Discovery of the Hepatitis C wins the 2020 Nobel Prize for Physiology or Medicine.

Images : courtesy Nobel Foundation and Wiki Commons.

Liver cirrhosis - a dreaded medical jargon, which affects the liver - primarily due to the Hepatitis virus, is something that has caused immense sorrow for me and other students and alumni of Sainik School Bijapur - the Ajeets. Two of my very close friends - Tipusultan and Gurupad Hegadi, fellow Ajeets, have succumbed to this dreaded disease - Liver Cirrhosis, within a year of each other on July 13, 2019 and 17th August, 2020, respectively. One of the major causes for liver cirrhosis is a virus - the Hepatitis virus, which comes in three major variants A, B and C. World Health Organisation - WHO, estimates that worldwide some 290 million people are living with the Hepatitis virus including  the Hepatitis C virus, which alone infects more than 70 million people, and kills 400,000 people annually. It is therefore no wonder that the Nobel Assembly at the Karolinska Institute has decided to award the coveted Nobel Prize (2020) for Physiology or Medicine, jointly to three scientists, Harvey J Alter, the US National Institutes of Health, Maryland, Michael Houghton, British virologist presently at the University of Alberta in Canada and Charles Rice, Rockefeller University, New York, “ for their discovery of the Hepatitis C virus”. The three of them will share the handsome Nobel Prize  money of 10 million Sweedish Krone (8.2 Crore Indian ₹). This years laureates and their works reminds me of yet another connect with my school, where we were assigned an interesting task - treasure hunt, the finding of which depended on clues each navigating to the final destination for finding that illusive treasure. The discovery of the Hepatitis C Virus (HCV) by the three scientists has followed this path with each of them - Alter, Houghton and Rice, in that order, getting a clue or to use the words of Newton in the context ‘standing on the shoulders of the other’ to reach their final treasure destination of the discovery of the HCV. 

The ultimate result - the discovery of the Hepatitis C Virus by the three scientists, has helped in decisively fighting against the blood-borne hepatitis transmission, a major global health issue, which causes cirrhosis and liver cancer in people around the world. It is perhaps this discovery and understanding the underpinnings of the Hepatitis C virus (HCV) that has prompted the UN to announce, in its Sustainable Development Goals (SDG - 2015), their aim for the elimination of this dreaded disease by the year 2030. The discovery of Hepatitis C virus is a landmark achievement in that direction. Thanks to this discovery, highly sensitive blood tests for the Hepatitis virus are now available and these tests have essentially eliminated post-transfusion hepatitis in many parts of the world, thus helping in greatly improving the global health. The seminal discovery of Hepatitis C Virus by this year’s Nobel Laureates, has also paved the way for the development of effective antiviral drugs and in the development of the HCV vaccines, which will help in not only reducing the mortality rates but also in guiding the global health workers on to the right path towards elimination of this virus. 

The significance of the discovery of the HCV and understanding of the viruses can be appreciated and well recognised in the current context of the Covid 19 global pandemic, which is caused by yet another virus - the SARS- COV2, virus, which is the cause for the current ongoing Covid 19 pandemic that is plaguing the world. The study and understanding of the viruses help the medical fraternity in bringing down the mortality with pharmaceutical therapeutics and so also finding  candidate vaccines to get rid of the virus. Scientists and pharmacists from across the world, including India, are striving hard to invent variety of pharmaceutical therapeutics like the Remdesivir, which we understand has been used for the treatment of President Trump, who is admitted with Covid infection and so also for inventing vaccines for combating the Covid pandemic. Lot of the vaccine candidates are already in advanced trials stages and it is anticipated that by next year there will be definitive vaccines to combat the Covid 19 pandemic. The rapid pace at which the medical research has progressed for Covid 19 has been aided by the understanding of the viruses including the discovery of the HCV. In all cases the beginning of the vaccine development starts with the understanding of the virus, which causes the disease and therefore it is natural that the discovery of the Hepatitis C virus, which is the cause for many global deaths, by this years Nobel laureates is destined to play a pivotal role in not only combating and elimination of the HCV virus by 2030 but also in combating the current Covid 19 pandemic.

