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
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'.
used the more concise 'treasure your exceptions!'
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).
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
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 neuroacanthocytosis, 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