Lou Reed died this morning of liver disease. He had a transplant in May, obviously it wasn’t enough. At least Lou went out on a “Sunday Morning”.
Which was one of the best songs on the single best—and most shocking—rock album of all time—Velvet Underground and Nico. For some reason, I can’t remember why now, I had to wait weeks for it to show up at the Sam Goody shop in Willowbrook Mall. Some problem with the Andy Warhol cover, I’m guessing. Anyway. That record was so shocking I couldn’t stop listening to it. Plus, it was good for driving my father out of the living room late at night so I could have it myself.
To this day—and the album came out in 1967, when I was 14—I can list the way it changed my half-baked personality and shaky thought processes. Almost as much of an adolescent life sculptor as sex and drugs…maybe more.
PS—the regular “It Might Get Messy” entry for this week is immediately below. Suggest we all send Laurie Anderson our sympathies. And pull out all the Velvet Underground CDs we own.
About the worst thing that can happen to a human being is venomous snake bite. Whatever the venom’s primary mode of action, incredible tissue destruction always follows a venomous bite (only a half to two thirds of bites by poisonous snakes actually inject venom. The rest are “dry” bites that are not dangerous and have no symptoms other than a little bleeding).
Evolutionary drivers for the conversion of otherwise ordinary and harmless saliva glands to venom factories vary among different varieties of snake. In the mambas and boomslang, African arboreal species, the venom is evolved to act rapidly—probably an adaptation for eating birds, which need to be put down swiftly before they can fly away.
Black mamba in action
One of the first things that happens in a mamba bite is blood thinning. With the blood morphed so it slides through the vessels like a NASCAR machine on steroids, the venom quickly reaches heart, lungs and muscles where other modes-of-action—tissue degradation or respiratory suppression—drop the bird in place before its fight-or-flight hormones can carry it away.
Black mamba fangs on display
In contrast, venoms of viper snakes tend to cause rapid and massive destruction of circulatory system, muscles, and organs. In this is the clue to the evolutionary origins of venom. Of necessity—lacking limbs to hold prey and cutting or tearing teeth to rip it into bite-size pieces—snakes swallow their food whole. And often they swallow food items of enormous size relative to the size of the snake.
Viper eating food bigger than its head
This engenders some physiological problems in an ectothermic (“cold-blooded”) animal. Specifically, digesting a huge meal takes time. So much so that the food item can begin to rot before it is broken down into absorbable (is that a word? Spell checker seems to like it…) molecular fragments. Having a vat of rotting flesh in the gut is problematic. Decomposition microbes can pour out of the food, killing the snake by rotting its gastrointestinal tract. Indeed, in captivity, maintaining digestive health of snakes is a technical issue of importance.
Anyway. Evolutionarily, it seems that venom is primarily an adaptation for feeding, not self-defense. Injecting a fat dose of tissue-destroying toxin into a prey item begins digestion processes even before the food is ingested. Eating is safer and more efficient when venom is involved.
This also means that snake venom is chemically complex. A variety of physiologically active substances, almost all of them proteins, are present in snake venoms. The composition varies from species to species, and even among individuals of the same species. But in general, snake venom is a complicated soup of bioactive chemicals, many acting as enzymes. Some of them tear tissues apart and destroy cells, some control blood clotting and circulation, some affect respiration, muscle tension, and nerve functions.
Why a lecture on snake physiology here at this cancer-themed weblog? Because the chemical complexity of venom gives it enormous pharmacologic potential. That potential is being explored for medicinal purposes—including cancer treatment.
An excellent (although grammatically weak—could’ve used a good technical edit) review of snake venoms in cancer treatment is titled Therapeutic Potential of Snake Venom in Cancer Therapy: Current Perspectives [1]. Chemicals purified from venoms have been shown to bind specifically to tumor cells. Such chemicals may be applied to tag and identify tumors or to carry other, anti-tumor substances to the diseased tissue. Other venom chemicals can re-program cell death into tumor cells that refuse to die as they would normally. Some venom components inhibit tumor cell reproduction, destroy tumor cell membranes, or constrain cell metabolism. Tumor cell adhesion and migration can be inhibited by venom chemicals, preventing tumors from finding susceptible places to settle. In addition, venom compounds provide indirect but useful functions including pain inhibition, inflammation reduction, or enhancement of blood and lymph flow.
So snake venoms may prove to be a valuable pharmacy of cancer-fighting chemicals. Identifying, testing, and applying these chemicals of course takes time, money, and technical expertise. In other words, it’s going to be a long time before the therapeutic potential of venom is realized. Of course, it would be less time if the U.S. government could function without shutdowns interrupting research programs periodically.
