Inflammaging

Almost every death of a person I know in my age cohort is attributable to cancer.

The following hypothesis has previously made sense: medicine has advanced to such an extent that fewer people are dying of heart attacks, strokes, or sudden trauma; chronic diseases are far more difficult to treat, hence there are more deaths from cancer. However, the aforementioned is only a partial explanation; researchers have discovered that aging immune systems are less able to fight off cancer. [bold added]

(Image from Science Direct)

...studies of individual immune cells in human lung tumors, as well as in old mice, have revealed how chronic, or pathogenic, inflammation in older people—dubbed inflammaging—interferes with the immune system and fuels cancer growth...

Inflammation is the immune system’s reaction to a threat. Immune cells circulate in the body, attacking invaders such as viruses and cancer and calling for backup—more immune cells—when necessary. Working correctly, they can beat back Covid-19 or heal a cut on the finger. But the immune system can also overreact, fueling inflammation that gets in the way of healing or leads to disease. It misfires like this more as people age....

Often the assumption is that older people get sick more easily because their immune systems weaken, says Dr. Thomas Marron, a thoracic medical oncologist who heads the early-phase trials unit at Mount Sinai’s Tisch Cancer Institute. That does happen, he says, but at the same time, “we really are seeing this sort of hyperactivation.”

“The body is just basically like a flower bed primed to grow cancer as you get older,” he says.

As a person ages, the immune system has to work harder to kill infections or mutations, like cancer. But the immune system itself is aging and produces fewer of the type of immune cell that targets and kills cancer cells. At the same time, it makes more of a type of immune cell that responds initially to infections. Known as myeloid cells, with aging they become more inclined to overreact and create inflammaging. These inflammatory cells may provide a “hit” necessary for older cells with mutations to turn cancerous, says [Dr. Miriam] Merad of Mount Sinai.

Combatting defective immunity systems is only of several approaches that are being explored in the race to cure cancer. 54 years after Richard Nixon announced a War on Cancer the path to an eventual victory no longer appears to be impossible.

Giving Thanks for President Biden

When then-candidate Trump was nearly killed last July, most Americans, not just Republicans, gave thanks to God, the universe, their lucky stars, or whomever one gives thanks to when disaster is averted. The Republic will survive the election of President Trump, but perhaps his assassination would have made its continuance problematic.

The Bidens after his diagnosis was announced (NBC)

And if Republicans are totally honest with themselves, they should give thanks that President Biden served his entire term of office. If he had been stricken--or had stepped down voluntarily--any time during the past four years, an incumbent President Harris might well have won the election. Yes, IMHO, there was a cover-up of Mr. Biden's deteriorating mental condition by Democrat insiders and the media, but he chose to cling to office, and for that choice, however misguided, Republicans should be grateful.

Today it was revealed that President Biden is suffering from advanced prostate cancer. So let's join the majority of Americans for whom politics is not the be-all and end-all of existence and pray for him and his family.

Cancer: Too Much Information

We're lucky we live close to two research centers

This is troubling but not surprising: many oncologists can't stay abreast of new developments in cancer research. [bold added]

Cancer care is getting more complicated, thanks to a better understanding of cancer’s molecular underpinnings. Doctors now think of cancer as more than 100 distinct diseases, with cancers including lung, breast and bladder broken into subtypes.

That complexity is contributing to a divide in how patients fare depending on where they go.

Oncologists at magnet cancer centers that dot the U.S. develop expertise in just a few cancer subtypes. They draw from a rapidly expanding arsenal of new drugs for specific and sometimes rare cancers, including experimental ones that aren’t widely available.

But most people get treated locally to be near home and jobs. Local oncologists, faced with a range of cancers, can’t stay up-to-date on everything. The National Comprehensive Cancer Network updated its nearly 90 guidelines across cancer types more than 200 times in the past year.

