* “No One Knows What Universities Are For: Bureaucratic bloat has siphoned power away from instructors and researchers.” A process that has been underway for decades and that is now largely complete.
* “It’s 2024 and Drought is Optional.” We can solve a lot of problems with technology, if we choose to. The tragedy is choosing not to, and choosing stasis over abundance.
Get cancer[1] and you’ll be inundated with advice about food, most wrong and much contradictory: avoid sugar; processed food kills; meat promotes cancer; ketogenic diets are incompatible with cancer; milk is dangerous; milk is healing; cancer is impeded by vegetables; honey is good; tea is safe; coffee is dangerous; tumors like Adderall. I think people latch onto diet-based advice, like they do prayer, as a mechanism of control, even if the mechanism is faulty, in a situation where any control is highly medical and scientific and thus beyond the typical person’s abilities. Today, the most common form of nutrition advice is to avoid sugar, even though no evidence suggests that a low-sugar diet will eliminate or reduce cancer (“cutting out all sugars doesn’t actually fight existing tumors”)[2]. Sure, it’d be nice if one could follow a particular diet advice in order to eliminate tumors. “It’d be nice” is not the same as “it is true.”
There’s a human tendency to crave control even if craving control isn’t well correlated with true control over a chaotic, uncertain world. One sees this, for example, in people who erroneously think driving is safer than flying—a driver has some control, but, on a per-mile basis, flying is way safer. We imagine that that we’ll evade the drunk driver, the woman distracted by her smartphone, the dude yelling at his kids. In reality, we don’t control the cars and distracted drivers around us. By contrast, no amateurs fly large planes, the pilots are sober experts, and the FAA extensively digs into any crash to figure out how to prevent the same thing from happening again.
We collectively (and bizarrely, in my view) accept 40,000+ car fatalities every year in the U.S. alone. To me this is insane, but I’m the weirdo in that most people don’t think statistically and accept the fact that people they know and sometimes will be seriously hurt or killed in car crashes. In Sweden, however, there’s an effort to understand the factors underlying serious car crashes, and, because of that effort, “Today, Sweden has some of the lowest rates of road traffic fatalities in the world.” In the U.S. and much of the world, we tend to blame individual drivers, instead of systems; systems, however, can (and should) be improved. In Sweden, “officials were no longer allowed to design roads for idealised drivers who never became distracted or exceeded the speed limit. They had to make roads for real people who made mistakes.” Drivers still drive, but the roads are built to limit the ability of people to kill and maim one another. Real control happens at the level of the system.
I’m not saying striving for control is bad; given the frantic, relentless efforts Bess and I have put into keeping me alive, it’d be peculiar and hypocritical if I did. Striving for greater control is good, but grasping at illusions is not, particularly if those illusions are deleterious to the desired outcome, like, for me, staying alive via clinical trials. Individuals influence their cancer risks; not smoking, or not smoking much, is an obvious way. And it is true that high sugar intake is a risk factor for developing cancer. Once someone has cancer, though, eating sugar (or not), or eating meat (or not) isn’t going to affect the cancer’s course. What will is the usual: surgery, chemotherapy, radiation therapy, oncology treatments (like the bispecific antibody I got, or the antibody drug conjugate (ADC) I’m on now). I’ve been on a low-sugar diet for more than a decade, and that didn’t stop a squamous cell carcinoma from growing in my tongue. There’s a correlation between a low-sugar diet and avoiding cancer, but it’s far from r = 1.0.
One year ago today, I went into surgery expecting that I’d lose half my tongue to a squamous cell carcinoma recurrence. The evening before, Bess and I got legally married;[1] it was a short, but charming, crash ceremony. I say “crash ceremony” because we wanted to marry before surgery, and on afternoon of May 24 I learned a spot had opened for the next day. It was only luck—if you could call any part of this story “lucky”—that Bess and I had picked up our marriage license a few days earlier, expecting to wed sometime before the planned surgery date of June 8 or 9.
The tumor itself has only been confirmed on May 11: I got a “hot” PET scan on April 26. Mayo Phoenix initially scheduled follow-up CT scans a few weeks later to figure out what was going on, but Dr. Hinni, the ENT surgeon at Mayo who saved my life, did not like that delay (he dislikes any delay, a trait which has likely saved my life on several occasions) and ordered them stat, so on May 1 I went in to find out whether I was likely to live or die.
