“Woman-to-Woman-to…Huberman:” What journalism looks like from the inside

May 6, 2024 By Jake Seliger in Critics, Culture, ideas, Publishing Tags: Culture, huberman, Media Leave a comment

This is written by a woman (and friend of mine!) who wishes to remain anonymous.

When the article about Andrew Huberman was published in March, I wasn’t surprised, because “Sarah” had contacted me months before, seeking answers from women she says didn’t know about her, though they were having sex with her then-partner, Andrew.

On a Sunday night in February, I received a text from an unknown number—the texter introduced herself as “Sarah,” the woman Andrew shared his life with for the last five years. She shared deeply personal, deleterious, and unsubstantiated details about Andrew cheating on her with four to ten women, spreading rumors about her, and verbally abusing her. She assumed I was one of those hapless women, and she apologized for being the one to tell me. She was cloaking gossip in virtue, though she reassured me that she held no ill will against me and saw me as another victim. All of this happened before ending her opening message to me by asking me, “woman-to-woman,” to bring her comfort and closure by admitting that I was sleeping with Andrew.

I felt a mix of shame, suspicion, confusion, hurt, degradation, empathy, and curiosity. Who was on the other end of this message? Could I trust her, or him, or them? Was this a trap? What sort of nightmare love triangle did Andrew drag me into? “Triangle” is probably not even the right geometric shape. I asked her how she found my contact information. It was hard not to feel solidarity with her, she was kind and spilling her guts about her heartbreak—yet, her approach was unapologetically intrusive and felt manipulative.

Sarah said she found my name in Andrew’s journal one day and instinctively took a photo of the page and later googled me to find my number. When I asked why she’d assume I had an “affair” with Andrew after reading my name in his journal, she replied: “Because of him talking about a long-term relationship…with somebody beautiful. I looked at your picture and you seemed beautiful and private.”

I admit some susceptibility to flattery, and yet it was as if Sarah thought I owed her answers regarding my relationship with Andrew. After I felt confident that this was the woman that Andrew had been seeing for the last few years, I told her that I’d not seen Andrew since before the pandemic. She rapid-fire texted:

“So he cheated on me with you in the early part of our relationship?”
- No, I’ve been in relationships.
“Oh, he reached out, but you didn’t accept.”
- No.
“Were you in a relationship with him? Or was it just more casual?”

I told Sarah I’d not been romantically involved with Andrew since before their relationship started in ~2018.

She declared how relieved she felt and we discussed in limited detail our histories with Andrew. Sarah said nothing about going to the press and I said I wasn’t interested in any sort of PR takedown of him. It’s possible she wasn’t planning to at that moment, but I felt she had an agenda beyond closure. I thought she wanted revenge.

I told her I’d known Andrew for nearly 20 years and was aware that he had some struggles in his relationships—and don’t we all! Sarah said she was also aware of his past. Despite what she said earlier in her texts, Andrew had nothing but very positive things to say about her whenever I spoke to him. He told me all about their struggles with fertility and how much he loved their shared life with her children from a former marriage. While Andrew and I had dated off and on for many years, he did not reach out to me for anything romantic when they were together, indicating to me that he must be quite committed and in love with her. I expressed compassion and empathy for her and with any woman he’s not been truthful to, but I also expressed sympathy for Andrew because I know that, despite himself, he wants a life partner. The whole thing seemed sad to me.

After Sarah realized I saw Andrew as more than what she and these other women experienced (he is more than that), she acknowledged Andrew was generous and kind with her in many ways throughout their relationship. She repeated to me that part of her healing process is knowing the full truth. I am sure she meant this, though I don’t know where she picked up this notion or how she knows it’s true. I think she should read Esther Perel’s books. The sense that she was seeking more than “healing” persisted. The truth came out when the article hit.

I can’t decide what stood out to me more when I first read it: that Sarah cherry-picked whose contact info she provided to Kerry Howley, conveniently excluding me, or that a story which doesn’t amount to much more than a gossip column about an accomplished neuroscientist-turned-podcaster’s propensity for wandering made the front cover of New York Magazine. There’s no abuse of power, no exploitation, no inspirational story of female empowerment—there’s simply an opportunistic journalist writing an unflattering portrayal of Andrew Huberman as a narcissistic, philandering liar. Is someone’s admittedly salacious private life news?

Howley might’ve squandered an opportunity to empower women who may have felt powerless in their relationships or perhaps open a dialogue about the complexity of human relationships gone awry. Something about how these women found themselves involved and, in some cases, in love with a man who seemed unreliable and even deceptive in his personal life while earning a public reputation as thoughtful, insightful, and charming. Instead of complexity, she chose simplicity. Howley didn’t explore the characters or backgrounds of the women in this story. Who are they? What were they seeking? Had she done more diligence of her own, Howley would’ve at least alluded to the background of one of them whose company was investigated for consumer fraud and sued by former employees for wage theft—clear instances of deception and abusing one’s power. The latter of the two was settled out of court and as they say, guilty people don’t settle (looking at you, Michael Jackson).

Instead, Howley wrote about a series of anonymous women who say they thought they were in a monogamous relationship with a man, only to find out it was not monogamous at all. She highlighted how he repeated the same lines over and over again to these women. A lot of the language sounded familiar to me—oh wait, that’s because I’ve known Andew for years. I’m pretty certain my vernacular doesn’t reinvent itself every time I’m in a new relationship, and I’m pretty sure that’s true of most people. The article also includes a number of barely corroborated, seemingly petty things Andrew lied about to demonstrate his supposed lack of moral compass. One that stood out to me was that he lied about living in Piedmont, a wealthy enclave in the East Bay. Andrew’s home, while technically not part of the Piedmont zip code, was a literal stone’s throw away. The article felt like a jilted-lovers’ fantasy come true: an expose detailing every dark and mortifying secret about your cheating ex.

Perhaps there just wasn’t a great story to tell and that’s why it merely reads as gossip. Were Howley and the New York Magazine editor also duped into sleeping with Andrew Huberman under the guise of monogamy and a great future together? Did they do it anyway, for the story?

Look, I get it. I have a pretty deep well of empathy for a woman scorned; I tell friends that I’ll provide transportation across international borders should they seek revenge and need to make a quick getaway. What I really want my friends to know when I make that joke is, if anyone ever betrays their trust, I’ll empathize with their feelings of anger and hurt and won’t judge them for acting out while they process it.

I’ve been inspired by women who seek revenge on their exes, particularly when they empower themselves as women in the process. The difference between empowerment and disempowerment is important. One such example is the article that Justine Musk penned herself about her ex-husband, Elon Musk. Justine didn’t write this anonymously or use it as an opportunity to unearth gossip from all corners of Musk’s life (even though I think he deserved it then and deserves it even more now), weaving together a hit-piece without any substantive commentary on the complexities of life and relationships. Justine bravely laid bare her participation in the slow relinquishing of her own identity and career in support of her talented but painfully insecure partner, who turned around and dumped her anyway. The story inspires because it’s multifaceted, introspective, and offers insight into how someone might find themself in that exact same situation. And perhaps a roadmap to escape it.

The Sarah I communicated with in February sounded capable of writing something more cogent and inspiring. Something revealing, and introspective, while also untangling the complexities of getting involved with someone we can’t fully trust. I think Howley failed her by turning this article into the hack job that it is. I don’t know whether Sarah or these other women found closure or peace of mind by participating. I can’t help but feel like this article could serve as a lesson for Andrew and for them, but one that the author failed to articulate anywhere among its 10,000 words. What stories aren’t being told as this one is? What would someone with a broader, more humane vision of the world than Howley’s have done with the material? If we’re going to talk about lying, why don’t we talk about Sarah’s motives, and what she said when she approached women on Howley’s behalf? Why aren’t we looking into the relationship between Sarah and Howley?

Much of the legacy media has turned into a hit-piece machine. It’s sad, but also common, and yet I still think many people don’t realize how the media sausage gets made. Once a journalist has a point of view, they often act like a prosecutor. We saw what the New York Times did to Astral Codex Ten writer Scott Alexander. Now we have this attack against Huberman. I don’t condone his dating habits, but I also don’t think this amounts to a public story. Ryan Holiday published Trust Me, I’m Lying: Confessions of a Media Manipulator back in 2012. A dozen years later, it remains distressingly relevant. I want someone to investigate Howley and Sarah, and tell us how the article came together. That’s the story that’s most important to the public interest, because so many of the media’s sleazy operations are cloaked in secrecy. I can reveal just a little bit of that story: “journalism” can pretend to be a private story when it’s actually prep for a public social attack.

Many of us have unfortunate periods in our romantic histories, or pathologies we battle in our relationships today. But if you become famous, you become a target for the Howleys and New York Magazines of the world.

I don’t think there is a there there with this story. I think Sarah and Andrew did have real love and a real relationship, and she knows Andrew. She knows about his childhood, about his struggles to get where he is, about his deep desire for a loving family. Regardless of how much Howley attempted to undermine and trivialize it. I’ve had men betray me and I’ve fantasized about their personal or professional demise. But over time I’ve come to see them more fully. They are more than the hurt they caused me, and they were more to me than the hurt they caused me. Someone once told me that the only thing more emotionally damaging than feeling abandoned or betrayed by someone you trust, is abandoning our own sense of truth and morality. I believe that. But, if you’re my friend or a woman in need and your man has cheated on you, you know where to find me if you need a getaway car.

In which the squamous cell carcinoma tumors in my neck grow by 20% in two months

March 18, 2024 By Jake Seliger in Culture, Essays, Personal Tags: cancer, clinical trials, Essays, personal 6 Comments

The four tumors in my neck grew by an average of about 20% from Jan. 16 to Mar. 11—and that’s after they shrank by about 20% between Sept. 27, when I got my first dose of the bispecific antibody petosemtamab, and Jan. 16. Existing published data shows that “Of the patients who responded [to petosemtamab], the median DOR was 6.0 months.” I’m a bit under the six-month mark, and three neck tumors are substantially larger:

* 38 x 27 mm -> 43 x 33 mm

* 29 x 16 mm -> 35 x 18 mm

* 22 x 14 mm -> 29 x 21 mm

(I don’t understand how radiologists evaluate a three-dimensional object like a tumor with two-dimensional measurements,[1] but radiologists are, like pathologists, part of the hidden, antisocial,[2] subterranean section of the medical system, rarely interacting with humans (or light), sleeping by day and waking by night, and subsisting on a diet primarily of human blood, supplemented by small mammals when none is available.[3] So I’ve not gotten a chance to ask what’s up with the two-measurements thing when there ought to be three.)

No tumor is yet impinging on critical structures, which is nice, although one is poking out of my neck, which is less nice. One oddity is that my lung tumors are stable and one even seems to have resolved, despite the growth of the tumors in my neck. Dr. Sacco, my oncologist at UCSD, said she’s never seen a patient’s lung and neck tumors diverge in response like mine. If that means anything, I don’t know what.

So now Bess and I back to scrambling for a new trial—and “scrambling” is the right word, despite all of our effort to avoid having to scramble. Most trials mandate a 30-day washout period,[4] and I got my last petosemtamab infusion on March 13, and thus a goal is to receive the new trial drug by Monday, April 15. I thought I had two good options for a Seagen trial of an antibody-drug conjugate (ADC): one at UCSD at one at MD Anderson (“MDA”) in Houston. I thought (incorrectly, it appears) that UCSD would host Seagen’s “A Study of SGN-PDL1V in Advanced Solid Tumors,” but there are two issues: one is that there are actually two different Seagen trials that I’m eligible for. The other is that there’ve been delays in opening a Seagen trial at UCSD. My tumors are growing too fast to wait around to see when it might open. Some trial sites report years’ worth of delays for something as finicky as “the drug company doesn’t like the hospital’s supplier of saline,” or something equally ludicrous. Maybe an astrologer told Seagen now isn’t an auspicious time?

Adding to the complexity, “PDL1V” is one Seagen trial. The other is SGNTV-001, which is the innovaTV 207 trial. SGNTV appears to be the trial available at UCSD.

