Aspirin's journey from nature to nurture

This story actually begins in 400 BC.  The hero is Hippocrates, the father of modern medicine.  From him we learned that a powder made from the bark and leaves of the willow tree can be used to help heal headaches, pains and fevers.

But there was a “gotcha”.  The problem was that salicylic acid caused stomach bleeding and a means of buffering the compound was needed.  The first person to do so was a French chemist named Charles Frederic Gerhardt.  In 1853, Gerhardt acetylated the salicylic acid to create acetylsalicylic acid.

Gerhardt's product was fantastic, because with the acetylated version you got all the healing properties without the stomach bleeds.  However, Gerhardt never studied commercialization and entrepreneurship at Monash University.  As a result of this educational oversight he had no desire to market his discovery and he abandoned it.

Fast forward to 1897, and chemists working at the Bayer chemical company in Germany independently rediscovered Gerhardt’s formula.  In the maverick spirit of the time they tested it on one of their scientist’s long-suffering, arthritic father.  The pain relief was immediate, the father was delighted, and by 1899 Bayer was selling aspirin in many countries.

Today, aspirin is one of the most widely used medications in the world, with an estimated 40,000 tons of it being consumed every year.  The patent has long expired but the trademark continues in many countries and Bayer, remarkably, continues to be the world-wide dominant supplier.

In many respects Aspirin is a miracle drug.  It has applications well beyond simple pain relief, and there is considerable optimism about its potential.

But potential is one thing.  We are well past the days of maverick medicine and simple results.  This potential needs to be proven beyond doubt.

Move beyond pain and fever management and cast your mind to longevity.  Average lifespans are increasing at an incredible clip.  Remarkably, for the last 200 years, every five years or so the predicted lifespan for a newborn baby increased by one year.

But living longer is not the holy grail.  Living longer with good end-of-life quality is what it’s all about.  There are many reasons to think that aspirin can assist in delivering this goal.

One of the main reasons to have confidence in aspirin is that we are learning that inflammation underlies many of the illnesses of ageing.  Low doses of aspirin, of course, suppress low-grade inflammation.

But how good can it be?  Is aspirin a too-good-to-be-true story?  Can it really help to prevent heart disease, stroke, cancer and Alzheimer’s?

Perhaps.  But like most fairy tales, there is a wicked witch.  In this case the villain is increased bleeding.

As we speak, the trade-off between increased bleeding and disease prevention is unknown.  It is critically important to know the extent of the trade-off, one way or the other.  GPs wonder about this issue every single day.

To quantify the trade-off, Monash University is leading an international trial known as ASPREE. 
To achieve a meaningful result, the trial has to be big, really big.  ASPREE is the biggest aspirin trial in the world.  It aims to determine whether the potential benefits of aspirin outweigh the risks for people over age 70.  It is hoped that the ASPREE trial will give us a definitive answer and quantify the contribution of preventative aspirin to end of life quality.

ASPREE would not have been possible without the financial support of the United States’ National Institute of Ageing.  For their confidence in the expertise of Australian Researchers we are deeply grateful.

The NIA’s confidence resulted from the fact that since the early 1990s at Monash University’s Department of Epidemiology and Preventive Medicine, under the leadership of John McNeil and colleagues, we have built our expertise and the supporting infrastructure for biostatistics, data management, epidemiology and clinical medicine.

Having all of these in the one institution is what makes it possible for us to undertake a huge study like ASPREE.

Interestingly, some early aspirin pilot studies were undertaken at Monash University by John McNeil and Chris Salagy in the early 1990s, but there was no possibility of obtaining the funding for a full trial.

So the idea lay on the backburner until tensions arose in America between the FDA and the American Heart Association.  The AHA issued a recommendation to use aspirin to prevent heart disease, particularly for people at high risk.  However, the FDA refused to give aspirin an official indication for primary prevention.  Two opposing views, hence the need for a definitive trial.

Because of the ASPREE trial design, bonus data will emerge.  In the first place, it is worth noting that the participants are healthy at entry, so it will be possible to look at the health of older Australians, on matters ranging from hearing to living conditions.

Cognitive function is measured regularly so ASPREE will provide a unique vehicle for studying the onset and progression of Alzheimer’s disease and dementia.

Furthermore, blood samples are taken from most of the patients, and stored in liquid nitrogen at nearly -200 degrees Celsius.  This means that if in future new biomarkers are postulated to diagnose, for example, Parkinson’s disease, researchers will be able to go back to the stored blood and test to see if the predictor diagnostic actually works. 

The questions regarding health of the elderly are extensive, even covering dental health.  The extent of investigation and the continuity of the investigation goes beyond primary health, and for this reason our Faculty of Business and Economics is eager to participate. 
ASPREE will finish in 2017 on current funding, but to follow up the preventative effects of aspirin on cancer there is some hope for extending the trial for a further five years.

ASPREE’s reputation is such that it is attracting world-leading co-workers and PhD students to Monash University.

All up, it is an amazing project. 

Learn more about ASPREE and follow the project on the ASPREE website.