* “The positive case for Joe Biden.” Arguments rarely heard, and it’s largely about policy, unlike the identity and horse-race nonsense that predominates what passes for coverage. This is interesting too: “Biden led by 49 points among voters who relied on newspapers.” By contrast, “Among voters who rely on social media, Trump led by four points. Among voters who rely on cable news, Trump led by eight. Voters who get their news from YouTube and Google favor Trump by 16 points.” Many if not most people have poor epistemology, and, as Bryan Caplan argues in The Myth of the Rational Voter, most people don’t bear direct costs for that.
* Debugging tech journalism. Like most journalism, there’s a strong pull, driven by audience interest, in negativity and salaciousness. We get what we ask for, which is consistent with the links immediately above this one.
* Argument that supernormal returns to real estate are over. I’d probably bet against this, at least for high-productivity cities, because I think knowledge-spillover effects from in-person proximity are likely to continue, and are not likely to be replicated from working at home. The best argument against my view is self-driving cars: self-driving cars will obviate the need for most parking lots, which will open huge amounts of existing urban / suburban land to development, which should reduce prices. What we think of as “the age of the car” is really “the age of the parking lot.”
* Eli Dourado on sociopolitical collapse. The bits about the complexity ratchet are notable. Still, I don’t think any “civilizations” have collapsed in the ways he’s describing since the Industrial Revolution, though there are ways to imagine this now (nuclear weapons, pandemics).
* “Is the backlash to universities becoming real? Taxpayers, politicians, and employers are realizing that campus leftism has gone too far. The question is whether it’s too late to stop it.” Maybe.
* “Revolution of the Broletariat: From the christ-like resurrection of america’s frat boy to the chad-ification of tech, anti-masculinity is over; chad maximalism has arrived.” Maybe? Entertaining, though not sure I buy it.
In March I learned that the previous clinical trial I’d been on, petosemtamab, had stopped working, and the tumors in my neck were an average of 20% bigger: a lot of growth in an ominously small space. That news set off a furious, exhausting, consuming effort to find the next clinical trial; pick the right one, and I’d get more time with Bess. Pick wrong, and die. The eventual answer was PDL1V, a Seagen-Pfizer antibody-drug conjugate (ADC) that has caused and is causing a lot of side effects—but it’s also working. On April 4 and 5 I got CT scans to qualify for the PDL1V trial, and the CT scans were ugly: the radiologist reported “Progression of disease including tumor interval enlargement and increased extent” and found “enhancement” or “worsening” in every tumor, as well as some lymph nodes. Two large lumps grew from the left side of my neck and jaw. Every day, I felt worse, and headaches began in the last week of March or first week of April. I wasn’t sure whether I’d make it to the next treatment. In mid-March, Bess and I debated whether I should get a round of systemic chemotherapy in order to increase the probability of me living long enough to reach the next treatment. PDL1V, however, requires no more than two previous lines of systemic therapy, and we learned that Seagen-Pfizer would consider an extra round of chemo, even the same chemo that I received in August and September 2023, as a new “line” of therapy—rendering me ineligible for PDL1V.
* On the need to pay teachers for performance, not based on seniority. I expect that the spread of micro schools, vouchers, and charter schools to push schools towards pay-for-performance, rather than pay-for-not-performance.
* “Boeing and the Dark Age of American Manufacturing.” There can be an amazingly long time between bad decisions being made and the results of those bad decisions being widely seen, felt, and acknowledged.
* Zoning out American families. When you see articles about the falling birth rate, connect them to the articles about restrictions on housing construction. We raise the cost of housing and then are somehow surprised when people can’t afford kids. The boomers whose votes foreclosed the construction of new housing are now paying for that in part through no or few grandkids. Scarcity policies are ultimately self-defeating, but hardly anyone thinks this way.
* “For most people, politics is about fitting in.” Notice how rarely people are motivated by ideas, or even consistency. Most people can’t recall what they argued or said they believed a few years ago.
* Weak argument that some college students are abandoning Ivy-League-type schools. Still, things are the same—business-as-usual—until they’re not. Similarly, see “Normal Kids Get F*cked: Elite universities went to war against fraternities and fun while indulging Hamas-admiring collectives, and the students have noticed.” Not the headline I’d have chosen, but the selective enforcement of rules and principles is notable. I have a half-written rant about how it’s impossible to write satires of academia, and it has been for years, but I’m not sure it’s worth finishing or posting, due to obviousness.
