11/4/18 The Changing Effectiveness of Insecticides and Cancer Therapies

Bruce and Me

I once got a bad case of Redbugs (chiggers) Well, I under-reported that significantly. I’ve gotten a bad case of them more than once. I’ve gotten them dozens of times, sometimes from head to toe, with thriving colonies in tender places, growing like new subdivisions in good, suburban school districts, the Redbugs looking for favorable home sites on which to build and raise their families. It’s easy to do here in Mississippi. Chiggers and mosquitoes are two things Mississippi scores high in on nationwide rankings. Forty-ninth in poverty, which, thanks to California, means Mississippi is no longer at the bottom. Forty-ninth in education (or fiftieth, depending on who you talk to), based primarily on the amount of money spent per student, which is not necessarily an indication of the quality of education, though Mississippi takes that prize, too, based on standardized test scores. First in Chiggers, somewhere near the top in mosquitoes, considering the number of West Nile Virus cases we have here, none of which is anything to brag about or call attention to unnecessarily. I don’t suppose any Chamber of Commerce brochure preparing presentations for potential industrial clients ever described the baleful ranking in education or the prominence of Redbugs.

Establish your business in Mississippi where your children can fail to meet their potential while enjoying and becoming personally acquainted with the State’s uniquely intense biological diversity,” said no Powerpoint presentation ever. Were it not for Eden’s serpent, Chambers of Commerce might win the original, all-time power-prevarication award with their ability to out-spin any political party on any issue, turning negatives into beaming rays of sunshine penetrating the darkest clouds.
Eunice had begun to notice a few cockroaches in her house. She didn’t like that, because I reckon no one in the whole history of the world likes to see cockroaches, or evidence of them, in or around their foodstuffs. The day after hearing clickety-clack footsteps crossing her beautiful hardwood living room floor and looking up to see a cockroach the size of a small Pomeranian eyeing her intently, alternately waving its antennae up and down, side to side, like rapiers in the hands of a rum-soaked, sea-legged pirate, trying to decide, she thought, if she were a meal or the object of romantic intentions, and how it might make its first thrust with those waving rapiers, she made a trip down to the local farm co-op to get some bug spray.

Do you have anything good for roaches?” Eunice asked the clerk.

No, ma’am. Everything we sell is bad for roaches,” replied the clerk, a smart-aleck grin on his face.

Something bad for the roaches is just what I need,” said Eunice. She bought a pint of concentrated Permethrin, a pyrethroid insecticide, on the advice of the clerk, and a small compression sprayer.

This will kill roaches, redbugs, ticks, fleas, ants, bedbugs, earwigs, crickets, scorpions, millipedes, beetles, centipedes, and spiders,” he said. “And you can mix it up at a 5% solution and dip your dogs in it, but DO NOT use it on cats.”

She briefly wondered why cats were off limits, but decided she didn’t care since she didn’t have cats and had she had any, she thought to herself, she detested the roaches more than she might like the cats, particularly the Bluebeard-Bartholomew Roberts roach she could hear walking across the floor. She hurried home, mixed it up in the recommended concentration, and emptying all the cabinets, stripping the sheets from the mattresses and the cushions from the furniture, sprayed her whole house down, drenching it in enough permethrin to kill entire planets of roaches and several million cats.
In a couple of days, she saw no live roaches, only dead ones. She was clear of roaches for a whole two months before she saw a roach or two, deciding it was time to spray again. She mixed up a new batch of permethrin and sprayed away, satisfied to herself that a once a month spraying would keep her house free and clear of all sorts of bugs. She was proud of her good sense, and of her thriftiness, since doing it herself was a lot cheaper than calling a pest control service.

A couple of weeks later, Eunice noticed that she was seeing more roaches than she thought she had a right to. She mixed up her monthly batch of permethrin half-a-month early and sprayed away. “That’ll get them good,” she said to herself. “A double dose.”

