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Harvey J. Alter, Michael Houghton, and Charles M. Rice. – these are the three winners of The Nobel Prize in Physiology or Medicine 2020. They were awarded the prestigious honor for their discovery of the Hepatitis C virus.
The Hepatitis C virus (HCV) causes a liver disease called hepatitis C. The virus can cause acute hepatitis which can result in poor appetite, light fever, physical weakness and pain whereas chronic hepatitis which can result in anything between liver failure and death. Although it usually starts without symptoms, this silent but progressive disease eventually leads to serious conditions like cirrhosis and liver cancer. Once the disease has reached this far, it can only be treated with costly and resource-intensive liver transplantations – until now.
The World Health Organization estimates that around 71 million people are patients of chronic hepatitis C and every year around 400,000 people lose their life to hepatitis C. This is likely an underestimation since many cases go undiagnosed. We have always known hepatitis C to be a deadly virus. However, there has never been much we have been able to do about this.
To find a cure for the virus, we would first have to study it. Researchers had spent the better part of over four decades trying to isolate and further study the deadly virus up to now with little to no success. Every conventional method we knew was put to the test and yet the virus had successfully fooled us every time escaping from our clutches.
We first recognized HCV as a unique virus in 1975 when Harvey J. Alter realized that most cases of hepatitis had nothing to do with hepatitis A or B. As a significant number of patients receiving blood transfusions developed chronic hepatitis due to an unknown agent, Alter transmitted the blood from those patients to chimpanzees. His transfusion studies showed that the agent had the characteristics of a virus while being a new and distinct form of chronic viral hepatitis. As the disease was similar to hepatitis A and B but was likely caused by a virus other than hepatitis A or B, it was fittingly named “non-A, non-B hepatitis”.
After we realized that it was a separate virus that was causing this hepatitis-like disease the next step was to find the virus and study it. To do that we would have to isolate this virus. The second laureate of the award, virologist Michael Houghton, along with three others attempted to isolate the genetic sequence of the virus in 1989 from the serum, “an amber-colored, protein-rich liquid which separates when blood coagulates”, of a chimpanzee who was experimentally infected with “non-A, non-B hepatitis”.
They created a collection of DNA fragments from nucleic acids found in the infected blood. Based on the assumption that antibodies against the virus would be present in the blood of hepatitis patients, they identified cloned viral DNA fragments responsible for producing viral proteins. By screening the antibodies, they isolated one positive clone, or replication, which turned out to be derived from a novel RNA virus belonging to the FLavivirus family. It had a 90% resemblance to hepatitis A and hepatitis B. This was the virus previously named “non-A, non-B hepatitis”: hepatitis C. For the first time, a molecular-based approach was used to identify a novel virus.
Now that the virus had been identified, work on establishing a blood test to help identify Hepatitis C infected blood began. Its success immediately led to a dramatic decrease in the number of post-transfusion cases of the disease.
The only thing left to do before moving towards finding a cure was to understand the characteristics of the virus which made it so deadly in the first place. Charles M. Rice, along with his colleagues, partook in doing particularly that. The question of whether HCV was the only cause of this disease now loomed. In other words, could a molecularly cloned virus reproduce the Hepatitis C disease?
Rice investigated the molecular requirements for viral replication and was unable to observe replication in animals. He then speculated that the clones used contained inactivating mutations in the genome. RNA viruses of this type are error-prone and thus acquire random mutations in their genomes during replication. As the individual clones could be defective, he sequenced numerous clones and compared them. Several of them contained potentially inactivating mutations that could be removed through genetic engineering. When he had the repaired genome, he had what he hoped to be a functional virus. After injecting this genome to chimpanzees, he observed clinical signs of hepatitis and that infectious virus was present in the blood, persisting over time. This provided decisive evidence that cloned HCV alone was able to cause the disease and induce an infection.
We have come a long way. From declaring the search for a new life-taking virus in the 1970s to having the ability to cure over 90% of hepatitis C cases through targeted HCV encoded protein eradication, we have certainly made strides in the right direction. The developments of highly effective blood screening programs along with the antiviral drugs have contributed to eliminating HCV from many parts of the globe. However, there is still much left to be done – hepatitis C continues to infect millions and take hundreds of thousands of lives every year. Hepatitis continues to be the leading cause of cirrhosis, a disease that claimed the lives of over 1.2 million people in 2015. The research done by Harvey J. Alter, Michael Houghton, and Charles M. Rice will go a long way in helping us produce effective antiviral drugs against hepatitis C on a global scale and eradicate this virus from the face of the planet once and for all.
Citations:
- “Hepatitis C.” World Health Organization, World Health Organization, www.who.int/news-room/fact-sheets/detail/hepatitis-c
- “The Nobel Prize in Physiology or Medicine 2020.” NobelPrize.org, www.nobelprize.org/prizes/medicine/2020/press-release/
- “EASL in the EU.” Journal of Hepatology, vol. 54, no. 4, 2011, p. iii., doi:10.1016/s0168-8278(10)01117-7.
- Chen, Stephen L, and Timothy R Morgan. “The Natural History of Hepatitis C Virus (HCV) Infection.” International Journal of Medical Sciences, Ivyspring International Publisher, 2006, www.ncbi.nlm.nih.gov/pmc/articles/PMC1415841/
- Pietrangelo, Ann. “The Top 10 Deadliest Diseases in the World.” Healthline, Healthline Media, 10 July 2019, www.healthline.com/health/top-10-deadliest-diseases
- Feature Image By James Cavallini/Science Source.