In any case, I’m not going to be around long enough to benefit from snake venom pharmaceuticals. But I may be around for a longer time than it seemed just a few months ago. I still have issues with mucous production, throat inflammation, weakness and discomfort, and of course my diet is limited to weird milky medical foods dumped directly to my gut via polyvinyl tubing. But once that whining is out of the way, I’m getting better. This week we drove up to Amherst, Massachusetts where I was (oddly) a guest-of-honor at an awards dinner provided by the Association for Environmental Health and Sciences, the not-for-profit for whom I write a weekly column on environmental sustainability (www.aehsfoundation.org, go to the lower left of the home page to click through to the PeopleSystems column). I had a great time driving the 6 hours each way, listening to music and enjoying being functional. At the conference, I was pretty much exhausted, but had a wonderful evening at the dinner. Many old friends were there, some of whom had made long trips to get there to share the event.
To those friends and to all of you reading this, you have my eternal gratitude and love. I could not have fought me way through the past few years without you. Knowing you are pulling for me, and that only by surviving could I hope to see you again, are powerful motivators. Thank you. Talk to you next week!
Notes
[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627178/
Hagfish are hilarious. I know you never thought of it that way. But National Geographic has a video from the New Zealand Natural History Museum, showing various predatory fish choking on the mouthfuls of slime generated when they grab a hagfish, and it's pretty funny, see
http://video.nationalgeographic.com/video/news/animals-news/new-zealand-hagfish-slime-vin/
When I was in school, we learned that hagfish and lamprey eels made a single class of related organisms, the Petromyzontiformes or jawless fishes. Indeed, hagfish have a bony, rasping, two-part tongue that functions like jaws, used to catch polychaete worms and to tear at deep-sea carrion. Turns out that they are primitively jawless. Until a single 300 million year old fossil was discovered, we thought hagfish had secondarily developed their jawless structure. No, turns out they come that way evolutionarily. They are the only organism known to have a cartilaginous skull and no vertebrae—they are actually invertebrate chordates, like the sea squirts and amphioxus [1]. Hagfish are about as long as your arm, and far more disgusting [2]:
First pic immediately above is of Gene Helfman, with whom I learned ichthyology at UGA, holding up a little hagfish slime. See, that’s the thing about hagfish. Their primary characteristic is the ability to produce bucketloads of proteinaceous slime. It’s possible that mucilage and other animal protein glues might be replaced, if some nutty “natural products” entrepreneur pipes up, by packaged hagfish slime. It would be green and sustainable—hagfish don’t need to eat for months at a time, and over that period can produce enormous amounts of mucous. Although, now that I think of it, such an entrepreneurial endeavor would presumably leave us with large quantities of horse, donkey, dog and cat carcasses to process where they now go into the retorts at Elmer’s glue factories.
Anyway. My primary residual problem at the moment (well, discounting not being able to eat, drink, or talk and having been surgically reconstructed in cosmetically unattractive fashion) is mucous production. The slab of chest muscle and arm epidermis that the surgeons used to separate the airway from the gastrointestinal tract in my oral cavity continues to irritate, and that generates boatloads of slime.
I gather that this problem is expected to go away at some point. I’m not sure what that point is, though. I’m now many months out from the last radiation and chemotherapy treatments. You’d think I’d be healthy by now. But I believe the key issue is the arm skin that they pulled inside to build the partition. Apparently, the hairs that were on my arm are still visible at the surgery site inside. Dr. H says that they couldn’t use muscle alone (without the skin) because the muscle tissue would get too flabby. The epidermis has cellular toughness that helps it hold up in its new role as throat component. Dr. H also says that eventually, the (former) arm skin will transform itself into a supple and effective barrier that will help keep me from chronic pneumonia associated with leakage of liquids down the airway into my bronchi and lungs. But for now, I have to put up with constant production of hagfish-like levels of excess mucous.
At least I can cough it out and into paper towels for disposal. Most people in my condition have to use a mechanical suction apparatus to slurp the stuff out of the bronchi on an ongoing basis. Indeed, last time I left the hospital, I was held up a day while the suction pump was being delivered from the medical supplier. Doctors weren’t comfortable sending me home without the means to suction sloppy gunk out of my airway as needed.
But, in fact, I have never used the suction gear. Coughing seems to work just fine for me. I do, when I travel, make sure I take the (rather heavy and cumbersome) suction kit with me just in case. But hopefully I will avoid the requirement for its use. It’s humiliating enough to be in my condition without the added discomfort of having to slide long rubber cannulae down my throat and into my bronchi and pumping up extracellular excretions.
