A Day In The Life...: Moby Dick has been spotted...the chase is on!

Overlooking the Atlantic Ocean at Martha's Vineyard Spring 2000

One night at mid-watch, after several months of sailing in the Pacific, Atlantic, and Indian Oceans searching for the Great White Whale called Moby Dick, Captain Ahab was on the deck of the Pequod and catches the scent of a whale. At dawn, Ahab notices an impressive wake of a large whale and states: "There she blows!--there she blows! A hump like a snow-hill! It is Moby Dick!" This began a three day chase which...you have to read the end of the blog to find out what happens in the novel.

After several months of searching the vast genetic oceans filled with DNA, Moby Dick has been spotted on chromosome 15...the chase is on! We have found the gene that is causing Mitochondrial Disease in our family. (See Spencer Update--Hope for previous mentions of this search for the gene/Moby Dick)

Nightwatch
Nauset Lighthouse, Cape Cod 2000

This search and find was no easy task. I feel fortunate that we have some of the most brilliant scientists and doctors working for us. To give you an idea of just how difficult this search was, I will give a little genetics tutorial. There are approximately 20,000 genes in the human genome. These are called nuclear genes and are located on chromosomes. Chromosomes are long strands of a molecule called DNA (deoxyribonucleic acid).

Humans get 23 chromosomes from our mom and 23 chromosomes from our dad. The chromosomes are found in the nucleus of our cells and thus called nuclear genes/chromosomes/DNA. It is estimated that 1,500 of the nuclear genes are solely dedicated to the mitochondria. That is 7.5% of all the genes in our bodies are dedicated solely to making proteins in the mitochondria. This should give an idea of how important this organelle is to our bodies. It does more than just produce energy.

There is also something called mitochondrial DNA that we only get from our mothers. This mitochondrial DNA (or genes) is completely separate from the nuclear DNA (or genes) and contains 37 genes. A genetic defect in either the nuclear genes or the mitochondrial genes can cause Mitochondrial Disease.

Spencer and Sydney 2004
Science Museum
London, England
Original DNA model
discovered by
James Watson and Francis Crick

James Watson and Francis Crick
Discovered the molecular structure
of DNA (deoxyribonucleic acid) in 1953
Francis Crick declared: "We have
discovered the secret of life".

As I have mentioned, we have two whaling boats searching for the gene(s). TGen with Dr. Narayanan as one captain located in Phoenix, AZ and Medical Neurogenetics with Dr. Shoffner as the other captain in Atlanta, GA.

I spoke with Dr. Narayanan by phone this week and he informed me that he and other scientist at TGen had found the gene that is causing Mitochondrial Disease in our family. The gene is called MTFMT which encodes mitochondrial methionyl-tRNA formyltransferase, which is required for the initiation of translation in mitochondria (http://www.omim.org/entry/611766). Many thanks to TGen and Dr. Narayanan for this incredible breakthrough!!! We now know exactly what is going on at the cellular level. This is so vitally important for finding treatments that will ultimately allow us to modify the phenotype--essentially making the symptoms less severe.

It seems that whenever I get either good or bad news from our doctors, I am at work. My emotions are not easily hidden (I inherited this from my mother). After I hung up the phone with Dr. Narayanan, tears of joy welled up in my eyes. How many times have I spoken with our doctors only to hear more devastating news. How many times have my eyes welled up with tears of sadness over the past few years. Not on this day! Tears of joy, thankfulness, and hope filled my eyes. I paused to call my wife and share the wonderful news.

A coworker asked if I was ok. I replied, "allergies...it must be those juniper trees again...wait, those trees pollinate in the spring...does someone have one of those therapy dogs or cats in the waiting room?" I showed my office staff the TGen article about our family and stated this remarkable company has found the gene.

We have a very busy practice and I see a lot of patients every day. I'm sure many people have thought, through the years, "That PA has pink eye. I hope he doesn't shake my hand. Oh no!, he just touched my neck searching for lymphadenopathy with those hands that must have pink eye germs all over them. I'm headed home to shower."

When we saw Dr. Narayanan this past fall, he reported he and TGen had analyzed all the genomes of our family, and there was no sighting of Moby Dick, but they were going back again to look a second time with newer technology.

Interestingly, Dr. Shoffner said the same thing when we saw him in August. I got a call from Dr. Shoffner's office several weeks ago who stated that our insurance company, had denied his request to look at more genes. I thought, "How in the hell can they do this?" I called them and argued with them. I said, your criteria for genetic testing for Leigh's Syndrome states: any neurological decompensation or bilateral basal ganglia lesions in the brain. Seth meets this criteria so what grounds do you have to deny this test? The test got approved.