Two weeks later, as fresh roach eggs hatched out, she was again overrun with roaches. She sprayed weekly. She sprayed every other day. She had roaches everywhere and no clue of what to do. She had more roaches than she had ever seen before. It’s as if the planet’s worth she had killed had been replaced by a whole galaxy of roaches, a few of them passing Pomeranian sized and looking somewhat Fox-Terrierish to her way of thinking. You didn’t just hear them walk about; they marched in unison like a platoon of soldiers at first, then a company, then a battalion, soon like a regiment with drum and bugle corps and bagpipes, or at least she dreamed of them that way. She was lost in terror and called up Bubba’s Home Pest Control Service. Bubba, somewhat cockroachish himself she later decided, promised to come right on out.

Pyrethroids are powerful modern insecticides with a short half-life, meaning that they break down into far less toxic compounds in a short time They affect the neurotransmitters of insects. They confuse the electro-chemical signals that go from the brain to organs, muscles, and exoskeleton attachments paralyzing and killing the insect. Bad neuro-transmitters means that every body part can be fully functional, but the control system has failed, meaning that while the parts themselves are not damaged, they no longer do what they’re supposed to do, getting mixed signals, or no signals at all. If your neurotransmitters get confused enough to signal your diaphram to push instead of pull, well, about the time you recognize something is wrong, you take your final, permanent sleep. It’s the same with a cockroach.

Older insecticides like Chlordane, Dieldrin, Aldrin, and Lindane, and even more modern ones like Diazinon and Dursban have been removed from the market because they tend to hang around killing stuff for a long time. Chlordane put down a hundred years ago is still highly toxic and likely still killing termites and poisoning anything else that comes into contact with it in the soil, freely furnishing a whole host of maladies for insects and for the human inhabitants of homes where it was used inside a house to kill pests. It was a mite stronger than the job called for, but it sure kept a home bug-free if you could stand it, which, unfortunately, you likely couldn’t. Whole homes have been torn down and the top layers of soil have been expensively carted off to hazardous waste dumps because of Chlordane contamination.

Insecticides are peculiar, persistent things, though not nearly so peculiar or persistent as insects. Eunice’s first spraying of permethrin had killed all the roaches in her house except a single male and two females. With a total of three roaches in her house, it was easy to miss them, making her think she had eliminated them all. The roaches the permethrin didn’t kill were very sick, though, and would soon die except for one of the females, who recovered quite nicely except she now walked somewhat sideways like a crab since one of her neurotransmitters did not signal quite like it should. But before they died, they all managed to reproduce.

The ill-but-ardent Lothario of a male was biologically driven to share his genetic information as much as he could, but he only got two chances: The female who later died as a result of her permethrin exposure, and the one who survived with a bad gait. With two batches of permethrin-exposed roach eggs sequestered in out-of the way places, it wouldn’t be long before the new broods hatched out.

The baby roaches of the mother roach who died soon died themselves, long before they reached sexual maturity and were able to reproduce. The residual permethrin was still toxic to them. The baby roaches of the mother roach who survived, though she was now able to occupy a handicapped parking spot in any shopping center, were a different matter.
Somewhere on some chromosome, a gene that facilitated neurotransmitter production had its RNA sequence slightly altered, slightly changing the DNA of the roach. Let’s make up a genetic location and call it Gene 23q on Chromosome 14. C14G23q, based on having been exposed to permethrin, had resulted in a mutation which caused the roaches displaying that genetic mutation to have no permethrin-caused neurotransmitter disruption, though they likely found the permethrin distasteful and offensive to their senses. As these roaches grew to maturity, they also transferred this mutated gene to their offspring.

For a few generations, there weren’t enough roaches in Eunice’s house for her to get a good look at them making her think she still had them under control, but it didn’t take many generations of permethrin-resistant roaches to overwhelm her. After a few generations, the permethrin resistant roaches even began to like the taste and smell of permethrin, since having grown up with it, that’s how they thought things were supposed to taste and smell. In a way, to those roaches, it was perhaps like the taste of ripe black olives: a mature taste, not one particularly enjoyed by youngsters, though I daresay if youngsters were fed nothing but black olives, they would enjoy them pretty much.
Bubba used a different insecticide than permethrin, since he had asked Eunice what she had been using. The new insecticide was very effective and though Eunice at first thought Bubba had a certain cockroachiness about him which later morphed into her thinking he was more like a slug, she admired his ability to get rid of her roaches. Being a pro, Bubba had access to some insecticides that Eunice didn’t, and he knew to alternate insecticides on a regular basis to prevent genetic immunity mutations. Bubba didn’t know anything about genetics other than by instinct. He had felt the call of nature to pass his own genetic material to Eunice, though that same call of nature had warned Eunice, through some pheromonal signal, that Bubba had no genetic material that was of any interest to her. It took her several tries to make that clear to him. After he finally understood, he just focused on keeping her home roach free, which was a relief to Eunice. He was quite good at it, too. He never wondered or even gave a passing thought as to why alternating insecticides that work by different methods were required in his business, he just knew by training that that was what he was supposed to do.