As always, I thank you for being here for me. Next week I’m going to Amherst to receive the AEHS Lifetime Achievement Award, an honor which I’m more than proud to be awarded. After that, I start cooking for Thanksgiving. Given that I didn’t expect to be alive to see this Thanksgiving, it’s going to be The Best Thanksgiving Ever. Followed by the winter holidays. Which I’m glad to get another shot at as well. My love to you and yours. Talk to you next week!
Notes
[1] http://www.ucmp.berkeley.edu/vertebrates/basalfish/myxini.html
[2] http://www.whaletimes.org/hagfish.htm
Marie Curie was born in Warsaw in 1867. She received multiple degrees from the Sorbonne. Impoverished, she apparently lived on buttered bread and tea during her academic years, and was symptomatically malnourished. She was 29 years old when Henri Becquerel discovered the radioactive nature of uranium salts (he inherited a vial of same from his chemist father).
Curie, her husband Paul, and Becquerel were awarded the Nobel Prize in physics in 1903. In 1911, Curie received a second Nobel, this time solo, in chemistry for her discovery of radium and polonium (the latter named in honor of Poland). As an aside, it is worth noting that Curie’s daughter won the 1935 Nobel for work on the synthesis of radioactive compounds.
Years of working with radioactive materials, and her cavalier attitude to same (she frequently carried a vial of radium in the pocket of her lab coat) did not serve Curie well. She was chronically weak and ill from radiation poisoning. She died at a French health spa of aplastic anemia, caused by a lifetime of radiation exposure.
Radiation exposure has long lasting and severe effects. Tissue damage at the exposure site is intense. The tradeoff in cancer treatment is the destruction of DNA in tumor cells vs. the same (and other impacts) in affected healthy tissues.
In my case, shockingly (at least to me), I am still not fully recovered from the radiation treatment last spring. On the PET scan a few weeks ago, my throat in general took up visible amounts of radiation tagged sugar, indicating the area has yet to return to baseline levels of metabolism. This is problematic because high metabolic rate is also indicative of tumors. We can’t rule out recurrent or residual throat cancer until my throat area is back to baseline metabolism.
I also continue to have an odd problem with my lips. The epidermis sloughs off in slabs, and the skin is chronically thick and rough. This issue is resolving, albeit slowly. For the first few months after treatment, my lips were continually cracked and bleeding. Now they’re more like severely chapped, although the radiation effects are different from standard chapping—the dead epidermis comes in larger and thicker chunks than simple dried skin.
Anyway. I met with my new “Palliative Care” doctor this week. He went over my medications, of which I continue to require a bucketload. Dr. S generally approves my mix of prescribed and over-the-counter medicines. He had some suggestions about balancing my OTCs, but overall is happy with how I’m proceeding.
As am I. I still sleep long hours, am weak enough so that a middling walk (with or without the dog) tires my leg muscles, spend most of my time in a reclining chair, and produce ridiculous quantities of thick, ropey mucous from my throat. The latter in particular is a social difficulty. It’s hard to interact with people if you’re hacking up mouths full of phlegm regularly.
But even that is getting better, I think. My throat still feels funky—I’m not certain how to separate ongoing irritation from the “new normal” of a system that has been surgically rearranged so a slab of muscle and epidermis from my chest and arm nominally partition my airway and gastrointestinal tract. So I don’t function as well as before the cancers and associated treatments. On the other hand, I’m still alive. Which, at this point, is somewhat remarkable and cause for celebration.
Thanks for being here, everyone. My love to you and yours. Talk to you next week!
References
These web portals are sources for the biographical and technical material in this week’s posting:
http://www.cancer.gov/cancertopics/factsheet/Therapy/radiation
http://www.nobelprize.org/nobel_prizes/physics/laureates/1903/marie-curie-bio.html
http://www.nobelprize.org/nobel_prizes/physics/laureates/1903/becquerel-bio.html
It Might Get Messy
All diseases are matters of chance. At the level of fundamental epidemiology, chains of probabilities determine the behavior of diseases in a population. In simple terms, the chance that you’ll encounter the disease organism (or other cause, such as chemical exposure) and the chance that you’ll receive a critical dose (sufficient microbes or molecules to cause illness) define your likelihood of getting sick. Consider two basic examples. Bubonic plague is endemic in ground squirrel populations throughout southwestern U.S. When I walk through a patch of brush pockmarked with ground squirrel burrows, I have a certain chance of encountering plague bacillus (primarily by having a flea leave its squirrel and jump on to me and take a meal), and then a certain chance that the flea will inject enough bacteria cells to trigger the disease. For a second chemical exposure example, when I hike in woods of the Patuxent Preserve, there is a chance I will step near a copperhead snake, and then a chance that the snake will bite me and inject enough venom to make me sick (mostly by digesting the tissues of whatever limb the snake bites).
