Hepatitis B
Author: Baruch S. Blumberg

Overview

The book is an intimate exploration of hepatitis B virus (HBV), what the author said is one of the top ten infectious killers of people and the cause of ‘a terrible affliction‘. Noting that the virus plagues ‘perhaps half of the world’s population‘, the book portrays the diverse ways the deadly virus inflicts its harm, from acute and chronic hepatitis to primary liver cancer – ‘one of the most common and deadly cancers known’. The book’s strength perhaps lies in the skilful way it links the genetics and biology of the disease to its epidemiology and clinical manifestations, and in how it juxtaposes these with the exciting history of the discovery of the virus and the development of its effective vaccine. In what also turns out to be a thrilling adventure in research, the book is replete with lessons in the scientific process – from observation and hypothesis generation to field work and laboratory experiments. In this way, the author succeeded eminently in his major goal of enlightening ‘the general community of the methods and the processes that scientists use’. And complementing the book’s lucid scientific narrative is its revealing autobiographical account of its Nobel prize-winning author – one who attended a high school which produced ‘no fewer than three Nobel prize winners’ (pages 1, 4, 9 and 212).

Synopsis

The unifying theme of the author’s career trajectory was his curiosity about the interaction of hereditary and the environment, a fascination that led him to study tropical infectious diseases. Particularly intrigued by how ‘inheritance, human behavior, and the environment interrelate in the context of disease’, the author set out to understand how inherited differences give rise to ‘differential disease susceptibility‘. And the seeds of this scientific fixation were planted quite early in his career in Suriname and Moengo where he was intrigued by how the manifestations of filariasis were influenced by location, cultures, and behavioral patterns, and by how filariasis could exist in healthy carriers. The author’s early experience also had a ‘profound effect’ on fashioning the methodology he applied to his later research into hepatitis, remarking that it taught him ‘to rely on observations in the field’, and that it made him realise how ‘new observations led to new hypotheses‘. Other defining phases of his future success were his time as a house staff at Bellevue Hospital, an experience that showed him ‘the great variation in susceptibility and response to disease’, and the early research work he did at Oxford, what he referred to as ‘a turning point in my scientific training’, where he learnt how to ‘follow a problem for its own intrinsic value‘ (pages 13-19, 23, 30-31 and 40).

Given the author’s record in hepatitis research, it was rather surprising to learn that he neither set out to investigate viruses, nor to discover the cause of hepatitis. Rather, the vague goal that set the direction of his research was his intention ‘to find human biochemical and immunologic characteristics that were practical to study and that might be related to disease’. With this hypothesis-free research approach, what he referred to as a ‘form of inductive science‘, the author began by investigating ‘the distribution of the polymorphic traits in populations living under very different environmental conditions’, and his quest led him to study such diverse peoples as the Basques in Spain, the Yoruba and Fulani in Nigeria, and the Inuit in Alaska. Applying starch gel electrophoresis as his key technique, he sought ‘genetic patterns in serum protein variation‘ in these groups, but his breakthrough only came when he later discovered that the serum of subjects who had received multiple blood transfusions contained ‘an antibody against an inherited antigen variant present in the blood of the donor that they themselves had not inherited’. It was this insight that the author said led him to first identify a new inherited human lipoprotein, the Ag protein, and then the Australia or Au antigen – named after the country where most of the blood samples came from. The author went on to discuss how this discovery led to the conclusion that Au was acquired rather than inherited; that it was ‘a blood-transmitted infectious agent; that it was ‘associated with hepatitis‘; and that it was ‘part of the hepatitis virus‘ (pages 32, 40-43, 46-64, 67-70, 79 and 85-99).

The remarkable impact of the discovery of the Australia antigen was lucidly illustrated by the author’s remark that it created ‘a sudden change‘ in his research focus, referring to how ‘the wind switched, and we were sailing off in a new and challenging direction’. Metaphorically referring to how his team ‘released the genie from the bottle’ with their first publication, the author went on to describe how their hypothesis unexpectedly introduced them ‘into ‘the realm of hepatitis research‘ as ‘outsiders‘ who had upset the paradigm and stoked the ‘hostility‘ of ‘the main body of hepatitis investigators’. His subsequent research was similarly consequential in further characterising hepatitis B to be ‘as simple as viruses get’ – being ‘one of the smallest DNA viruses that infect humans’, and in identifying all four hepatitis genes and antigens – surface, core, polymerase enzyme, and X protein. The book also narrated the later application of the Au antigen test to screen blood donors to reduce the risk of post transfusion hepatitis, noting how this process attached a stigma to those with positive hepatitis blood test results – what the author said was ‘an eerie foreshadowing of the problems encountered with human immunodeficiency virus‘. And perhaps most groundbreaking of all, the author related the story behind the invention and deployment of the HBV vaccine, what he portrayed as probably ‘the most significant outcome of our research’; in this narration, he also detailed ‘the campaign to prevent primary cancer of the liver’, what he labelled as ‘the most important outcome of research on hepatitis B’ (pages 71, 88-89, 101-105, 113-127 and 135-160).