You may have read the above paragraphs and thought: “Seagen trial one, Seagen trial two, who cares?” But the difference may be critical to whether I live or die. Few people understand how maddening and challenging the clinical-trial system can be, which is part of the reason I’m describing what’s happening to me. The SGNTV trial is one that, back in August or September, a research oncologist who hosted an SGNTV trial site told us wasn’t looking so good.

We listen carefully to oncologists and take what they say seriously. But data from 2022 says that “Tisotumab Vedotin Shows Promising Efficacy and Manageable Toxicity Profile in Phase 2 Study of SCCHN:” “Results from the phase 2 innovaTV 207 study (NCT03485209) showed a confirmed objective response rate (ORR) of 16% and an overall disease control rate of 58%, along with a tolerable safety profile.” By the standards of recurrent/metastatic squamous cell carcinoma (R / M HNSCC), 60% is pretty good. An abstract from 2023 reports that “15 pts with SCCHN were treated” and “Confirmed ORR was 40%.” “Stable disease” also qualifies as “pretty good” by R / M HNSCC, and “ORR” doesn’t include patients who have “stable disease.” “Stable disease” is anything that is plus or minus thirty percent in size from the original. The disease control rate of petosemtamab was around 70%, and petosemtamab is arguably the most promising drug for what I have.

Should I try for PDL1V, or SGNTV? Although finding an open trial site is a challenge, so is ranking the trials. PDL1V is being held at MDA, where I also established care back in November (I wrote about that in “Finally, some good tumor news, but, also, hacking up blood is probably bad”). But the physician with whom I established care there is out of town until Mar. 25. MDA has, let us say, not made it easy to consult with someone else about a PDL1V trial slot. Waiting two weeks and then finding out that there isn’t a slot available at MDA could be fatal. Bess and I are working to figure out if we can talk to someone else at MDA about a PDL1V trial slot. None of the other 12 places I established care are hosting either of these trials, so we’re back to searching on clinicaltrials.gov for other host sites and trying to beg our way in quickly.

Is SGN-PDL1V likely to be better than SGNTV-001? PDL1V began in 2022, and SGNTV began in 2018, so PDL1V is newer. Are clinical trials like graphics cards, in that newer is better? I don’t know. The oncologist who said SGNTV didn’t look great said so in 2023, but more data has presumably been generated between September and now.

The third drug is NT219. We’re trying to get an appointment at Cedars-Sinai hospital in LA to learn more about it. There’s hardly any published data about NT219. UCSD had an NT219 trial, but that’s not open any more. Has NT219 failed? On clinicaltrials.gov, no sites are listed as recruiting. Drug companies keep early data close to their chests. The best bet is to talk to a clinical investigator involved in the trial and hope they drop an information nugget, or make a vague hand motion indicating whether a drug is doing well or poorly. Many, but not all, are loath to say, “My observation is that x% of patients are responding to the drug,” and the ones who do play a heavily weighted role in my deciding how best not to die.

“Not dying” is hard. I’ve got an appointment at a PDL1V site in Salt Lake City, Utah, at South Texas Accelerated Research Therapeutics (START)—Rocky Mountain. The organization’s name may be “South Texas” but that the site is in Utah. I’m also working on getting into START—San Antonio. The variability among hospitals in terms of intake and acceptance is massive—both START sites, like UCSD, have made getting appointments and getting into their systems straightforward. It’s almost as if they realize they’re a research institution and want research subjects. I can’t decide if it’s mostly individual initiative within the systems that accounts for differences, or if organizational culture between different hospital organizations accounts for how patient-friendly versus patient-hostile hospital sites are. A lot of clinical trial insiders complain about the difficulty of patient recruitment, and, given how hard it is to get into a study after saying “Hey, I’d really like to be in this study,” I have a few ideas as to why.

If I were in charge of clinical trials, I’d be working hard to make patient intake easy—a subject I talk about in “Puzzles about oncology and clinical trials.” Those puzzles continue to puzzle. Among businesses that sell to consumer, there’s a rabid obsession with user interface and user experience (UI/UX), because getting those wrong can lead to outcomes that range from “make less money” to “go bankrupt.” In a lot of medical situations, there seems to be no conscious, deliberate effort at improving UI/UX or intake. And after a decade and a half of promises about health-record sharing via electronic medical records (EMRs), I still wind up sending a ton of PDFs to intake coordinators, who then, I assume, manually attach them to the local EMR. One PDL1V site, UC Davis, requires that all records be faxed to them. This is not a joke. The records they request run to 100+ pages. UC Davis, as the name implies, is part of the University of California system—as is UCSD. I’d imagine they’d be able to pull records from another UC hospital, but no. Fax or die. Faxing it is.

You may think that me describing the clinical-trial process is pointlessly, tediously boring, but I’m doing it most of all for other people in similar situations. Don’t give up! Persevere despite the struggle. You are not alone. The system should be fixable, and, though I personally can’t fix them, I can explain my experience and thus hopefully shed light on the process in a way that helps others.

Between late December and March, life had slowly slid into a new normal. Although I’m not physically well compared to where I was before the cancer recurrence, I had more energy than I did in that bleak period of surgical recovery and systemic chemotherapy. A low bar, but one I managed to shuffle over. I’ve managed to do a lot of writing, and to help Bess do a lot of writing. I’ve been emailing advice and guidance to other people with cancer who are navigating clinical trials. I’ve been trying to live a positive, meaningful life.

It feels like my Interregnum Is over, and I’m back to wondering If this Is It. I know, intellectually, that I may be able to survive the month-long washout period, and that the next trial drug may work. But I also know that the month-long washout period may be long enough to get bone or brain metastases. The next trial drug may not work. And, even if it does, after the PDL1V trial, there is no other highly promising trial that I’m aware of. There are some okay trials in phase 1a, but most 1a trials don’t really work. NT219 requires that participants have had no more than two systemic lines of therapy, and SGNTV has the same requirement. So doing PDL1V means I won’t be able to do the other two. I might have to move to New Jersey for a drug called RAPA-201.

There are a huge number of issues to track, and limited information. We’re seeking more information but often not getting it. Life is usually an incomplete-information game. It’s more statistics and less calculus. Sometimes, one makes life-or-death decisions based on incomplete information.

I recently read an interesting though flawed memoir called The Trading Game, by Gary Stevenson, and the narrator describes the eponymous game that helps get him a job as a currency trader:

The trading game was supposed to be a simulation of trading, but actually, it was just a numbers game.

It ran using a special deck of seventeen numbered cards: some higher, some lower. In case you ever want to play it yourself, the full deck of cards was a -10, a 20, and all the numbers 1 through 15. Each player is dealt their own card, which they could look at, and then another three cards are placed, face down, in the center of the table. The game works by players essentially making bets against each other on what will be the total numerical value of the eight cards in the game (each of five players has one card, plus the three in the middle).

Conceptually, you can think of it like this: you are all buying and selling some asset and the total value of that asset is the sum of the cards in the game. You only have certain information (your own card); more information (the cards in the middle) is revealed as the game goes on. If you have a high card, say the 15, or the 20, then that gives you inside information that the total will probably be quite high, so you want to make “buy” bets that it’s a high total. If you have a low card like the -10 you probably want to make “sell” bets that the total is low. If you get a middle card like a 6 or a 7, then I guess you’ll have to make something up.

The betting system Is mainly what made the game a “trading game,” Ie It was designed to mimic the way that traders make bets in the markets: “price-making” and “price-taking” using “two-way markets.”

I feel like I’m playing the clinical-trial game. Instead of numbers on cards, I know there’s a large pot of hidden efficacy data that I can’t access. It’s siloed in databases run by hospitals or drug companies. Occasionally, some of that data is released publicly, and it becomes common knowledge. Often, however, I don’t know whether a given clinical trial is -15, or 20, or, most commonly, somewhere in between. Petosemtamab was close to a 20—maybe a 15 or something. I’m trying to trade on what public data exists, and what I can glean from conversations with oncologists, to make the optimal decision.

The analogy is inexact, but I wonder what happens to the people who don’t fully realize the kind of “game” that’s being played with their lives. If their oncologist even brings up the option of clinical trials (few actively refer patients to studies), it’s probably to whatever happens to be available at the hospital where they practice, regardless of the quality of the drug.

And the FDA doesn’t care; the FDA’s goal is to make itself look good, or as not-bad as possible, regardless of the number of people who fill the invisible graveyard while waiting for potential treatments to fatal disease. People running the trials are at the mercy of the incentives set by the FDA within the system. Some individuals within the system are amazing, and that fact is part of the reason I’ve been telling people with head and neck cancer to establish care at UCSD if doing so is feasible and reasonable. My top-level feeling, though, remains what I wrote about in “Who cares about your healthcare? What’s commonly overlooked in the ‘health’ care system:” no one is going to care as much as you and your family.

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care. As you can infer, I probably have a lot of flights in my future.

[1] Bess read this and said that radiologists look at the two longest vectors. But that leaves a lot of room for the third axis, doesn’t it?

[2] I kid: I assume radiologists are as social as any other sort of doctor, though I can’t be sure because I hardly ever interact with them.

[3] Although I was kidding about the antisocial thing, this part is serious.

[4] During the washout period, I’ll ideally also be “screened” for study eligibility—CTs, MRIs, PET scans, labs, palm reading, awaiting drug-company sponsor approval. Not having to go through the process of waiting for appointments to establish care at new cancer centers can shave a few weeks off the process.

Food and friends, part 2: Edible food-like substances and the need to swallow again

February 28, 2024 By Jake Seliger in Culture, Personal Tags: cancer, Essays, food, personal Leave a comment

Part 1 is here, although “Edible food-like substances and the need to swallow again” is meant to stand alone. Part III is here.

I went into the May 25 surgery that unexpectedly took my entire tongue weighing around 155 to 160 lbs. When I came to, I probably didn’t weigh much less than I had when the anesthesia hit, but I felt like the heft of my body had been replaced with the weight of all that had gone wrong, and I was what was left over. Insubstantial. Without appetite.[1] Although it’s a cliché that you feel dread in “the pit of your stomach,” I instead felt dread in my nasal cavity—a horrible nasal tube was anchored with a stitch into my right nostril. It snaked up my nose and down my esophagus, terminating in my stomach.[2] Tube feeds were how I “swallowed,” although I had no agency in the process: a nurse pressed a button on the machine and the machine pumped food, regardless of my feelings or sensations.

Any calories had to go in through that tube. To say I hated consuming calories via nasal tube is an understatement. If I’d had an “off, forever” switch available to me in those first days after surgery, I’d likely have flicked it. Instead, I had oxycodone and dilaudid, which weren’t as good as an “off” switch, but adequate doses did make me feel like I was nowhere. Like most medical treatments, though, oxycodone and dilaudid come with a cost: opioids are severely constipating, and taking them may have led to what was one of the most dangerous moments after surgery.

In the hospital, it felt like every 10 minutes something or other had to happen: medications, cleanings, probings, vitals. “Tube feeds” weren’t just unpleasant because of the uncomfortable tube— the feeds themselves were a source of both pain and nausea. The word “feed,” makes me sound like I went from being a man to some kind of farm animal or hamster or alien. Or may an alien hamster farm animal? Before the surgery I never once looked at Bess and said, “Hey, why don’t we sit down to feed,” or “Baby, let’s go out to feed.” And if I ever did, I was joking.

The tube feeds made me nauseous and gave me terrible reflux. Part of the problems no doubt came from the surgery trauma and all the drugs I was on. But the ingredients in the substance itself couldn’t have helped. I had two choices, or assignments, depending on who was in command of the tube feed situation on a given day: either Nutren® 2.0 (made by Nestle Health Science) or Boost® Balanced Nutritional Drinks. Calling “Boost” a “nutritional drink” is like calling a junkyard a “pristine Redwood forest.” Boost’s website lists the ingredients as “WATER, GLUCOSE SYRUP, SUGAR, MILK PROTEIN CONCENTRATE, CANOLA OIL, AND LESS THAN 2% OF COCOA. [. . .]” I don’t think humans are supposed to eat diets rich in glucose syrup (which is just another sugar), sugar (this is also a sugar), and canola oil (the writer and gadfly Gary Taubes wrote a persuasive book called The Case Against Sugar). Whatever the problems I was having with digestion, I don’t think those problems were aided by vitamin-infused liquid sugar solutions.