Also, our insurance company denied our claim with Spencer and said we were responsible for about a $20K bill. They stated there was not enough evidence to warrant testing on Spencer. This poor customer service rep did not realize who she was speaking with. She did not realize that Mitochondrial Disease has consumed my life for over 3 years. She did not realize I have become like the whale harpooner Queequeg in the novel Moby Dick to my children and to others fighting Mitochondrial Disease. She did not realize that I have a medical background and have sifted through all the data on all my kids.

With the realization that the idiom, 'You can catch more flies with honey than with vinegar," is true, I kept the tone at bay. Realizing this was over her head and that the evidence for doing the tests was overwhelming, she tried to pass me off to the doctor who reviewed the data and denied the insurance claim. After being on hold for 10 minutes, she came back on the phone and said, "He was not available." I thought to myself, "Coward!" She then said, "You can appeal this denial."

In closing this post, I will write more about Moby Dick. Those who have followed this blog know that I love this book written by Herman Melville.  Brad, a dear friend of mine, taught me much about life through the eyes of Moby Dick. So, as I have journeyed through life over the past few years, I have included Moby Dick as one of my traveling partners.

The book is narrated by Ishmael who decides to go on a whaling expedition. "Call me Ishmael" is the famous opening line as Ishmael introduces himself to the reader and says he has decided to go on this voyage because he essentially is depressed:  "...whenever it is a damp, drizzly November in my soul; whenever I find myself involuntarily pausing before coffin warehouses, and bringing up the rear of every funeral I meet; and especially whenever my hypos get such an upper hand of me..."

The voyage turns out to be Ahab's (the captain of the ship) personal vendetta to find and kill Moby Dick, a large sperm whale. On a previous whaling expedition, Moby Dick permanently disfigured Ahab and bit off his leg. He has a prosthesis that is made from a sperm whale's jaw bone.   Ahab is a controversial character who is "grand, ungodly, god-like," egocentric, persuasive, motivated, and full of fear and shame.   Captain Ahab's monomaniacal pursuit of Moby Dick eventually becomes the goal of the entire crew.

The Great White sperm whale is powerful and unlike any other whale anyone has encountered. Moby Dick manipulates his encounters with mankind in a manner beyond the capacity of a normal whale. But no one really knows the true nature of this sperm whale and it is up to the reader to decide. Is Moby Dick a representation of deity, Ahab's obsession, Ahab's shame? Is Moby Dick a freak of nature due to several point mutations in his genotype, a force of evil, or is he just a large, intelligent mammal that would leave men alone if they would stop bothering him?

Captain Ahab sees Moby Dick as a facade, a mask for some force of evil. He sees Moby Dick as the Dark Side of the Force. Ahab resents Moby Dick because of what the whale did to him in the past. Ahab becomes so focused on destroying this whale that it becomes his sole purpose for his life.

I have come to see Moby Dick in a variety of ways depending on my situation. Today, Moby Dick represents Mitochondrial Disease. Ahab's passion to conquer the whale represents the faces thousands of children and adults who suffer from this disease with no cure and no effective treatments.

Ahab, is the hero this time. Ahab, knowing he was going up against a force that was more powerful than he had the capacity to deal with, continued to fight despite the odds. He was focused on this mission and did not let distractions get in his way. On day 3 of the chase, the remaining crew continued to pursue the whale. When the whale is spotted again, some of Ahab's final words are, "Aye, he's chasing me now; not I him--that's bad." Ahab did not turn and run. He continued the fight all the way to his death.

Ahab's fight represents Seth, Spencer, Sydney, Ellie, Desmond, Andy, Sebastian, Mae, Lawson, and many others who "[have] this disease, but [don't] let the disease have them." It represents Mylee, Ryder, Zach, and Shannon (three young children and a mother) and many others who passed away last year who "had this disease, but didn't let the disease have them." You are my heros! You give me the courage to continue this fight! Mitochondrial disease which appears at times as inscrutable as Moby Dick has become my metaphorical Moby Dick.

Our family has been given a gift this week by TGen which we are so warmly and deeply appreciative of. A remarkable gift that allows us to take the fight of Mitochondrial Disease to another level. Other gifts have been that so many of you have helped us along this journey. You know who you are. Whether your gifts have been silent prayers, sharing our blog with others, notes of encouragement, or donating to our cause, we are so warmly and deeply appreciative.

Below are photos taken of both the Atlantic and Pacific Oceans.