The Hepatitis C virus is a silent killer whose mortality rates are much higher than the ongoing Covid pandemic that is caused by another virus - SARS - Cov-2 ( Severely Acquired Respiratory Syndrome - Corona Virus 2). The Hepatitis Virus adversely affects the liver and causes liver cirrhosis, which may lead to cancer and death, if not attended timely with the liver transplant.Global studies estimate that there are 8.7 million people living with chronic HCV in India. Delhi-based, Institute of Liver and Biliary Science (ILBS), in the year 2014, had highlighted the approximate number of people living with chronic Hepatitis C infection to be around 12 million. According to another analysis it is estimated that the prevalence of chronic HCV infection in India could be somewhere around one per cent. In India HCV disease is mostly prevalent in the states of Punjab, Haryana, Andhra Pradesh, Puducherry, Arunachal Pradesh and Mizoram. According to one estimate Hepatitis C is killing more people than HIV/AIDS in India. All this means that we, Indians, must hail the decision of the Nobel committee to recognise the discovery of the hepatitis C for the coveted Nobel Prize award in Physiology or Medicine for this year.

The word Hepatitis is derived from two Greek words hepar - meaning "liver", and itis - meaning "inflammation". The HCV causes the deadly liver disease and accounts for nearly 12-32 per cent of liver cancer and 10-20 per cent of liver cirrhosis cases in India alone. Most unfortunately Hepatitis is a silent killer disease and most people with chronic Hepatitis B or C are not even aware of this infection and therefore are at very high risk of developing cirrhosis or liver cancer. HCV is also a major global health issue and in its recognition and with an objective of creating global awareness about hepatitis, every year the world observes ‘World Hepatitis Day (WHD) on 28 July and this year (2020) the theme for WHD was ‘Find the Missing Millions’. The WHD theme helps in creating awareness of the global burden of viral hepatitis and hopes to influence real change in global society. As stated above, an estimated 290 million people are living with the Hepatitis Virus and therefore identifying and finding the ‘ missing millions ‘ and linking them to medical care is of paramount importance, failing which millions will continue to suffer, and many of these precious lives will be lost. In that sense the Nobel recognition this year to the three scientists, who have played pivotal role in the discovery of Hepatitis C virus, is quite befitting and this discovery is helping their fellow scientists to understand the underpinnings of not just the HCV but also other viruses like the SARS- COV2 virus which causes Covid 19 virus. 

A look back in history reveals that the first description of hepatitis dates back to approximately 400 B.C.E and this is ascribed to the Greek physician Hippocrates - father of western medicine. By the middle of the twentieth century - 1940s, the doctors knew there were two main types of infectious hepatitis. The first, transmitted by the hepatitis A virus, which could spread via contaminated food and water and caused a short-term infection that is typically resolved within weeks. Hepatitis A is far less lethal in comparison with its cousin viruses B and C. Hepatitis B and C are spread by blood and body fluids and they are more harmful and insidious, since they silently infect the patient for years before serious complications like the liver cirrhosis and cancer are evidenced. By the 1960s researchers started studying about a new variant of the hepatitis virus.  In the year 1967, Baruch Blumberg, an American scientist, discovered the hepatitis B virus, while working for the National Institute of Health, USA, for which he received the 1976 Nobel Prize in Physiology or Medicine. Unfortunately, even the discovery of the hepatitis B was unable to explain all cases of chronic hepatitis infections, a disease that was becoming more common even in apparently healthy people who had received or donated blood. This pointed to the presence of yet another type of virus, which was then classified under the category of Non A Non B Hepatitis-NANBH. 

This years Nobel laureate, Harvey Alter was working as an young scientist  at the National Institute of Health in Bethesda, where his senior Blumberg had discovered the hepatitis B virus. While studying hepatitis spread by blood transfusions, during the early 1970s, the young Alter discovered that plasma from patients who didn't have hepatitis B could also transfer the disease. He observed and inferred that some patients were being infected by an unknown virus agent - NANBH. He later conclusively demonstrated that blood from these patients could transmit the disease to chimpanzees. Despite this significant progress, the identity of the new virus responsible for NANBH remained illusive. The unsuccessful search for the unknown agent (NANBH) employing all the traditional methods that had allowed the discovery and characterization of hepatitis A and hepatitis B continued for more than 10 years.