A third of 120 patients who sought a second opinion at Memorial Sloan Kettering Cancer Center in New York had their treatment changed, a 2023 review found. MD Anderson Cancer Center in Houston said about one in five of its new patients are rediagnosed or restaged. Patients at academic centers have better outcomes for cancers including lung and multiple myeloma, studies show.

“It’s possible that one out of five patients in America is getting the wrong treatment,” said Dr. Peter WT Pisters, MD Anderson’s president.

I don't fault oncologists for finding it hard to do keep up with the research while treating patients by day. This is one obvious application for artificial intelligence, i.e., sifting through haystacks of information to find the needle that may apply to a patient.

Meanwhile, it behooves us all to stay alive as long as possible to give us the best chance for the science to cure the diseases that might kill us.

Dr. Bryant Lin

Bryant Lin teaching a class on Oct. 23 (Merc photo)

A member of our family has been seeing Dr. Bryant Lin at Stanford Health for years. Lately Dr. Lin has been unavailable. Now we know why; he has been battling lung cancer.

“If you look at the survival curves, you would give up. But you may be one of the lucky ones. You need to have optimism, tinged with reality,” said Lin, a beloved clinical professor and 50-year-old nonsmoker with two teenage sons who was diagnosed with advanced metastatic lung cancer earlier this year.

...Lin initially dismissed an annoying cough that started last spring. But it continued to worsen, causing him to wheeze.

“I’ve never had a puff of smoke of anything in my life,” he said.

In one week, he got stunning news. What he assumed was just a normal spring allergy was diagnosed as stage IV non-small cell cancer, which had already progressed to his bones and liver, with 50 lesions in his brain.

The diagnosis, about a month before his 50th birthday, “was so drastically different than what I was expecting,” he said. He was quickly hospitalized...

Lung cancer causes more deaths than any other cancer, with survival rates decreasing as the severity increases. While smokers make up the majority of those cases, 15% to 20% of people with lung cancer are non-smoking, like Lin. There is new evidence of an increase in the incidence of lung cancer in nonsmokers, although no one knows why. It is largely a silent disease that goes undetected for a dangerously long period.

The gene mutation that causes the cancer disproportionately affects those of Asian descent.

While not cured, Lin’s scans are strikingly improved after an innovative medicine called osimertinib, which targets his specific mutation. It blocks proteins that control cell growth and division. His cough is gone, and he is almost symptom-free...

With roles reversed, Lin says he is learning both how to be a patient and how to more fully be a doctor.

He urges doctors to not focus just on “medical science things” but the emotional and practical challenges of their patients. He urges patients to build tight community of support and deepen their relationship with their doctor, who can act as an advocate when things go wrong.

He’s not sure how much time he has left. “One year? Two years? Five years?” The class, he said, “is to give back to my community as I go through this.”

After receiving his terminal diagnosis, Dr. Bryant Lin continues not only to fight the disease but teaches classes at Stanford Hospital, including his own life experience in the content. None of us know with certainty how we might react to such news; character reveals itself in such moments.

Microplastics Filter

My son bought and installed a microplastics filter under our kitchen sink. He's concerned about keeping his boomer parents healthy, and, unlike me, he keeps abreast of environmental news.

I've been skeptical about all the climate doomism that makes our lives expensive and needlessly worse--get rid of our incandescent bulbs, gasoline cars, and reliable nuclear and fossil fuel power plants!--but there might be something to the concerns about microplastics, which are in the seas around us: [bold added]

Microplastic particles are widespread in Monterey Bay anchovies and the diving seabirds that eat them as a main food source — which could possibly impact the birds’ reproductive systems, according to a new study.

Scientists at UC Santa Cruz, UC Davis and the San Diego Zoo Wildlife Alliance studied microplastic pollution in Monterey Bay by testing microplastic particles in the water and in anchovies and common murres, a bird species found in abundance in the region.

They found that 58% of anchovies and 100% of murres had microplastic particles in their digestive tracts, according to the study published Nov. 4 in the Environmental Pollution journal.