Scientists must develop new insecticides all the time: those that will kill the pests without killing anything else that my come into contact with them, in the way that permethrin is fatal to cats. Apparently the manufacturers, users, and the Environmental Protection Agency are willing to risk the danger to the cats for the benefits of the permethrin. If you are a cat lover, keep permethrin out of your house and train your cats to catch cockroaches. This will work out for everyone.

Now, for something completely different, almost.

I had posted the following on Facebook:

I have five good things to report about my trip to Houston and the Big-as-Texas Cancer Center (BATCC)

1. My lovely wife went with me.
2. The great joy of re-uniting after 35 years with old-friend, fellow musician, and fellow cancer survivor Donald Thrailkill (Bruce), who wisely insisted on coming to see me at the hotel and accompanying me to my appointment, for which I am truly thankful.
3. The poignant and powerful brief time Bruce and I were able to visit and share similar experiences with, and listen to, a gentleman from Houston who is dealing with the fear and uncertainty of multiple cancers. (It is beyond remarkable what one cancer patient will tell another).
4. The plans my excellent caregivers at BATCC are making on my behalf.
5. The weather is much better today.

Exhausted now, and headed home.

There is something that should be conspicuous by its absence.
I did not get good news and will require full blown treatment again as I am entering a new phase of this CLL of mine.
Phase 1: Diagnosis
Phase 2: Watch and Wait for progression
Phase 3: Progression and Treatment
Phase 4: Remission for five years (in CLL patients, since there is no real remission, but a status called no detectable residual disease, meaning that ii is still there, but their instruments are not sensitive enough to see it.)
Phase 5: Failure of Remission and return of symptoms
Phase 6: Clinical Trial participation with the drug ruxolitinib
Phase 7: Three years of little or no progression or symptoms because of the ruxolitinib, or perhaps in spite of it…no one knows for sure, though it certainly seemed to give me much of my life back for which I am truly thankful.
Phase 8: Failure of ruxolitinib and rapid progression
Phase 9: New treatment regimen yet to be decided

I suppose one only gets so many phases until there aren’t any left, but no one knows when that might occur. For all any of us may have known, there could have been an abrupt halt after phase 2, with Phase 3 saying “Sudden demise by auto accident rendered the need for further CLL monitoring and treatment unnecessary”)

Much like Eunice’s cockroaches, something in their genetics has changed that has made my CLL cells ignore the JAK-7 enzyme-attacking ruxolitinib. JAK-7 is an inflammation producing enzyme that appears on the surface of several types of cells, including CLL cells. The inflammation causing enzyme is thought to make significant contributions to CLL symptoms even to those with few detectable CLL cells. It worked for a while in me. It worked for three years, one year longer than the trial was supposed to last. Gooday at BATCC thought I was one of the ones who had been having a positive response at the root of the disease, and perhaps I did for a while. But something changed. What changed was not the ruxolitinib, but the JAK-7 bearing cells. The cells in our body are alive: not as cogent, sentient beings, but alive in the sense that they have cellular respiration (convert fuel into energy), they react to a stimulus, they grow, and they reproduce, which are four of the five things required to define life. Cancer is a funny thing, though. The cancerous cells are alive enough that they want to survive despite anything toxic thrown at them, yet eventually their survival ultimately results in the death of their host, which in turn causes their demise. It is an ugly scenario.

While I was reluctant and disappointed to give up on the ruxolitinib, Gooday was adamant.

“It’s not helping you anymore, and based on the rate of growth of your CLL cells, you need real treatment. You are even displaying some of the undesirable side effects of the drug after having lost its benefits. Off the ruxolitinib you go,” he said.

