A Century of Progress

By Roger Bertholf and Steven Kroft - June 29, 2022

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Anniversaries are natural moments to reflect on the passage of time—where we started, where we have been, where we are and even where we are going. A 100th, or centurial, anniversary feels particularly momentous. Thus, as ASCP turns 100, it seemed appropriate to provide a retrospective on the enormous progress we have seen over a century of time in the field of pathology and laboratory medicine. To accomplish this, we asked members of our editorial boards to look back to the founding of the ASCP in 1922 and comment on the changes that have taken place in their specialties since then. Their outstanding essays are published on the Critical Values web site, and we highly recommend visiting them.

Geoffrey Wool, MD, PhD, is Coagulation Associate Editor for American Journal of Clinical Pathology (AJCP). He describes how our understanding of hemostasis and thrombosis has evolved over the past 100 years. In 1922, Dr. Wool points out, only three coagulation factors were known: calcium, thrombin and fibrinogen. The traditional Roman numerology for the factors didn’t begin to be developed until 1943 and wasn’t formally adopted until 1959. The coagulation cascade with which we are all familiar was only completed in the 1960s. The prothrombin time test was first described in 1935 and the activated partial thromboplastin time assay was developed in 1953. Dr. Wool concludes his essay with a comment on how unique features of COVID-19, including the limitations of conventional coagulation assays to predict thrombosis and the emergence of the novel entity of vaccine-induced immune thrombotic thrombocytopenia, highlighted some limitations of our current understanding of the coagulation system. He ends with this observation: “As we look forward to another successful 100 years in the hemostasis field, we must remember that dedicated, knowledgeable and skilled laboratory professionals are the foundation of our work.”

Yvette McCarter, PhD, is Microbiology Associate Editor for Laboratory Medicine (LM). She notes the sobering coincidence that in 1922, the world was just emerging from the Great Flu Pandemic, which claimed an estimated 50 million lives worldwide, with 675,000 of those in the U.S. The current COVID-19 pandemic is estimated to have caused over 5 million deaths worldwide, with about 1 million of those in the U.S. Thus, remarkably, the first 100 years of ASCP history are bookended by global public health catastrophes. And while it took over a decade for the causative agent of the 1918 pandemic to be discovered, the remarkable advances in virology allowed the causative agent of COVID-19 to be fully characterized in a matter of months. This, in turn, allowed clinical laboratories to rapidly develop and deploy accurate tests to detect the virus, and in so doing profoundly impact the course of the present pandemic in a way that was impossible 100 years ago. Regarding this dramatic evolution, Dr. McCarter cites two developments that have had particularly profound influences on clinical microbiology: automation and molecular techniques (without both of which, the clinical laboratory response to COVID-19 would have been impossible). She opines: “While automation has had a significant impact on the ability of clinical microbiologists to contribute to patient care, the evolution of molecular techniques has changed the clinical microbiology paradigm from conventional laboratory methods that rely on phenotypic expression of antigens or biochemical products, to molecular methods for the rapid identification of infectious agents.”

Andrew Fletcher, MD, is Medical Director of Consultative Services at ARUP Laboratories in Salt Lake City, Utah. Dr. Fletcher offers a fascinating perspective on the evolving role of the clinical laboratory in medical care, centering his comparison of 1922 and the present day on a single laboratory, the Finley Hospital Laboratory in Dubuque, Iowa, which has been in continuous operation for just over 100 years. He quotes the late Dr. F.P. McNamara, a pathologist who joined the Finley Hospital medical staff in 1921, as saying that clinical laboratories were “having a hard time” proving their worth. It is astonishing to anyone practicing laboratory medicine in the 21st century that 100 years ago many doctors, according to McNamara, were critical of the laboratory, complaining that it had “assumed too great an importance” in medical practice. He went on to say, prophetically, that laboratory “sciences are developing so rapidly that it is practically impossible for the practitioner to keep in touch with all the advances.” In contrast, the 2022 version of the Finley Hospital clinical laboratory is a modern, vibrant facility that performs nearly 200,000 tests per year. Dr. Fletcher observes that even after 100 years of evolution, clinical laboratories still face the same challenges of under- and overutilization, and of educating their clinical colleagues in the appropriate application of laboratory techniques to diagnosis and clinical management.