The study also comes two months after California became the first state in the United States to begin requiring water agencies to test for microplastics, which can be found everywhere from clothing, food packaging, drinking water and the ocean. Another recent study by Stanford University scientists found that whales are ingesting “colossal” amounts of microplastics that mainly come from the fish they feed on.

The troubling increase in cancer among young people causes us to ask what's different about us when we were kids in the 50's and 60's, and the leading factors seem to be excess sugar to less sunshine and exercise. The ubiquity of microplastics may be an answer, too.

There But for the Grace of God Go I

Everyone I know has had a family member--sometimes it's my acquaintances themselves--who's had cancer. Whether or not the patient survives, it's a grueling experience for everyone. Years of tests, chemotheraphy, surgery, and/or radiation, plus the financial strain of paying for everything, await.

Fortunately--I realize that's not the appropriate word--most of the cancer victims I'm familiar with were retired or close to retirement, which means that they had Medicare or other health insurance to absorb most of the costs, and they probably didn't need to work to make up money shortfalls.

There is a growing cohort of Americans who are diagnosed long before retirement age, and, even if they survive the cancer, experience financial ruin. [bold added]

The economic burden of a cancer diagnosis is getting strikingly worse in the U.S., as drug and medical costs soar and more patients live longer with the disease. About 55% of cancer drugs introduced between 2019 and 2023 cost at least $200,000 a year, according to Iqvia’s Institute for Human Data Science. And an increasing number of patients are working-age, a group more likely to report financial hardship after diagnosis compared with older adults.

Nearly 60% of working-age cancer survivors report facing some financial difficulty. Many patients struggle to afford care and end up taking on debt, with some getting payday loans or running up credit cards. Cancer alone accounts for some 40% of medical campaigns seeking financial help on GoFundMe, research shows...

Among common diseases, cancer creates a uniquely difficult financial strain known as financial toxicity. Treatments with expensive medicines start immediately and come with a string of nonmedical costs. Chemotherapy and other treatments can leave patients too weak to work for weeks or months. This can result in a twofold blow, with patients losing income and their employer-sponsored health insurance. The financial fallout can last for years...

Many patients have to take time off—or actually stop working—after a cancer diagnosis. Patients who get chemotherapy are more likely to stop working within four years than those who don’t.

Could one straightforward way of relieving the financial burden be to buy up medical debts--for cents on the dollar because they've been sent to collections--then forgive them?

Undue Medical Debt (aka RIP Medical Debt) does exactly that--it's rated four stars by Charity Navigator--and is a 501(c)(3) organization that my church has donated to. RIP Medical Debt opened its books to economic researchers to find out whether paying off medical debt made a difference in people's lives. The results were disappointing:

[Stanford Prof. Neale] Mahoney and his collaborators find no evidence that buying and then forgiving medical debts that are in collections improved on average beneficiaries’ finances, access to credit, or their physical or mental health. People were even less likely to pay existing medical bills after their debt was eliminated.

Prof. Mahoney and other researchers, as well as RIP Medical Debt, are studying if earlier interventions might be more helpful.

Meanwhile, we're just lucky that we were able to enjoy good health during our working years. If either of us had been diagnosed with cancer in our 40's and 50's, when we didn't have much savings and had mortgages and tuitions to pay, then our lives would be immeasurably more difficult.

Priorities

Menthol shelves are well stocked (WSJ photo)

The Biden Administration has been criticized for overstepping the constitutional powers of the Executive (e.g., forgiving $billions of student loans, banning fossil fuel power plants) and ignoring Executive responsibilities (e.g., controlling the Southern border). However, I suspect that the majority of Americans would approve this action that would save hundreds of thousands of lives: [bold added]

The Biden administration proposed a national ban on menthol cigarettes, advancing a regulatory plan that could sweep from the market more than a third of all cigarettes sold in the U.S. The products represent more than $20 billion in annual sales.