I was barely alive and unsure about which side of the life-death line I would wind up on, which was not an ideal position for investigating alternatives to Nutren® or Boost®. At some point, a few days after the surgery, interventional radiology installed a PEG tube, and that installation let doctors remove the nasal tube. Getting the nasal tube out was an improvement, although injecting Nutren® or Boost® via PEG tube wasn’t, as you’d imagine, a real satisfying eating experience. In the hospital, I got enough calories to not die, and I guess that was enough from a medical perspective, if not a human one.

The Mayo ENTs said I’d likely be able to swallow again one day, albeit by blending food. I didn’t believe them. I couldn’t imagine much of a future and drifted in a present defined by either miserable, excruciating pain and nausea, or by opioids that allowed me to feel like I didn’t exist. I got out of the hospital in early June, and food injections continued to be a massive struggle, in part because I didn’t get the right injection pump until two weeks after discharge. My digestion improved when a friend suggested I try “Liquid Hope,” a liquid food product made from actual foods. The ingredients include ones I actually ate before the surgery: “Filtered water, organic garbanzo beans, organic green peas, organic carrots, organic hydrolyzed pea protein.” Garbanzos, peas, and carrots are good for humans in the way “hydrolyzed palm oil” is not.

For someone who prides himself on cooking and likes to try lots of different foods, this period was hard, and made harder by the belief I wouldn’t eat for life. I didn’t get to swallow again until late July, when Mayo speech pathologist Jessica Gregor showed me that I could, despite my reluctance and fear of choking, and she lovingly bullied me (that is Bess’s phrase) into choking down a glass of melted, diluted ice cream. It was the first thing I’d tasted in two months. It was a revelation. By then the trache tube was out of my throat and the trache wound had healed. I wrote about those first swallows in “On being ready to die, and yet also now being able to swallow slurries—including ice cream:”

With Jessica, I swallowed some ice cream slurry: the Van Leeuwen’s honeycomb flavor. We melted it and blended it with some extra milk, to thin it. And, although I was intensely skeptical that this would result in a meaningful sensory experience, there are taste buds at the back of the throat and esophagus. So I could taste ice cream. Since that night I’ve tried lots of things. Anything acidic, like lentil-soup slurry with too much lemon, doesn’t work well yet. Anything salty, same problem. But savory foods work and so do sweet ones. There’s a fun bakery and wine shop in Tempe called Tracy Dempsey Originals that we’ve been going to. Tracy Dempsey makes spectacular ice cream flavors—particularly her cardamom with fig jam. It turns out I can eat things like cookies and brownies if they’re blended with milk or coffee.

Over many months of practice I’ve gotten pretty good at swallowing. Swallowing isn’t like it was before the surgery, but I can taste foods at the back of my throat and, to a lesser extent, in my cheeks. I’m much better at handling acid, salt, and spice than I was when I wrote “On being ready to die.”

One of the scarier moments hit in the first few days after I began swallowing again. I was trying to drink water, and some of it got caught in my airway—I don’t know how, exactly. Bess was home and heard me making some horrible noise like a fish on a boat. She ran over to help but didn’t know what to do, as there wasn’t much to do, and she justifiably feared worsening the choking problem. I think she pounded on my back as I alternated between trying to expel the water and take a breath. I couldn’t get a breath in. I don’t remember which happened first, or how, though I do remember thinking: “I’m about to die by drowning.” And I remember the desperate gasps as I began to get air again. I’d wrongly thought water would be easier than solids, but melted ice cream was, for a while, the only thing that required a mere struggle, as opposed to a titanic struggle.

I’d lost so much taste and texture sensation when I lost my tongue, just as I’d lost much of my life’s animating energy, along with one of my chief means of hanging out with friends and friends-to-be, but enough taste sensation remained for me to enjoy the ice cream. Although that enjoyment was mixed with the terror of drowning.

Part III will continue in a few days. If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care.

[1] Appetite for anything: food, sex, life, status—all the things that make us human and keep us going.

[2] Horrible, but probably better than dying.

The dead and dying at the gates of oncology clinical trials

January 29, 2024 By Jake Seliger in Culture, Essays, Personal Tags: cancer, clinical trials, Essays, oncology, personal 3 Comments

If you find this piece worthwhile, consider the Go Fund Me that’s funding ongoing care.

I was reading Tyler Cowen and Daniel Gross’s book Talent: How to Identify Energizers, Creatives, and Winners Around the World, and in it they write: “You can open doors for other people at relatively low cost (perhaps zero cost) to yourself just by making some options more vivid to them.… You embody something, and that something will stir some others into action” (237). That’s a lot of what Bess and I are doing when we write about clinical trials, where getting the wrong answer means death: thus, our extensive focus on it, and the healthcare system more broadly. We’re trying to open doors, especially for people who are sick or who don’t realize what their options are.

Right now, according to “The pharma industry from Paul Janssen to today: why drugs got harder to develop and what we can do about it,” apparently “Only 6% of cancer patients take part in clinical trials nationally in the US, for instance, and the number is generally lower in other countries and for other conditions.” A lot of cancer patients don’t need clinical trials and are healed by existing treatments, but, even granting that standard-of-care often works, 6% seems low—it may be low because of poor guidance combined with fatalism. If my experience is representative,[1] a lot of cancer patients aren’t getting adequate help understanding the system and finding a trial. Bess and I only succeeded in finding a clinical trial to keep me alive because of our own perseverance and obsessiveness; we were explicitly encouraged by multiple oncologists not to bother and to let me die. My primary oncologist at the Mayo Clinic Phoenix offered zero guidance, aid, or advice. I can’t tell how common this is, though feedback so far seems to indicate the answer might be “pretty common.” For a normal person without some of our traits, background, and resources, getting an optimal clinical trial would be far harder, if not impossible—and it was already hard for us. I’m still puzzled that more people with poor prognoses on standard-of-care treatments aren’t working to get the best clinical trials they can.

What’s the barrier? Mindset, and discouragement from oncologists, is probably one problem. A guy named Richard Chen, whose profile says he wrote two books on clinical trial recruitment, said: “First, FDA’s remit is not, and has never been, to get therapies to patients.” He also said: “Its primary mission first and foremost, is to prevent unsafe drugs from injuring patients.” If the FDA’s remit isn’t to get therapies to patients, that’s bad, and its remit should change. The second comment is pure, unintentional comedy. Right now, I’m a dead man walking. The FDA is preventing “unsafe” drugs from injuring me, so that I can be “injured”—which is to say, killed—by a recurrent/metastatic squamous cell carcinoma infestation. If I’m injured or killed by a drug, that’s not so different from my ultimate trajectory anyway, and the knowledge that can be created from my situation might accelerate treatments and save the next guy’s life.

Moreover, we already have an example of a medical area that works well with minimal FDA interference: surgery. Maxwell Tabarrok describes the situation in “Surgery Works Well Without The FDA: The best evidence against the FDA:”

Despite extreme information problems and a complete absence of federal oversight, surgery seems to work well. Compared to similar patients on the waiting list, 2.3 million life years were saved by organ transplants over 25 years. The WHO claims that “surgical interventions account for 13% of the world’s total disability-adjusted life years.” Coronary artery surgery extends lifespan by several years for $2300 a year. Cataract surgery and LASIK can massively improve quality of life for a few thousand dollars.

Regarding drugs, particularly drugs for people who are already effectively dead, like me, we should be moving closer to a surgical model.

I think Chen is a smart and well-meaning person. But he’s so bureaucratized, and he’s so imbibed the FDA’s line, that he doesn’t realize the Kafkaesque absurdity of telling me, a dying man who’s failed all standard therapies, that the FDA is protecting me from potentially unsafe drugs, so that I can safely die of cancer. If the FDA didn’t flex their paternalism quite so aggressively, terminal patients could at least consent to try something that might help them, which is better odds than trying nothing and waiting for a certain end. Look, if the FDA wants to have long trial periods for dubious drugs like those meant to lower cholesterol or whatever, fine. Once a person has a fatal diagnosis, however, that person is probably, like me, a lot more inclined to take a flyer on what’s available and see what happens. And we should be allowed to do that. We’re terminal, not without capacity. If the FDA’s remit is, ultimately, preventing patient injury, maybe they should ask themselves if they’re causing injury with their current approach?

Knowledge among patients and oncologists seems to be another barrier, according to “Why drugs got harder to develop:”

Many patients are willing to take part in clinical trials in principle, but awareness is poor. About 50% of the time when patients are invited to clinical trials they accept, but 90% are never invited to participate, mainly because most patients are not treated in settings that conduct trials. Patients are also not necessarily aware of or educated about the benefits of trials, and how they may enable them to access a high standard of care. Leading clinical research centres often have too many studies and not enough patients. When it comes to the trial itself, the site may be far from where the patient lives, requiring them to travel or even relocate for the duration of the trial — without adequate support for doing so.

Poor awareness is consistent with my experience—no one explicitly told me to seek clinical trials. Bess writes about the dearth of oncologists referring their patients to clinical trials in “Please be dying but not too quickly: part three” and I’ve written about this issue as well, but, as I mentioned above, if I’d followed my then-oncologist’s guidance, I’d have done some palliative chemo and then died. That doesn’t seem like an optimal outcome. If I die, Bess will be lonely. In spaces like oncology, I’d expect patients to be more like me—that is, highly motivated to attempt to not die. I don’t wholly understand what’s going on, which is why I titled my last essay on the subject “Puzzles about oncology and clinical trials.”

I guess (or infer from behavior) that most oncologists aren’t penalized or rewarded for helping their patients find and enter clinical trials. In the emergency room, a doctor who routinely misses heart attacks or strokes will find his or her license attacked and him or herself in a court room. In oncology, there’s apparently no real effort to consistently help patients who’ve exhausted standard treatments. It’s not, I guess, part of the professional elements of the profession, which I find surprising. Sure, many patients are likely elderly and too sick to pursue clinical trials, but a fair number must be like me: motivated and able to undertake somewhat arduous efforts to prevent or delay death.

One reason too few people participate may be logistical:

To get enough patients to fill up large trials companies need to conduct trials at multiple sites. The more sites involved in a trial, the greater the logistical complexities involved in coordinating that the protocol is executed appropriately across sites, the data is collected to a good standard, and the drug is distributed to all sites as needed. This all increases costs. More sites also increases variance in execution, and improper trial conduct can delay or even sink a development program. According to data from Tufts university, >80% of trials fail to recruit on time, actual enrolment times are typically around double the planned timelines, and ~50% of terminated trials result from recruitment failures. An estimated 11% of trial sites fail to recruit a single patient, and another 37% don’t reach their target enrollment criteria.

There are efforts to create “virtual” trial sites—in other words, to allow clinical trials to proceed at local sites that reach some minimum threshold of competence. To use myself as an example, if the petosemtamab trial I’m doing at UCSD included a real virtual site component, petosemtamab could be shipped to HonorHealth in Scottsdale or one of the Ironwood Cancer Centers in Chandler, and I could receive my infusions and monitoring locally, with the data reported to UCSD and/or Merus (the drug company). Although that would mean “more sites involved in a trial,” it also means less responsibility at each site. The “recruitment failures” issue is interesting in light of the fact that almost no trial sites seem to do basic, modern marketing.

I’m not hugely optimistic about fomenting real change. Real change is slow in a society like the United States, which has been characterized since the 1970s overwhelmingly by complacency, stasis, and status-quo bias. One sees that in our inability to build new housing, our inability to build new ships for the Navy, our refusal to accelerate subway development, our preference for interminable litigation over infrastructure, the Jones Act, the FDA, dishonest and tuition-seeking universities, and the innumerable other veto players who, like Richard Chen, are great at saying “no” and unable to say “yes.” I hope we can build O’Neill Habitats that will allow a re-opening of the frontier and a new space where the dreamers who are tired of hearing “no” can instead create a new polity where it’s possible to say “yes.” The United States is huge on safetyism instead of true safety—and human flourishing.[2] We can and should do better. I doubt we will, however, because the people who most need FDA reform are dead. They’re not writing. They’re not doing podcasts. They’re not agitating Congress.