Right now, from a society-wide perspective, the healthcare I’ve been getting to keep me temporarily alive against a squamous cell carcinoma onslaught probably fails the cost-benefit test.[1] In the short term, resources are finite and the tremendous financial cost of care likely isn’t worth the benefit of my life, relative to the costs of other interventions that would heal people with less serious maladies and longer life expectancies. Probably it sounds strange for me to say: “Keeping me alive isn’t justified,” but I think it worthwhile to be intellectually rigorous and honest even about sensitive matters like the literal monetary value of life. In some abstract metaphysical sense, human life might be beyond value, but we practically put a price tag on lives and risk to life all the time (example: “Studies of real-world situations produce relatively consistent results, suggesting that average Americans value a year of life at $100,000 to $300,000”).
I don’t have a strong view about the particular numbers, but the general principle is sound, and outfits like Givewell.org search “for the charities that save or improve lives the most per dollar.” Givewell’s top charities right now are for malaria prevention (“In 2022, we directed funding to the Malaria Consortium to support this program at an estimated average cost-effectiveness of $5,000 per life saved”) and vitamin A deficiency amelioration (“In 2022, we directed funding to Helen Keller International to support this program at an estimated average cost-effectiveness of $5,000 per life saved”). Unfortunately, “charities” like Greenpeace prefer to murder children by holding up “golden rice” that has vitamin A in it, but you can read more about that terrible choice at the link. Five-thousand dollars is less than the cost of a typical treatment I receive, but the mystery statements I get from my insurance companies indicate that more than $5,000 is being spent on me per month (though the numbers have more than a whiff of the made-up about them).[2] Recurrent / metastatic head and neck squamous cell carcinoma (R / M HNSCC) is incurable, too, so extra dollars don’t buy much time, and the time they do buy is degraded by pain, fatigue, inability to swallow, and so on.
The big caveat to saying that I’m not worth keeping alive, though, outside the value the people who love me claim I provide, is that I’m also generating data for clinical trials helps move the state-of-the-art forward. Participating in the MCLA-158 / petosemtamab trial, for example, yielded one more data point showing that petosemtamab shrinks notoriously hard-to-treat R / M HNSCC. By pursuing treatment through clinical trials, I’m helping others in the future (more on that later). Still, my quality of life is low, and while treatment has been extending my life, it almost certainly won’t lead to remission. Even if a clinical-trial drug somehow leads to complete remission, I’ll never be able to sleep or speak normally again. Life without good speech or sleep or swallowing or chewing is not easy, yet I’m trying to continue to contribute to the human enterprise within the many limitations I’m subject to. A few months ago, my brother casually referred to me being disabled, and I was momentarily confused: Who was he talking about? But he was in fact right: I’m disabled and unlikely to ever be able to think or work in the way I did before losing my tongue, which also lowers the value of any healthcare I receive.[3]
Some of these musings are adapted from Derek Parfit’s Reasons and Persons, and more directly from Peter Singer, who is I think the first to posit hypotheticals along the lines of “You are wearing an expensive suit and shoes worth many thousands of dollars. You see a child drowning in a pond. Would you leap in to save the child, and ruin your suit in the process?” Everyone says yes. But then why not donate the same amount of money to save a child in Somalia, or wherever? Aren’t those two morally and logically equivalent? Yet hardly anyone lives that way, myself included. There is some kind of immediacy bias in the human mind, where something proximate to us registers as more vital than something distant in space and time.
The rejoinder to the idea that one should curtail status consumption to donate to save distant people is usually something like: “They are poor and their healthcare systems work poorly due to social and government dysfunction; fix that dysfunction so that they become rich and the apparent trade-off will go away.” Countries like South Korea and Taiwan used to be desperately poor and now are rich because they adopted smart policies. Nothing is stopping many African countries from doing the same. India abandoned autarky and embraced markets, and now it is far richer than it used to be. Countries like Syria and Iran are not poor due to a lack of donations, they’re poor due to horrific governance by Assad and mad, freedom-hating mullahs.
Hypothetically, even a billionaire would probably hesitate to pay $1 billion for a single extra day of life; the vain and egotistical would prefer to build a monument or something, versus one day more. Most of the world’s poorest people would find a way to pay $1 if it could extend their life by five years. Between those extremes lie real-world tradeoffs, which are of course hardly ever so clean.
Insurance further muddies matters, because if someone else is picking up the tab, most of us want more treatment than we would otherwise. European countries with public health systems solve this problem through committees that decide which treatments are worth it; they also wrangle with drug companies to set price caps (the U.S. is the market in which drug companies make all their money, and consequently the FDA is the limiting factor on new treatments, which is why I complain so much and so vociferously about them). It’s not surprising that I personally would prefer other people pay more for me, and I personally would like to pay lower premiums, while everyone else would like the same for themselves. Moral hazard is operating. The U.S. has mostly chosen a high-cost, high-care regimen, while European countries have mostly chosen a lower-cost, lower-care regimen, which limits care for the walking dead like myself.
