The winners are: Harvey Alter from the USA, Mike Houghton from the UK and Charles Rice from the USA (expansion)
The Nobel Prize in Physiology or Medicine was awarded jointly to three researchers for the discovery of the hepatitis C virus, the same virus responsible for chronic hepatitis as well as for a group of diseases called viral hepatitis: Harvey J. Alter, Michael Houghton and Charles Rice. Alter was the first researcher ever to prove that an unknown virus was responsible for chronic jaundice; Houghton was able to crack the genome of the virus and Rice proved that this virus is the virus that alone can cause jaundice.
Summary
The 2020 Nobel Prize was awarded to three scientists who made a decisive contribution to humanity's fight against blood-borne hepatitis, a significant global medical problem that causes diseases such as cirrhosis and liver cancer. The three researchers are responsible for pioneering discoveries that led to the discovery of the hepatitis A and hepatitis B viruses, a discovery that was essential for further progress, but most cases of blood-borne jaundice remain unexplained at this point. The discovery of the hepatitis C virus revealed the cause of the remaining previously unexplained cases, and allowed the development of new tests and drugs that resulted in the salvation of millions of people.
Hepatitis - a global threat to human health
Hepatitis, or hepatitis, a combination of the Greek words for liver and inflammation, is primarily caused by viral inflammation, although other factors, such as alcoholism, environmental toxins, and autoimmune diseases, also contribute to hepatitis. In the 1s, it became clear that there are two main types of hepatitis. The first, called hepatitis A, is transmitted by contaminated water or food, and usually has few long-term consequences for the patient. The second type is transmitted by blood and body fluids and is a much more serious threat since it may cause a chronic condition, with the development of cirrhosis and liver cancer (Figure XNUMX). This type of hepatitis is insidious, since it causes a silent infection of healthy people when the serious problems emerge in their bodies only after many years. Blood-borne hepatitis leads to significant morbidity and mortality rates and causes more than a million deaths per year worldwide, and is therefore a global medical concern on a level similar to AIDS and tuberculosis.
Unknown cause of inflammation
The key step in the successful intervention against inflammatory diseases is identifying the factor responsible for them. In the 1976s, researcher Baruch Shmuel Bloomberg determined that one of the types of blood-borne hepatitis was caused by a virus known as the hepatitis B virus, and this discovery led to the development of diagnostic tests and eventually to an effective vaccine against it. Bloomberg won the Nobel Prize in Physiology or Medicine in XNUMX for "discoveries regarding new mechanisms for the origin and spread of infectious diseases". At that time, Harvey J. Alter, who worked at the National Institutes of Health (NIH) of the USA, studied the cases of hepatitis in patients who received blood transfusions. Although blood tests for the long-discovered hepatitis B virus have reduced the number of cases of transfusion-induced infections, Alter and his colleagues alarmingly demonstrated that a large number of such cases still exist. Tests to detect inflammation caused by the hepatitis A virus were also developed at this time, and it became clear that this virus (A) was not responsible for the unexplained cases.
At the time, it was a source of great concern that a significant number of these transfused patients developed chronic hepatitis due to an unexplained cause of inflammation. Alter and his colleagues showed that blood from those hepatitis patients could transmit the disease to chimpanzees, the only animals other than humans that are susceptible to this disease. Further studies have also shown that the unknown cause has characteristics of a virus. Alter's methodical studies led to the definition of a new and distinct form of chronic viral hepatitis. At the time, this mysterious disease was called "non-A or B hepatitis".
Discovery of hepatitis virus C
The discovery of the new virus became a top priority at this point. The researchers used all the traditional methods to detect viruses, but despite the great effort in the field, the virus evaded detection for more than a decade. Michael Houghton, who worked at the pharmaceutical company Chiron, took on the challenge of isolating the genetic sequence of the mysterious virus. Houghton and his colleagues created a collection of DNA segments from nucleic acids found in the blood of a chimpanzee infected with the disease. Most of these segments came from the chimpanzee's own genome, but the researchers predicted that some would come from the unknown virus. Based on the hypothesis that blood taken from hepatitis patients will contain antibodies against the virus, the researchers used the serum of such a patient in order to identify cloned viral DNA segments that code for the virus proteins. Following extensive research using this method, one positive clone was found. Further work proved that this clone came from a new RNA virus that belongs to the Flavivirus family and is called the hepatitis C virus.
The discovery of the hepatitis C virus was absolute; But one piece of the puzzle was still missing: Is the virus alone capable of causing the disease? In order to answer this question, the scientists had to investigate whether the cloned virus was capable of replicating and causing the disease. Charles Rice, a researcher at Washington University in St. Louis, along with other research groups examining RNA viruses, had previously noticed that there is an uncharacterized region at the end of the hepatitis C virus genome that may be important for the replication of the virus. Rice also noticed genetic changes in samples of isolated viruses and speculated that some of them might prevent the virus from replicating. Using genetic engineering, Rice created an RNA variant of the hepatitis C virus that included the defined region of the viral genome and was without the inactive genetic parts. When this RNA was injected into the liver of a chimpanzee, the virus was detected in its blood and pathological changes similar to those seen in humans with the chronic disease were seen. This result was the definitive proof that the hepatitis C virus alone was capable of causing the unexplained cases of transfusion-induced hepatitis.
The importance of this Nobel Prize-winning discovery
The discovery of the winners of this year's Nobel Prize in Medicine regarding the hepatitis C virus is a milestone in the ongoing fight against viral diseases. Thanks to their discovery, especially sensitive blood tests for the detection of the virus are now available to humanity and in fact have almost completely eliminated hepatitis caused by blood transfusions in large parts of the world, while significantly improving global health. Their discovery also enabled the rapid development of antiviral drugs targeting hepatitis C. For the first time in history, the disease can now be cured, a fact that raises hope for the complete eradication of this disease among our world's population. To achieve this goal, international efforts will be required to promote the development of more effective blood tests and antiviral drugs that are available worldwide.
Important articles
- Alter HJ, Holland PV, Purcell RH, Lander JJ, Feinstone SM, Morrow AG, Schmidt PJ. Posttransfusion hepatitis after exclusion of commercial and hepatitis-B antigen-positive donors. Ann Intern Med. 1972; 77:691-699.
- 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, Holland PV, Morrow AG, Purcell RH, Feinstone SM, Moritsugu Y. Clinical and serological analysis of transfusion-associated hepatitis. Lancet. 1975; 2:838-841.
- Alter HJ, Purcell RH, Holland PV, Popper H. Transmissible agents 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.
- Kuo G., Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, Dienstag JL, Alter CE, Stevens CE, Tegtmeier GE, Bonino F, Colombo M, Lee WS, Kuo C., Berger K, Shuster JR, Overby LR, Bradley DW, Houghton M. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989; 244:362-364.
- 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.
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