“They said it couldn’t be done….they said nobody could do it.”---Ligget & Myers Slogan
When we were kids, there were few absolutes, not many certainties in life. One guarantee, however, was that no one would ever find a cure for polio. The other was that the Red Sox would never win the pennant.
As we negotiated life’s trails, other impossibilities became apparent. The mad bombers of the Irish Republican Army would never make peace with the government of England. The United States would never elect as president an ignorant misogynist with Hitlerian tendencies. Cancer would never fall to the Armies of Medicine. The Berlin Wall would stand forever.
None of these were as impossible, however, as the likelihood that our old pal, Michael O’Hara Garcia, the self-styled Lothario of Gainesville, would some day not have a date. MOG would prowl the streets of town in his spiffy Silver Phaeton, shooting arrows at young ladies on the sidewalks until one fell. His eventual success was inevitable, as much a guarantee as the sun setting each day in the West. When, on one rainy day, this failed to happen, we were seized with amazement. If Garcia could be defeated in his Quest, anything might happen. And pretty much anything has. About the only thing we can still be certain of is that no one will ever shoot an automobile into space and send it off to Mars. All other impossibilities are fair game.
Tales Of Long Ago
I was named after my maternal grandfather, Bill Gosselin, a formidable man easily met, a fellow fond of conversation, racing dogs and alcoholic spirits. The fact that Bill Gosselin was an absolutely confident and fearless character is easily proven when one considers that he voluntarily married my grandmother, Celia, then known as Alphonsine. There are many ways of describing Celia. “Not especially cuddly” would be one of the kindest.
Bill opened a neighborhood bar on Union Street in South Lawrence. He named it The Whippet Club and painted a couple of the dogs on his green-and-cream windows. The tavern did well, which was not a great miracle in South Lawrence, where 101% of the population was known to bend an elbow. At five years old, I often got to sit at the bar, where the patrons posed me baseball questions. “Ask him anything,” my proud grandfather would announce, and they did. The MLB standings. The batting averages of the entire Red Sox roster. The starting lineup of the St. Louis Browns. I knew it all, and I had to. Not everybody earned a seat at Bill Gosselin’s bar.
Perhaps it was his lung cancer or maybe just his innate joie de vivre, but my grandfather drank more than his share. When my grandmother showed up to pour him into the car at closing time, my job was to sit in the back seat and hold his hat. By the time I was six, he was in bad shape, restricted to the house and visited by traveling nurses daily. I watched as they cleaned a foul-smelling silver dollar-sized opening in the side of his neck, then bandaged it back up. More than once, he fixed his eyes on me and warned, “I got this from Camel cigarettes, Billy. Don’t ever smoke.” That image was etched into my brain. I never touched the stuff. In those days, practically everyone equated cancer with death. You got it, you died. A diagnosis was grounds for jumping in the river or high-diving from a tall building. Fortunately for the citizens walking below, suicide was a mortal sin, the last thing you want to commit when the Silver Elevator is on the way.
The Cancer Vaccine
For years, Cancer has been The Last Holdout, the machine-gunner in the world’s Alamo, holding off Santa Ana’s vast armies and anything else that was thrown at it, including kazillions of dollars in research grants. Decades ago, scientists were “on the edge” of success. They’re still out there, carving holes in its defenses but not getting all the way through. Until, it seems, perhaps now. Could this be the day Michael Garcia doesn’t get a date? Dr. Ronald Levy is cautiously optimistic.
A new cancer treatment at Stanford University using immune-stimulators to target tumors in mice is having shocking results. After injecting a combination of two immune boosters directly into solid mouse tumors, Levy’s research team stated the vaccination eliminated ALL traces of the specifically targeted tumor from the animal’s entire body, including metastases that were previously untreated.
“When we use these two agents together, we see the elimination of tumors all over the body,” Levy told the Stanford Medicine News Center. “This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”
One of the two immune agents used in Levy’s study, published in the journal Science Translational Medicine, has already been approved for use in humans and the second is currently involved in a lymphoma treatment trial.
The study explained that when an immune system detects cancer cells in the body, its T-cells attack the tumor. Over time, however, the tumor devises ways to overpower the immune cells and continues to grow. In Levy’s experiment, the cancer-fighting T-cells from the immune system were rejuvenated when a microgram of the two immune boosters was injected into a mouse’s lymphoma tumor. Those same cells then moved on from the tumor they destroyed to locate any other identical cancers in the body. The T-cells did not move on to a colon cancer tumor also found in the animal, however. Okay, so nobody’s perfect, right?
“This is a very targeted approach,” Dr. Levy declares. Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T-cells are recognizing.” Good enough for me, Doc.
The experiment was replicated in 90 other mice and was successful in 87 of them, allowing the researchers to declare them cancer-free. The cancer did recur in three of the animals but the tumors later regressed after another round of immune treatments. The study was also successful in mice that had breast, colon and melanoma tumors. “I don’t think there’s a limit to the type of tumor we could potentially treat,” Levy said, “as long as it has been infiltrated by the immune system.”
