Prof Paul D Griffiths

Gut Feeling

Gut Feeling tells a story that arises out of a level of professional frustration. The science and medicine are sound, but so, unfortunately, are the bureaucracy and the missed opportunities for making medical progress. I have spent my life in academic medicine and know that there are many researchers like me who feel that, if we could only sweep away the countless obstacles placed in our way, modern medicine could address the problems of ill-health much more swiftly.

Many of my personal interactions with fellow researchers, regulators and pharmaceutical companies have been stimulating and constructive. You will discover that Stephen’s experiences are somewhat different, because the people in Gut Feeling are fictional. Nevertheless, you may know real people who have made similar comments.

The Stealth Virus

One December, as I sat amongst my family on Christmas Day, I tore open the gaudy paper which wrapped what was obviously a framed picture. But it was not the colourful photograph I had expected of my three children; revealed before me was a grainy black and white electron micrograph of my favourite virus. Somewhat bemused, I turned the present over. There, on the back, I found an inscription: a picture of your first love from your second love. My wife smiled. I quipped that I was glad to see that she knew her place in life and then had a few moments to explain what the picture was all about to my sons before they rushed to open their next presents.

Brenda had hit the nail on the head with that year's present. Quirky, insightful, unexpected and challenging, it still adorns my office wall, providing an amusing anecdote for visitors. But what lay behind the image? Why had this virus got under my skin to the extent that it had? The virus, like my wife, continues to be quirky, insightful, unexpected and challenging.

I first came across cytomegalovirus (or CMV for short) as a medical student, when I was pursuing some research in the virology laboratory in my spare time. Little was known about CMV then, but it appeared to be a common infection which only produced disease if the patient had an immature or damaged immune system; that is, a fetus or someone receiving immunosuppressive drugs to stop them rejecting an organ transplant. CMV grew only slowly in the laboratory cell cultures, so textbooks dismissed it as a puny, insignificant thing, only able to cause disease when the patient was immunocompromised.

This did not make sense to me. Our immune system protected us against a multitude of viruses. If we damaged that system with immunosuppressive drugs, would you not expect patients to suffer from the most aggressive viruses first, followed by the puny ones later? The immune system also protected women against having babies damaged by rubella; why did this not also work for CMV? I decided to do some experiments and the more results I got, the more I became convinced that the textbooks had got it all wrong about CMV.

The virus had evolved to infect everyone when life expectancy was only 25 years and CMV was perfectly balanced and able to live in harmony with our immune system. It was the evolving changes in human behaviour that had upset this balance. The occasional cases of disease that came to medical attention were due to medical science progressing enough to enable organ transplantation or to social changes allowing women to delay pregnancy until later in life without having acquired immunity to this infection in childhood because of smaller families and improved hygiene.

As more and more results came in from around the world, it was clear that CMV was a major source of disease for many groups of patients, including the elderly, those who were admitted to intensive care units and people with HIV infection. Yet, most doctors continued to ignore CMV, because the virus did not reveal itself. There were no telltale signs that it was infecting people; only medical detectives studying groups of patients could discern its true effects. Most medical attention was focused on the more obvious infections such as smallpox, measles, TB, malaria and HIV so it was easy to ignore CMV, which continued to make a silent contribution to many different diseases. The patients still suffered from CMV, but with no easy clinical diagnosis to make, we stuck with defined diseases that we could name. Patients were not told about CMV, because we did not know what to tell them. We could not explain it, because the natural history of this infection and the way it caused multiple diseases were all too complicated.

Time has moved on and with it medical knowledge. That is why I decided to write this book, waiting until we had something positive to offer in the form of clinical trials of vaccines, to set against the concerns that might be raised in people's minds.

There has to be an explanation for how The Stealth Virus has managed to keep out of the limelight for so long. I decided to allow CMV to tell us, so the first chapter gives this virus a voice. Because it has co-evolved with humans for hundreds of millions of years, CMV can be personified and presented as having intelligence, wanting only to maintain itself in the community without attracting attention by causing overt disease. According to its perspective, CMV disease is the result of humans changing their natural world to become a cleaner, longer living life form which has evolved to allow them to reproduce later in life, swap major organs and suppress their immune systems with drugs or with other infections like HIV.

Each chapter of the the next section contains personalised stories of different patients affected by CMV - with examples of the young, the old and the famous, reflecting the wide range of people affected. This forms a series of case histories, based on real medical practice, to illustrate how much suffering is caused by CMV. All names are fictitious, except for Pope John Paul II who suffered from CMV in 1981. Woven into these chapters is an accurate chronological description of the work of researchers around the world who have identified how much disease CMV causes, how this can now be diagnosed and subsequently controlled by antiviral drug treatments and by vaccines. To maintain a non-technical style for the book, I based each chapter around the people who made the discoveries, so that the scientific concepts can be absorbed passively by the reader. Key references are grouped together into a separate section at the end so that they do not interrupt the narrative flow.

The last chapter ends with the positive note that CMV is now preventable by vaccination and that large scale clinical trials are about to begin in 2013/ 2014. This illustrates why this book is needed and why it is timely. Indeed, knowing what we know now, it is difficult to see how this important pathogen has evaded the attention of medicine, science and the wider public for so long.

That injustice is about to be corrected as we provide information to the community about the new CMV vaccines. There is now the possibility of screening all newborns for this virus and screening all pregnant women (which is already implemented in Italy). There is a need for an accessible source of information for anyone who wants to read more than a brief patient information sheet. The case histories in my book are so compelling that I hope women will be motivated to think about the transmission of this virus and how to avoid it, for themselves or their daughters.