The Food and Drug Administration on Thursday published proposed rules laying out the details of the plan. The ban would prohibit the sale of menthol cigarettes and all flavored cigars. The FDA said it is considering allowing exemptions on a case-by-case basis for certain products, such as heated-tobacco devices or cigarettes with very low nicotine levels. The ban wouldn’t affect menthol e-cigarettes...

The plan, which has been in the works for more than two decades, is the biggest move the federal government has made to curb cigarette sales since the FDA gained regulatory control over the tobacco industry in 2009.

The policy could save hundreds of thousands of lives, FDA Commissioner Robert Califf said Thursday. He said in his career as an intensive-care cardiologist, he had seen many people die of smoking-related diseases.

The government has the legal authority to enforce the ban, so what's the holdup? Politics from its own base (hint: it's not Big Tobacco):

The Biden administration is reversing course on its plan to ban menthol cigarettes, after the White House weighed the potential public-health benefits of banning minty smokes against the political risk of angering some Black voters in an election year.

The administration said Friday that it is delaying a decision on whether to impose a ban, contending that it needs more time to consult with outside groups on the matter. There is no timeline for the administration to revisit the decision, as President Biden competes with former President Donald Trump for votes in November.

Menthols account for more than a third of all cigarettes sold in the U.S. each year and are predominantly used by Black and Hispanic smokers. Some 81% of Black smokers used menthols in 2020, compared with 30% of white smokers and 51% of Hispanic smokers, according to a Wall Street Journal analysis of data from the National Survey on Drug Use and Health.

The Administration has no hesitancy in banning carbon-producing activities because it knows better than the people what's good for them (Pew--August, 2023: "This ranks climate change 17th out of 21 national issues included in a Center survey from January.") However, it refuses to outlaw menthol cigarettes, which are certain to cause thousands of deaths in the near future. That's one inconsistency that is tough to explain, if only there was a single truth-searching reporter that would ask them about it.

Living Fossils

Alligator gar (Yale News)

No, this isn't a post about politics.

"Living fossils," (Darwin's term) specifically the gars, have little species diversity and have evolved so slowly that their genome is nearly the same as gars during the age of the dinosaurs. Importantly, understanding gars' cellular mechanisms could lead to a cure for cancer (!).

The researchers speculate that gars have an unusually strong DNA repair apparatus, allowing them to correct somatic and germline mutations — alterations to DNA that occur before and after conception — more efficiently than most other vertebrates.

If confirmed, these findings could have profound implications for human health, said [Prof. Thomas J.] Near, the Bingham Oceanographic Curator of Ichthyology at the Yale Peabody Museum.

“Most cancers are somatic mutations that represent failures of an individual’s DNA repair mechanisms,” he said. “If further study proves that gar DNA repair mechanisms are extremely efficient, and discovers what makes them so, we could start thinking about potential applications to human health.”

Another Eureka moment in science, this time from a species that is little changed from its ancestors a hundred million years ago.

My Friend Bill

We lost my friend Bill last week. The immediate reason for his death was a fall at home, but the real cause was the cancer that had weakened him.

In the old days I suppose that I wouldn't have called him a true "friend"; I hadn't even met his wife in person or been to his house or he to mine.

Over the years we had a number of meetings and business lunches with other people, trying to get something going. Since the start of the COVID lockdown we had talked on Skype two or three times a month, trying to see if there was any business we could do together. The cupboard was bare, since his expertise lay in a business that was highly dependent on the coronavirus-devastated travel and leisure industry.

Once we had exhausted the usual discussion of potential prospects our conversation turned to each other's health, travel plans to Hawaii (me Honolulu, him Maui), and our love of old cars. He always ended with his cheery "I'll make some more calls and get back to you."

I have other endeavors, business and otherwise, that require more time and attention, and I told myself that our scheduled conversations were for his benefit, to keep his spirits up. Only now I realize that they were for me as well.

