I got my introduction to Cancer at an early age, call it six, when visiting nurses came to tend to my maternal grandfather. Bill Gosselin, in his fifties then, had been a hard-living character, a bar owner, a competitor who raised and raced whippets, a no-holds-barred extrovert who drank and smoked with reckless abandon and feared nothing. One of my foremost jobs in early life was to sit in the back of my grandmother’s Chevrolet on certain nights and hold my grandfather’s hat while his employees poured him into the car, an occupation I became quite adept at. None of his excesses troubled me because they were all just a part of “grandpa,” an exciting man who doted on me, took me everywhere and carefully explained to me what he considered the important things in life, like friendship, business, women and baseball. I took in all this information as if came down from the Hand of God; if grandpa said it, it must be so. I still think he got most of it right.
When the nurses arrived, they removed gauze and tape from the gaping hole, bigger than a silver dollar, in the side of his neck, allowing the distinct odor of cancerous flesh to burst into the room. Then, they cleaned the affected area and rebandaged. All the while, Bill Gosselin sat calmly, more than once looking right at me and warning, “Billy---I got this thing from smoking Camels. Don’t ever smoke cigarettes or the same thing might happen to you.” That image is etched in stone. I never smoked a cigarette. Nobody argued with grandpa.
In a matter of months, Bill Gosselin died at Massachusetts General Hospital in Boston. I saw him one more time when my grandmother led me up to his casket, surrounded by flowers in her living room. He looked untypically still, as if someone had made off with the real Bill Gosselin and left us a mere shell of the man. If Cancer could take down a titan of this magnitude, what could it do to mortal men? And what if it took more than just cigarette abstinence to escape it?
Throughout the chess game of life, Cancer has proved a devious opponent, often requiring heroic measures to keep your queen intact. You close one door, Cancer opens another. You zig, Cancer zags. You watch in horror as one friend after another is hemmed in, ultimately checkmated by the clever adversary. Pamme Brewer dies at an early aged of uterine Cancer. Betsy Harper falls prey to Melanoma. Marilyn Todd is routed by Glioblastoma. And sooner or later, it’s your turn.
“Please Allow Me To Introduce Myself….”
From the age of 55 on, I have made a point of annual physical exams with Dr. James DeStephens in Gainesville, prior to which seven or eight tubes of blood are taken and assayed, lipid profiles are examined, Homocysteine, CRP and Testosterone are monitored and a physical exam is administered. If you can get wise to this Cancer business just as soon as it arrives at the depot, you might be able to handcuff the monster, stuff it in a squad car and haul it off to the pokey. For example, a PSA (Prostate Specific Antigen) Test will provide you with a number suggesting how conditions are in the netherlands, not Holland, but your very own personal darker regions. Because that devilish little prostate occasionally likes to play silly games with the numbers, however, a digital rectal exam is also advised. In my mid-sixties, my PSA numbers were sterling, but my should-be-smooth interior felt “a little rough,” according to Dr. D., who recommended a urologist. Cancer was a probability, I realized. The battle was on.
I visited Dr. Jack Paulk in Ocala, the dean of Marion County urologists, a gruff, no-bullshit practitioner and part-time cattle rancher. A biopsy established that I did not yet have prostate Cancer but rather a condition called Prostatic Intraepithelial Neoplasia (PIN), which inevitably led down the dusty trail to P. C. I asked Dr. Jack what we could do to head it off at the pass. Not much, he opined. “We usually just wait til it gets here, then radiate it or cut it out,” he admitted.
I am not much for the inevitably of unfortunate events, so I sought succor elsewhere. The University of Tennessee was conducting a study to determine the effectiveness of a promising breast Cancer drug called Toremefene against prostate Cancer. According to the information dispensed to candidates, Toremefene’s side-effects included an occasional blood clot here and there, but who’s going to worry about an enemy 500 miles away when the Huns are at the door? I am generally not one to suspect collusion but I do think Cancer and Heart Disease are on speaking terms and occasionally will set up some poor sap for an assault from behind. In this case, that sap would be me, victimized by a serious blockage in the left anterior descending artery. I was busy setting a bear trap when the lion attacked from the underbrush and left me in the hospital for four days. I hate it when that happens.