Alzheimer’s Advances
If the right one don’t get you, then the left one will”---Tennessee Ernie Ford
It’s all just fine to successfully navigate the Straits of Cancer and other dangerous facsimiles, but what good does it do you if you can’t remember your way home? Alzheimer’s Disease is rampant across the land and there’s scarcely a one of us without a relative or close friend tainted by the blight, a dreary and hopeless progression which starts with the loss of a few names, progresses to an inability for self-care, evolves into calling the cops to report Martians have landed in the parking lot and winds up with the afflicted sitting in a chair, staring out into space as if he had just tried to read Pynchon’s Gravity’s Rainbow. Talk about a no-fun antagonist. Alzheimer’s is the Antichrist. Researchers have not been particularly optimistic about a cure. And Mighty Mouse, usually a dependable rescuer, apparently has business elsewhere. What to do? Where is the White Knight galloping to the rescue?
Enter Dave Schubert of the Salk Cellular Neurobiology Laboratory and his faithful companion, experimental drug J147, not only an elixir for Alzheimer’s but a reverser of aging in mice. (Which could explain the Mighty Mouse absence; perhaps he’s been reversed back to pre-school, or worse.)
In a paper published on January 7th in the cheerily-named journal Aging Cell, Schubert’s group reports that J147 binds to a protein found in the mitochondria, the energy-generating powerhouse of cells, making aging cells appear more youthful. “This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s.” says Schubert. His group originally developed the drug in 2011, after screening for compounds from plants with an ability to reverse the cellular and molecular signs of aging in the brain. J147 is a modified version of a molecule found in the curry spice curcumin. In the years since, researchers have shown the compound reverses memory deficits, potentiates the production of new brain cells and slows or reverses Alzheimer’s progression in mice. At the time, they still didn’t know how the drug worked at the molecular level.
In the latest findings, led by Schubert and Salk Research Associate Josh Goldberg, the team used several approaches to home in on what, exactly, J147 is doing. They identified the molecular target of the drug as a mitochondrial protein called ATP synthase that helps generate ATP within mitochondria. They illustrated that by manipulating its activity, they could protect neuronal cells from multiple toxicities associated with the aging brain. Moreover, ATP synthase has already been shown to control aging in C. elegans worms and flies.
“We know that age is the single greatest contributing factor to Alzheimer’s, so it’s not surprising that we found a drug target that’s also been implicated in aging,” says Goldberg. Schubert adds, “I was very surprised when we started doing experiments with how big of an effect we saw. We can give this to old mice and it really elicits profound changes to make these mice younger at a cellular and molecular level. People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke, but it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.”
Changing Pace
While most treatments for Alzheimer’s focus on improving memory, researchers at Ohio State University’s Wexner Medical Center have a different notion. They want to slow down the decline of problem-solving and decision-making skills with a newfangled brain pacemaker. For the first time ever, researchers surgically implanted thin electrical wires into the frontal lobes of the brains of patients with Alzheimer’s disease to determine whether using the gizmo could improve cognitive, behavioral and functional abilities in patients with this form of dementia. The deep brain stimulation implant is similar to a cardiac pacemaker device, but the wiring is implanted into the brain instead of the heart.
The first study of the pacemaker involved only three people, but all showed improvement. After two years of deep-brain stimulation, LaVonne Moore, 85, of Delaware, Ohio, is able to assemble ingredients and cook a meal, something she was unable to do prior to the treatment. Her husband, Tom, commented, “LaVonne has had Alzheimer’s Disease longer than anybody I know and that sounds negative, but it’s really a positive thing because it shows we’re doing something right.” Next, OSU researchers intend to explore non-surgical methods to stimulate the frontal lobe, a less invasive option.
Alzheimer’s is a neurodegenerative disease, which means it involves damaged and dying neurons. Most Alzheimer’s drugs in development have focused on preventing that damage, but a few researchers are developing treatments to reverse it. In 2017, Dr. Roberta Brinton developed allopregnalone, which seems to spur neurogenesis. Dr. Brinton is now preparing for Phase 2 trials with the drug, which has the potential to become the first regenerative therapy for Alzheimer’s.
The Last Word
Since not all of our readers live in Geezerland, a note of encouragement to those of you with teeth. Many of you would rather attend a rap marathon in Djibouti than visit a dentist, but there’s good news on the dental front. How about No-Drill Tooth Repair? British researchers have announced a novel technique that could make dental fillings obsolete. Their work illustrates that teeth can repair themselves naturally, using stem cells to stimulate the growth of dental tissue. Who knew? Should we sell all our stock in the Implements of Dental Torture industry? Could be.
Scientists at Dental Institute at King’s College London found that small amounts of tideglusib, an Alzheimer’s drug currently in clinical trials, promotes the growth of dentin (that material under the enamel that can repair teeth) and jump-start tooth regeneration. In experimentation with mice---and what would we do without them---researchers soaked a small biodegradable sponge with the drug, then put it in the tooth pulp, where stem cells reside. New dentin began to grow and---voila!---within mere weeks the sponge decomposed and in its place was a perfectly restored tooth. Now, if we could just do something about that name. Nobody wants a miracle drug that sounds like a sticky, if brotherly, detergent.
That’s all, folks….
