Why rare disease research isn't just about rare diseases

Alkaptonuria (AKU) is the focus of the AKU Society. It's a debilitating disease, causing bones to turn black and brittle, leading to early joint degeneration. Many patients are left disabled and in considerable pain. However, for Sir Archibald Garrod and William Bateson, AKU helped them to understand genetics.

Sir Archibald Garrod was a true pioneer, relying on simple observations to understand fundamental aspects of human biology. He was an Edwardian doctor who specialised in metabolic medicine before it was called that.

After treating several patients with AKU, and looking at their family histories, he realised the disease followed patterns. It was quite common for brothers and sisters of patients to also have AKU; for grandparents to be as affected as their grandchildren; and for it to be more common in the children of a consanguineous marriage. He came to realise that AKU was somehow inheritable, centred around an 'inborn error of metabolism'.

While investigating the mysteries of AKU, Sir Garrod became friends with William Bateson, a Cambridge scientist with an interest in the work of Gregor Mendel, the monk famous for early experiments into the genetics of garden peas. Bateson realised that AKU and its inborn error was actually a Mendelian recessive character; a compound that was inheritable along a predictable pattern and which caused disease.

For the early 20th Century, this was groundbreaking. Ideas of inheritance and genetics were only just being formed and there was little understanding of how diseases could follow family lines. The work from Garrod and Bateson showed that a disease could be inherited as determined by a biochemical compound. This helped develop the idea of a genetic condition, and gave AKU its claim to fame as the world's first genetic disease to be recognised as such.

Garrod went on to present AKU, along with three other inheritable diseases (albinism, cystinuria and pentosuria) at a 1908 lecture. It was here that his term, 'an inborn error of metabolism', became known and this eventually led to the creation of a medical society: the Society for the Study of Inborn Errors of Metabolism in 1963.

Bateson, meanwhile, took the AKU example and founded modern genetics. He is even credited with naming the word 'genetics', along with the well-known terms 'heterozygote', 'homozygote' and 'allele'. In 1910, he founded a journal to help explain this new phenomenon of science, called the Journal of Genetics.

Sir Garrod summed up the importance of his research with rare diseases as: 'The study of nature's experiments is of special value; and many lessons which rare maladies can teach could hardly be learned in other ways'.

William Bateson used the more concise 'treasure your exceptions!'

This idea of a rare disease informing wider knowledge about fundamentals of biology is now well established. We have shown it in AKU research, as AKU (which affects around 80 people in the UK) is an extreme form of osteoarthritis (which affects more than eight million).

Our partners at the University of Liverpool compare bone samples from AKU patients with osteoarthritis patients. They discovered 'trabecular excrescences' in AKU bone — microscopic lumps created when the bone reacts to the disease. The research team also found these excrescences in osteoarthritic bone; a discovery about a disease affecting millions and that would not have been made without AKU research.

There are plenty more examples of the benefits of researching rare and extreme form of diseases. I'll give just three examples: work on familial hypercholesterolemia led to the development of statins to treat high cholesterol; congenital lipodystrophy, which causes an inability to store fat correctly, led to a better understanding of insulin resistance and diabetes; and a group of rare diseases called  euroacanthocytosis, marked by progressive muscle weakness and degeneration of the brain, are now being studied to understand more about how the brain deteriorates in common diseases such as Alzheimer's and Parkinson's.

That is why we founded a new charity, called Findacure: The Fundamental Diseases Partnership. 'Fundamental diseases' is applied here to extreme and rare genetic disorders, which offer a unique opportunity to better understand other diseases, including many common conditions. We believe that by studying fundamental diseases, we can understand the processes behind common diseases and learn new methods for their treatment.

To find out more about fundamental diseases and the role they play in understanding and treating other diseases, please see the Findacure website.