Similar probabilities pertain to cancer. With this addition: for many cancers, there is a nonzero chance of spontaneous appearance. Otherwise, there is a chance that some environmental exposure (like smoking) will trigger one or more cells to mutate into a tumor, and then a chance that your immune system will fail to deal with it, and then you’re off and running in cancer land.
My cancers—of the tongue, throat, palate, and parotid gland—are classic smoker’s cancers. Except I’ve never smoked. I have, however, abused my oral cavity. Heavy and longstanding consumption of alcoholic beverages, heavy use of alcohol-based mouthwash, and heavy use (from my teens to my 30s) of epinephrine inhalers for asthma could all have contributed to cellular malfunction leading to tumor formation.
Or, it could be that none of the above had a thing to do with it, and that my tumors began with spontaneous mutations of cells in place. According to the American Cancer Society (http://www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer) men in the U.S. have about a 1 in 2 (or 50%) chance of developing serious cancer in their lifetime. Women are about 1 in 3 (33%).
Think of what this means statistically. For a specific environmental exposure to cause an increase in cancer, it occurs in the context of a 33% of developing cancer in any case. The probability is 0.33. For many kinds of risk assessment, USEPA applies a threshold of 1 additional cancer in 10,000 to 1,000,000 exposures as an “acceptable” risk limit. That pushes those additional cancers pretty far out on the probability scale. 1 in 10,000 means a 0.3301 chance, 1in a million is 0.33001. Not much of an increase in the context of overall cancer rates.
Think of this the next time you hear of some food additive, pesticide, or chemical “doubling” or “tripling” cancer rates. In most cases, this means the probabilities increase from 0.3301 to 0.3303, or 0.33001 to 0.33003. These are not big increases. In fact, in epidemiological studies (where actual cancer occurrence, rather than predicted cancer “risk”, is the measure) such “doubling” or “tripling” of cancer rates is likely to be undetectable because of normal statistical variance in the test populations. That is, the 0.33 cancer rate is an average, with statistical variation that might be 10%, 20%, even 100%, of the average. Under these circumstances, detecting increased cancers from use of a chemical like methylethyldeath (MED) in food or cosmetic products is not possible. The putative “doubling” of cancers due to MED is simply an arithmetical artifact of the risk model. It is not something that could be detected even if it occurs, because with a third of people getting serious cancers anyway, doubling or tripling the rate out in the fourth or fifth decimal place is a trivial increase.
Now, you are asking why I am subjecting you to this technical harangue. It is because there are important choices to be made regarding how we manage our environment. The resources of money, time, and technical expertise that can be applied to environmental management are finite. If we choose to spend resources reducing exposure to methylethyldeath, we must take resources away from other environmental management activities. Such as assuring sufficient potable water, air free of breathable particulate pollution, sustainable soil quality, and protection from infectious diseases. Environmental management is a “zero sum game”. There is a finite pot of money on the table, and if MED “wins” some of that money, other players (clean water, clean air, infectious disease) “lose” money.
As a society, human beings must make rational choices when investing in environmental management. Reducing smoking rates and eating a healthy diet both can reduce real-world cancer cases enormously. More than enough to be measurable in epidemiologic studies. And more, in most cases, than MED compounds like alar on apples (remember that?) or nitrates in lunch meat products.
To come back to my case, beverage alcohol is a powerful carcinogen. The probability of cancers additional to baseline are high enough to be easily measured in epidemiology studies. There is a good chance I gave myself cancer by choosing to drink heavily for decades. But there is also a chance I would have contracted these same cancers had I been a teetotaler without chronic mouth infections (the latter explain my heavy use of mouthwash) and without asthma. There is no way to tell—it’s a matter of chance.
Anyway, I am continuing to heal and strengthen. I get in a walk to the point of being tired nearly every day now. Assuming I remain cancer-free and continue to have time to devote to recovery, I may achieve something akin to a decent quality of life.
And, on my walks this week, I got a few decent photos. The first one up—the garter snake eating the enormous toad—entertained me for more than half an hour in the woods. That’s how long it took the snake to immobilize and ingest the toad. And all I could think of while I watched was that the toad was pissed off at himself for making a right instead of a left at the nearby hawthorn bush. Because that left would have reduced his chances of running into the garter snake!
Photos follow. I thank you all most deeply for being here. I can’t emphasize enough how important you have been for my war with cancers. Pat yourselves on the back and have a glass of good wine……
