The first known human cases of COVID-19 occurred in December 2019. About a month passed before the virus was identified and the entire genome sequence was identified. This year’s Nobel Prize in Physiology or Medicine honors a 25-year battle to identify the virus we now know as hepatitis C.
The hepatitis viruses are a bit confusing. There are now five known, and while they are united by their ability to attack the liver, they are quite different in most other ways. The main viruses are hepatitis A, hepatitis B, and hepatitis C, and they are caused by three largely unrelated viruses — some even differing in their genetic material, using DNA versus RNA — with very different properties.
One of the first differences recognized by the medical research community was how the viruses spread. Hepatitis A infections can be caused by contaminated water or food; B and C, on the other hand, are usually spread through contaminated blood or needles, making them a threat to the blood supply. The hepatitis A virus had been identified first, leading researchers to focus on the blood-borne B and C. B was identified next, which is when this year’s Nobel laureates come into the picture.
In the early 1970s, Harvey Alter at the US National Institutes of Health worked with a group trying to improve the safety of the blood supply. That group further confirmed that hepatitis infections still occurred even after the blood was screened for hepatitis B. This led to the obvious conclusion that there must be another virus around. A new search began.
The long quest
The search was not easy. Unlike many other viruses, including SARS-CoV-2, hepatitis C does not infect any of the small mammals we use for immunological research. To this day, the chimpanzee is the only other species we know of that hep C infects him. In addition, it is an RNA virus and RNA is easily degraded unless great care is taken in sample acquisition and handling. The enzyme we now use to make DNA copies of RNA – which makes research into the virus so much easier – was not discovered until the 1970s and was not introduced to the market until much later.
So we have to wait until the late 1980s before a candidate virus for hepatitis C was described. The work it found was truly heroic. Michael Houghton, then at the biotech company Chiron (later bought by the pharmaceutical giant Novartis), isolated fragments of RNAs from the blood of an infected chimpanzee, converted them into DNA and placed them in a virus that infects bacteria. The infected bacteria would then produce proteins encoded by these fragments, including fragments of the virus. Antibodies from hepatitis C patients were then used to determine which fragments actually came from the virus.
In the end, Houghton and his team managed to identify a single fragment of a previously unknown virus. But that was enough; they eventually described the entire virus using the fragment.
However, showing that this virus was the one that caused hepatitis C turned out to be another hurdle. The original virus identified by Houghton did not cause infections when transmitted to chimpanzees. Nor have other RNA sequences been identified since then. But Charles Rice, at the time at Washington University in St. Louis, recognized that RNA copying systems are typically very error-prone. So he scanned multiple sequences of the virus and found which DNA base (A, T, C or G) was most present at each position, and constructed what’s called a consensus sequence. A virus created using this consensus sequence was found to cause hepatitis symptoms.
Incremental but important
A few general thoughts on the price. First, hepatitis C may not seem like a major health problem, but that’s because the initial infection usually has relatively minor symptoms. The problem, on the other hand, is that the infection often persists at low levels and will cause cirrhosis of the liver and liver cancer. Many of those infected will require liver transplants, and without the discoveries of these new laureates, the infection would still spread through blood transfusions or the use of blood products — and the blood products that carry risks could potentially allow the antibody-containing plasma to be tested as a treatment. for COVID-19.
Despite the general significance that makes Rice, Alter, and Houghton’s work Nobel-worthy, they really aren’t responsible for instances of sudden breakthroughs or mind-boggling insights that people like to associate with the Nobel Prize. The prize is more a matter of hard work by large teams and with many employees, the kind of incremental progress that characterizes biology.
In that sense, it is again informative to consider the COVID-19 pandemic. While progress has been faster – we have better tools and a much easier virus to work with – progress has also been made in the form of numerous preliminary, incremental results. These will prove essential over time to get a complete picture of the virus, its spread and the symptoms it causes. The nature of biological research doesn’t change much, simply because the world attaches much more importance to it.
Editor’s note: as a result of last year’s prizes, we entered into a discussion about the prizes. The end result was that we decided to report more quickly on the day of the awards ceremony and investigate whether there were facets of the work that merited more in-depth coverage that could be done later. At this point, we see nothing about this year’s Medicine Prize that would suggest that more detailed coverage would be informative to our readers.