Still, sometimes change happens, and the bureaucratic inertia is somehow overcome. For example, voucher and charter schools seem to continue to ascend, despite entrenched and intense monied union interests opposing them, and decades after their intellectual foundations were laid. Marijuana legalization seemed unlikely until it happened. Psychedelics look like they’re on the path to medical legalization, at the very least, and possible general legalization; based on my experiences, psychedelics are both safer and far more interesting than alcohol. SpaceX has revolutionized the space game, and I’d have incorrectly predicted failure. Tesla is the sole bulwark against state-affiliated and subsidized Chinese companies owning the entire electric car market. Who knows what’s possible? I don’t hope for this, but if someone in some senator or senior house member’s family gets cancer, and that senator or house member learns what I’ve learned, FDA reform might become a vital issue for that person. Few people I’ve seen online have defended the current system (there are some—just not a lot).

The fact that the current ossified, slow system has persisted as long as it has is an argument for it continuing. Good enough is good enough, right? Moreover, the way the press responds to events helps perpetuate stasis: if a drug has negative side effects, including potentially death, that gets plastered all over the news. Investigations are launched. Scapegoats are sought. If a drug works, and saves lives, the response is muted. The articles go unread. The beneficiaries are happy but don’t start campaigning for more and better medical treatment, faster. One person who dies from a drug outweighs one hundred who might be saved by another. It reminds me of all the press given to any kind of airline accident, even one without casualties, while 40,000 people a year die in car crashes, without most of them making headlines.

One person on LinkedIn said this about Bess’s clinical trial essay-guide:

An extraordinarily damning overview of the way things operate currently, that puts everything we complain about from within the industry into perspective. Thanks for sharing this Brad [Hightower—mentioned above] – as you say, a must read that underlines how we must all work together to improve things.

It might be a damning overview, but it also turns out that seemingly everyone working in or adjacent to clinical trials knows about the problems already. That includes everyone from the researchers themselves to the drug companies to the hospitals to the oncologists to the support staff. If a lot of people have known for a long time how bad the system is, and no one has managed to coordinate sufficiently to make substantial improvements, that implies that the problems will persist. Can Bess and I be the catalysts that finally galvanize some change? That’d be great, and yet I’m pessimistic. There’s a saying in investing: “The market can stay irrational longer than you can stay solvent.” Call this Seliger’s Law: “A broken system can stay broken for longer than people have the time, energy, and ability to try fixing it.”

Still, Bess and I would like to try to make the world a better place, to the extent we can, and within whatever limits our abilities and skills may impose, and trying to nudge the clinical trial system into a better equilibrium is part of our effort. It’s too late to save my tongue, but it may not be too late to save the tongues and lives of others. In an alternate world, petosemtamab, or a cancer vaccine, would’ve been approved and available in Oct. 2022. I’d have gotten surgery, and then petosemtamab, which is way less toxic than chemotherapy. Maybe that wouldn’t’ve saved my tongue—but maybe it would’ve. Oncologists are reluctant to use chemotherapy, but modern alternatives like petosemtamab should help people like me in the future.

Cancer vaccines exist, though trials are moving achingly slowly. A company called Transgene is testing a cancer vaccine called TG4050 on patients with initial head and neck cancer diagnoses—the same diagnosis I had in Oct. 2022. TG4050 is moving to a Phase 1b and 2 trial; according to the company, “The compelling initial Phase I data presented with NEC at ASCO 2023 showed that all evaluable patients treated with TG4050 monotherapy developed a specific immune response and remained disease-free.” I wish I’d remained disease-free; instead, I have no tongue and am likely to die soon.

Despite my pessimism, “Why drugs got harder to develop” says:

Yet, even though there are major forces pushing against drug developers, there is a sense that the industry is still underperforming, and that it could do more. One reason for optimism can be seen in the recent flattening of the slope of Eroom’s law following decades of declining productivity. It remains to be seen whether the recent uptick is a sustained turnaround or not. The pessimistic view is that it is illusory, a result of how drugmakers have side-stepped fundamental productivity issues by focusing on developing drugs for niche subpopulations with few or no options where regulators are willing to accept less evidence, it’s easier to improve on the standard of care, and payers have less power to push back on higher prices: rare disease and oncology in particular. It’s no coincidence that investment has flowed into areas where regulatory restrictions have been relaxed and accelerated approvals are commonplace: 27% of FDA drug approvals in 2022 were for oncology, the largest therapeutic area category, and 57% were for rare/orphan diseases.

That seems better than nothing. Maybe Congress and/or the FDA is responding to the Richard Chin logic I note above. The FDA has created systemic problems, and it can also create systemic solutions. For example, the FDA doesn’t really account for the time-value of money,[3] which is especially important in a high-interest-rate environment:

As a more general point, it would help if regulators could be more predictable and transparent in their decision making. In a survey of drug and device industry professionals, 68% said that the FDA’s unpredictability discouraged the development of new products. It can be hard to predict how regulators will react to a certain dataset in the context of high unmet need, so companies can be inclined to ‘submit for approval and pray’, even after receiving negative feedback on the data package from regulators during prior interactions.

“Hard to predict” means that many people stop pushing a drug before they start. Companies are competing for investable cash with all other companies; the more time-consuming (read: expensive) the FDA makes the process, the fewer drugs will even be attempted. “Why drugs are harder to develop” suggests the FDA be more accountable to patients:

A straightforward start to improve transparency across the industry would be for the FDA to disclose the formal ‘complete response letters’ (CRLs) issued when they reject a drug which contain the reasons for rejection. Making this information public would give future developers insight into the regulator’s thinking on a disease, with minimal downsides. How companies represent their CRLs to the broader market today is often misrepresentative of the actual reasons for rejection, potentially misleading patients as well as future investors and drug developers in the indication.

I’m not the only one thinking about reform; pretty much everyone in the industry is. To return to a point I raised at the beginning of this essay, reforms could also make clinical trials easier for patients to access. Bess and I spent thousands of dollars and countless hours learning how the clinical trial system works and then how to participate. Initially, no one comprehensively helped us on this journey; my original oncologist at the Mayo Clinic Phoenix was and likely still is sluggish. Mayo Phoenix has a great ENT department but appears to be poor in oncology, which is surprising for an organization with a reputation for cancer care. Bess and I had to learn what we know piecemeal, which is part of the reason we’re trying to describe comprehensively what we’ve learned and how other people’s experiences can be made better.

The best trial for head and neck cancers is petosemtamab, and that trial is being hosted at UCSD. Bess and I are lucky enough to have the resources necessary to get me there twice a month from Arizona for infusions, thanks in large part to the generosity of friends and strangers who’ve contributed to the Go Fund Me. I’ve been saying that being sick for an extended period of time has at least three components to it: health itself; financial well-being; and managing healthcare. Drop any one of the three and the other two are likely to fall too. Very few people can help my health or healthcare directly, but the contributors to the Go Fund Me have made the financial challenges easier.

What’d make things better for everyone, however, is reforms like virtual trial sites. The healthcare team at UCSD has been great, but being infused locally would negate the need to be away from home six days a month, the cost of flights, hotel, and the huge energy expenditure all that entails. The process of getting a clinical trial medication can and should be less expensive and arduous than it is. I can see why most people who might want to participate in the better clinical trials for their illness run out of money and energy to pursue those trials. Bess and I were ready to move anywhere. Fortunately, we’ve not had to move somewhere expensive and far from family and friends. We were ready to, though. We may still have to one day—and maybe, but hopefully not, soon.

Both of us also wish that there were greater transparency around which trials are doing well in terms of patient outcomes and which trials aren’t doing so well. We’ve learned via experience that right now, there’s no substitute for establishing care at a bunch of sites and listening to the oncologists there. Oncologists running trials will often tell you how things are going for trials that’ve been running for a while. If they’re enthusiastic about a trial, it’s often because they see a lot of patients doing well on it. They have observational data that outside docs and institutions have to wait months, maybe years, to get wind of.

Sometimes they’ll also steer patients away from trials that aren’t producing enough positive results. I’m grateful to the docs who’ve quietly advised us against floundering drugs. Some oncologist meetings produce non-public intel about which trials are most promising, provided enough patients have received the drug in question; the oncologists won’t know much if you’re like the first or fifth or tenth human to be dosed with a novel substance, but a lot of these trials have built up years of data. If a site has run through dozens or as many as 100+ patients, the oncologists will have a sense of whether it’s working, even if nothing “official” has been released.

This is one of innumerable tiny facts and practices about effectively participating in clinical trials that we’ve discovered. I’ve never read anyone else who’s put out things like this, just like I’ve never read anything remotely like Bess’s clinical trial guide-essay, “Please be dying, but not too quickly.” Somehow, a lot of this essential information isn’t making it into the larger information ecosystem. The lack of quality information has been driving my writing over the last five months, including my last essay, “On not being a radical medicine skeptic, and the dangers of doctor-by-Internet.” We collectively can and should be doing better. I’m trying to be part of the solution. In reading this, and passing it to others, you’re part of the solution, too.

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care.

See also Alex Tabarrok’s “Conditional Approval for Human Drugs,” in which he says “I think that the FDA’s excellent arguments for conditional approval apply to human drugs as well as to (other) animal drugs and even more so when we recognize that human beings have rights and interests in making their own choices.” And he also ends on a hopeful note: “Dare I say it, but could the FDA be lumbering in the right direction?”
Part III of Bess’s clinical-trial odyssey has recommendations for improvements.

[1] Which I hope it isn’t, and yet the emails I’ve been getting indicate that my experience is distressingly common.

[2] The book Where is My Flying Car? by J. Storrs Hall is good on this. We should have so many nuclear power plants that power is almost too cheap to meter, we should have O’Neill Habitats that re-open the political frontier in order to let the non-complacent gather and advance the human condition, and we should have progressed much further in curing cancer and making biology a variable rather than a constant. That we’re content to creep and crawl on the earth rather than soar into the heavens is an indictment of our whole society. Too many lawyers, too few makers.

[3] Bess asked what the time-value of money is. Briefly, it’s how much an investment or investor would lose or gain from alternatives. Take a simple example: you can invest a million dollars in a company running a clinical trial, or in a money-market fund paying 5% a year. If you invest in the money market fund, you wind up with $1,050,000 at the end of the year. If FDA delays cost you a year, you’ve effectively lost the $50,000—you have more like $950,000! Inflation matters in these calculations, too.

This is also why delays to housing construction are so evil.

Will things get better? Suicide and the possibility of waiting to find out

January 23, 2024 By Jake Seliger in Culture, Essays, Personal Tags: cancer, Culture, Essays, personal, suicide 5 Comments

If you find this piece worthwhile, consider the Go Fund Me that’s funding ongoing care.

Suicide is a one-way valve: once done, it can’t be undone. I’d known the May 25 surgery that took my tongue would be hard and have a long recovery period, but I didn’t understand what “hard” and “long” truly meant, and during that post-operative June and July, when the level of physical misery was not, for me, compatible with life—not long term—I told Bess about “the question.” But if I delayed, the choice could always be made later. Knowing the option for exit remained allowed me to keep living, or whatever that simulacrum of living was, to see how things played out, despite how bleak life was. Many burdens can be borne for a short time, provided that there’s legitimate hope for a brighter future. Maybe there was. Maybe there wasn’t. I wouldn’t know if I was dead.

Back then I’d look at the man in the mirror, bloated, hideous, covered with stitches and thought, though I knew the answer: who or what is that? I’d expected to lose half my tongue to cancer, but when I awoke from surgery, I discovered the whole thing gone, along with some important nerves in my neck. For more than a month, I wasn’t able to breathe comfortably. Mucus production dominated my life, apparently due in part to the loss of the cancerous nerves. The days I spent in the hospital after the surgery were among the darkest in my life, and all the darker because of a thought: What if it doesn’t get better than this? The question wasn’t rhetorical. I saw the answer whenever I looked into the void.

