A researcher at the University of Minnesota Medical School noticed that a small number of patients who received a transplant went on to develop a rare form of cancer called post-transplant proliferative disorder.
He was particularly curious when he found out that most of the patients had been exposed to a strange pathogen called the Epstein-Barr virus, which has fascinated and puzzled virus-hunters for decades.
It seems that certain people are more prone to difficulties managing the virus immunologically due to their genetic makeup.
While hit-and-run viruses, such as the one that causes the death of people in Africa, tend to make headlines, other viruses, such as the one that causes the death of people in the US, tend to be less well-known. It is impossible for the immune system to get rid of these infections because they remain in the tissues for the rest of our lives. Over the past 40 years, there has been mounting evidence that EBV is not as benign as it may seem.
For millions of years, EBV has coexisted with humans. It hides in a type of immune cell called B cells, where it stays for decades. We don't know we have it because more than half of children in England have contracted it by the age of 12. There is only one time when teenagers or young adults are affected by the disease and that is when they become immune-suppressed and start to develop mononucleosis.
About 200,000 cases of cancer worldwide are associated with the presence of the virus in our bodies. There are associations between the diseases of the head, neck and stomach. It is estimated that 40% of Hodgkin lymphoma cases in the UK are related to an infectious disease, with those who have previously had glandular fever being at a higher risk. There are a number of autoimmune disorders that have been associated with EBV.
The medical world has known about these links for a while, but most doctors have not been up to date on what to do about it. The main problem is that the virus is ubiquitous and it is inside the majority of the world's population. Modern medicine has largely taken the approach of pretending that the problem does not exist because there are less than 300 cancer cases in the UK connected to the virus.
The clinicians don't want to deal with it because they don't know what to do with it.
This may be about to change. In January, Science published a landmark study that showed overwhelmingly that the disease multiplesclerosis is caused by the virus.
More than 10m blood samples from US military personnel collected over 20 years were examined by scientists from the Harvard Chan School of Public Health and they found that those who were exposed to the virus were more likely to later develop multiplesclerosis.
The sheer number of people involved in the study made it possible to prove this association for the first time.
The study shows that the leading cause of multiplesclerosis is EBV, despite the high prevalence of the disease in the general population. Most smokers will never develop lung cancer, and similarly, most people who have been exposed to the virus will not develop the disease.
Why is it that most of us can coexist with the disease and never develop it, but for some, it becomes a pathway to chronic illness?
There is a delicate balance between the immune system and the virus. EBV hides out in the body's B-cells to avoid being wiped out by the immune defenders called T-cells. If the host's T-cells are not functioning properly, the virus can move into other tissues and cause damage.
EBV can suppress the normal dying process of infected cells… they can then grow and develop into a tumour
In some cases of long Covid, the symptoms have been linked to reactivation of EBV, a mechanism that has been proposed as a cause of chronic fatigue syndrome.
Ascherio suggests that the inability of the body to keep the virus in check means that it ends up in nerve cells.
He believes that the presence of the virus in the central nervous system causes an immune reaction because of similarities between the myelin sheaths and the EBV proteins. This causes the body to attack its own cells.
The factors that cause cancer are more complex than the ones that cause the flu. It appears that if a cell has other abnormal genes, it can grow and develop into a tumours.
It is thought that certain lifestyle factors can increase the chances of this happening. Tobacco smoke, pesticides, and food Additives can be used to interact with the immune system or amplify its genome within B cells.
According to Alan Rickinson, a cancer researcher at the University of Birmingham, the chances of an EBV-positive tumours are very low.
One of the cancers that has been linked to EBV is nasopharyngeal cancer. People of southern Chinese ethnicity have been shown to be more genetically prone to getting the disease, but this is not the whole story. A combination of genetics, lifestyle factors and exposure to the virus is what leads to the likelihood of someone developing the disease.
Rickinson says that studies from Hong Kong highlighted the practice of swerving infants on salted fish, which is known to contain potential carcinogens.
In the 1980s, when the connection between the virus and certain cancers began to emerge, Balfour set his sights on developing a vaccine to prevent people from getting it.
Over the next 30 years, his efforts were repeatedly knocked back as pharmaceutical companies pondered whether or not such a jab would be economical.
It will take a very large study of long duration to demonstrate that an EBV vaccine prevents MS
The discovery that the main cause of multiplesclerosing choriosclerosing choriosclerosing choriosclerosing choriosclerosing choriosclerosing choriosclerosing choriosclerosing choriosclerosing choriosclerosing chorio I think the evidence is very, very strong that it is necessary for the person to have EBV.
There are now three vaccines in the works. Moderna and the US National Institute of Allergy and Infectious Diseases are conducting phase 1 clinical trials of an mRNA vaccine for the virus, while the US National Institute of Allergy and Infectious Diseases is working on their own jab.
Moderna's clinical trial is targeting people in the 18 to 30 age range, but the ultimate goal is to give the vaccine to infants. There are many questions and challenges that need to be answered.
One obstacle is that it will take a long time to demonstrate that a vaccine prevents multiplesclerosis, so most likely experimental studies will need to rely on intermediate outcomes, such as whether the vaccine prevents mononucleosis.
The other question is whether the vaccine will need to provide what scientists call sterilising immunity, preventing the virus from binding at all to human cells, in order to prevent cancers andMS, or whether simply limiting the severity of the infection will be sufficient.
There are few vaccines that cause sterilising immunity, according to a professor at the University of Massachusetts Chan Medical School.
There are a number of candidates that can stop the replication of the virus in a test tube, but there is a drug that can clear it.
There is a sense of hope that progress is being made in an area that has been neglected for a long time.
He says the Science paper has been a gamechanger and a sort of vindication of something he believed in.
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