Goodbye, my friend. RIP.

Probiotics: Not So Fast

Our home-brew kefir collection

We have been adding probiotics to our diet in the furtherance of gut health. (For example, we've been drinking kefir for the past two months.)

As with any foods or treatments that have become popular due to purported health benefits, probiotics research has ramped up. One study by the University of Texas cautions that supplements may actually do more harm than good. Dr. Lorenzo Cohen: [bold added]

My personal results were mirrored by a study that our MD Anderson team had just presented at an international meeting. The provocative findings received a lot of publicity. The preliminary results showed that patients who reported taking an over-the-counter probiotic supplement had a lower probability of responding to immunotherapy as well as lower microbiome biodiversity. But those eating a high-fiber diet were about five times more likely to respond to immunotherapy and had high gut bacteria diversity, including bacteria previously linked to a strong immunotherapy response....

Yet I now believe that the cheapest and safest way to improve our microbiome and gut health is to make simple dietary changes to feed the development of good bacteria and crowd out the bad. There is no pill, special food, unique diet or quick fix for what ails our health and diet. The key is simply to focus on eating a diverse, whole-food, plant-centered, high-fiber diet.

Dr. Cohen seems to be saying that we shouldn't get our probiotics from a pill or a bottle but have to do it the hard way. How does he expect to get any grant money?

From the early 20th century: Swamp Root cures
"internal slime fever". At least it's plant-based.

That Paradisiacal Day

New gene-based treatments for cancer show immense promise----and have immense costs:

Novartis AG listed its newly approved cell therapy for cancer at $475,000, while Gilead Sciences Inc. priced its rival drug at $373,000.

But the price of the drugs is just the beginning, hospitals and insurers say. Administering these therapies can add hundreds of thousands of dollars to the tab, including lengthy hospital stays and use of other services and medicines.

(WSJ graphic)

The Wall Street Journal estimates that the full cost of these state-of-the-art treatments ranges between $464,000 and $968,000. For rich people and their families there's little question that most, if not all, will opt for the treatment even if success is not guaranteed.

However, many cancer patients either won't have the money or will choose not to diminish their estate by up to a million dollars to extend their lives for an uncertain period.

Cancer newly afflicts over a million Americans each year:

In 2018, an estimated 1,735,350 new cases of cancer will be diagnosed in the United States and 609,640 people will die from the disease.

It will be years before the costs will have come down sufficiently to make a dent in the number of cancer deaths. Until then, dear reader, diet, exercise, and get regular check-ups so that you will make it to that paradisiacal day.

Counselor, Heed Thyself

A friend with whom I have some business dealings gave me the bad news; he halted chemotherapy because the treatments haven't worked. No, the doctors haven't yet given a prognosis.

He wanted to talk about business. Okay.

He will call the lawyer. He'll forward the data to the tax accountant, after which I'll handle discussions. For computer issues he will talk to the IT guy. My friend was filling his calendar with detail.

After he was done talking, I assured him that I'll take care of any administrative matters that he's unable to finish.

Then I said, please think about saying things that you've always meant to say to your children and grandchildren. That's what's important. The legal and accounting stuff I can handle.

He got emotional, and we hung up a few seconds later.

Another way to show your love

I don't regret giving him advice, but I do feel guilty because I have done little to prepare for my own demise. Financial affairs are in minimally adequate shape---there's a will, a trust, and named beneficiaries where needed---but there's nothing about who I was, what I've learned, my dreams and regrets, or my hopes for those who will come after me. If they never met me, they won't know me at all.

Now that I'm mostly retired I have time to work on completing these important but (so far) not urgent tasks. As my friend showed, they may be more urgent than I think.

Note: the NIH's National Cancer Institute (cancer.gov) has published an informative booklet for friends and family: When Someone You Love Has Advanced Cancer.

