This year’s Nobel Prize in Medicine or Physiology is shared among three scientists for the discovery of the Hepatitis C virus. The winners are US researchers Charles Rice and Harvey Alter and British scientist Michael Houghton. The trio’s work dating back to 1970s and 1980s helped in saving millions of lives. This was a significant advancement to fight the blood-borne pathogen which wreaked havoc worldwide causing cirrhosis and liver cancer in people. The discovery of Hepatitis A and B viruses have been critical, but the cases of blood-borne hepatitis remained unexplained. The finding of the Hepatitis C virus explained the remaining causes of cases of chronic hepatitis (liver inflammation) which made blood testing, new medicines possible that saved lives.
Hepatitis is caused mainly by viral infections, but it can also be due to alcohol abuse, environmental toxins, and autoimmune disease. By 1940 it has become apparent that there are two major forms of hepatitis that are infectious. The first type- Hepatitis A is transmitted via polluted water or food and has a little long-term impact on the patient. The second type was transmitted via blood and bodily fluids and raises a more serious threat as it leads to a chronic condition such as cirrhosis and liver cancer. This type of hepatitis affects gradually and silently on healthy individuals by raising serious complications much later. Blood-borne hepatitis raises significant morbidity and mortality which causes millions of death worldwide every year. Thus, making it a global health concern on a scale comparable to HIV (Human Immunodeficiency Virus)- infection and tuberculosis.
Identifying the causative agent is the secret to effective action against any infectious diseases. In 1960s, one of the forms of blood-borne hepatitis was caused by a virus that was known as the Hepatitis B virus which led to various development in diagnostic tests and vaccines. This reduced the number of cases that occurred via transfusion related to hepatitis. But, at the same time, people receiving donated blood were getting chronic hepatitis even after the discovery of the Hepatitis B virus which raised a huge concern. Around this time, tests for Hepatitis A virus infection were also established and it became apparent that the cause of these mysterious cases was not Hepatitis A. Prof Harvey Alter noticed when observing transfusion patients at US National Institute of Health (NIH) discovered another infection. The blood from infected patients, when transferred to chimpanzees, showed that the disease spread to chimpanzees besides humans who were the only susceptible host. This mysterious illness came to be known as “non-A, non-B” hepatitis.
Now, it became crucial to identify the novel virus. The traditional techniques known for virus hunting were all used, but the virus was unable to be isolated for over a decade. Prof Michael Houghton managed to isolate the genetic sequence of the virus in 1989 at the pharmaceutical firm in Chiron by combining molecular biology and immunology-based techniques in cloning the virus. Prof Houghton and his colleagues created a collection of DNA fragments from nucleic acids found in the infected blood of a chimpanzee. Most of the fragments came from the genome of the chimpanzee but the researchers expected that some would be of the unknown virus. The assumption was based on the presence of antibodies against the virus from the blood of hepatitis patients. The researchers made use of the patient sera to identify cloned viral DNA fragments coding for viral proteins. This was followed by an extensive search until one positive clone was found. On further analysis, the clone was derived from a novel RNA virus belonging to the family of Flavivirus and named Hepatitis C. This virus was highly implicated as the missing agent by the presence of antibodies in chronic hepatitis patients.
The final piece was if this virus could alone cause hepatitis this means scientists have to investigate if the cloned virus could replicate causing the disease. Prof Charles Rice at Washington University in St. Louis along with other groups working with RNA viruses, observed a previously uncharacterized region at the end of the Hepatitis C virus genome that could be crucial for virus replication. Prof Rice also noted genetic variations in the isolated virus sample and assumed some of them might hinder virus replication. With the help of genetic engineering, Prof Rice generated an RNA variant of the Hepatitis C virus which included the newly defined region of the viral genome that lacked inactivating genetic variations. This was then injected into the liver of chimpanzees in which detection of the virus in the blood and pathological changes as seen in humans were noted. He confirmed that the cloned hepatitis alone causes chronic infection in chimpanzees and replicate the disease found in humans.
The hepatitis C virus belongs to the group of Flavivirus which includes dengue virus, West Nile, and yellow fever virus. The virus is a common cause of liver cancer and a reason why people undergo liver transplantation. It is estimated that globally 71 million people are infected with chronic hepatitis C virus. The number of individuals chronically infected develop cirrhosis or liver cancer. The discovery of the Hepatitis C virus is an achievement in the ongoing battle against viral diseases and due to this finding, we now have highly sensitive blood tests. These have essentially eliminated post-transfusion hepatitis worldwide and improving global health greatly. This also led to the rapid development of antiviral drugs mediated towards hepatitis C. The first time in recorded history, the disease can be cured promising of a better tomorrow raising hopes worldwide.
Reference: https://www.nobelprize.org
Author
