“The major problem that we encountered along the way was an absence of federal funding for our research. This discovery of POLG mutations in Alpers syndrome was funded entirely by gifts and donations from families, private foundations, and philanthropic donations.”

The cause of Alpers syndrome had remained a mystery for almost 70 years since its first description by Bernard Alpers in 1931. A number of leads over the decades failed to reveal the cause, until our 2004 paper reported the first two mutations in POLG linked to the disease. Within two years, the discovery of POLG involvement in Alpers syndrome was confirmed by several laboratories around the world and over 40 new causative mutations are now known.

In addition, the field has grown so rapidly that we now know that mutations in POLG can cause at least seven different diseases in children and adults, with a combined disease frequency of nearly 1:10,000. As many as 1:50 people may be silent carriers of POLG mutations. Indeed, mutations in the mitochondrial DNA polymerase gamma (POLG) may be the most common single cause of inherited mitochondrial disease yet discovered. Scientifically, our 2004 paper was a compelling conclusion to our 1999 paper that showed for the first time ever, that a human disease (Alpers syndrome) was linked to a biochemical defect in a DNA polymerase (POLG).

In practical terms, our discovery led directly to a rapid DNA test to diagnose Alpers syndrome. Over 80% of the cases can now be diagnosed by screening for just five common mutations. Before the advent of a DNA test, Alpers syndrome could only be confirmed by post-mortem examination. Today, doctors can diagnose the disease with a simple blood test, and prenatal diagnosis is also possible.

We became involved in this research as part of our long-standing interest in the mechanisms of mitochondrial DNA (mtDNA) evolution, replication, and repair, and because of an interest I had in understanding why so many of the drugs we use to treat AIDS were toxic to mitochondria. Basically, we wanted to answer the question, "How does one mtDNA become two?" and to study how this process changes in different cell types, at different stages of development from embryogenesis to the aging, and to understand what happens during incidental viral infections.

The major problem that we encountered along the way was an absence of federal funding for our research. This discovery of POLG mutations in Alpers syndrome was funded entirely by gifts and donations from families, private foundations, and philanthropic donations. We owe a great debt to all these people who made this discovery possible with their heartfelt support and active efforts to raise public awareness for mitochondrial disease.

Our immediate goals for the future of this research involve the development of a mouse model of Alpers syndrome, with the aim of better understanding the disease and developing new treatments, not only for Alpers syndrome in particular, but also for several other mitochondrial disorders that share common threads of pathogenesis.

It is our hope that when these studies are merged with others in our lab, such as the use of rapid optical methods for diagnosing mitochondrial dysfunction and the role of mitochondria in wound healing and regeneration, that we will be able to develop methods for earlier diagnosis, and perhaps even reduce the risk of developing more complex disorders like diabetes, Alzheimer dementia, autoimmune disorders, heart disease, and cancer.

I believe there are two important messages that come from this work. First, there is the message that grassroots support of science in America can make a difference for people that is felt around the world when government support of basic research in the life sciences falters.

Second, there is the message that the blossoming of mitochondrial medicine over the past decade has announced the emergence of a fully mature new discipline in biology and medicine. Mitochondrial medicine may be the new kid on the block, but it is now clear that the health and illness of the mitochondria in our cells, critically determine our own health and our susceptibility to disease. This fundamental understanding now unites all medical specialties.

The National Institutes of Health (NIH) currently have no unified infrastructure for ensuring continued support for mitochondrial disease research in America. The time is ripe—both the grassroots support and the scientific clout are present—for the initiation of United States Congressional discussions to create a new "National Institute of Mitochondrial Medicine" to ensure progress and answer the swelling need for new research in this important area of medicine.