It Might Get Messy

Indeed, this week it will. Some of what follows is a little…gritty. May be hard to take if you’re inclined to be squeamish. I suggest those of you with weaker stomachs skip to the last third of the piece, where a nice, positive payoff awaits.


North Africa was in something of an uproar the first couple centuries A.D. Carthage was facing war with Rome, along with business competition from other seafaring city-states and a shifting climate that all combined to make things uncomfortable. Country-boy young Androclus ran into a Roman patrol while retrieving his sheep one afternoon, and was unceremoniously added to the slave staff serving the nominal Roman administrator. In the course of his duties, an opportunity to escape presented itself. Slipping away from the work squad detail, he found a convenient cave and ducked inside.


Only to find the cave already occupied by an adult male lion, but one sick from a thorn-infected paw. Androclus patched the lion up and it recovered swiftly. In gratitude, the lion hunted for and fed the two of them for years. 


Eventually Androclus, feeling a need to rejoin the human world, emigrated to Rome, where he was immediately arrested and sentenced to be “thrown to the lions”. On Coliseum day, they heaved Androclus into the pit with the lions in front of a standing-room-only crowd. One of the lions took a good hard sniff, hugged Androclus, and backed up to protect him from the rest of the animals. It was, of course, his buddy from the cave, captured in the interim and consigned to the Coliseum himself.


From Androclus to Lieutenant Ripley, saved from certain death when the Alien sniffs out the embryo inside her, scent has been an important factor in ecology and evolution. 


Possibly less so in humans than in other organisms, and certainly than in many other vertebrates. For example, humans have 350 genes coding for odor receptors, mice 1,100. However, it has been hypothesized that, while humans have jettisoned smell as a basic tool for environmental exploration, it may yet have enormous importance in interpersonal and intrafamily relationships, and be a dominant factor in breeding behavior (who among us can deny that the heady aroma of extra-large pizza and pitchers of cheap beer is a sexual stimulant from our post-adolescent days?). Humans seem to make up for the depauperate infrastructural hardware via expanded commitment of cerebral resources to sorting out inter- and intra-family activity and relationships based on odors. 


Here’s the thing. I can smell my tumors. And they are absolutely disgusting. Something like a combination of agave syrup, Vietnamese fish sauce, Chinese oyster sauce, cheap grappa, and the carcass of a several-days-ago road-killed squirrel all simmered together. Nightmarish. I try to alleviate the odor by keeping windows open and fans on in the rooms I hang out in (and given the fatigue levels, I spend a fair amount of time hanging out) to minimize the intensity of disgust Cathy and Molly have to tolerate.


Actually, they say they can’t smell them. I’d say they’re just being polite, but believe me, this is not an odor you can be “polite” about (cross-reference Ms. Jennifer’s first shot of the Chinese shit: “How bad could it be?”). There is a growing scientific interest in odors associated with cancers, from perspectives of diagnosis and treatment (dogs have been found to be able to sense some tumors before other non-invasive diagnostic techniques can); evolutionary selection processes (elaborate and physiologically difficult mechanisms generate and maintain tumor odors, it is a nontrivial metabolic investment); and physiological responses (it has been found that the immune system of healthy mice activates and mobilizes in response to the scent alone of tumor-bearing mice). 


From the evolutionary perspective, there is a single gene of particular importance. The p53 gene of vertebrates codes for proteins that help determine whether cells under intense stress should initiate DNA repair responses, or, if things are sufficiently bad, shut down and die. Embryos riddled with cancers and pre-cancers may be spontaneously aborted by mechanisms involving p53. If p53 is mutated in the clones comprising tumor cell masses, it is a bad prognostic sign. Radiation and chemotherapy are relatively ineffective in the context of mutated p53, because unmutated p53 is needed to stabilize the tissues being hammered by the radiation and drugs. No normal p53, no stability—continued cancers.


My oncologist sent me home with a sample vial to get her some bronchial phlegm. During my first exam this week, she said she can not only smell my tumors, she thinks she smells an infection. I was inclined to dismiss the latter, except here, 2 days later, I find myself coughing and congested. Under the circumstances, and pending getting the culture results back, I wouldn’t bet against Dr. Z’s nose on this one. 


And why would organisms make the physiological and metabolic investment in generating intense and specific odors for certain tumors? Well, cancer-susceptibility is partially inherited (although only a few specific cancers are directly transferred genetically). Mating with partners with active tumors may just be too much of an evolutionary risk. I’m thinkin’ that tumors might smell to make potential mates aware. Getting your particular slice of the genome to survive with the fittest is difficult enough without adding increased probabilities of malignancies to the mix. Stinky tumors, perhaps, help minimize the momentum of tumorous genomes in the population as a whole. 


The p53 gene in my tumor biopsies is “positive”. It took me a couple rounds with the doc to establish that “positive”, in this case, means “good”. My p53 is normal and unmutated. Giving the chemo and radiation therapies a better shot.


The chemo and radiation are certainly giving me some shots this week. My entire oral and throat apparatus, from lips to shoulder tops, feels like tag teams of professional wrestlers have been pounding on it with two-by-fours 24/7. I am pretty much exhausted and very uncomfortable full time, and I feed myself liquid goop piped directly into my GIT. My speaking voice is totally degraded—nothing but a drooly and incomprehensible slur. Neither telephone nor in-person dialog is actually possible in any productive fashion. But there’s no sense whining. What needs to be done is being done. I leave you with photos of the radiation treatment machinery [thanks to gorgeous rock star radiation tech Traci for the great photography]:

the custom-sculpted plastic form that holds my tumors in proper position for radiation basting:

and me bolted to the table under the form, about to be dosed:

I really like the contrast of the post-space-age linear accelerator (debuted at GBMC in January 2010, just in time to work out the hardware and software kinks for me) that generates and applies the radiation with unprecedented precision and intensity, vs. the medieval torture look of the rivet-the-patient-in-place positioning form… . 


BONUS THIS WEEK! New material up all around the horn. A couple of archival pieces at http://sustainablebiosperedotnet.blogspot.com/ and http://theresaturtleinmysoup.blogspot.com/, but they’re good ones and they had a limited run the first time years ago. All new spring ecology celebration at http://docviper.livejournal.com/ . Visit any and all that you have a spare moment to check it out. Thanks for all the good wishes. I love each and every one of you, and I’m glad you’re out there in the world. That seems to shift the balance between man and the universe just a smidge in my favor (see nominally related essay at this week’s sustainablebiopshere). I’m grateful and humbled.


Notes


Gene numbers and evolutionary importance of sense of smell, as well as interesting general review, is Sarafoleanu, C.M., M. Georgescu, and C. Perederco 2009. Importance of the olfactory sense in the human behavior and evolution. Journal of Medicine and Life Vol. 2 April – June 2009, pp 196 -198.


General aspects of cancer-as-evolution: Purushotham, A.D. and R. Sullivan 2010. Darwin, medicine and cancer. Annals of Oncology 21:199-203.


Mouse immune-system response to tumor smells: Alves, G.J., L. Vismari, R. Lazzarini, J.L. Merusse, and J. Palermo-Neto 2010. Odor cues from tumor-bearing mice induces autoimmune changes. Behavioral Brain Research 214:357-367, Epub edition June 2010.