Michael Houghton, while working at a Pharmaceutical company - Chiron Corporation, was one of those scientists was in the hunt for the NANBH agent. In the year 1982, using a molecular approach based on the screening of DNA fragments, which were isolated from infected chimpanzees, Houghton and his team were able to arrive at a preliminary understanding of the illusive agent, which was causing liver cirrhosis. The initial screenings identified only genetic material from the host. Attempts to enrich viral sequences by eliminating host sequences that were also found in an uninfected control liver did not yield any result and were unsuccessful. They realised that Isolating the hepatitis C virus was harder. 

The breakthrough came in 1989, when Michael Houghton, who holds a PhD from Kings College, London, and his former coworkers, George Quo and Qui-Lim Choo, used a combination of molecular biology and immunology-based techniques to clone the virus by introducing viral DNA from an infected animal into bacteria, and using human antibodies to the virus to screen for its genetic sequence and identified  the mystery pathogen and sequenced the genetic code of the new virus. This new discovery came to be known as the hepatitis C virus. They discovered that the new virus - Hepatitis C, resembled viruses from a family called flaviviruses. These findings formally established a relationship between infection with the newly discovered hepatitis C virus and the occurrence of NANBH around the world. This discovery also led to a blood test that could screen for hepatitis C, which was quite revolutionary and it helped in vastly reducing the number of disease cases that resulted from blood transfusions worldwide.

The works of Houghton and his team were still unable to provide that conclusive answer to one question. Did the virus alone cause the disease? But then Houghton and his teams combined work had established a critical link between the unknown agent NANBH and HCV infection. The answer to this question was provided by Rice, who was then working at the Washington University in St. Louis, and his colleagues. Interestingly enough Rice had no intention to study the hepatitis C virus. He was more interested in studying yellow fever virus, which is also a family of the flavivirus, to which HCV belongs. However, by then Alter and Houghton had published their seminal papers on a ‘mysterious hepatitis virus’ in Science in 1989 and this paper fortuitously came to the notice of Rice. The paper gave that  uch needed impetus to Rice to study this new virus. To start with Rice’s interest in studying this new virus started off as a small side project and he says ‘that really nobody in lab was excited about this new study’. It was that time of the period when the scientists could not even grow the virus in cells and therefore the attenuated interest his team was understandable. From there, Rice and his team used the works of Houghton and his colleagues to build on their works and were successful in fleshing out the pathogen’s genome sequence, clone the viral RNA and infect it with animals. Rice and his teams works ultimately demonstrated that the hepatitis C virus alone was responsible for the cause of the disease. 

The combined works of the scientists has saved millions of lives and their works also demonstrate that science does not have any barriers. This years Nobel laureates  — Harvey J. Alter Michael Houghton and and Charles M. Rice — have ‘built on the discovery of the Hepatitis A and B viruses”, the Nobel Committee said, and their "discovery of Hepatitis C virus has revealed the cause of the remaining cases of chronic hepatitis and made possible blood tests and new medicines will continue to save millions of lives until this deadly HCV is eliminated as envisaged in the SDG of the United Nations. Their seminal works and their discovery has helped fast forward the development of effective antiviral drugs, which are now the need of hour in the current Covid 19 pandemic times, which is plaguing the world and India alone accounting for six million plus cases and fatalities which have just exceeded hundred thousand. The positive part of it is that close to 5.6 million people have recovered from this pandemic. Had it not been for our better understanding of the virus, part of which stems from the works of the three laureates of this years Medicine Nobel prize, there would have been that many more fatalities and lesser recoveries. 

Thanks to the pioneering work of the three laureates- Alter, Houghton and Rice, and many of their colleagues who built upon their findings to identify HCV carriers, the global health workers are now able to eliminate contaminated blood and blood products and develop effective drugs, to combat the global menace  of HCV. We have now come to a stage where HCV induced hepatitis in many cases has become a curable disease. Their works have also aided in the development of anti viral pharmaceutical medicines, which can cure more than 95% of the hepatitis patients. Therefore the joint discovery of the HCV by the three scientists and their team can be rightly characterized as a “landmark achievement in our ongoing battle against viral infections”, particularly in combating causes of cirrhosis and liver cancer in people around the world.

Long live science and scientific temper, which alone is rational and non canonical.