Many laboratory procedures that are commonplace today were not available (or even conceivable) 100 years ago. Uttam Garg, PhD, Clinical Chemistry Associate Editor for LM, cites newborn screening as an example. Although the term “inborn errors of metabolism” was coined in 1902 by British physician Sir Archibald Garrod, no tests were available for these genetic disorders until the ferric chloride test for phenylpyruvic acid in urine was introduced in 1934 to detect phenylketonuria, caused by a mutation in the PAH gene coding the enzyme phenylalanine hydroxylase. The ferric chloride test was somewhat crude and insensitive, though, and was replaced in the 1960s by the Guthrie test, which could be performed on dried blood spots. Dr. Garg points out that newborn screening is one of the most successful public health programs in medical history. Contemporary newborn screening programs typically utilize liquid chromatography and tandem mass spectrometry to screen for abnormal concentrations of metabolic products in dried blood spots, improving both sensitivity and throughput.

Commenting on advances in breast cancer diagnosis and treatment over the past 100 years is Marilin Rosa, MD, Breast Pathology Associate Editor for AJCP. Dr. Rosa reminds us that, at the time the ASCP was founded in 1922, the standard treatment for breast cancer was radical mastectomy, a surgical procedure introduced by William Halsted in 1882 at Roosevelt Hospital in New York City. However, in the 1920s, the necessity of the profoundly disfiguring procedure was being questioned, as surgeons experimented with more conservative surgery combined with radiation to treat breast cancer. Radical mastectomies are rarely performed today, since less invasive mastectomies or “lumpectomies” combined with radiotherapy and/or chemotherapy are preferred approaches to treating breast cancer. Dr. Rosa further makes the very interesting observation that oncologic pathology has evolved from a strictly diagnostic service to a sophisticated combination of staging, molecular characterization and classification of tumors, all of which directly guide therapy. As such, pathologists have greatly expanded their role in medical care by not only providing a diagnosis, but also in advising clinicians on the most appropriate and effective treatment on an individualized basis for every patient. The expanding role of pathologists has undoubtedly contributed to the improvement in breast cancer survival from 5% to over 90% in the past 100 years.

The development of modern blood banking and transfusion medicine practice certainly deserves a place among the most important advances in the history of medical practice. Although blood groups, compatibility testing and storage with anticoagulants were all known prior to 1922, widespread blood transfusion remained a rare practice until 1937, when the first blood bank was established. Prior to blood banking, transfusions involved end-to-end vascular anastomosis, a procedure fraught with risks to both patient and donor. Modern transfusion medicine services include testing of blood products for various infectious agents (first done in the 1950s), isolation of specific components of the collected blood, such as platelets or coagulation factors and, most recently, transfusion of plasma collected from recovered COVID-19 patients for the therapeutic benefit derived from the presence of antibodies to SARS-CoV-2. But global disparities exist in the availability and use of blood for transfusion, and in the safety of the blood supply. Dr. Richard Gammon, Transfusion Medicine Associate Editor for LM, predicts that stem cell technology, biotherapies, and cord blood banking will be major areas of future focus in transfusion medicine, along with the possibility that blood donation may be replaced by synthetically produced substitutes.

