SELECTED WORKS WITH BIO-BIBLIOGRAPHY

At the beginning of the 20th century, therapeutic agents were still relatively few, and many common diseases that are easily cured today were still considered life-threatening. As improvements were made in diagnostic techniques and new drugs were discovered, the laboratory galvanized the authority of medicine by endowing it with the ability to identify and cure disease.

Clinical labs began to evolve into permanent institutions within hospitals as new diagnostic tools were derived from advances in physics. These included radioactive isotopes, electrophoresis, microspectrophotometry, electroencephalogram and electromyogram. Other techniques such as ventriculography, intracardiac catheterization and tomography greatly extended the physician's understanding of body function.

In 1840, the only laboratory the average European physician was likely to have used was that of a pharmacist; but by 1900, a host of laboratory types emerged, including physiological laboratories, pharmaceutical and pharmacologic laboratories, as well as forensic, public health, and microbiological laboratories. The lab, in one form or another, became an "obligatory passage point" for researchers who wanted to make new discoveries.

Developments in microbiology attested to the link between the diagnosis and treatment of disease. The arrival of antibiotics and sulfonamides was especially important in curing many previously fatal diseases. The accidental discovery of penicillin by Sir Alexander Fleming (1881-1955) in 1928 was paramount in initiating the antibiotic era. The Scottish scientist had been studying the natural bacterial action of the blood and antibacterial substances that would not be toxic to animals. While working on the influenza virus, he observed a mold that had accidentally developed on a staphylococcus culture plate. Around the mold was a bacteria-free circle. Fleming experimented with the mold and found it could prevent growth of staphylococci, even when diluted 800 times.

Later, Paul Domagk (1895-1964), a German anatomic pathologist and bacteriologist, discovered that a red dye called prontosil rubrum protected laboratory animals from lethal doses of staphylococci and hemolytic streptococci. Prontosil was a derivative of sulphanilamide. Domagk was not convinced the substance would be equally effective in humans, but when his daughter became very sick with a streptococcal infection, he gave her a dose of prontosil in desperation. She made a complete recovery, but these results were not divulged until 1935 when other clinicians had tested the new drug on patients. Domagk's discovery of the antibacterial action of the sulphonamides gave medicine and surgery a new weapon against many infectious diseases.

There were many outstanding biochemists of the time. One who conferred a repertoire of tests to the laboratory was Otto Folin, a Swedish professor of biological chemistry at Harvard (1907). Between 1904 and 1922, Folin developed quantitative analytical methods for several urine analytes including urea, ammonia, creatinine, uric acid, total nitrogen, phosphorus, chloride, total sulfate and acidity. He also attempted to measure blood ammonia and introduced Jaffe's alkaline picrate method for creatinine. Folin showed the effect of uricosuric drugs on blood and uric acid levels in gout; introduced the colorimetric method for measuring epinephrine, and published the first normal values for uric acid, nonprotein nitrogen (NPN), and protein in blood. Folin was also responsible for establishing the relationship of uric acid, NPN and blood urea nitrogen to renal function. The Folin Cicalteau reagent, among others developed by Folin, is still used today for protein determinations.

New discoveries about the biochemical nature of blood made possible the transfusion of blood between humans, which greatly advanced the success rate of surgery. In 1900, the Viennese pathologist Karl Landsteiner (1868-1943) discovered the concept of the human blood types and the following year, described the ABO blood group. Accounts of previously unsuccessful blood transfusions from animals to humans reported that the foreign blood corpuscles were clumped and broken up in the human blood vessels, thus liberating hemoglobin. Landsteiner reported a similar reaction in transfusion of blood from human to human. Shock, jaundice and hemoglobinuria accompanied these early blood transfusions. After Landsteiner's classification of blood types into the well-known A, B, AB and O groups in 1909, the catastrophes of earlier blood transfusions were eliminated by transfusing blood only between individuals of the same blood group. Later, Landsteiner studied bleeding in newborns and contributed to the discovery of the Rh factor, which relates human blood to the blood of the rhesus monkey.

Another icon of modern blood banking is Charles Drew, MD (1914-1950), an African-American physician from Washington, DC. Early in 1940, the American Red Cross and the Blood Transfusion Betterment Association of New York began a project to collect blood for shipment to the British Isles. Eight New York City hospitals collected blood for what became known as the Plasma for Britain Project. During this project, Drew successfully used the laboratory experiments and blood research done by others to mass produce plasma. Drew heard that the British had successfully modified a cream separator to separate plasma from the red cells in blood, so he ordered two of the machines and constructed similar equipment to produce clear plasma on a large scale. Drew became a leading authority on mass transfusions and blood processing methods and was later asked by the American Red Cross and U.S. government to establish a similar program for the Plasma for Britain Project.

