20 years ago, today…

When I was younger, the opening lines of the Beatle’s seminal ‘Sgt. Pepper’s Lonely Hearts Club Band’ resonated with a sense of genuine nostalgia, which was most likely what Messrs Lennon and McCartney had intended.

Twenty years must have seemed an aeon in the eyes of those four, talented young men. Especially since they spanned (for them) the early post war years of genuine privation. I was just remembering today another journey. It is 20 years ago today that another four young men (well three young men and one slightly older) met to discuss the cardiovascular complications associated with human immunodeficiency virus (HIV).

Having the privilege to work in (and for) one of the largest international drug companies, one that had made massive strides in taming the virus, we were exposed to almost every aspect of the disease and its treatment. Two of us had served on the wards where the first patients in the UK were treated – Thomas Macaulay Ward at the old St Stephen’s Hospital (the hospital mow long demolished and replaced). We were intimately aware of the battle that was ongoing. In those early days, working in the labs we often wondered why the blood samples from those poor emaciated patients would seem ‘fatty’.

At the time of our meeting the world’s increased understanding of HIV, including elucidation of the processes of transmission and replication, had led to the development of relatively effective therapies to minimise and manage the clinical consequences of infection. The drugs had undoubtedly improved rates of morbidity and mortality in infected patients. However, the improvements in quality of life and life expectancy were accompanied by an increase in the number of patients demonstrating cardiac complications, occurring either as a result of the infection itself or the drugs used to control the virus.

We knew that cardiac involvement occurred frequently in patients with HIV/AIDS. And yet, there seemed little written that summarised the cardiac conjunction of disease and drugs. What could four young scientists do? We were, you might say, trapped by the system – expected to serve our term as ‘apprentice’ scientists and not to step out of turn by expressing our ‘opinion’ regarding the science. Nevertheless, we were young and bold. We were determined to make a statement by gathering what was known about the disease and its cardiovascular complications. It was clear to us that that the myocardium, pericardium and/or endocardium were involved pathophysiologically. Myocarditis was clearly one of the most common types of cardiac involvement observed in HIV patients, the cause of which we knew was difficult to identify; this appeared responsible for myocardial dysfunction. Opportunistic infections, including HIV itself, had been suggested another cause of myocarditis. Dilated cardiomyopathy was often found in the late stage of HIV infection and myocarditis was possibly the triggering causative factor.?

The mechanism behind pericardial effusion remained unclear but it too could have been related to infections or neoplasms. Non-bacterial thrombotic endocarditis and infective endocarditis had been described in AIDS patients, both of which cause significant morbidity. Human immunodeficiency virus-related pulmonary hypertension was a diagnosis of exclusion, and symptoms and signs seemed to mimic other pulmonary conditions in AIDS patients. We also knew that cardiac Kaposi’s sarcoma and cardiac lymphoma were frequently encountered malignant neoplasms in AIDS patients – and that the prognosis was grave for patients with these conditions.

The process of research and synthesis of a statement ‘document’ was gruelling while ‘doing our day jobs’ and raising young families. We synthesised the findings of our research visually (see photo for the original thought process which, on reflection should have been included in our manuscript – hindsight!). From there we created a summary of over 150 scientific journals, finally narrowing that down to 40 key publications. We had little experience of publication between us and we had no interest from our superiors or employers. We lost one of our number early on, followed shortly after by another – it clearly seemed that we were conducting a thankless task. However, we persevered and submitted our first draft to?The?British Journal of Cardiology in April. I have to say that the response (below) from the Co-Editor at the time, Dr Henry Purcell was one of the nicest response letters I have ever received in over 100 subsequent publications. That in itself was reward enough; however, a few years later it allowed my co-author and great friend of 20+ years to revisit the literature again on the consequences of this terrible disease.?

So, what’s my point? Perseverance (especially in the face of disinterest from others)! I can’t emphasise how important it is to success, far beyond even the quality of your idea and the efficiency with which you execute it. I can’t say whether our final publication changed anything or saved anyone – but is stands 20 years later as a marker that we were there at that time. According to the Oxford dictionary, perseverance is the persistence in doing something despite difficulty or delay in achieving success. Persistence is not particularly glamorous, and therefore, our society does not speak much of it nor value it in its right measure. But the truth is that every success story is littered with bumps and fences. Any successful person who shares the story of their journey with you will talk about overcoming obstacles and facing difficult situations over and over again.

My observations over the last 50+ years of my life are confirmed in many published studies and that is, rather than talent, the true quality that distinguishes successful people is an exceptional commitment to their goals. So, if you are struggling to find the motivation this morning to keep going on what appears to be a thankless task, here are some ideas that might help:

• Break your goal down into small and attainable milestones. Once you are on the road and moving forward, the important thing is to ‘feel’ your progress. Achieving success will help you build trust and hope. Quick wins can trigger a spiral of positive behaviours.
• Complicated tasks provoke resistance. When you feel that resistance, force yourself to work just for 5 extra minutes. Just 5 minutes should be long enough to break that resistance and pave the way for the next ‘session’.
• And… begin with the end in mind. Have a clear vision of your destination, because in the middle, everything looks like a failure.

You have to take responsibility for yourself – there will be few along the road willing to help out (sadly), it is more likely that you will be told what you are trying to do is not possible, or not your job. It does not matter whether you are studying for exams, building a career or training to run your first marathon. Your success depends on your ability to focus on your goal again and again (and again), despite the difficulties. To keep trying, without giving up.

So where are those four young men today? Sadly, I haven’t spoken to the two collaborators we lost along the way. However, I am proud to say that I speak with the third (Dr Scott Purdon) almost daily and we are always looking for the next adventure we can enter together.?

Tim Hardman?is Managing Director of?Niche Science & Technology Ltd., a bespoke services CRO based in the UK. He is also Chairman of the?Association of Human Pharmacology in the Pharmaceutical Industry, President of the?European Federation for Exploratory Medicines Development?and an occasional commentator on science, business and the process of drug development.