The Superman Disorder?

When I was 13 years old I was diagnosed with Gilbert's Syndrome, a genetic disorder affecting the promoter of a gene for the enzyme glucuronyltransferase, which conjugates bilirubin. 5-10% of the population have GS, and it is benign, leading only to elevated levels of unconjugated bilirubin in blood tests and occasional slight jaundice, which friends of mine have sometimes remarked on.

What seems weird, though, is that in the last few years there has been a raft of statistical epidemiological studies suggesting that us GS guys have a huge, invisible health shield! Those of us with the disorder appear to be  protected, sometimes strongly,  against cancer, cardiovascular disease, respiratory disease and kidney disease, and have lower BMIs, reduced cholesterol, more elastic arteries, reduced inflammation status and all sorts of other yummy stuff. There was even an article published last year showing success in the bottom line: in a study of 25,000 people over 350,000 person-years the overall mortality  of us Gilbert's Grenadiers was only half that of normal people.

Why would this be? The suggestion (albeit disputed) is that protection arises at least in part because unconjugated bilirubin is a powerful antioxidant, and therefore protects against oxidative stress. That would then be a bit like having had your ration of five fruits and vegetables before you even get up in the morning.

I'm not buying it, of course. There has to be a catch somewhere, doesn't there? Hyperbilirubinemia in infants can lead to irreversible kernicterus, or brain damage. Also, drug toxicity would appear to be worse in some cases for us guys. So I'm waiting for the negative metabolic effects of GS to be elucidated using systems medicine approaches. But until that time, I'm formally in the superman club!

Fortuna Imperatrix Mundi

Two Moments of Life beyond my control, on New Year's Eve, and yesterday:

31 December 2010: My partner Stephi is diagnosed with pulmonary metastatic myxoid liposarcoma. Multiple visits to Vanderbilt University Hospital ensue. Thoracotomy February 15th. Chemotherapy with highest-possible doses of doxorubicin (the "red devil") and ifosfamide (liquified mustard gas) planned starting in March. Prognosis: tough, uncertain battle ahead.

21 February 2011: Pathology results indicate that the resected masses were histoplasmosis, a fungal infection. No chemotherapy. No life-threatening disease. Prognosis: A slow but sure recovery from the pulmonary surgery ahead, back to a normal life.

Fortune: Empress of the World.

We are powerless against the whims of Fortuna.
But when her wheel turns in our favour, we must grasp the chance she has given us.

Shakespeare, in Julius Caesar, wrote:

"There is a tide in the affairs of men, Which taken at the flood, leads on to fortune. Omitted, all the voyage of their life is bound in shallows and in miseries. On such a full sea are we now afloat. And we must take the current when it serves, or lose our ventures"

CAUTION: graphic descriptions of disease and violence below.

Excerpt from “The Emperor of All Maladies: A Biography of Cancer” by Siddhartha Mukherjee. Mukherjee, a doctor, describes watching a two-year-old leukemia patient’s condition deteriorate as another drug fails:

"The patient “turned increasingly lethargic. He developed a limp, the result of leukemia pressing down on his spinal cord. Joint aches appeared, and violent, migrating pains. Then the leukemia burst through one of the bones in his thigh, causing a fracture and unleashing a blindingly intense, indescribable pain."

Excerpt from "JOKER ONE: A Marine Platoon's Story of Courage, Leadership, and Brotherhood" by Donovan Campbell.:

"The little kids stood in a tight knot on the sidewalk right next to our third vehicle, waving at us as we hopped in the Humvees, pleading for us to hand out more gifts.... Another explosion rang out, and the crowd of small children disintegrated into flame and smoke. From somewhere behind me, Marines started screaming out the worst words a platoon commander can hear: "Doc up! Doc up! Someone get a corpsman! Doc up!"I jumped out of the Humvee and looked around. I can't give specifics of the scene—I was too busy scanning the whole area and sorting out the enemy threat in my head—only a general impression, and it was of a macabre tableau from hell. The rocket had missed us. Instead it had impacted squarely in the middle of the crowd of small children. Dead and wounded little ones were draped limply all over the sidewalk, severed body parts mixing in with whole bodies, or in some cases flung even farther, into the street. Blood, always the blood, streamed onto the sidewalk and into the dirt, where it settled darkly in pools or rivulets. Across the whole scene drifted smoke and dust. The Marines jumped out of the vehicles and ran helter-skelter among the children, collecting the wounded and their body parts, applying first aid where they could. The docs were working frantically. I noticed, strangely enough, that they 'adn't bothered to put on their latex gloves."

Now for Jeremy's Soapbox:

We just don't get it. Why do we just accept cancer, heart disease and the other deadly afflictions? We just seem to seem to grin our teeth and bear it. People must not care, and here's why - because they only spend 0.2% of their wealth on finding ways to stop diseases. The US GDP is about $13tr and yet according to the OECD we spend only $26bn on health R&D i.e., 0.2%. Obviously we just don't care. Yet there are 1.5M new cancer cases per year in the US, and 500k cancer deaths. 1 in 4 of us will die of it, and a further 1 in 4 from heart disease. This absolutely dwarfs anything terrorism will ever do to us. If we make the effort research WILL stop these diseases. If people knew that themselves and their loved ones would be spared these diseases, wouldn't they want more than 0.2% of their income dedicated to it? Apparently not. Life is indeed cheap. We live for today, and don't care of tomorrow. Needed basic research is not funded, promising molecules are not synthesized and tested and clinical trials go unperformed.

As for energy research, improving and encouraging homegrown energy sources, while not eliminating international conflict, will surely lessen the pressure to go and fight foreign wars. Yet we pump trillions into stalemate conflicts while neglecting this simple way forward for both national and energy security. Again we fail to get it.

Science can cure cancer, heart disease, Alzheimer's, multiple sclerosis and the other hellish diseases. Science can mitigate the need to fight foreign wars, increasing national security via energy independence with renewable energy. Curing dreaded diseases and achieving energy independence is possible. But it takes time and resources and the short-term nature of the financial world makes it difficult for industry to do the groundwork research needed.

Energy and health research and development should be a top priority over the next twenty years. We must make sure the world's brainiest kids go into science and receive the support and motivation they need to do their research.

Why do we casually accept Middle Eastern oil as the lifeblood of our energy economy, and

two-year olds dying in excruciating pain?