The 20th century marks the beginning of a quality movement in hospitals and laboratories that began with physicians and healthcare workers. As part of that movement, those who ran hospitals began to appreciate the skills that clinical chemists could bring to the hospital laboratory. In the early part of the century, many hospitals began reorganizing their laboratories so that they were headed by biochemists. Professional organizations emerged as self-regulating groups that helped ensure the skills and knowledge of laboratory professionals would pass the scrutiny of the hospitals that employed them. These professional organizations also served their members by lobbying for advantageous legislation.

Initially, the laboratory inspections were based on a single page of standards, including a requirement for an adequately staffed and equipped laboratory. In 1918, the first call for a method of certifying technologists on a national scale was presented by John Kolmer, who published "Demand for and Training of Laboratory Technicians," which included a description of the first formal training course in medical technology. Also during that year, the Pennsylvania State Legislature passed a law requiring all hospitals and institutions, particularly those receiving state aid, to install and equip an adequate laboratory and to employ a laboratory technician on a full-time basis.

By 1920, clinical laboratories in large hospitals were distinct administrative units of service directed by a chief physician. They usually consisted of four or five divisions, including biochemistry, clinical pathology, bacteriology, serology, immunology and radiology. Trained, often salaried, professionals staffed each laboratory. An American Medical Association (AMA) survey on the issue of staffing showed that 14% of all clinical laboratories were commercial or reference laboratories. In spite of possible economies of scale, reference labs performed only a small share of tests over the next several decades.

The American College of Surgeons figured prominently in ensuring that hospital laboratories remained under the control of pathologists by promulgating certification standards that required hospitals to have a laboratory with a pathologist in charge. Because pathologists had a monopoly on laboratory tests in the hospital, these labs became extremely lucrative as the number of available tests increased.

Physicians in the clinical lab have always played a large role in the status of other lab professionals. Until the last 20 to 30 years, physicians have managed to resist corporate domination throughout the history of medicine. Doctors were motivated not only to preserve their autonomy, but also to prevent third parties from making a profit that might otherwise go to the doctor. In 1934, the AMA stated in a section of its code of ethics that profit from medical work "is beneath the dignity of professional practice, is unfair competition with the profession at large, is harmful alike to the profession of medicine and the welfare of the people, and is against sound public policy." This is not to say that the AMA did not want physicians to make profits for themselves; only that they should not become part of a larger organization whose function it was to make money. Whether the motivation for this policy was capitalistic or humanitarian is still the subject of debate. This policy helped physicians establish a medical infrastructure that allowed them to delegate to other healthcare professionals work that was repetitive and time-consuming.

To maintain their autonomy, physicians needed technical assistants to help them use hospitals and laboratories without being employees of these facilities. The allied health professional began to emerge in the first years of the century with the encouragement of the doctors who needed them. Doctors needed technical assistants who were competent enough to work in their absence yet not threaten their authority. These professionals were developed by physicians in two ways: (1) the encouragement of a kind of responsible professionalism among the higher ranks of subordinate healthcare workers, and (2) the employment of women in these auxiliary roles who could be professionally trained but would not challenge the authority or economic position of the doctor.

The code of ethics for technicians and technologists was and continued to be that these professionals agree to work under the supervision of a physician, refrain from making written or oral diagnoses, and refrain from advising physicians on treatment options without the supervision of a physician or pathologist. Meanwhile, other groups of non-physician clinical laboratory scientists were striving for professional recognition of their own. The American Society of Medical Technologists (ASMT), now known as the American Society for Clinical Laboratory Science, was originally formed as the pathologists prevented a subgroup of non-physician MTs from becoming an autonomous profession. ASMT established committees to serve the needs of its members and implemented a process to certify MTs who had acquired specialized laboratory expertise. Between the end of World War II and 1962, the ASMT began to reassess its views on personal licensure and regarded it as a positive step toward professional recognition. In the late 1950s, MTs sought governmental recognition of their educational qualifications through personnel licensure laws and position reclassification in the Civil Service and armed forces.

The commercialization of laboratory medicine over the past several decades has been characterized in three phases. During the academic phase (1950-1970), laboratory science became accepted as its own discipline within medicine and medical education; second phase (1970-1985) was marked by the establishment of professional groups, such as the Clinical Laboratory Management Association, as well as management-oriented sections of already established organizations, such as the Society for Clinical Pathologists, and the Association of Clinical Chemists. During the third "business" phase (1985-present), laboratory medicine was still an academic discipline, but it appeared to be inseparably linked to financial concerns, at least as long as managing costs of healthcare remained national concern for nearly every country on earth.