Don't Fight It, Embrace It

(from sherylcrow.com)

In 2006, 13 years after she became an international star, Sheryl Crow was diagnosed with early-stage breast cancer. It caused her to re-assess her life.

The best lessons in life are the ones that stop you in your tracks. I was staring down a beast in the mirror, and it was saying, “You need to start changing some things.”

She let go of her belief about the way life's supposed to be ("You fall in love, you have a great relationship, and then you have children") and adopted two sons. She also embraced her age.

In the past 10 years, once I let go of trying to be younger and needing to have a pop-radio career, I’ve found the space to write about things that really matter.

Accepting one's age is different from determining what is the perfect age: [bold added]

Researchers like Dr. [Jay] Olshansky are trying to understand the mysteries of longevity and at what ages we feel our best and why. They measure worry and stress levels at different times in our life and peak years for having fun...

If people could live forever in good health at a particular age, it would be 50, according to a 2013 Harris Poll.

There are also arguments for 70 ("when people are less anxious but still healthy") or 30 ("when they are at their physical peak or have the most friends"). Of course, the answer will vary according to individuals' preferences, e.g., wealth, physical attractiveness, mental acuity, etc.

Maybe Sheryl Crow has the right attitude. Accept how you are now for maximum happiness.

Fearfully High

A 14-year Kaiser Permanente study of 274,000 Northern California members tracked the incidence of dementia in patients who had displayed no symptoms at the age of 64.

The data were used to develop "cumulative risk" estimates for the six ethnic groups in the study; blacks had the highest risk (38%) while Pacific Islanders had the lowest (25%).

Your humble blogger's Asian ancestry projects a risk at the low end of the scale (28%), in the same ballpark as the risk of cancer (35%). Both are fearfully high.

The Longest War

From President Obama's State of the Union address, an uncontroversial goal:

For the loved ones we’ve all lost, for the families that we can still save, let’s make America the country that cures cancer once and for all.

In its 45th year, the War on Cancer is the longest "war" America has ever fought, and victory may seem to be as elusive as when it started. It is difficult, however, for us non-scientists to appreciate fully the significant advances that have been made across multiple disciplines to combat this fearsome enemy.

A cancer diagnosis was a nearly automatic death sentence a few years ago. Today improved drugs and radiation treatments, early detection, and lifestyle changes have all factored into longer survival rates and a decline in cancer deaths. Still, about 600,000 Americans die each year from the dread disease.

Tumours inhibit the maturation of dendritic cells that activate
the immune system (Center for Colorectal Disease image)

One example of the creative thinking in a war that's being waged on many fronts: Stanford researcher Edgar Engleman wondered why the dendritic cells that are part of the body's immune system don't react to cancer. [bold added]

when cancer is present, the dendritic cells act as if they were asleep at the wheel, he says: They don’t respond to the antibody signal to engulf and metabolize the tumor, they don’t present the tumor antigens to the T-cells, and so the T-cells don’t mobilize.

So to counter the soporific effect of the cancer, Engleman gave the dendritic cells a “wake-up” jolt, in the form of substances known to stimulate them, as an adjunct to the antibodies. The result was astounding. “When we gave the two things at the same time, BOOM, then we got an explosive antitumor immune response that cured the tumors in the mice. Reproducibly, over and over again.”

Not only did the combination injection kill the primary tumor, but it wiped out distant metastases as well. That’s huge because, as any oncologist will tell you, in most cancers it’s the metastases that are deadly. Moreover, there was no autoimmune reaction, no toxicity, no collateral damage whatsoever. The results were published last spring in the prestigious journal Nature.

Because the antibodies are present in all healthy individuals (albeit in varying concentrations) and the stimulant substances are commercially available, in theory the approach should be eminently scalable.

The process of shepherding Dr. Engleman's idea through clinical studies and the FDA will take years and millions of dollars, not to mention locating a drug company that will view his approach as a worthy investment versus others in the pipeline.

Declaring war is easy. Actually winning it is very, very hard.