The journey of 48 years- The Nobel Prize-winning Hepatitis C discovery.

Every person who is connected to medical research world is celebrating because The Nobel Prize in Physiology or Medicine 2020 is given to the researchers Harvey J. Alter, Michael Houghton and Charles M. Rice as they helped in the discovery of Hepatitis C virus. You may think that every year Nobel prizes are given so what’s new this year or why are researchers celebrating in such a grand manner. As the title suggest it took 48 years for this discovery to get a noble prize. Can you even imagine that the research paper you have published today inspite of getting so much recognition takes 48 years to get the ultimate Nobel prize. After the Covid19 pandemic every researcher is being questioned about vaccine but this is the perfect example how things work in research world. Its not an overnight discovery but takes investment of entire life.

For the people who don’t know What is the Hepatitis C virus?

It is a small virus of the family Flaviviridae (size 55–65 nm). It is enveloped and its genome is positive-sense single-stranded.

Why is it dangerous?

It causes liver inflammation, which may lead to chronic liver conditions like cirrhosis and liver cancer.

How the search for non-hepatitis A and B virus started?

During the 1960s both the hepatitis A and hepatitis B was discovered but there were people who suffered from hepatitis like symptoms but was not suffering from both the viruses. So, the first hero of this story came to play, who is none other than Harvey J. Alter.

In 1975 he and his colleagues were working with 22 patients who had symptoms of transmission associated hepatitis virus. When they took the serological test and looked for antibodies related to hepatitis A and hepatitis B virus, the test showed negative, as there were no presence of antibodies. They became sure that there was an involvement of another virus, which had similarities with these viruses.

So in 1975 Alter decided to conduct experiment which will help to have a clear view of the transmission characteristics of this non-A, non-B hepatitis virus. He took serum or plasma samples from four patients who were suffering from the acute or chronic non-A, non-B post transfusion hepatitis and inoculated it into 5 chimpanzees. They were surprised to see that both biochemical and histological evidence of hepatitis developed in the chimpanzees after 13·4 weeks of inoculation. Though they came to know that there is a non-A, non-B hepatitis transmissible agent, which had a characteristic of virus Alter, was not able to isolate the genetic sequence of the virus.

The discovery of the Hepatitis C virus.

So in 1989 the second hero entered the story i.e Michael Houghton. He felt the need for the isolation and identification of this unknown virus. What he did was he took the plasma of a chimpanzee who was infected with this virus. Then he prepared a complementary DNA library from the genome fragments generated from the plasma sample. He believed that though much of the fragment was from the genome of the chimpanzee itself it also contained some genome from the virus. After making the library, he took patient serum samples who was suffering from the disease and so had antibody against it. When he screened the polypeptide from the complementary DNA with the patient serum antibodies. He found a complementary DNA clone which encode an antigen associated specifically with the non-A and non-B hepatitis virus infection as it binds with the patient serum antibodies. He was shocked when he came to know that it was an RNA molecule with at least 10,000 nucleotides and is positive-stranded with respect to the encoded antigen polypeptide. Soon he named it Hepatitis C virus and told that it is similar to the togaviridae or flaviviridae. Thus for the first time Hepatitis C virus was in the frame of the researchers.

After this discovery, many researchers tried to sequence the viral RNA but faced many problems because of the virus quasi species property (lots of variation due to mutation). In order to complete the trio of these two researchers the third hero (researcher) took the entry in 1997.

Does the virus alone can cause hepatitis?

In 1997, this question arose among the researchers, which is mainly related to the replication of the virus. Charles M. Rice took patient sample infected with Hepatitis C virus and when he prepared a library of complementary DNA, he noticed a previously uncharacterized region in the end of the Hepatitis C virus genome, which may be important for the viral replication. He prepared an RNA variant, which contained those regions, and when he injected it into the liver of chimpanzee, he could detect the virus in the body and all pathological symptoms were observed. Thus, he was able to explain that the Hepatitis C virus alone could cause transfusion-mediated hepatitis.

These prominent discoveries associated with Hepatitis C virus helped the world to fight back the chronic liver disease associated with this virus. The cases declined, new drugs were discovered against it, rapid detection test was available. Thus, it helped the world have healthy living life and finally after so many years it has gained its ultimate recognition. Let us celebrate not only this discovery but also thousands and millions of discovery who did not get the recognition but have helped the human species in every possible way.

Reference

Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med. 1975; 292:767-770.

Alter HJ, Purcell RH, Holland PV, Popper H. Transmissible agent in non-A, non-B hepatitis. Lancet. 1978; 1:459-463.

Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989; 244:359-362.

Kolykhalov AA, Agapov EV, Blight KJ, Mihalik K, Feinstone SM, Rice CM. Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science. 1997; 277:570-574.