The Origin and History of the Science and Profession of Clinical Biochemistry
Dr. Andrew MacRae

The Scope of Clinical Biochemistry

Clinical Biochemistry is one of the medical professions. Specifically, it is one of the several subdisciplines collectively referred to as Laboratory Medicine. As the name implies, Laboratory Medicine constitutes all of the practices of Medicine that relate to laboratory investigations for the purpose of diagnosis and treatment of diseases. Whereas some subdisciplines of Laboratory Medicine deal with tissues, cells, or infectious elements, Clinical Biochemists are primarily involved in investigations of the biochemical constituents of the fluids of the body.

These investigations include qualitative and quantitative assessment of individual molecular elements of blood plasma, spinal fluid, urine and other body fluids. The amount of a substance in the blood or other fluid, or the nature of the substance, forms the basis for a diagnosis, or a medical assessment of the course of the disease or treatment. A simple example is the measurement of serum glucose levels, or "blood sugar", in the diagnosis of diabetes.

There are several hundred different compounds that are measured, some more routinely than others. In each instance the quantity or the qualitative nature of the compound is related to a particular disease or disorder. It is the Clinical Biochemist who assesses the relationship of the compound to the disease, establishes the test for the compound, and issues the report to the Physician together with a medical interpretation of the findings.

The Origins of Clinical Biochemistry and its Role in Medicine

The practice of what is now called Clinical Biochemistry can be traced throughout the entire history of Medicine. Hippocrates (460-375 B.C.) referred to an early "test", namely an inspection of urine, saying:

Bubbles floating on the surface of the urine denote affections of the kidneys,
and that the disease will be long. (Aphorisms, Section VII, Number XXXIV)

Hippocrates' test of urine remains in medical practice today, although it has been transformed by modern knowledge and techniques. We now know that the bubbles referred to by Hippocrates are caused by protein, and an excess of protein in the urine indicates kidney disease. In modern medical practice we are not restricted to an inspection of the fluid as was Hippocrates; we measure the amount and nature of the protein in urine, the source of Hippocrates' bubbles. This trivial example portrays the evolution and nature of Clinical Biochemistry. A "test" for bubbles by an ancient physician has been replaced by more specific tests for both the amount and nature of the causative agents in the disease, and the professionals who specialize in the discovery and testing of these causative agents in bodily fluids are Clinical Biochemists.

The ancients were restricted to assessments of the only available bodily fluid, namely, urine. In the period between Hippocrates and 1500 A.D., physicians made slow progress in discovering the various aspects of urine that could be used as markers for the causes and nature of diseases. Urine was assessed for its volume, colour, appearance, odour and weight. The original writings on the weight of a known volume of urine as an indicator of disease can be traced to the first century B.C. The instruments used in these tests were the matula (a spherical vessel with a long neck) for visual assessment and for measuring volume, and the pan balance for measuring weight.

By modern standards these tests and observations were rudimentary; however, in their day, they were often the most important means of making a diagnosis, and the same tests persist today, with only modest refinement. The names of several ancient diseases were based on the findings of the "laboratory tests" of the time.

Diabetes is an example of the role that, what we now call Clinical Biochemistry, had in the evolution of medicine. The word diabetes originates from the Greek word for syphon, and refers to the large volume of urine that is symptomatic of the disease. The "laboratory test" of the time was the measurement of the volume of urine produced by the patient. The test result, the observation of the unusually large urine volume, was the basis for the name given to the disease.

At a later time, a second test was added to further differentiate this disease. It was discovered that some patients with diabetes produced urine that had a sweet odour (and taste), whereas the urine from other patients with similar urine volumes was sour. Diabetes had to be further differentiated on the basis of this test result: diabetes mellitus (sweet) and diabetes insipidus (sour).

In more modern times, diabetes mellitus has been further differentiated on the basis of another biochemical test, namely the amount of insulin in the blood. Hence we have insulin-dependent diabetes mellitus, and non-insulin-dependent diabetes mellitus. Throughout the course of medical care for this group of diseases, spanning many centuries, the diseases have been named on the basis of the laboratory tests of the day.

The Evolution of the Profession of Clinical Biochemist

Several centuries ago, Physicians started to perform tests on blood. The earliest tests on blood were similar to those used at the time for urine, namely visual observation and weighing a set volume. Blood tests had the advantage that the fluid being studied was closer to the source of the disease, being the fluid that bathes the tissues, rather than the fluid that the body selectively discharges.

The first concepts of the chemistry of the urine and blood as a determinant of the disease were published in the 16th Century A.D., although these ideas were based on even earlier postulations dating to the first century B.C. Thereafter the scope of testing expanded substantially, albeit slowly, as did the discoveries. By the year 1600, the practice of distilling urine and blood was a new addition to diagnostic medicine. The aim of this latest test was to assess the salt, sulphur and mercury constituents of these body fluids. In the 17th Century, the laboratory contained improved apparatus including the thermometer. Fermentation studies led to theories of the role of carbon dioxide, and the role of acid and alkaline substances in digestion.

Throughout the Middle Ages, Physicians incorporated more tests in their assessment of patients, and some physicians began concentrating their practice on the study of these blood tests. By the 17th Century there were scientific centres wherein Physician/Chemists performed their research. A noted example was Gresham College which was centred in Oxford, England. This group of "experimental natural philosophers" later formed the nucleus of the Royal Society which was established in 1662. Robert Boyle was a member of Gresham College, and his publication in 1684 was a milestone in the evolution of chemical examination of blood as a diagnostic tool in medicine. John Locke, while still in his mid-thirties and prior to his fame as a philosopher, assisted Robert Boyle and performed distillation experiments on blood.

In more modem times, the work of Banting and Best seventy years ago is representative of the evolution of physicians into specialists in laboratory-based medicine. Sir Fredrick Banting was the surgeon turned biochemical theorist, and Charles Best was the medical student who tested the glucose content of blood and extracted the elusive insulin.

As this trend toward specializing increased, the extent of testing expanded, as did the use of sophisticated equipment replacing the basic senses used by the ancients. However, the fundamental nature of testing continues today to be both quantitative and qualitative assessments of biochemical constituents of body fluids.

Symbols associated with Clinical Biochemistry

The practice of Clinical Biochemistry is founded on the concepts of quantitative and qualitative testing, leading to a diagnosis. These concepts have been combined in the proposed motto for the Academy:

Quanto Qualique Diagnoscere

The symbols of the Caduceus for medicine, a urine flask for qualitative studies, and a pan balance for quantitative tests, could be combined in an appropriate manner in the Coat of Arms.

The Canadian Society of Clinical Chemists (CSCC) is the professional body from and within which evolved the Canadian Academy of Clinical Biochemistry (CACB). Since 1966, the CSCC has used the symbols of the twining snakes about the neck of a volumetric flask (see appended article from the CSCC Newsletter on the origins and meaning of the Society's symbols). Since the CACB is a subsection of the CSCC, it would be appropriate for the CSCC symbols be part of the CACB's Coat of Arms.

One suggestion seems quite appropriate: the twining snakes about the neck of the flask could arise from a double helix (the structure of the DNA molecule) within the flask. A pan balance could frame the flask, with the pans suspended on either side of the flask and the armature of the balance above the flask. The triangular shape of the armature of a balance mimics ancient Greek architecture, appropriate for an Academy. A final symbol, common throughout the history of Clinical Biochemistry, is light. The absorbance of portions of the spectrum of light has been used to describe the colour of fluids and their constituents, and the selective production of light-absorbing compounds is a long-standing principle used in quantitative testing.