A Happy Ending

I am writing this addendum in Rome where Garret has just been inducted into the Italian National Academy of Sciences (Accademia Nazionale dei Lincei). The Academy was founded in 1603 and is the oldest honorific scientific academy in the world. It is located across the river Tiber from the Vatican in the Palazzo Corsini. Garret will be joining the Academy’s illustrious members including, Carlo Patrono, Galileo Galilei, Louis Pasteur, Albert Einstein and Enrico Fermi.

Lara Marlowe, the eminent Irish Times correspondent, was Garret’s elegant escort and he was surrounded by his family – John and Missy, Genevieve and Andrew, and Hugo and friends. The South African artist William Kentridge who received the International Prize for Plastic Arts, gave a wonderful talk about how he made murals on the embankments along the Tiber in Rome. He is a delightful character who by chance invited Lara and I to the private ceremony where the President of the Society welcomed all of the inductees.  The subsequent simple public ceremony sparked some serious fun before and after the event, culminating in Garret’s cousin James giving all of the friends and family chocolates with their initial – apparently, a Dutch Christmas tradition. I never cease to be amazed at the beauty of Rome – it is such a joy to be able to come here with Garret and to meet up with all our Italian friends – particularly Carlo, Angela, Livia, Matteo, Bianca, and Antonello.

My manuscript describing the discovery of a new form of frataxin (isoform E) in human red cells was finally accepted for publication in Scientific Reports on November 2^nd after 6 months and 6 days and 5 revisions!  Deficiency in the protein frataxin causes the neurodegenerative disease of Friedreich’s ataxia, which results in patients dying from heart disease around age 36.  Paradoxically, there is a small group of patients with mutations in the start region of the FXNgene who can make isoform E but not the full-length form that is processed in mitochondria.  It will be fascinating to determine whether expression of isoform E confers protection for this small group compared with regular Friedreich ataxia patients who make reduced amounts of both red cell and mitochondrial frataxin protein. Calico, where Garret did his sabbatical is trying to discover new drugs that can prolong healthier life.

As I discovered (when visiting Garret) Calico works on naked mole rats as their model because they live five times longer than they should and do not suffer from cancer or heart disease.  As mentioned in our blog “The Evening of the Day” when we were in the Portland wine bar, I was astonished to learn from Uniprot that the mRNA for naked mole rat frataxin codes for an almost identical protein to frataxin isoform E we discovered in human red cells.  This raises many questions about the etiology of Friedreich’s ataxia – perhaps it is a disease of aging not just mitochondria.  I look forward to working with naked mole rats and other long-lived species such as the Brandt’s bat to determine whether frataxin isoform E is involved in DNA repair and telomere length control.  Perhaps the morals from our incredible trip is that perseverance is everything and never underestimate the value of informed luck.