Scott Alexander observes that he’s “seen patients with terminal illnesses who are very happy they chose to just let it progress and not spend their last few years in medical trials, and other patients who are very happy that medical trials gave them another year or two with their family and whatever else they were trying to accomplish.” For me, I’m continuing to do clinical trials for the sake of Bess, and spending more time with Bess. Absent her, I’d have taken the opioid road in June 2023. Recovery from the total glossectomy demanded 24/7 care that I wouldn’t have been able to receive from anyone else, and I wouldn’t really have had enough to live for. We humans really live for one another,[4] and without other people and especially love, why bother?
Some of the healthcare I’ve received easily passes the cost-benefit test. Take the R / M HNSCC that’s killing me: I got a partial glossectomy in Oct. 2022. Mine had some high-risk features, but I was assured that, with radiation therapy, it wouldn’t recur (Bess recalls the exact words being, “Don’t worry, this won’t be what kills you”). If it hadn’t recurred, the costly surgery and radiation would’ve led to many more years of positive, fulfilling life. Hardly anyone will find surgery and radiation pleasant, but they left me without substantial, disabling deficits. In retrospect, however, I obviously should’ve been given chemo with the radiation, but at the time I was pleased to not need chemo, and I foolishly didn’t look deeper into the data on recurrence—which is common for HNSCC—and I didn’t seek second opinions. Some of those second opinions might’ve said: “Get the chemotherapy.”
Docs are justifiably reluctant to impose systemic chemo because of the side effects, and they have to weigh present bodily ravages against theoretical future ones when coming up with a treatment plan. But the future of cancer treatment is much less violent. Transgene, for example, has a personalized vaccine that is supposed to prevent HNSCC recurrence: “In the head and neck cancer trial to date, all patients treated with TG4050 have remained disease-free, despite unfavorable systemic immunity and tumor micro-environment before treatment.” That’s a tremendous boon, particularly if it doesn’t involve the deleterious side effects of chemo or radiation. Most of these personalized vaccines have essentially no side effects. Moderna’s mRNA-4157 platform looks great, not only in R / M HNSCC, but in melanoma and lung too. Right now mRNA-4157 is only being tested in the recurrent / metastatic setting, as far as I know, but the logical time to use it is probably when initial surgeries are done: cut the cancer, sequence it, and then vaccinate against it to prevent recurrence. Technology is going to reduce the trade-offs between “painful, difficult treatments with difficult short- and long-term side effects” and “successfully eliminating cancer.”
The future, which I’m distinctly though barely missing, is going to be brighter than the present. I’m reading a biography of Richard Feynman, whose first wife died of tuberculosis (TB) in part because the scientific / medical establishment wasn’t able to get its act together regarding antibiotics: “the first clinical trial of streptomycin” began with only two patients in the fall of 1944, despite TB being a death sentence. And it wasn’t until August 1945 “that the Mayo trial had expanded to as many as thirty patients.” Finally, “In 1947 streptomycin was released to the public”—two years too late for Arline Feynman.
Arline was at the end of the era of deadly bacterial infections; I’m at the end of one era of cancer treatment and the dawn of another, but I’m going to miss surviving because I’m a few years too early, and because the FDA so effectively blocks innovation, even for those of us with terminal illnesses who are happy to trial a new drug when the alternative is certain death. The terminally ill are not incompetent children incapable of understanding risks and giving consent, and the paternalism of the FDA, which intends to protect us from potential pharmaceutical harm, does so by choosing death as the lesser evil for patients like me, instead of giving us the choice to risk theoretical harm in exchange for the possibility of a longer, better life. We should have a meaningful right to try.
Letting patients try isn’t just potentially good for the health of patients, it’s a financially sound decision for everyone: Pharma companies want to sell drugs. Insurance companies could save the extensive costs of ongoing treatments by supporting payment for innovative therapies like cancer vaccines that prevent recurrences. Since 45% of cancer diagnoses are in patients aged 20 – 64 years old, it would benefit the government by having a large chunk of taxpayers able to rejoin the workforce. That’s money in everyone’s pocket. That’s human flourishing, which the FDA is blocking.