Though I knew the answer, I didn’t like it. Worse than what I saw in the mirror was what I felt: an inability to be comfortable, in any position, anywhere. Breathing hurt, and I felt like I was drowning all the time. It wasn’t possible to clear sufficient mucus from my airway or nasal passages to breathe. Waterboarding is a form of torture, and, while I hope never to experience it directly, the descriptions I’ve read of it resonate with what I felt after the surgery. I was dependent on machines to keep me relatively alive. One day I hope man and machine can merge in a beautiful symbiosis, but my partial merger with the machine world was not like that—yes, they kept me alive, but I was fighting them, and they were fighting me, rather than us working together towards some greater mechanical whole.

If anything kept me alive, it was Bess. Every moment hurt, but I saw how fiercely she clung to the idea that things might get better. She was so diligent about caring for my wounds, cleaning the surgical sites, and monitoring my progress; it had to be because she expected progress. She might’ve been subconsciously motivated because she’s a doctor and can’t ignore a medical task, or, alternately, she was deluded by love and false hope. But her own optimism helped me understand there was a chance things would get better, however much everything, moment by moment, hurt. Which was good, because things hurt. A lot. I breathed through a trache tube in my throat that was constantly clogging and suffocating me. Pushing bags of liquid food through my PEG tube using a pump was a relentless struggle. I barely had the energy to walk across the room. The level of absolute, continuous exhaustion is hard to convey to anyone who’s not been through something analgaous. With normal exhaustion, sleep is curative. I couldn’t even sleep well because I couldn’t breathe well.

The pain wasn’t solely physical; it was also the pain of trying to understand where I fit into the world and how to live; not just existentially but quite literally how to manage simple day-to-day tasks that were now impossible. When I got out of the hospital, I immediately faced a barrage of fucked-up bureaucracy: the hospital and medical suppliers kept calling me and wouldn’t talk to Bess without my verbal consent, which I couldn’t give, because I couldn’t speak. Insurance wanted to fight. We weren’t sent home with the right food pump. It took two weeks to get said pump. Most adults figure out how to exist in the sometimes-insufferably bureaucratic society we inhabit; I couldn’t do so, because I couldn’t speak, or think, or move. David Brooks just wrote an essay, “Death by a Thousand Papercuts,” that captures a little of what I felt:

[Administrators’] power is similar to what Annie Lowrey of The Atlantic has called the “time tax.” If you’ve ever fought a health care, corporate or university bureaucracy, you quickly realize you don’t have the time for it, so you give up. I don’t know about you, but my health insurer sometimes denies my family coverage for things that seem like obvious necessities, but I let it go unless it’s a major expense. I calculate that my time is more valuable.

My time wasn’t valuable[1] but I lacked the means to pay the time tax. I was already suffering so severely in the physical realm that I didn’t have the wherewithal to fight for the pump and the food and medications. Even now, I’m facing potential mystery bills generated by United Healthcare; the person at the Mayo Clinic who is supposed to interface with the specialty pharmacy says the specialty pharmacy won’t talk to her[2], and, while the specialty pharmacy hasn’t generated any bills directly to me yet, I sense that they’re coming. Maybe it sounds absurd to be talking of bureaucracy in an essay about suicide, but probably it makes sense to anyone whose entire life has ever been at the mercy of one[3]. Bureaucracy can be a form of exhaustion and misery. It eats at your resolve. It’s its own kind of slow death.

During the summer, I couldn’t see a way forward towards a better life, and I knew that if I couldn’t get to a better, more tolerable life, I wouldn’t want to live further. Bess worried horribly about me, though I did promise her that I wouldn’t leave without telling her first. She worked frantically to keep me here, and to make life as good as it could be, given the privations of the surgery and cancer. She did as well as anyone could. But the suffering persisted. I don’t know precisely where the line was between “tolerable” and “intolerable” except that I was on the wrong side immediately after the surgery. Probably each person has to decide for him or herself where the line is. I don’t generally favor suicide—I prefer hope to despair, life to death, success to failure—but I don’t consider it taboo or unthinkable, either. Life and human consciousness are in general good, and, as far as we can tell, rare in the universe. They should be fostered, though not at the expense of all other values and costs.

In the months after the surgery, I felt like I had no slack—no physical slack, no energetic slack, no intellectual slack. I hardly had the ability to do anything or to think anything. Commonplace tasks felt like climbing the Himalayas. And I was besieged by tasks: doctor appointments, wound care, antibiotics, food, managing the healthcare team and system. I didn’t have energy or attention for anything. Life’s pleasures, whether normal or small, weren’t available: sleep, rest, food, coffee, sex, showers. I was technically alive but felt like I shouldn’t be.

There’s a weird tendency for people to view others persisting despite suffering as if they’re watching the vapid inspiration videos infesting social media like so many varmints. They fantasize that suffering serves a purpose. It teaches us…something, beyond itself, I guess. Wisdom, or something. I think that’s true of some kinds of suffering, like completing a project at the limits of one’s abilities, or other activities that generate mental fortitude and knowledge. Other kinds of suffering, like medical suffering, seem more pointless. I’ve learned that medical suffering sucks, but I knew that going in. I don’t think I’m a better or wiser or more enriched person for having been through what I’ve been through; I’ve just been miserable. That kind of adversity isn’t worth the price of adversity.

I could construct a bogus story in which I’ve learned from the suffering of the last year, but I don’t think it’d be true. It’d just be a form of cope. Bess confirms that, for every person she sees who beatifically (and irrationally) convinces themselves that their suffering has a purpose, there are five more who are miserable and mean about the hand they’re dealt. She confirms I’m not miserable or mean,[4] but I am a realist. If I’ve learned anything, it’s what I already knew: technology is good; cancer is bad; using technology to defeat cancer and other forms of human immiseration is good. We should accelerate technological progress in the pursuit of improving human flourishing. In another world, a world with less FDA intransigence and blockage, I’d have gotten Transgene’s TG4050 cancer vaccine after my first surgery, and it would’ve prevented the recurrence that took my tongue. Fortunately, the FDA has been diligently protecting me from being harmed, and it has thus ensured that cancer will kill me. Thank you, FDA.

If suffering has done anything, it’s made me more willing to speak out for the importance of technological acceleration, and for the need to give people the option to take more risks and block fewer technologies. We can’t build AI to improve the human condition soon enough. Forty thousand people a year die in car crashes; if AI plus LIDAR leads to self-driving cars, great. MobileEye and Luminar are leaders in self-driving cars, but the other efforts to build out AI and, eventually, the machine god, shouldn’t be discounted.

I don’t know when I consciously realized that I might be doing well enough to ask myself more questions about how I might live as opposed to when I might choose to die—probably sometime in August or September. Improvements have been slow—so slow. I learned to swallow slurries again. For a long time, every swallow was a struggle. I choked so severely on water in late July or early August that I thought I might die. Bess witnessed it, and pounded on my back to attempt to help me, and said she found that episode terrifying, because the Heimlich maneuver isn’t efficacious against drowning.

As I became somewhat better able to breathe, and the number of medical appointments began to decline, I also planned for another set of privations in the form of chemotherapy. What happened on May 25 is called “salvage surgery.”[5] I guess the surgery salvaged my life, at the expense of my tongue, which had been replaced it with a flap of muscle from my thigh. But the flap felt like an inert, alien thing, that constantly alerted my brainstem to a foreign threat inside my own mouth. It was immobile and insensate and yet I felt it, constantly. Was I what had been salvaged? It sure didn’t feel like it.

Failure to eliminate head and neck cancer in the first go-round is extremely bad, though my surgeon, Dr. Hinni, got clean margins in May. The question became: should I do any chemotherapy in an attempt to eliminate any remaining cancer cells? No one gave us a clear answer, because one doesn’t exist: Bizarrely, no one had comprehensively studied the question. Almost all the oncologists Bess and I consulted with said they either didn’t know the answer, and most said that the choice was really 50/50. It seemed we had to “decide what we wanted,” which seemed like a great way to run a Montessori preschool, but a less great way to decide on life-altering cancer care. Oncologists are strangely loathe to provide real, data-driven recommendations. There’s a lot of misplaced hope and enthusiasm for debilitating therapies, while, at the same time, thinking outside the box seems to be viewed with unearned futility.

I looked at the odds of surviving a second recurrence—essentially zero—and decided to go for chemo. My first chemo infusion was scheduled for July 24, and on July 21 I got CT scans to see whether I could begin performing jaw exercises that might improve my mobility; those scans showed the recurrence and metastases. That horrible surgery had bought a mere two months. Chemo went from “maybe curative” to “palliative, and an attempt to buy time.” I was barely healed enough from surgery when the chemo began, and so the physical improvements were setback by chemo.

Yet even though the chemo was miserable, I’d gotten better enough to have pulled back from the brink. I was getting a little better at swallowing. I was able to breathe without constant, continual pain. The PEG tube that protruded from my stomach was a constant bother, but one that was manageable enough. Progress was just slow. Unbelievably slow. Every day, I pressed forward as best I could. I used the exercise bands. I walked a little farther. I tried to push in as much nutrition as possible. I adjusted medications to help me sleep. Most importantly, I spent time with Bess. The purpose of life is other people. For me, that’s presently instantiated by being with Bess, by being with friends and family, and by writing. The writing is an attempt to help others, especially the people who are facing their own cancers. Oncologists apparently aren’t, as a group, going to do enough to help people who need clinical trials, so I’m stepping into that gap.

There’s a common distinction between surviving and thriving. Many people who survive traumatic or horrifying events never thrive after. Esther Perel has spoken about the difference between Holocaust survivors who managed to thrive after, as her parents seemed to, versus those who didn’t, as two of my grandparents seemed not to.[6] I’ve been trying to thrive, as best as I can discern how, with the aid of Bess, and despite the challenges of the incurable disease that’s killing me, held at bay right now only by the clinical trial petosemtamab.

For now, not exiting was the right decision, thanks to the aid I received and am recreiving from many others around me. I’m trying to lead a generative, positive life with what time I have left, and writing is a key part of that effort. Few people understand how bad the FDA is, or the degree to which the FDA is retarding progress in oncology in particular, and consequently letting cancer patients die. Perhaps there are too few faces to associate with the statistics about cancer deaths, and so I’m attempting to associate a single person with the bureaucratic edifice that is the FDA, killing through its nominal mission to “protect.”

One day, maybe soon, may not, it will be time to enter the one-way portal. The preferred, antiseptic modern term is “death with dignity.” But the people around me and with me keep me alive, and show that we really do live for one another. The physical challenges are still great, but not as severe as they were last summer. I’m able to get up and engage in meaningful activity most days. I don’t want to be a burden—a burden on family, friends, or society, and by my own judgment I think myself not too great a burden for others. That line will likely be crossed in the next year, but it’s not been crossed yet. And the clinical trial I’m participating in—and the one after it, and, if that one is successful enough, the one after it—is generating the data necessary to make effective cancer drugs available to other people. My role is small—I’m not inventing the drug, I’m not manufacturing it, I’m not setting up the trials themselves—but it is a role, and it is one someone has to fulfill. Fulfilling it generates some meaning in my life, and meaning is an essential component of thriving. Maybe there will be other roles for me, before the end.

I’ll probably never be as effective as I was before the cancer, but I’ve been working, every day, at being more effective and less of a burden to the degree that I can achieve either. There’s plenty of physical pain in my life—as I write this, I have cuts on the pads of my fingers that won’t heal, I’m bleeding or barely not bleeding from my toenails, and my lower lip cycles between cracking and bleeding from those cracks. But the pain is bearable enough. I can breathe well enough. I’m able enough to write. So much has been taken, though enough remains for me to remain. I still believe what I wrote in “I know what happens to me after I die, but what about those left behind?”:

At some point, the suffering may be too much, and then I hope to exit by my own hand, gracefully, not having been wholly unmanned by disease. “Unmanned:” it’s an old-fashioned word, and one that appears in the appendices of The Lord of the Rings, when it is time for Aragorn to department the world. His wife Arwen pleads with Aragorn “to stay yet for a while” because she “was not yet weary of her days.” Aragorn asks her if she would have him “wait until I wither and fall from my high seat unmanned and witless.” I didn’t imagine that I might face the same question so soon, and yet it’s here, before me, and I hope to depart before the pain robs me of my mind and leaves me witless and suffering. Aragorn says that “I speak no comfort to you, for there is no comfort for such pain within the circles of the world.” And that I fear is true of Bess, too, that there will be no true comfort for her pain. Her parents will help her, our friends will help her, she will not be alone—and yet the pain at the moment of my own departure will remain.

