Nobel lecture of Harvey Alter

In 2020 the Nobel prize for medicine was awarded to Harvey Alter, Michael Houghton and Charles Rice for their role in the discovery of the hepatitis C virus. I now watched the videos of the corresponding Nobel lectures. For my taste the lecture of Alter was by far the most interesting of the three. I think that he was also the one who played the most fundamental role in this discovery. At the beginning of his lecture he emphasizes the point that the most important discoveries in science often come as a complete surprise and not as a result of planned research programmes. Alter was 85 when he got the prize and so he had to wait a long time for it. The papers documenting his fundamental contributions were published in 1989. A central part of this work was the collection and preservation of blood samples from patients undergoing open heart surgery. Why was this group chosen? One of the most important modes of infection with hepatitis B and C used to be blood transfusions. This continued to be the case until tests were available to screen donors for these diseases. This kind of surgery involves extensive blood transfusions and so the chances of infection were relatively high in these patients. Also these patients suffered from relatively few other diseases which could have been confounding factors. These blood samples were an invaluable resource in the search for the virus. They were the basis of painstaking analysis over many years.

One important feature of hepatitis C is that it becomes chronic in 70 per cent of cases. This looks like a failure of the immune system to handle this disease. What are the reasons for this failure? One concerns quasispecies. The hepatitis C virus has an RNA genome and the copying of RNA is very error-prone. This leads to a huge variety in the genomes of virions in a single patient. This in turn results in rapid mutations of the virus. If an antibody has developed to combat the virus then selective pressure will quickly cause a new form to become dominant which is not vulnerable to that antibody. It seems to me that if this type of effect is to be captured using mathematical model it will require a stochastic model. Deterministic models of the type I have studied in the past are probably not helpful for that. In the lecture it is also mentioned that the number of T cells (CD4+ and CD8+) declines very much in chronically infected hepatitis C patients. No explanation is offerred as to why that is the case. Deterministic mathematical models might be able to contribute some understanding in that case.

The lecture contains the following interesting story. There was a time at which liver cancer was much more common in Japan than in the West. The reason for this was that that cancer was in many cases a late stage effect of hepatitis C. During wars in the early part of the 20th century many Japanese soldiers injected drugs with shared needles and this was what spread the disease. It was observed that there were many cases of jaundice (the most striking symptom of hepatitis) on the battlefield. Decades later many of these men developed serious liver disease, including cancer. Japanese doctors predicted that a similar phenomenon would be seen in the West when the effects of recreational drug use became manifest. They were right.