There are other substantial, lesser-discussed costs to consider: for example, many trials are only available at a handful of hospital or clinic sites around the country, and finding an appropriate trial, even for patients in large metro areas with research-heavy institutions, means having to travel to the trial. I’ve not only been spending insurance companies’ money (“insurance companies’ money” is another way of saying “almost everyone’s money”); I’ve also had to pay for flights, accommodations, and incidentals to receive any treatment at all via clinical trials. We’d live in a better world if the FDA and drug companies would move to virtual, decentralized clinical trials, in which instead of me expensively shipping myself to a trial site, the drug company ships the drug in question to a local site that passes whatever quality metrics might be necessary, and I get treated locally.
Many potential sites already exist. HonorHealth Research is one, located in the Phoenix area about a fifteen-minute drive from me, and it seems like a reputable place for clinical trials. There’s no reason I can discern for not being able to ship the drug products to HonorHealth, give them specific instructions (“8mg of dexamethasone 1h prior to infusion, 50mg of Benadryl, watch for infusion reactions…”) and then have the doctors and nurses at HonorHealth carry out those instructions. Unfortunately, right now that’s not how the system works, and so I wind up on a lot of airplanes, when a 200ml bag of petosemtamab or PDL1V or whatever could instead be shipped to Phoenix.[5] The carbon footprint of flying me around has to be far greater than that of flying something that is like 1/200th of my mass. America is not easy on the environment and so much superfluous flying makes things harder, despite my subscription to ClimeWorks’ direct air carbon capture service.[6]
Beyond that, not all care is automatically covered by insurance, and Bess and I have to make hard decisions about what might be worthwhile and what might not be. I’m thinking especially of circulating tumor DNA tests, as well as tumor DNA testing; though DNA tests can identify targetable mutations that could guide me to effective treatments, they are considered “not medically necessary” by insurance companies. Not medically necessary for whom?[7]
I don’t know if there’s a takeaway from this essay, other than that life is hard and many decisions aren’t easy. I also appreciate everyone who has donated to the Go Fund Me my brother set up, and which has allowed me to pursue clinical trials and live far longer than I would’ve otherwise. Bess and my family and my friends appreciate that, too! A future in which personalized vaccines prevent the hardship I’ve experienced, and the death I’m to experience shortly, is also good, and the FDA is bad for holding back medical progress and inflicting so much misery on me. We can and should do better, rather than letting poorly structured bureaucratic mandates harm and kill thousands, if not millions, of people like me annually.
[2] I have not yet been eradicated, but neither has malaria, despite the charges. I’d wager that cancer will eradicate me before humans eradicate malaria, alas. There are malaria vaccines rolling out now, which is a tremendous advance in terms of human flourishing, and yet malaria vaccines wind up not dominating the news, which focuses on picayune status fights among political actors.
[3] I’m still dancing for my bread! Hence this new essay.
[4] Which is one of the many problems with pervasive narcissism.
[5] This is likely the FDA’s hand, because any misstep from an “approved” lab or site or infusion center might mean a multi-million dollar loss, as the data is considered unreliable. There are sites that spend years trying to open a study, but are denied, because of a minor squabble with something in their lab that doesn’t meet mystery criteria. Since most hospital-quality labs across the country are capable of performing the same clinical testing, I find it hard to believe that this is actually a clinical concern. Anything that makes the system slower, worse, and more expensive reeks of FDA regulation.
[6] Despite the present precarity of the biosphere, and the fact that we’re blowing by a 1.5 degree C temperature rise from pre-industrial times, I’d like the future of humanity to be positive. Hardly anyone is remotely serious about making happen, however. Indifference and lassitude are human nature, I infer. I’m not exempt.
[7] “Not medically necessary” is sometimes insurance company shorthand for “It’s more cost effective for you to die than for us to pay for this, even if there is established evidence that it could lead to scientifically validated treatment(s) for you.”
* Gary Shteyngart sent on a massive cruise ship and, surprise! he finds it distasteful and absurd, though in a humorous way. I mean, people on cruise ships would probably find book festivals boring, too. I would likely find a car or horse race unbearably tedious, and so I don’t go to either.
* “From Intellectual Dark Web to Crank Central.” Consistent with my read. A publication like Quillette is impressive because it has retained its taste for heterodoxy without lying, or ignoring important things that are true. I heard someone say that often the only people worse than the institutionalists are often the anti-institutionalists—maybe it was in “Losing Faith In Contrarianism: There are institutional incentives that make contrarian views that catch on mostly wrong.” Granted, “contrarianism” over time scale? Yesterday’s contrarianism is often today’s obviously right belief.