 

An enlightening and practical theme of the book is its exploration of the clinical profile of HBV, and the author addressed this within the context of its diverse presentations. Noting that HBV classically manifests as acute hepatitis which resolves after weeks or months, the book also discussed the other clinical courses of HBV, from rapid fulminant hepatitis which follows 1 percent of acute infections, to chronic hepatitis which develops in 5 percent of people who experience acute hepatitis. He also detailed the risk of developing chronic liver disease and primary liver cancer, but he emphasised that most HBV infections only produce immunity without causing any acute clinical symptoms, a situation that results in a healthy HBV carrier state in up to 20 percent of infected people. Similarly enlightening is the book’s discussion of the unsettling epidemiology of HBV, noting that ‘over half of the world’s population have been infected or will become infected with HBV during the course of their lifetimes‘, and detailing its almost countless transmission routes, from childbirth, breastfeeding, open skin lesions and circumcision, to sexual intercourse, needle sharing, tattooing and miscellaneous ‘bizarre mechanisms‘. These transmission mechanisms made the author remark that ‘HBV has managed to insinuate itself into the main functions that allow humans to perpetuate themselves: childbirth, sexual union, and family interaction’ (pages 116 and 160-168).

 

The author accompanied his exploration of hepatitis B with an engaging elucidation of his philosophy of science in which he asserted that ‘the scientist doesn’t deal with truth but is concerned with having sufficient evidence to accept a statement as if it were true’. Arguing that ‘it is difficult to prove that a hypothesis is true beyond any doubt‘, he explained that ‘a principal goal of science is to provide narrative explanations of natural events’, and that this quest may take the research enterprise in seemingly random directions, such as when new data ‘generate hypotheses that are not directly related to the initial hypothesis‘. On this supposition, the author contended that ‘research is a continuous process with no logically determinable end’ because ‘it continues to provide more answers and even more questions that broaden the understanding’. And beyond the objective aspects of science, the author also showed that research has a significant intuitive side, and he illustrated this with how he made the decision to pursue the Australia antigen rather than other antigens, adding that there was no obvious rational basis for doing this. And striking a cautionary note, the author outlined several traps that threaten the unwary scientist, one of which was the tendency to attribute a biological activity to the name they give their new discoveries. Referring to this as the ‘abandonment of unbiased judgment in the service of self’, the author said this is ‘one of the great dangers of the scientific process’ which threatens the ‘objective evaluation of data’ (pages 25-26, 76, 81 and 84-85).

Opinion

This well-written and exhaustive book narrates an enlightening account of a pernicious virus which takes a heavy toll on health. An exploration of the scientific enterprise as a whole, the book sets out the history of the discovery of HBV and the subsequent developments which not only defined its biology, but also influenced its epidemiology. As it outlines the complex course of science, the book also demonstrates the often paradoxical and serendipitous factors that influence its final outcome. In narrating his own momentous research, the author explains his driving philosophy and conveys the sense of excitement and wonder that characterised his journey to the discovery of HBV. Written by a frontline researcher who made the discovery, the book provides helpful insights into the value of open-mindedness in all research undertakings.

Overall assessment

Hepatitis wreaks a devastating burden across healthcare, and this elucidation of the virus and its mechanism of action is a valuable resource for researchers and clinicians alike. By charting the multifaceted interactions of humans with the hepatitis B virus, the book conveys invaluable lessons of contemporary relevance to all who undertake laboratory and field research work. With themes ranging from letting the observed data to generate hypotheses, to using laboratory research to improve clinical care, this is an inspiring account of the bench to bedside philosophy of medicine, and I recommend it to all doctors.

Book details

Publisher, Place, Year: Princeton University Press, Princeton, 2002
Number of chapters: 13
Number of pages: 244
ISBN: 9780691116237
Star rating: 5
Price: £14.08