Aragorn and by extension Tolkien understood death with dignity. For a lot of the summer, I felt unmanned and witless. Now I’m sufficiently manned and witted to be writing this, to be cooking, and to consider a future I probably won’t get, but I might. I don’t want to be caught off guard by success, like a teen boy whose efforts to get laid work when he thought they never would. The incremental improvements have added up, and suicide is an all-or-nothing proposition. The decision not to die last summer was the right one. The show goes on. Life goes on. For now, I am a part of it.

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care.

[1] In the monetary sense: my marginal product of labor then was $0/hour. Bess wants me to point out that my time is inherently valuable to me as a human being.

[2] The specialty pharmacy also told her that they won’t talk to us. “They don’t speak directly to customers.” When the bill comes, I guess I’ll just send it back with an explanation that if they won’t interface with me, I won’t interface with them. Something tells me that will change their policy.

[3] Or who has read Kafka.

[4] Some of the nurses on the post-surgery recovery floor told Bess I was nice. I was trying to do unto others as I’d have them do unto me, and I hope I succeeded.

[5] The term for the surgery after the first surgery to remove head and neck cancer, and associated adjuvant treatment like radiation, fails

[6] They died before I was born, so I have no ability to judge for myself.

Why don’t schools teach debugging, or, more fundamentally, fundamentals?

January 16, 2024 By Jake Seliger in Academia, Culture, Essays, Teaching Tags: Academia, education, Essays, personal, Teaching 8 Comments

If you find this piece worthwhile, consider the Go Fund Me that’s funding ongoing cancer care.

A story from Dan Luu, from back when he “TA’ed EE 202, a second year class on signals and systems at Purdue:”

When I suggested to the professor that he spend half an hour reviewing algebra for those students who never had the material covered cogently in high school, I was told in no uncertain terms that it would be a waste of time because some people just can’t hack it in engineering. I was told that I wouldn’t be so naive once the semester was done, because some people just can’t hack it in engineering.

This matches my experiences: when I was a first-year grad student in English,[1] my advisor was complaining about his students not knowing how to use commas, and I made a suggestion very similar to Luu’s: “Why not teach commas?” His reasoning was slightly different from “some people just can’t hack it in engineering,” in that he thought students should’ve learned comma usage in high school. I argued that, while he might be right in theory, if the students don’t know how to use commas, he ought to teach them how. He looked at me like I was a little dim and said “no.”

I thought and still think he’s wrong.

If a person doesn’t know fundamentals of a given field, and particularly if a larger group doesn’t, teach those fundamentals.[2] I’ve taught commas and semicolons to students almost every semester I’ve taught in college, and it’s neither time consuming nor hard. A lot of the students appreciate it and say no one has ever stopped to do so.

Usually I ask, when the first or second draft of their paper is due for peer editing, that students write down four major comma rules and a sample sentence showcasing each. I’m looking for something like: connecting two independent clauses (aka complete sentences) with a coordinating conjunction (like “and” or “or”), offsetting a dependent word, clause, or phase (“When John picked up the knife, …”), as a parenthetical (sometimes called “appositives” for reasons not obvious to me but probably having something to do with Latin), and lists. Students often know about lists (“John went to the store and bought mango, avocado, and shrimp”), but the other three elude them.

I don’t obsess with the way the rules are phrased and if the student has gotten the gist of the idea, that’s sufficient. They write for a few minutes, then I walk around and look at their answers and offer a bit of individual feedback. Ideally, I have some chocolate and give the winner or sometimes winners a treat. After, we go over the rules as a class. I repeat this three times, for each major paper. Students sometimes come up with funny example sentences. The goal is to rapidly learn and recall the material, then move on. There aren’t formal grades or punishments, but most students try in part because they know I’m coming around to read their answers.

We do semicolons, too—they’re used to conjoin related independent clauses without a coordinating conjunction, or to separate complex lists. I’ll use an example sentence of unrelated independent clauses like “I went to the grocery store; there is no god.”

I tell students that, once they know comma rules, they can break them, as I did in the previous paragraph. I don’t get into smaller, less important comma rules, which are covered by whatever book I assign students, like Write Right!.

Humanities classes almost never teach editing, either, which I find bizarre. I suspect that editing is to debugging as writing is to programming (or hardware design): essential. I usually teach editing at the sentence level, by collecting example sentences from student journals, then putting them on the board and asking students: “what would you do with this sentence, and why?” I walk around to read answers and offer brief feedback or tips. These are, to my mind, fundamental skills. Sentences I’ve used in the past include ones like this, regarding a chapter from Alain de Botton’s novel On Love: “Revealed in ‘Marxism,’ those who are satisfying a desire are not experiencing love rather they are using the concept to give themselves a purpose.” Or: “Contrast is something that most people find most intriguing.” These sentences are representative of the ones first- and second-year undergrads tend to produce at first.

I showed Bess an early version of this essay, and it turns out she had experiences similar to Luu’s, but at Arizona State University (ASU):

My O-chem professor was teaching us all something new, but he told me to quit when I didn’t just understand it immediately and was struggling. He had daily office hours, and I was determined to figure out the material, so I kept showing up. He wanted to appear helpful, but then acted resentful when I asked questions, “wasting his time” with topics from which he’d already moved on, and which I “should already understand”.

He suggested I drop the class, because “O-Chem is just too much for some people.” When I got the second-highest grade in the class two semesters in a row, he refused to write me a letter of recommendation because it had been so hard for me to initially grasp the material, despite the fact that I now thought fluently in it. My need for extra assistance to grasp the basics somehow overshadowed the fact that I became adept, and eventually offered tutoring for the course (where I hope I was kinder and more helpful to students than he was).

Regarding Bess’s organic chemistry story, I’m reminded of a section from David Epstein’s book Range: How Generalists Triumph in a Specialized World. In his chapter “Learning, Fast and Slow” Epstein writes that “for learning that is both durable (it sticks) and flexible (it can be applied broadly), fast and easy is precisely the problem” (85). Instead, it’s important to encounter “desirable difficulties,” or “obstacles that make learning more challenging, slower, and more frustrating in the short term, but better in the long term.” According to Epstein, students like Bess are often the ones who master the material and go on to be able to apply it. How many students has that professor foolishly discouraged? Has he ever read Range? Maybe he should.

Bess went on:

Dan’s story also reminds me of an attending doctor in my emergency medicine program; she judged residents on what they already knew and thought negatively of ones who, like me, asked a bunch of questions. But how else are you supposed to learn? This woman (I’m tempted to use a less-nice word) considered a good resident one who’d either already been taught the information during medical school, or, more likely, pretended to know it.

She saw the desire to learn and be taught—the point of a medical residency— as an inconvenience (hers) and a weakness (ours). Residency should be about gaining a firm foundation in an environment ostensibly about education, but turns out it’s really about cheap labor, posturing, and also some education where you can pick it up off the floor. When I see hospitals claiming that residency is about education, not work, I laugh. Everyone knows that argument is bullshit.

We can and should do a better job of teaching fundamentals, though I don’t see a lot of incentive to do so in formal settings. In most K – 12 public schools, after one to three years most teachers can’t effectively be fired, due to union rules, so the incentive to be good, let alone great, is weak. In universities, a lot of professors are, as I noted earlier, hired for research, not teaching. It’s possible that, as charter schools spread, we’ll see more experimentation and improvement at the ˚K –12 level. At the college and graduate school level, I’d love to see more efforts at instructional and institutional experimentation and diversity, but apart from the University of Austin, Minerva, the Thiel Fellowship, and a few other efforts, the teaching business is business-as-usual.

Moreover, there’s an important quirk of the college system: Congress and the Department of Education have outsourced the credentialing of colleges and universities to regional accreditation bodies. Harvard, for example, is accredited by “The New England Association of Schools and Colleges (NEASC).” But guess who makes up the regional accreditation bodies? Existing colleges and universities. How excited are existing colleges and universities to allow new competitors? Exactly. The term for this is “cartel.” This point is near top-of-mind because Marc Andreessen and Ben Horowitz emphasized it on their recent podcast regarding the crises of higher education. If you want a lot more, their podcast is good.

Unfortunately, my notions of what’s important in teaching don’t matter much any more because it’s unlikely I’ll ever teach again, given that I no longer have a tongue and am consequently difficult to understand. I really liked (and still like!) teaching, but doing it as an adjunct making $3 – $4k / class has been unwise for many years and is even more unwise given how short time is for me right now. Plus, the likelihood of me living out the year is not high.

In terms of trying to facilitate change and better practices, I also don’t know where, if at all, people teaching writing congregate online. Maybe they don’t congregate anywhere, so it’s hard to try and engage large numbers of instructors.

Tyler Cowen has a theory, expounded in various podcasts I’ve heard him on, that better teachers are really here to inspire students—which is true regarding both formal and informal education. Part of inspiration is, in my view, being able to rapidly traverse the knowledge space and figure out whatever the learner needs.

Until we perfect neural chips that can download the entirety of human knowledge to the fetal cortex while still in utero, no one springs from the womb knowing everything. In some areas you’ll always be a beginner. Competence, let alone mastery, starts with desire and basics.

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care.

Earlier reading: “Most people don’t read carefully or for comprehension,” another response to Dan Luu.

[1] Going to grad school in general is a bad idea; going in any humanities discipline is a horribly bad idea, but I did it, and am now a cautionary tale for having done it.

[2] Schools like Purdue also overwhelmingly select faculty on the basis of research and grantsmanship, not teaching, so it’s possible that the instructors don’t care at all. Not every researcher is a Feynman, to put it lightly.

On not being a radical medicine skeptic, and the dangers of doctor-by-Internet

January 11, 2024 By Jake Seliger in Culture, Essays, Personal Tags: cancer, Culture, Essays, medicine, personal 6 Comments

In part 1 I wrote about the struggles that come with complex healthcare problems, like the cancer that’s killing me, the efforts to treat it, and the numerous ancillary problems those treatments have caused. I lacked meaningful guidance on important topics like clinical trials or how to significantly decrease the incapacitating side effects of chemotherapy. I had to seek out other interventions that would significantly improve my quality of life, like a low-profile mic-key PEG tube. Instead of being guided by experts, I often had to crowd-source recommendations and double-check (and drive) treatment plans, or else so much would have fallen through the cracks. I’d likely be dead. My experiences should help guide others in similar situations, so they can better advocate. But I’m not a radical skeptic and, though I’d like to see improvements in healthcare and other institutions, I also don’t see fantastic alternatives at present levels of technology. If you find this piece worthwhile, consider the Go Fund Me that’s funding ongoing care.

What I’m suggesting isn’t the same as getting your medical degree from Dr. Google

Patients love to tell doctors what to do, and it drives doctors crazy. Online, and sometimes in the legacy media, you might’ve seen quotes from doctors complaining about know-it-all patients who attempt to incorrectly drive treatment. Demanding inadvisable treatment isn’t just bad for the doctor’s sanity; it’s bad for the patient’s health outcomes. Bess, to cite one example who happens to be sitting next to me as I write this, is barraged by ER patients demanding antibiotics for their viral illness or steroids for their chronically sore backs—even though these treatments won’t address the problem and may cause real harm—all because the patient “knows their body,” evidence-based medicine be damned. Many, if not most, people aren’t great at gathering and evaluating evidence, or reading, and even doctors don’t appear to be great at statistical literacy.