I was not happy. I am still not happy, but it was I who noticed that the ruxolitinib had become ineffective, and I had prepared a list of my symptoms so that I wouldn’t forget and leave anything off. It’s so easy to forget to ask your physician things that are important to you, and so easy to remember them as soon as he is beyond your reach. Always make a list. Always bring it with you. Always have it ready to hand when the doctor comes in. Always go over every item on the list. You and your physician will both benefit from this.

The ruxolitinib had served me well for three years. Most of those who started on the trial were off it now. I was one of the lucky ones. A few, even luckier, are still benefiting from the drug. Unfortunately, I am no longer among their number.
Much like Eunice’s cockroaches, I have a morphed (however slight) colony of CLL cells, now unaffected by the drug which once effectively targeted them. If doctors could figure out how to stop this, then all cancer treatments that start out effective would stay that way. Just like new insecticides have to be invented all the time, since insects are remarkably adaptable, new medicines have to be invented since cancer cells are even more adaptable.

The immunotherapies and targeted gene therapies being developed are starting to be developed exponentially faster. There are now hundreds of “biologicals” on the market with thousands more just around the corner. It is an exciting time for cancer researchers as these targeted immunotherapy drugs are all better than the chemotherapies of old, and when I say old, I mean therapies that were current within the last decade.

The chemotherapies were designed to target fast-growing cells, which meant that they may damage fast growing cells of any type, thus the bald-headness and continuous mouth and throat sores of those in chemotherapy, since the cells in your hair and mucous membranes are among the fastest growing cells in your body. Ever burnt your tongue and lip with a bite of a too-hot piece of pizza? Ever notice how the burn is nearly gone the next day? See what I mean? If you burn your finger, it takes days or weeks to heal, yet burn your tongue and it’s nearly healed up within 24 hours.

Some chemotherapies were like Chlordane. They’ll likely kill the cancer but are so toxic the patient may not survive the treatment. Some patients died from their cancer. Some survived the cancer only to be killed by the treatment. It is a risky business. The very thing they hoped to cure them killed them. Well, they eventually got rid of their cancer but only in a most undesirable way. Who wants that?

I have some permethrin. It kills roaches and redbugs. I wonder if it will kill CLL cells? Or, will it just make them angry? I better leave it to Gooday and his able crews to decide on the best treatment. Nurse Alice mentioned a phase 3 clinical trial with a new drug that has a name I cannot recall to which patients were having extremely good responses. There is one slot left on this trial and I am hoping to get on it. If for any reason I cannot, I will likely be treated with ibrutinib (Imbruvica), which is an effective immunotherapy agent, already tested and available on the market. Many are having great success with ibrutinib after having failed to achieve remission or responses with other drugs.

I am not asking for condolences or sympathy, but I do sincerely appreciate your thoughts and prayers. Things are what they are. I have survived with this disease for ten years now, I am simply entering into a new phase, phase 9. Phase 10 could be complete cure. Phase 10 could be adverse reaction to new treatment resulting in demise of the patient. Phase 10 could be complete and ultimate deliverance from CLL by completely unrelated but undesirable methods. Phase 10 could be a mysterious spontaneous combustion. No one knows.

The one thing I do know is that while the news I got was not unexpected, it was still disappointing. There’s lots of disappointments in life. Some people start out disappointed and end that way. The lucky ones of us just experience a few disappointments along the trail and get on with the rest of our lives. Every road has a few potholes. Sometimes we don’t see them in time. Sometimes we see them and still hit them.

Sometimes, cats get sprayed with permethrin, too.

I’m glad I’m not a cat.

I’m glad that Bubba is not treating me. Gooday and Hemopsaien are treating me, though, like Bubba, they have to employ different methods from time to time else the cockroaches get out of hand.

And…If you did not think there was any connection between cockroaches and CLL, you were mistaken.

Everything is connected.

At least I don’t have a case of the Redbugs.

©2018 Mississippi Chris Sharp

3 thoughts on “11/4/18 The Changing Effectiveness of Insecticides and Cancer Therapies

  1. Oh, dear friend, beautifully written, as ever.  All I don’t want is to see you suffer in any way.  I am hoping the treatment is swift and all of those nasty cockroaches swimming around inside you will soon take their leave for good.  Meanwhile, your friends are here and love you fiercely. Talk soon, deb

    Like

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