Prior to the eponymous cervicovaginal cytology test pioneered by Dr. George Papanicolaou in the 1930s, cervical cancer was a very common cause of cancer-related death in women. Currently, it is not among the top 10 causes of cancer-related death in women. AJCP Cytopathology Associate Editor Charles D. Sturgis, MD, traces the history of the “Pap” test, noting that it “has saved more lives than any other clinically utilized cancer prevention test.” Cytology laboratories, Dr. Sturgis notes, are among the most highly regulated clinical laboratory services. High error rates in Pap smear interpretations observed during the 1960s led to passage of the Clinical Laboratory Improvement Act in 1967 (CLIA ‘67), subsequently revised through the Clinical Laboratory Improvement Amendments in 1988 (CLIA ‘88), familiar to all clinical laboratory professionals as the statutory framework for all clinical laboratory practice in the U.S. Modern strategies for detecting cervical cancer include liquid-based cytology, a variety of immunohistochemical studies, methods to detect human papilloma virus (HPV; a primary cause of cervical cancer) and molecular analyses.

LM Hematology Assistant Editor Alexandra E. Kovach, MD, tells the story of pathologist Sidney Farber’s pioneering work in the treatment of childhood acute lymphoblastic leukemia (ALL) with the dihydrofolate reductase inhibitor aminopterin, a therapy she characterizes as “one of the greatest medical achievements during the last century.” Dr. Kovach describes the central role that laboratory professionals play in staging and monitoring the disease by analysis of cerebrospinal fluid (CSF) for nucleated cells and blasts. She offers a critique of alternative methods that exist for detecting and characterizing the abnormal cells found in the CSF—namely, flow cytometry and molecular analysis—concluding that technical obstacles preclude their mainstream use at this time. However, Dr. Kovach speculates that the more sophisticated laboratory methods may become prominent in monitoring ALL in the future.

Sanjay Mukhopadhyay, MD, AJCP Associate Editor for Pulmonary/Thoracic Pathology, reviews the most important advancements in thoracic pathology over the past 100 years. Among the discoveries cited by Dr. Mukhopadhyay as having significantly influenced the field of thoracic pathology are immunohistochemistry, computed tomography (CT), molecular testing and advanced diagnostic techniques such as bronchoscopy and endobronchial ultrasound-guided transbronchial needle aspiration. He also mentions new treatments, such as lung transplantation, molecular targeted therapies and immunotherapy, which have improved the prognosis of many lung diseases, including cancer. Finally, Dr. Mukhopadhyay notes that, in 1922 when the ASCP was founded, the link between smoking and lung cancer had yet to be established, and over the past several decades the steady decline in tobacco use has had a significant effect on the prevalence of smoking-related disorders, including lung cancer.

Perhaps due to some combination of a politically polarized populace, the 24-hour news cycle, pervasive consumption of social media, a somewhat disorganized governmental response to the pandemic, or the terrifying prospect of a rapidly mutating, highly infectious respiratory virus, the COVID-19 pandemic caused many to distrust government officials and medical experts. Thus, when a vaccine was developed for the virus, many refused to take it, suspicious of ulterior motives or inadequate attention to safety. It is easy to attribute vaccine resistance to the current political climate, but LM Reviews Editor Deniz Peker, MD, reveals that resistance to vaccination has existed for as long as vaccines themselves. In 1922, Dr. Peker recalls, San Antonio, TX, required all school children to receive the smallpox vaccine, and the legality of the mandate was challenged all the way to the U.S. Supreme Court, where it was upheld. Vaccine acceptance peaked in the 1950s, when Jonas Salk developed a vaccine for polio, a dreaded disease at the time. However, the anti-vaccination movement was partly revived by fraudulent research suggesting a link between vaccination and autism (with one paper describing the fraudulent studies published in LM, since retracted by the Editor). Regarding the vaccines for COVID-19, Dr. Peker warns that “skepticism and efforts to challenge vaccination mandates, including many lawsuits across the United States, remain an obstacle to efforts to curb the virus by vaccinations.”

We are sincerely grateful to our editors for these excellent essays, all of which highlight how the medical landscape has changed since ASCP was founded in 1922. We heartily congratulate ASCP on this remarkable milestone and join in the celebration marking 100 years of progress in pathology and laboratory medicine.