* Baseball is dying. It seems tremendously boring to watch, even moreso than football. Yet football seems to be thriving, for reasons not obvious to me, though it is more fun than baseball.
* That article about NPR’s extreme political bias. I stopped listening more than ten years ago; the problems go back further, I think, than this guy says. Their new CEO says things like “Our reverence for the truth might be a distraction that’s getting in the way of finding common ground and getting things done.”
When Francis Bacon said the remedy is worse than the disease, he wasn’t thinking of metastatic tongue cancer, where both disease and remedy are horrific in their own nightmarishly unique ways. Right now I’m facing a related dilemma, in that my cancer is aggressive and incurable, but the clinical-trial drug I’m taking is producing side effects that may themselves be deadly. Cancer treatment is of course violent: my tongue was cut out, my tissues burnt with radiation, my veins infused with both well-tested and experimental poisons. Cancer is violent too; the headaches I had before treatment left me with a foot in my own grave on May 24, 2023, the night Bess and I got married, and the night before the total glossectomy. We both knew I might not wake up from the surgery.
Despite the pain and the fatigue and the overall struggle, the choice to endure—to spend time with Bess, and writing, and trying to squeeze what I can out of life—has, well, endured. “Endure” means “enroll in clinical trials,” since the only existing treatments are palliative chemotherapy followed by death. When I was on petosemtamab / MCLA-158, the first clinical-trial drug, I endured full-body skin rashes and “paronychias” (infections and inflammation around the cuticles of the fingers and toes) that made it hard to type and walk. I bled a lot. When petosemtamab stopped working on Mar. 13, Bess and I scrambled madly, and I survived long enough to enroll in the Seagen PDL1V trial. I had high hopes that PDL1V would come with fewer side effects.
PDL1V is an antibody-drug conjugate (ADC), which, according to Seagen, means that the drug “specifically target[s] certain proteins that are found on the surface of tumor cells.” ADCs “recognize and bind tightly to targets expressed in tumors, while limiting binding to normal tissues.” Conventional systemic chemo causes numerous side effects because the chemo hits not only the cancer cells, but also all the other rapidly dividing cells in the body. ADCs are supposed to ameliorate that problem. PDL1V delivers a gnarly chemo agent called MMAE, which Wikipedia says “show[s] potency of up to 200 times that of vinblastine, another antimitotic drug.” I don’t fully understand what that means, although Bess says it basically has to do with a drug’s effects at a certain concentration, meaning that 1mL of MMAE is as powerful as 200mL of vinblastine. It does make MMAE sound like it’ll do bad things to tumors.
The question is, exactly how targeted is PDL1V? While I had fewer side effects from petosemtamab than the average patient, I appear to be on the other end of the curve for PDL1V—meaning it’s targeting the tumor, but it also seems to be targeting parts of me that aren’t tumor, too.
My first PDL1V dose was April 15, and I got through that week okay. Exhaustion and difficulty eating were the most prominent side effects. The second dose was April 22, and, like many ominous problems, the ones from that dose snuck up on me: by Tuesday April 23, I was feeling lightheaded, weak, confused, and generally out of sorts, which isn’t entirely unexpected when starting a new, experimental anti-cancer regimen. I’d seen the PDL1V side-effect list, too—fatigue, nausea, constipation, diarrhea, decreased appetite—a generic list of symptoms, and yet mine were consistent with them. Practically every medication carries a list of similar potential side effects, maybe because a lot of people are tired and have GI problems. Although I knew by Apr. 23 I was doing poorly and not eating enough (which is maybe not surprising given that I was sleeping or dozing for twelve hours a day), I checked my weight and discovered that I’d plunged from ~144 lbs down into the 133 – 136 lbs range. Crisis. It’s possible to starve to death by accident, since I’m never hungry and have to force myself to consume every calorie. But getting close to starvation will interrupt treatment, which is also deleterious. The world is full of perils, and Bess and I are navigating the cancer ones as best we can. If you’re reading this and wondering why a dip in my weight caused alarm bells, it’s because a series of seemingly tiny, benign problems can turn out to herald a crisis. I used to be robust, but now I’m fragile, and fragility demands diligence if I’m not to slip into the void.