Deprived of my wonder drug, I succumbed to prostate Cancer after three years. I had the wounded little organ removed at Shands Hospital by Dr. Li-Ming Su and his trusty Da Vinci robot, Vito. Fortunately for me, it was encapsulated and I had no further trouble, but the experience made me even more wary of the Big ‘C’. I am encouraged by the fact that neither of my two sisters, Alice and Kathy, ages 76 and 66, has been invaded as yet even though Alice smoked her lungs out as a teenager, but I am not taking anything for granted. I know the ogre is out there prowling the streets, snagging the occasional sucker who wanders too far into the shadows, injecting him with deadly venom and laughing off into the night. I am ready with my weapons of mass diversion---a healthy diet, exercise, regular exams and an abundance of optimism---to keep the Beast at bay. And now, from far across the planet, an ally appears in the tiny confines of Israel, bringing hope.
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| Drs. Hanan Itzhaki and Ilan Morad in formal wear. |
“We believe we will offer in a year’s time a complete cure for cancer. Our cancer cure will be effective from day one, will last a duration of a few weeks and will have no or minimal side-effects at a much lower cost than most other treatments on the market. Our solution will be both genetic and personal.”---Dan Aridor, Accelerated Evolution Biotechnologies Ltd.
Holy mackerel, Sapphire! Who IS this masked man who rides into our lives on a silver horse and promises deliverance from Evil? Is this a pipe dream? Doesn’t he realize that an estimated 18.1 million new cases are diagnosed worldwide each year? Every sixth death in the world is due to Cancer, a steadying consideration. But Aridor, chairman of the board of AEBi, and his faithful Israeli companion Dr. Ilan Morad, say their treatment---which they call MuTaTo (multi-target toxin)---is on the scale of a cancer antibiotic, a disruption technology of the highest order.
This game-changer is based on SoAP technology, which belongs to the phage display group of technologies. It involves the introduction of DNA coding for a protein, such as an antibody, into a bacteriophage---a virus that infects bacteria. That protein is then displayed on the surface of the phage. Researchers can use these protein-displaying phages to screen for interactions with other proteins, DNA sequences and small molecules.
In 2018, a team of scientists won the Nobel Prize for their work on phage display in the directed evolution of new proteins, in particular for the production of antibody therapeutics. AEBi is doing something similar but with peptides, compounds of two or more amino acids linked in a chain. According to Morad, peptides have several advantages over antibodies, including their smaller size and price and the fact that they are easier to produce and regulate. When the company first started, Morad said “We were doing what everyone else was doing, trying to discover individual novel peptides for specific cancers.” But shortly thereafter, Morad and his colleague, Dr. Hanan Itzhaki, decided they wanted to do something bigger.
So, Listen---Here’s My PLAN….
To get started, Morad said his group had to identify why other Cancer-killing drugs and treatments didn’t work or eventually failed. They found a way to counter that effect. For starters, most anti-cancer drugs attack a specific target on or in the Cancer cell. Inhibiting the target usually affects a physiological pathway that promotes Cancer. Mutations in the targets---or downstream in their physiological pathways---could make the targets not relevant to the Cancer nature of the cell and hence, the drug attacking it is rendered ineffective.
In contrast, MuTaTo (“you say MuTaTo, I say MoTahTo”) consists of using a combination of several Cancer-targeting peptides for each Cancer cell at the same time, combined with a strong peptide toxin that would kill Cancer cells specifically. By using at least three targeting peptides on the same structure with a strong toxin, Morad “made sure that the treatment will not be affected by mutations. Cancer cells can mutate in such a way that targeted receptors are dropped by the Cancer. The probability of having multiple mutations that would modify all targeted receptors simultaneously decreases dramatically with the number of targets used. Instead of attacking receptors one at a time, we attack receptors three at a time. Not even Cancer can mutate three receptors at the same time.”
“We used to give AIDS patients several drugs, but we would administer them one at a time,” Morad explained. “During the course of treatment, the virus mutated and the AIDS started attacking again. Only when patients started using a cocktail were they able to stop the disease.” Now, he said, people with AIDS are HIV carriers but they are not sick anymore.
Many Cancer cells activate detoxification mechanisms when in stress from drugs. The cells pump out the drugs or modify them to be non-functional. Morad says detoxification takes time, however. When the toxin is strong, it has a high probability of killing the Cancer before detoxification occurs, which is what he is banking on.
Many cytotoxic anticancer treatments aim at fast-growing cells, but Cancer stem cells are not fast-growing and they can escape these treatments. Then, when the treatment is over, they can generate Cancer again. “If it does not completely annihilate the Cancer, the remaining cells can start to get mutations again, The Cancer comes back, but this time it is drug-resistant,” Morad says.