At the dawn of the 20th century, it was almost exclusively the hospital that delivered a relatively meager menu of clinical pathology services. Technological advances in the 1950s paved the way for advances in automation, instrumentation, quality assurance, and quality control. Those advances led to ever more efficient analytical processes and great strides in the accuracy and precision of results. When computers and data processing came onto the laboratory scene in the 1960s, the lab became a repository of information and knowledge about disease. New concepts emerged — of sensitivity and specificity, predictive values of laboratory studies, and variations in test results caused by analytical, biologic and pharmacologic factors. The capital intensive developments of the 1950s and 1960s led to a trend toward large-volume testing in remote reference labs. The 1970s and 1980s brought more sophisticated computer systems to the lab that supported bar coding, which provided instant patient and specimen identification and tracking.

Only a few years ago, laboratory visionaries predicted that developments in molecular biology had the potential to change laboratory medicine in the same way that computed tomography and magnetic resonance imaging altered the practice of radiology. Speculation that routine hospital admissions testing done in the 21st century could include a panel of DNA probes in place of a chemistry profile or complete blood cell count now look more plausible than ever.

Since its inception in the mid-19th century, the laboratory has provided physicians with valuable information that support the accurate diagnosis and treatment of patients. It is the lab that gives all of modern medicine the authority that can only come from objective, scientific measurement and observation. Continued pressures from medical societies and government to keep test costs low are likely to spur further development of faster, more accurate, more precise tests that allow every earlier diagnosis and therapeutic intervention.

On the verge of the 21st century, the lab is providing more information about the human condition faster and more accurately than ever. It is strategically positioned for success in the healthcare industry — in the business of supplying critical information in the information age.

Addendum: It has already passed six years since the author of these lines finished his first consolidated effort on writing a "History of Bulgarian Medicine" /in English language/. This work ran parallel with several other activities — writing a dissertation on CHD in Bulgaria, striving to de-confound the mysteries of Internet and Computer sciences, and having overt family engagements, whatsoever. That is why, none of the above mentioned tasks were full fetched and never complied to their logical conclusion. If I had a publisher (which I don't), he would have long time ago cut my premises since publishers work on a piecemeal basis. However, it has been the authors fault that he works slowly; happily, better slowly than not at all.

We have been on the edge of major transformations at brink of 21st century. For the author, life has been dragging with much physical pain and some mental perturbations as well. Witnessing a globalization that have blackened our reality vision, an overwhelming majority of the population around the globe has been deluded about what actually is going on — is it the end of Communism and Cold War, or Climatic changes on grand scale, or even phony Satellite wars that have been dictating our late behavior. Thus it is not surprising that a former MD, and unsuccessful Philosophy candidate has been back on schedule, ipso facto.

Let us try to review what has been written up until now on the topic — i.e., having in mind the agenda of our booklist. There are two comparatively well written chapters on medical history, 1) from ancient times to modern days; and 2) biographies of well known Bulgarian medics from the Revival. There are numerous sketches, not in book format and unsystematized, on every aspect of socio-political and cultural life in that country. Those have valuable commentaries that given appropriate permutations would have contributed to a common encyclopedia on life in Bulgaria. Finally, there are piles of unreferenced material from our private archive which is scattered all around the house and awaits to be researched.

So, what has been on the menu for this particular session. Prof. Konstantin Chilov (1898-1955), a leading Bulgarian clinicist, founder of Clinical Laboratory science in that country and author of the first Compendium on laboratory techniques in Bulgarian. Automatically, we wish to reiterate that Dr. K. Chilov was not among the traditional doyens of Bulgarian medicine and couldn't be set alongside such authorities as Prof. S. Kirkovich, Prof. V. Alexiev, Prof. V. Mollov, etc. The latter were holders of the Revival tradition in Bulgarian science, coming from 2-3 generations of autocratic bulgarian families, while K. Chilov was proponent of the new liberal wave and was definitely a technocrat and visionary. He served long years in the 1930s at the editorial staff of the journal "Bulgarian Clinic", where numerous articles and short reviews were published from all fields of medicine. The journal was sponsored by Sandoz Pharmaceuticals. Also not clarified is Chilov's work at the Department of Clinical Therapeutics, headed by Prof. Vladimir Alexiev. Here the titular wrote the first "Textbook of Clinical Pharmacology" (1922), while Chilov was provost assistant at the same department. After 9 September 1944, Dr. K. Chilov attained professorship at the Therapeutics Block and held a leading position in Alexander's Hospital until diseased, ditto.

(i). Prof. Konstantin Chilov (1898-1955), a leading Bulgarian clinicist, founder of Clinical Laboratory science in Bulgaria.

(ii). Chilov's manual on "Clinical Laboratory Methods with Practical Applications. Sofia, 1938".