In cancer therapy for an incurable malady like mine, there’s no promised land short of an extremely improbable, though not impossible, “complete response”—or permanent remission—but there are temporary safe harbors in which one can float for a time between dangerous ocean sojourns. Petosemtamab was such a relief. Sometimes what appears to be a safe harbor turns out to be infested with unexpected challenges, much as another may turn out to be too shallow, or controlled by pirates, or full. Last month I wrote seven thousand words about the epic journey from the MCLA-158 / petosemtamab clinical trial that kept my tumors checked from Sept. 2023 to March 2023, in “The emotional trial of clinical trials: It’s like online dating except if you choose wrong you die” and “The clinical trial trials: death by a thousand cuts.” It’s like The Lord of the Rings, except that the wizards and high elves are drug researchers, the men of Númenor are oncologists, and I’m basically a hobbit, sustained to a degree by courage and fortitude but fundamentally buffeted by forces frustratingly beyond my control.
If you read mountaineering disaster stories like Jon Krakauer’s Into Thin Air, there’s almost always a pattern: under-preparation; inexperienced climbers; failure to fully understand and incorporate how rapidly weather can change at altitude; and, perhaps most importantly, not turning back the minute the weather is changing for the worse. “Under-preparation” and “failure to recognize the truth of the situation” is probably a good, simplified version, and that happened to me: I wasn’t adequately prepared with GI meds like Zofran, Imodium, Bentyl, Simethecone, and even basic Pepto-Bismol. Even worse, on Apr. 23 I didn’t recognize what was happening to me, but Bess identified dehydration as a potential cause. Diarrhea causes dehydration and that in turn causes weight loss. Bess scolded me for not telling her of my GI symptoms sooner so that she could play doctor for me. Then again, is it playing doctor if she is a doctor?
By Apr. 24, two days after the second PDL1V treatment, dehydration became a focus of our efforts. In many if not most cities, a bunch of IV hydration companies have sprung up to cater to the hungover and coming-down-from-drugs crowd, and we live in prime territory for those clinics because numerous alcohol-dispensing points are nearby. Bess and I inadvertently moved into an area called “Old Town Scottsdale,” which is known for its bars and parties; you may read “inadvertently” and think: “How does one ‘inadvertently’ move somewhere? That seems like a pretty deliberate act.” While the moving itself was advertent, we left New York in 2020 during COVID and I picked our apartment based on its (relative) walkability, it being within acceptable range of Bess’s work, and the number of coffee shops within easy biking distance. I didn’t think to check for nearby bars. Probably we should’ve moved to downtown Phoenix, but Bess’s impressions of downtown Phoenix were decades out of date, and she thought it only fit for seeing a concert or a play, then driving away as fast as possible, unless one wants to score meth or paid sex of dubious quality beneath the Van Buren underpass.
Anyway, we did what we did and mistakes were made, but living beside a bunch of IV hydration companies proved useful because one was a two-minute walk from our building. By Wednesday, Apr. 24, I was being rehydrated, like a desiccated plant. Although IV bags through the IV clinic aren’t cheap—$100 for one liter, $150 for two—they’re much, much cheaper and more convenient than emergency rooms, which is where I was headed. My weight was low, my hold on consciousness becoming more tenuous, my heartrate up and erratic, while my blood pressure was down, and alleviating those problems was well worth the cash.
Unfortunately, I kept experiencing what we’ll call GI distress, which included feeling like my guts were being stirred with a hook every time I ate. The first round of PDL1V on Apr. 15 had caused exhaustion from the night of Apr. 17 until at least Sunday Apr. 21, but it didn’t cause a ton of GI issues, so those caught Bess and me off guard. The second round brought more fatigue, along with persistent GI struggles.
On top of the GI issues, we did get the go-ahead for spot radiation from Seagen / Pfizer, via START-Utah, the organization that is hosting the PDL1V study. So on Apr. 24 I got the two liters of IV fluids and my first session of spot radiation. The spot radiation immediately caused my neck to tighten, my voice to become hoarser and raspier, and my ability to swallow to be impaired. Bess and others point out to me, too, that radiation is commonly exhausting even for people not getting chemo-like agents. Still, I think the PDL1V accounts for the majority of the exhaustion, though I can’t rule out some contribution from radiation. When I got extensive radiation from Dec. 2022 – Jan. 2023, though, I remember the first three weeks of it not being bad in terms of side effects, and then the side effects getting worse by the day after that. But I wasn’t on any chemo agents from Dec. 2022 – Jan. 2023. I was, of course, also in much better physical shape then, and now I often seem a bit like a shambling reanimated corpse whose parts do not fit or act together all that well any more.
There’s also some evidence that MMAE in particular radiosensitizes tumors, and so we may have gotten some synergistic chemo-radiation effects. I feared, however, that the treatment might shrink the tumors and leave my neck fibrotic, and me unable to swallow semi-effectively, or speak. Then again, the tumors could grow and cause the same problems. Here we again see the remedy-disease conundrum.