He explains that because Cancer cells are born out of mutations that occur in Cancer stem cells, most of the overexpressed proteins which are targeted on the Cancer cell exist in the Cancer stem cells. MuTaTo’s multiple-target attack assures they will be destroyed as well.
Finally, some Cancer tumors erect shields which create access problems to large molecules such as antibodies. MuTaTo acts like an octopus or a piece of spaghetti and can sneak into places where other large molecules cannot reach. Morad claims the peptide parts of MuTaTo are very small (12 amino acids long) and lack a rigid structure. “This should make the whole molecule non-immunogenic in most cases and would enable repeated administration of the drug.”
The MuTaTo Cancer treatments will eventually be personalized. Each patient will provide a piece of his biopsy to the lab, which would then analyze it to know which receptors are overexpressed. The individual would then be administered exactly the molecule cocktail needed to cure his disease. However, unlike in the case of AIDS where patients must take the cocktail throughout their lives, in the case of MuTaTo the cells would be killed and the patient could likely stop the treatment after only a few weeks.
The company is now writing patents on specific peptides, which will be a large bank of targeting toxin peptides wholly owned and hard to break, said Aridor. Morad claims that so far the company has concluded its first exploratory mouse experiment, which inhibited human Cancer cell growth and had no effect whatsoever on healthy mouse cells, in addition to several in-vitro trials. AEBi is on the cusp of beginning a round of clinical trials which could be completed within a few years and would make the treatment available in specific cases. The principals are extremely optimistic. “Our results are consistent and repeatable,” Aridor beams.
Not everyone has such a rosy outlook, but that’s to be expected. Bobby Fulton was ridiculed for his steamboat, the University of Florida laughed off the possibility of profits from Dr. Cade’s Gatorade and little Frankie Epperson’s friends hooted at his knee-slapping invention, the Popsicle. Who’s laughing now? Among the chief reasons for doubt about the project by Israeli scientists is the disinclination by Aridor’s team to publish results of their research in medical journals.
“We can’t afford it,” says Morad. “If we were a big company with a lot of funds, that would be the first thing we would do. If I have $100,000, what do I spend it on? We want to focus on advancing the research and developing more targeting peptides. It takes a lot of work and we are a small company. What would you do if you had to choose?”
The results of the pre-clinical trials were “very good,” according to Morad. “The trials proved that the molecules have the ability to kill Cancer cells, targeting only them and not other healthy cells. The effect is specific to the Cancer cells, leaving out other non-cancer cells, so the side effects will be much less. It will have side effects at the level of ibuprofen or a common aspirin.”
We’re rooting for you Dan, Ilan and Hanan. Hopefully, there will be no foot-dragging because we’re beginning to wilt out here in the colonies. All of your friends here in Pieland would like to be put on the list for free samples whenever you get around to it. We’ll send you a few shekels when we get a little ahead and we’re beaming positive thoughts to you 24/7. I’m sure in a couple of years we’ll all be laughing like crazy at the silly notion of dying from Cancer.
And to our readers---NO, this does not mean you can go back to smoking.
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| A little touch of smart-alec New England humor. |
Some of you will remember John Beresford Tipton, the secretive money-man from the old CBS television show, The Millionaire. Some old geezers have expansive electric train collections, which they operate decked out in engineers’ hats and overalls, others raise red-lipped batfish for fun and profit. JBT liked to give money away to needy beneficiaries, the only caveat being they could not tell anyone about the gift. Well, I’m here to tell you John Beresford Tipton lives today. Otherwise, how to explain my sister, Kathleen Scanlon’s good fortune in receiving an all-expenses-paid trip from Massachusetts to Atlanta for the super-costly Super Bowl between the New England Patriots and the Los Angeles Rams? And on the Patriots plane, no less. Kathy and her husband, John, got on the giant aircraft outside Foxboro at six on the morning of the contest, zipped off to the game and attending revelry and returned sometime before dawn. “An indescribable whirlwind,” she called it, the icing on the cake being a 13-3 Patriots victory.
The Scanlons are not wealthy, anything but. Like most people, they live week-to-week modestly, eschewing fripperies and glamour. Ah, but that’s just the kind of candidate John Beresford is looking for. Who knows, you could be next, assuming, of course that you live somewhere near Boston and are not foolish enough to be a New York Jets fan. Even John Beresford Tipton has his limits.
That’s all, folks. Finally.
bill.killeen094@gmail.com
