"Sicker than a Doorknob"

... was an expression that the late Ernie Pino, Mr. Malaprop of the Golden Spur, used to use. We won't even touch on its etymology.

But that is why I have been absent-- I have been sick for a while and just got worn out. I hasten to say that I am feeling a good bit better.

But it occurs that there is some biological and evolutionary interest in the matter as well as an excuse. WHAT I had was persistent bacterial pneumonia, a severe sinus infection, and infected ears, one on the edge (?) of an abcess. But WHY I had it may be of interest. I hope so anyway-- my writing on my malaria years back made more than one person say writers will write about anything.

You see, I have a (not very rare) genetic condition-- I carry a gene for at least one abnormal CFTR protein. Two copies cause the debilitating lifelong condition known as Cystic Fibrosis.

Until recently it was though that single gene "carriers" were perfectly healthy, and most informational websites still say so. But a few years back evidence began to mount that at least some single gene carriers begin to manifest some CF- type symptoms in their late forties and fifties. I am 57.

Around (I think) 2000 I saw a report on this in New Scientist magazine, and emailed my sister Anita, who is a health professional specializing in CF, enquiring. I was beginning to suffer from thick mucus and persistent sinus infections, and had to have nasal polyps removed. She replied with a list of symptoms. I had them all. She urged me to get tested and I found that I did indeed have a copy of the suspect gene.

We refer sardonically to the condition as "CF Lite", but this winter has been a bit heavier. Matt, who knows I have not been well, asked how I was doing yesterday. I replied:

"A LITTLE better. Yesterday I made myself walk up 3000 feet [from 6000 to 9000 feet] to the Peregrine eyrie-- kill or cure! As I suspected, after turning blue in the face I began to get relief. Mechanically heavy aerobic exercise busts through the accumulated mucus, and I stopped coughing every ten seconds for the first time in what seems like months.

"It is this damn ever- worsening single CFTR gene thing. I am frustrated because knowledge of it is still so new that you can barely find anything in the literature about it on the web-- most sites insist that single gene carriers suffer NO symptoms. I have had for at least a decade most of the non- pancreatic symptoms, and the lungs are approaching "mild" (??) but genuine CF symptoms. ( I have routinely gotten pneumonia and sinus infections every winter for a decade and they get worse). If my doc and my sister (a CF pro in Boston) didn't feed me info I'd swear I was paranoid. The CF establishment seems at times to say "if you had full blown CF you would be dead before you reached 57, so count your blessings". Fine, but I'm choking NOW.

"This winter, one cold-triggered bout of bacterial pneumonia and sinusitis (Dec?) followed by what I now think was partial recovery-- then a worse case running now for 6? weeks, and on its third round of antibiotics, second antibiotic. This is classic CF symptomology-- persistent lurking lung (and sinus and ear) bacteria becoming more and more antibiotic- resistant and hiding semi- imperviously in the mucus. [Both ears and sinus were incredibly painful as well and full of yellow green mucus as were my lungs. At least that part is good and over! And the walk uphill actually seemed to blast loose a lot of mucus I could not cough up before-- I feel a lot better.]

"At times the lung mucus has been solid enough for Beth (doc) to diagnose its thickness just by listening. I think it needs mechanical breakup but insurance won't cover formal CF treatments for single-copy CFTR cases. My climbing yesterday had some of this effect, but sleeplessness and lack of oxygen doesn't exactly fuel the energy for it! And the crap in my sinuses doesn't help breathing either.

"I am going to improvise a "seawater nebulizer" to attempt to copy the effect of a new CF treatment they are trying, but for free. (What I really need is one of those big nebulizers they use for Gyrs with Asper [Gyrfalcons, which are from the Arctic, get Aspergillosis fumigatus, a fungal lung infection-- as do true CF sufferers], but those COST!)

"It would be nice to breathe freely."

The Wiki article on the gene and the one on CF are excellent, but say nothing of single gene effects.

The second has a couple of good paragraphs on how heterozygotic copies of bad genes can confer evolutionary advantages (I told you I was going somewhere with this).

"The ΔF508 mutation is estimated to be up to 52,000 years old.[54] Numerous hypotheses have been advanced as to why such a lethal mutation has persisted and spread in the human population. Other common autosomal recessive diseases such as sickle cell anemia have been found to protect carriers from other diseases, a concept known as heterozygote advantage. With the discovery that cholera toxin requires normal host CFTR proteins to function properly, it was hypothesized that carriers of mutant CFTR genes benefited from resistance to cholera and other causes of diarrhea.[55] Further studies have not confirmed this hypothesis.[56][57]

"Normal CFTR proteins are also essential for the entry of Salmonella typhi into cells,[58] suggesting that carriers of mutant CFTR genes might be resistant to typhoid fever. No in vivo study has yet confirmed this. In both cases, the low level of cystic fibrosis outside of Europe, in places where both cholera and typhoid fever are endemic, is not immediately explicable.

"It has also been hypothesized that the prevalence of CF in Europe might be connected with the development of cattle domestication. In this hypothesis, carriers of a single mutant CFTR chromosome had some protection from diarrhea caused by lactose intolerance, prior to the appearance of the mutations that created lactose tolerance.[59]"

See also the book Survival of the Sickest by Sharon Moalem, which is about the whole paradoxical subject of bad gene evolution and persistence.