Over the week of Apr. 22 – 29, the giant bulges on the left side of my neck have flattened out, which may imply PDL1V’s effectiveness. One site leaked a huge amount of goo reminiscent of the necrotized lymph node that startled me into an emergency ENT appointment back in November; Bess thinks the goo is necrotized tumor. The headaches that were plaguing me from the end of March through a lot of April were reduced in intensity, so it’s possible that the next CT scans will show PDL1V working well. It’s also possible that the radiation, potentiated by the drug, will make the PDL1V appear to have worked better than it would have on its own, even though I only finished two of my five spot radiation doses.
But the side effects and weight loss of the last two weeks make me doubtful PDL1V is sustainable. I spent most of Apr. 24 – 29 in bed. On Apr. 26, I foolishly drove myself to Mayo for a second radiation treatment while Bess was at work, when I should have taken an Uber because I could barely keep my eyes open. Eventually the GI problems petered out, but they were gross, and extensive, and even Imodium and related meds did not fully eliminate them. From Apr. 30 – May 5, I felt gradually better, but the absence of new material here on The Story’s Story gives a sense of how I was doing physically and mentally. I started writing this essay about PDL1V side effects on Apr. 26. It’s not like me to take two weeks to write an essay like this.
I got a third PDL1V dose on Monday, May 6, and now I’m armed with an army of medications to combat potential side effects: a dose of Aloxi (“super Zofran”—an anti-emetic) and 4mg of dexamethasone with the PDL1V itself. Lots of Imodium. Bentyl and Simethicone, for gut pain and cramping. Ativan at night. I think a couple of others I’m not remembering right now. The side effects have been better than they were after the second dose, but they’ve still been rough. Dr. Call, my oncologist at START-Utah, says that we can reduce the PDL1V dose in an attempt to cut back the side effects while likely retaining the anti-cancer properties.
There’s another possibility, too: right now we have a slot for an immunotherapy called BGB-A3055. Next week I’ll get CT scans to check and see what the PDL1V has done so far. If PDL1V has minimal anti-tumor effect, then leaving the PDL1V trial is easy. But what if it shrinks my tumor size by 30% or more, at the cost of me feeling abysmal for two weeks out of three, and barely being able to eat? How long can I keep this up, even with supportive medication?
The questions likely don’t have answers. I’m tired of being tired, after a mere three weeks of treatment. Most likely, we’ll get ambiguous results from the CT scans next week: tumors that are, say, 15% smaller—which is great, but enough to endure the GI problems and exhaustion?
Cancer brings with it a whiff of medieval torture options: would you rather be placed on the rack or quartered? Either way you’re torn apart. Either way, a third option would be preferable, though there is only one to choose from: whether or not to endure the cure or the disease at all.
Bess is the main reason to persist. It’s dispiriting to have poured so much effort into finding PDL1V and getting into the trial, only to find myself on a ship that seems to have a serious hole in it, and some seaworthiness questions. Yet that’s part of the experimental-drug process.[1] We make choices based on incomplete information and do the best we can with those choices. I didn’t foresee being walloped by PDL1V GI side effects. I didn’t foresee either the sweaty, intense, month-long period from Mar. 13 to Apr. 15 when finding a clinical trial utterly consumed Bess and me. In early April, I wasn’t convinced I’d make it to the next trial. Yet I’m still here, despite having shed pounds that I didn’t and don’t have to shed. Surprises pile up. Some are pleasant: I didn’t think petosemtamab would work, or that I’d see 2024, and yet it did and we’re now well into 2024. I’ve gotten to spend a huge amount of bonus time with Bess.
For now, my choice remains to endure. The question, as I contemplate whether it’s better to persevere on PDL1V or transition into the next study is: will the new drug allow me to?
* “The new science of death: ‘There’s something happening in the brain that makes no sense.’” My view is that we don’t understand consciousness or the brain.
* Questions about biotech. Really impressive! Don’t be put off by a title that may seem anodyne. Questions about biotech are really questions about life itself, and whether we live or, in my case, die.
* “How I fell out of love with academia.” The problems are well known, but no one has managed to yet produce a better system. “Yet” being the key word.
* “Hamas Actually Believed It Would Conquer Israel. In Preparation, It Divided the Country Into Cantons.” Interesting if true. I’m struck by how often throughout history leaders have just made very bad choices. That striking feature makes me pessimistic about the future of humanity, given nuclear weapons, ego, and hubris.
The Story's Story 