I’m sympathetic to doctors’ views regarding patient knowledge or lack thereof, especially when doctors are trying to protect patients from unnecessary medications with real and serious side effects, and yet, at the same time, I continue to be (stupidly, foolishly) surprised at all the things not being done by the doctors who’re supposed to be driving my care. The first time something negative happens can reasonably be a surprise; the eighth time should not. They’re the experts and I’m the amateur, so why am I outperforming them in important ways? If Bess and I don’t drive, there’s no one behind the wheel, and that’s bad. Beyond my individual case, there’s also a larger question: What happens to trust in doctors as a whole when so many individual doctors aren’t providing the guidance or care they should?

Martin Gurri wrote a now-famous and excellent book called The Revolt of the Public and the Crisis of Authority in the New Millennium. It’s about, among other things, the loss of confidence in institutions of all sorts, including doctors and medical institutions. If you’re trying to understand the present better, The Revolt of the Public is a great, essential read. Patients need to listen to their doctors, yes, but for healthcare to benefit patients, doctors also need to listen to their patients. I’m not supposed to be an expert in every aspect of healthcare, and yet, as described in Part I, Bess and I have done and caught a bunch of things that the people who’re supposed to catch and do those things haven’t. In Poor Charlie’s Almanack, Charlie Munger wrote that “If, in your thinking, you rely entirely on others—often through purchase of professional advice—whenever outside a small territory or your own, you will suffer much calamity. And it is not just difficulties in complex coordination that will do you in.”* While it’s true that relying entirely on others isn’t a great idea, we all have to rely on others to some extent, and I’ve had to rely heavily on what doctors, nurses, physicians assistants, and others tell me. It’s hard to know what I don’t know.

Doctors go to school for four years and residency for a minimum of three. So why have I, a writer, had to double check so much? Why have so many of the plans that have kept me alive revolved around suggestions that Bess and I have made to oncologists and other experts—plans and treatments that wouldn’t have otherwise been considered? Bess and I did almost all the work and all the learning about clinical trials to keep me alive. It’s sub-optimal for me to do the double-checking because I don’t know everything the doctors know, or what I don’t know. Bess is an ER doctor and so doesn’t know oncology well. Still, Bess would agree that it only takes one minute for a doctor to ask him or herself: “if I was in my patient’s position, is there anything I can do to simply and easily make their situation better?”

I’m not anti-doctor. This isn’t a screed about how doctors are dumb (they’re not, in the main). Although I’m not writing a screed, I am describing what I’ve faced and experienced in trying to not die, including many of the unflattering parts. After I die, I know Bess will be consumed by crushing existential loneliness, and I want to delay that day as long as possible. Delaying that day as long as possible means that Bess and I are constantly fighting to get the care that doctors haven’t been providing. Bess has been able to keep a close eye on most emergent medical matters, and she’s activated the doctor-network to beg for help from peers in Facebook medical groups. She’s banged down the digital doors of so many oncologists, trying to crowd-source a sense of whether the path we’re on makes sense (we appreciate the help, I want to emphasize: many of you have literally been lifesavers).

We’ve gotten some real medical oncology help, to be sure: a head and neck oncologist at Mayo Rochester named Dr. Kat Price has been hugely helpful in clinical trials, chemotherapy regimen questions, and other matters. Dr. Assuntina Sacco at UCSD understands the clinical trial landscape and is more knowledgeable than we are about what’s out there. Both have, I think, asked themselves what they would want in my situation. But they’ve been the exception, not the rule, which seems crazy to Bess and to me—I guess we live in a crazy upside-down world. By writing about what I’ve seen and experienced, I’m trying to help others, and to warn them of the many challenges Bess and I have faced and, based on experience, are likely to continue to face.

Continue reading →

Puzzles about oncology and clinical trials

October 31, 2023 By Jake Seliger in Culture, Essays Tags: cancer, clinical trials, Essays 8 Comments

Some things about the clinical trial process—and the behaviors of the drug companies, hospitals, and oncologists that are part of the clinical trial process—puzzle me, because I notice problems and common, suboptimal practices that seem easy to fix and yet, from what I’ve experienced and observed, they persist. That slows medicine and science, which is euphemistic way of saying: “more people die, sooner, than would by using better practices and processes.” Patient care and outcomes suffer. Hard-to-fix problems like the FDA aren’t readily solved because those fixes likely demand congressional action, and most congresspeople aren’t pressured to act by voters, and the potential voters most interested in FDA reform have probably already died, or are in the process of dying, and thus are unable to make it to their local polling place.*

“Puzzles about oncology and clinical trials” is a companion to “Please be dying, but not too quickly: A clinical trial story and three-part, very deep dive into the insanity that is the ‘modern’ clinical trial system. Buckle up.” The clinical trial system could be a lot worse, and many treatments obviously get through the system, but, in its current state, the clinical trial system far from optimal, to the point that I’d characterize it as “pretty decently broken.” Interestingly, too, almost all parties involved appear to acknowledge that it’s broken, but no one can seem to coordinate enough pieces to generate substantial improvement. While the clinical-trial field is being seduced by AI models and large-scale tech “solutions,” most of which don’t yet work, some of the problems I’ve noticed and am listing here could be, if not solved altogether, then at least substantially ameliorated at the level of the individual or department, rather than the level of states, the country as a whole, or the FDA:

1. Many oncologists don’t appear to know the clinical trial landscape, even in their sub-specialty. As you might’ve read in Bess’s “Please be dying, but not too quickly” essay / guide, almost none of the head and neck oncologists Bess and I talked to knew the head and neck clinical trial landscape well. Most barely seemed to know it at all, apart from vague reputation (“MD Anderson has a lot of trials” or “Try the University of Colorado” or “I’ve heard good things about Memorial-Sloan Kettering (MSK)”). A lot of that advice was helpful, and I don’t want to scorn it or the oncologists giving it, but that advice also wasn’t at the ideal resolution.

It’s puzzling that more oncologists don’t learn the clinical trial landscape, given how many patients must, like me, reach the end of conventional treatments and want or need to try whatever might be next. To a non-expert outsider, the trial landscape is a bizarre, confusing world that takes enormous time and effort to understand. But to an oncologist or someone else working in the field, it shouldn’t take more than a few hours once every month or two or even three to keep abreast of what’s happening.

In head and neck squamous cell carcinoma (HNSCC), the ailment that’s killing me, there are a lot of trials, though most aren’t highly relevant and perhaps 30 – 50 “good” trials are recruiting at any given moment. The “good ones” mean ones in which a drug company is investing heavily in the drug and the drug is at least in phase 1b and more likely phase 2. Moreover, trials can last years, with varying periods of enrollment, so once an oncologist understands the “good” trials, those trials are likely to be relevant for years. Keeping up with the better trials, even via clinicaltrials.gov, shouldn’t consume lots of time. It took Bess an unbelievable amount of effort and energy to get up to speed from nothing, but the trial situation is like riding a bike: starting from a stop is much tougher than maintaining speed.

Bess spent 50+ hours a week for six straight weeks trying to learn the head and neck clinical landscape, and, with the help of a great consultant named Eileen Faucher, she basically did. Though Bess is a doctor, she’s not an oncologist and doesn’t have the baseline expertise that comes from treating head and neck cancer patients as a career. Bess doesn’t attend the yearly ASCO: head and neck conference where breakthroughs and the research landscape are discussed. Yet she, despite being in the emergency room, somehow became better versed in both the most promising experimental molecules and the up-to-date clinical trial offerings than any other single physician we spoke with (a few were well-informed, to be sure, and if you are well informed and gathering up your outrage, please release it!). The big picture wasn’t obvious at first, but it was discoverable to a determined, non-expert ER doc, and therefore it should be to experts.

Although I’m now in a trial hosted by UCSD’s Moores Cancer Center for a bispecific antibody called MCLA-158 / petosemtamab, Bess just reached out to her contacts at back-up trials, because I’m getting scans on Nov. 21, and those scans may show that petosemtamab is failing and we should try something else, instead of waiting to die. The rate of return for a few “how’s it looking?” e-mails or calls from Bess to trial coordinators and oncologists seems exceptionally high. In my view, community oncologists should do the same thing every couple months. UCSD has probably the best and most extensive program in the west. It would be easy for an oncologist like mine at the Mayo Clinic Phoenix, Dr. Savvides, to send an email every three or four months that says: “Any new trials I should know about, in order to better help my patients?” Instead, he seems to know almost nothing about the clinical trial landscape. There are also some good research centers in Arizona: HonorHealth Research in Scottsdale, Ironwood Cancer Centers, or the University of Arizona Cancer Center in Tucson.

Problems like mine are common, and HNSCC patients commonly experience recurrence and/or metastases (“About 50% of these patients will experience a recurrence of disease. Recurrent/metastatic SCCHN have poor prognosis with a median survival of about 12 months despite treatments”).

If a lot of patients wind up failing conventional treatments, like me, then it would seem logical that helping those patients find a good clinical trial should be part of the standard of practice, and even standard of care, for HNSCC oncologists.

Discussing how clinical trials work with a patient before the patient needs one is also important for improving the number of trials a patient is eligible for—and the speed with which the patient gets into a trial. If a conscientious oncologist knows that their patient is open to a clinical trial and knows what clinical trials are available at the time of a patient’s recurrence, they might be able to get that patient directly into a trial. Early action is particularly helpful because a number of phase 1b/2 clinical trials combine the experimental treatment with standard of care, but only if the patient has not yet received standard of care. How can the patient into a study so quickly? Their oncologist has to know about it at the time of diagnosis.

To use myself as an example, at Ironwood Cancer Center there’s a promising phase 2 trial of an anti-CD47 antibody called magrolimab for HNSCC patients. It combines the antibody itself with chemo and pembrolizumab (Keytruda), but only patients who haven’t had pembro are eligible. I have had pembro, so I’m not. Given the circumstances under which I had it—as a crash measure to try and improve matters before the massive May 25 surgery that wound up taking my whole tongue—I wasn’t a great candidate due to timing problems. Other patients, though, who don’t need or get surgery fast as I did, might benefit greatly from the magro trial. I got a “hot” PET scan on April 26. If I’d been told on or near that day: “Get an appointment to establish care at Ironwood Cancer Center and HonorHealth Research; if that hot PET scan is confirmed, you want to be in a position to combine a clinical-trial drug with pembro,” I would’ve done so. Pembro on its own only helps about ~20% of HNSCC patients, according to the big KEYNOTE-048 study.

Not telling patients to get ready to attempt clinical-trial drugs in the event of recurrence is insane.

I will note the important caveat that a lot of cancer patients who reach the end of conventional treatments aren’t good candidates for the kind of intensive clinical trial search and entry that Bess and I did. Most clinical trials require patients who have good mobility, life expectancies longer than 12 weeks, no metastases in places like the brain or spine, etc. A lot of cancer patients are elderly and immobile; for them, discontinuing care and making their peace makes sense. The financial challenges are also substantial. I’ve been fortunate to get a lot of support via a Go Fund Me that my brother set up, but a lot of people are likely prevented from doing out-of-state clinical trials due to financial challenges. but not everyone.

So what’s going on? Do most oncologists know their area’s clinical trials, and my read of the situation is wrong? Is HNSCC unusual? Is my assumption that most oncologists will see a reasonable number of people who fail conventional treatments and want to do the best trials wrong?

It’s possible that oncologists are just lazy, but after four years of med school, three of internal medicine residency, and three of oncology fellowship, I’m going to discount “lazy.” A much larger number are likely burned out, a subject I address some in “Why you should become a nurse or physicians assistant instead of a doctor: the underrated perils of medical school” from back in 2012. Maybe few patients demand help with clinical trials, and consequently few oncologists provide real help?

2. Hospital center sites and/or drug companies don’t appear to do much outreach to community or even specialist oncologists. It wouldn’t take much for hospital research centers and/or drug companies to find oncologists, or even oncology support staff, in the larger region of a given trial site and try to say: “Hey, here are the better and more promising phase 1b / phase 2 trials we’ve got.” Bess and I were told, repeatedly and independently, that it’s not worth traveling or moving for typical phase 1a does-finding trials, which seems accurate, but for us it sure is worth moving or commuting for the most promising trials. There are likely many others in our position, too.

