory an important role.
As members of the clinical chemistry fraternity we quirements: (a) significant contributions to the conception and design,
can take great pride in our heritage and look forward to acquisition of data, or analysis and interpretation of data; (b) drafting
the future with considerable optimism. or revising the article for intellectual content; and (c) final approval of
the published article.
Author Contributions: All authors confirmed they have contributed to Authors’ Disclosures or Potential Conflicts of Interest: No authors
the intellectual content of this paper and have met the following 3 re- declared any potential conflicts of interest.
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