“From Mystery to Miracle: The Extraordinary Journey of Hepatitis C Unveiled”
A, B, C, D, E: Hepatitis This concise, ominous alphabet symbolizes the five strains of viruses accountable for the existence of viral hepatitis, an illness currently afflicting approximately 400 million individuals worldwide.
Viral hepatitis comprises a diverse array of pathogens claiming the lives of 1.4 million people annually, surpassing the combined toll of HIV and malaria. Cirrhosis of the liver and hepatic cancer constitute the primary causes of these deaths, predominantly stemming from chronic infections associated with hepatitis B or C, transmitted through contact with contaminated blood.
Hepatitis
The discovery of the first strain, hepatitis B, dates back to the 1960s, attributed to the efforts of biochemist Baruch S. Blumberg. Subsequently, the unveiling of hepatitis A in 1973 by researchers Stephen Mark Feinstone, Albert Kapikian, and Robert Purcell shed light on its transmission through contaminated food and water.
Progress in screening for these two strains led to the identification of a third strain in the 1970s. Hematologist Harvey Alter’s investigation into unexplained cases of hepatitis in blood transfusion patients revealed an enigmatic, transmissible agent responsible for chronic infection, eventually recognized as non-A, non-B hepatitis.
A decade-long pursuit ensued, culminating in microbiologist Michael Houghton’s sequencing of the agent’s genome in 1989. It was categorized as a novel flavivirus, akin to the yellow fever virus, illuminating the underlying cause of non-A, non-B hepatitis.
The watershed moment arrived in 1997 when virologist Charles M. Rice and his team successfully induced clinical hepatitis in chimpanzees, establishing the direct link between hepatitis C and non-A, non-B hepatitis. This breakthrough laid the foundation for crucial hepatitis C tests to prevent infections through contaminated blood, as well as the development of effective antiviral medications for its treatment.
The pioneering work of Alter, Houghton, and Rice culminated in their 2020 Nobel Prize in Medicine, honoring their groundbreaking contributions in identifying the virus.
During the 72nd Lindau Nobel Laureate Meeting in June 2023, Knowable Magazine engaged Rice, now affiliated with Rockefeller University, in a discussion about the history of hepatitis C and the persisting challenges in its treatment and prevention. Below is an edited excerpt from the conversation.
Reflecting on the challenges during the initial stages of your research on hepatitis C, what were the primary hurdles you faced?
The quest to identify the causative agent of non-A, non-B hepatitis prompted intense research efforts, with Houghton’s team at Chiron leading the charge and reporting the partial sequence of the virus in 1989. The prospect of shifting our focus to this human virus, a part of the flavivirus family like yellow fever, presented a unique dilemma during my tenure at Washington University in St. Louis.
The absence of a cell culture system for the virus and the reliance on chimpanzees as the sole experimental model posed significant obstacles for laboratories studying the virus.
Our primary goals were to establish a viable cell culture system for virus replication and to develop genetic tools for its analysis, which was challenging given the limitations in RNA manipulation compared to DNA at the time. However, persistence ultimately paid off, leading to pivotal advancements in our understanding of hepatitis C.
Reflecting on the journey from the initial identification of the virus to the development of treatment, it appears to have been a relatively rapid progression. What is your perspective on this timeline?
I wouldn’t characterize the timeline as short, considering the numerous setbacks encountered in establishing a cell culture system and producing a functional clone. The span from the initial sequencing in 1989 to the introduction of the first antiviral compounds in 2011 encompasses a demanding 22-year period.
Furthermore, the early treatment compounds, combined with interferon therapy, exhibited limited efficacy with a 50 percent cure rate. It wasn’t until 2014 that the breakthrough of interferon-free drug cocktails emerged, revolutionizing the treatment landscape.
Many doubted the feasibility of developing a drug cocktail to eradicate the virus, but the success achieved by the biotech and pharmaceutical industry stands as a significant triumph. Nonetheless, I can’t help but wish the process could have been expedited further.