In terms of outreach, let’s use HNSCC as an example. How many head and neck cancer doctors can there be in the greater Phoenix area? 15, 20, maybe 30? It’s a highly specialized field. HNSCC is the sixth- or seventh-most common type of cancer, so it’s up there but far from number one. Phoenix, Tucson, Las Vegas, and Reno are all within easy commuting distance by plane to San Diego, and someone who prefers driving could commute that way. The petosemtamab trial I’m in at UCSD is probably the best available experimental treatment for HNSCC, and UCSD also has the BCA101 trial, which is another promising EGFR attack \ bispecific antibody. UCSD doesn’t seem to conduct a lot of deliberate outreach, or, if they are, it’s not reaching the oncologists Bess and I have been talking to. I don’t want to pick on UCSD—they’ve been great—and it seems that no clinical trial sites are doing substantial outreach.

If I were UCSD, I’d keep a list of the community oncologists of all the incoming patients. I’d send emails to those oncologists and their PAs every two or three months. It could be simple: “Hey Dr. Savvides—your patient Jake Seliger is doing well on the petosemtamab trial, and instead of dying rapidly, as expected due to the growth of his tumors, he’s able to live a somewhat okay life. If you have similar patients, please send them our way!” Yes, I know about HIPAA, and UCSD should get patient permission to do something like this.

I’ve seen speculation that hospital systems don’t want their oncologists sending patients outside the hospital system. So Mayo wants to keep its patients in-house, HonorHealth does the same, and so on with big hospital systems in every area. To put it bluntly, this is just keeping a patient and their insurance card close, only to watch them die.

It would not be hard for trial sites to hire search engine optimization (SEO) specialists and target pages at keywords likely to be of interest to persons searching for clinical trials. It wouldn’t be hard to bid on Google or Facebook ads targeting patients. To my knowledge, no trial sites do.

HonorHealth has been really good about keeping in touch with Bess and me via email and phone calls, which I appreciate.

3. Clinical trial sites don’t try to get their doctors licensed in other states.

If I were the boss at UCSD, I’d be paying for and facilitating my oncologists getting licensed in, say, Arizona and Nevada. If I were the boss at somewhere like HonorHealth Research, I’d want my docs licensed in California and Nevad. It’s not that hard or that expensive to get licensed in other states. Bess has done it! A lot of states are now taking part in the “licensing compact,” so that a doctor who gets licensed in state x can also practice in ten other states if they’re willing to pay the license fees.

Being licensed across state lines would allow those oncologists to see patients and screen them for potential trials at their institution from those states, likely via telemedicine. If insurance companies won’t pay for care across state lines, then it might be worth either eating the cost of the initial visits or charging a relatively nominal cash fee, like $100 or maybe a couple hundred bucks. This is, again, pretty low-hanging fruit of the kind that I’d expect a lot of businesses to be able to identify and knock down.

I’ve been told that a lot of clinical trial sites want to keep their patient rosters high and face pressure to get enough patients. I’ve heard from many principal investigators (PIs) that it’s difficult to fill a trial. It’s got to be hard to fill spots if patients are being aggressively disincentivized from joining at every step. How many are doing any of the things listed above? How many have created search-engine optimized pages for their trials? This isn’t costly relative to the expense of doctors, hospital care, intake, etc. The kinds of relatively minor changes I’m talking about won’t cost millions. An Arizona medical license can be obtained for $550 and a fingerprinting fee, and then it’s good for a couple of years.

On Facebook, one doctor said that there’s a lot of concern about “coercion,” and one doctor noted:

“Granted, hands are tied in lots of instances because it can’t come across as coercion. I would love to give your “insights” to our patients. Thank you for thinking of others while you are in the midst of everything.”

I’m not sure what specifically she means by “it can’t come across as coercion,” and when Bess asked she didn’t get a reply. Also, come across to who? How? Is the author worried about drug companies, the FDA, IRBs, or some other actor? Too much “coercion” is probably bad, but it doesn’t seem to me that trying to inform oncologists about relevant clinical trials is coercive. I personally would like some more coercion in this field, if it means I might learn about treatments that could save my life and the lives of people who come after me.

Still, I think that doctor is right about the way a lot of doctors think, or, worse, how a lot of administrators think; it’s easy to blame “HIPAA” or “coercion” or, worse, “medical ethics” for stasis. What passes for “medical ethics” is basically a joke, as shown most obviously during the pandemic, and when people cite “medical ethics,” they are almost always bizarrely non-specific about what “medical ethics” they mean, where those “medical ethics” come from, who upholds and interprets them, how they are evaluated, what “medical ethics” say about trade-offs, etc. There also seems to a be powerful, poorly supported paternalism that runs through the notion of “medical ethics.”

In my first public essay about me dying from recurrent / metastatic HNSCC, I talked about the FDA’s role in blocking medicines and consequently killing patients. The FDA’s villainy, which like so much villainy calls itself “good,” as in, “We’re denying you rapid access to potentially life-saving treatments for your own good, so please enjoy being protected while you die,” is the focus of that essay, but if we discount our ability to change the FDA, where else should we focus our attention? Changes at the margins ought to be possible, like those I’m proposing here. So far, this comment is one of the best I’ve seen about why change is hard.

It may be that most people are okay with the current state of affairs. Complacency and “good enough” define our age. There are real improvements over time—pembro is a miracle drug for a lot of people, to use one example, and although mRNA cancer treatments will probably arrive too late for me, they are likely to arrive at some point. If those real improvements move more slowly than they ought to, most people are okay with that, at least, until they or their loved one is dying of the disease.

This is kind of like how the crappy transit systems in the United States are enabled by widespread cost disease. Transit nerds know that NEPA is a huge problem for both transit applications and clean energy applications, but NEPA reform remains frustratingly out of reach. Even the few cities that really depend on good transit, like New York, can’t generate the institutional motion to reduce the cost of building out subways and thus allow the building of more. The U.S. can and should do better at transit, but the median voter can go get in his or her car and drive to wherever. Sure, the traffic might suck. Sure, there might be better ways. But the current way is good enough, and good enough has become good enough in a lot of the United States. Sometime in the 1970s, we became culturally uninterested in the future, in the possibilities of material abundance, and in making the world better for our children. I think we should switch back to having a sense of urgency and importance about the future, including the future of medicine.

I’ve already lost my tongue. My neck mobility is probably 30% of what it used to be, and it’s criss-crossed by constricting scars. I’ve lost forty pounds that I can’t seem to gain back. Even the treatments that are in clinical trials right now are only likely to slightly prolong my life, not save it. I’m a dead man walking, but maybe the next person won’t lose his tongue. In another world, petosemtamab (or Transgene’s TG-4050) was already widely available in October 2022.

In that imaginary world, I got the first surgery, which removed only a part of my tongue, and then got petosemtamab orders along with radiation. The petosemtamab killed enough of the remaining cancer cells that I kept my tongue and didn’t need the second surgery. I’m working normal hours and eating normal food. I’m not concerned about the child Bess and I are working on creating will enter this world after his or her father departs it. That alternate world exists in a space where the FDA moves faster and there’s greater urgency around moving treatments forward.

I’m open to and interested in explanations other than the ones Bess and I have posited.

If you’ve gotten this far, consider the Go Fund Me that’s funding ongoing care. In addition, for more on these subjects, see “Reactions to ‘Please be dying, but not too quickly’ and what clinical trials are like for patients.”

* Even absentee ballots probably won’t help much.

Puzzles about oncology and clinical trials: what we've learned from examining the field

“Please be dying, but not too quickly: a clinical trial story”

October 22, 2023 By Jake Seliger in Culture, Links Tags: cancer, Links Leave a comment

“Please be dying, but not too quickly: a clinical trial story” is Bess’s latest essay, and it describes 1. how I got into the petosemtamab clinical trial, which is among the better I could have gotten in; 2. how the process of finding a good clinical trial functions, which is useful for anyone in a position similar to the one Bess and I were in July, and 3. how the clinical trial process can and should be improved. People are dying (I’m one of them) while patients, doctors, and drug companies struggle against a system that appears to have evolved in a dysfunctional direction. We can and should do better.

Regrets:

August 12, 2023 By Jake Seliger in Culture, Personal Tags: regrets 2 Comments

I read Ryan Holiday’s “24 Things I Wish I Had Done Sooner (or my biggest regrets)” and thought I’d steal adapt the format; I wrote these quickly, with the goal of getting out answers—sort of like “Influential books (on me, that is).”

* Not trying to have kids sooner—much sooner.

* Not fundamentally growing up sooner—much sooner.

* Wasting time in humanities grad school (this is identical to the second point). It was fun at the time but the opportunity cost was so, so high.

* Student loans (which is also related to the second point). Not realizing that large parts of the higher ed system are powerful, important, and legitimate, but large parts of it are scams. Schools themselves obfuscate this basic point, which now seems so obvious to me; despite how obvious this is, no one cares enough to fix it. The student-loan system means schools have no skin in the game and incredible incentives to get students in the door, but no incentives to care what happens after they graduate. This is bad.

* There are lots of things that no one cares enough to fix, or that have established interest groups preventing fixes, and sometimes that’s just how the world is. Bullshit often wins, but it’s a mistake to let it win in your life.

* Not being able to connect normally with other humans (a family failure and one that, when young, I couldn’t even identify, let alone rectify). Diagnosis is a critical part of improvement and it took me way too long to diagnose some of those underlying problems. This regret is linked to a lot of other ones.

* Choosing what I rightly perceived to be the easy way with work.

* Short-term priorities over long-term ones.

* What matters long term? Family and people.

* What doesn’t? Stuff you buy. Status of a shallow sort. Whatever you imagine other people think of you (it doesn’t matter; all that remain is how you make them feel).

* Not knowing about or accessing the power of psychedelics. For a long time I imbibed and accepted the ’60s or ’70s narrative that psychedelics were for losers and could make you go mad. Michael Pollan’s book How To Change your Mind was essential here.

* Being afraid to be a beginner again.

* Chasing the projects of youth too far and too long.

* Being overly accepting of the “age is just a number” idea. There’s some truth in this saying, but a lot of cope, and it’s possible to get the truth without the cope. Most of us prefer the cope, however.

* There’s a lot I can’t control—including most things—but I can control my attitude. If I choose to. The “choosing to” is hard.

* You’re the sum of the five people you’re closest to and with whom you spend the most time. So choose well. I’ve often not.

* Smart, competent people congregate in particular places, and I wish I’d spent more time in those places and less time not in those places.

* Pretty much no one accomplishes as much alone as they do in groups dedicated in common goals and mutual improvement. I’ve spent a lot of my life searching for and not quite finding those kinds of groups, which makes me think about what I could’ve done differently.

* In different times and places, different important things are happening. I got overly interested in the dying dregs of literary culture, and have underinvested in what’s uniquely happening now. There’s still some utility in literary culture, but there’s a lot more elsewhere.

* You can’t do two things at once and multitasking is closer to no-tasking. Pick whatever you’re working on and ride it out. Cultivate flow.

* Some people are not going to get it and need firm boundaries. When you, or I, identify those people, pick the boundaries and hold them. The people who don’t get it also often least understand and respect boundaries.

* Life’s complicated and people have all kinds of things going on. Whatever people are doing probably makes sense from their perspective. Which doesn’t make what they’re doing right, but it may make it comprehensible.

* I don’t regret time spent building, making, and doing things. I do regret excess time passively consuming, particularly video.

* Habits compound. Including bad ones. The bad ones I regret, although I won’t list them here.

* Impatience with the right people is really bad. So is losing one’s temper with the right people.

* Incentives matter.

* Abundance is good and scarcity bad. Work towards abundance but don’t be ruled by material things either.

* No one, including me, gets to the end and is happy about staying on top of email. But don’t totally neglect logistics either. They have their place, typically at the end of the day.

* The people who win are the ones who love and master the details. And the ones who master the right ones. I too often mastered the wrong ones (like the aforementioned investing in the dregs of literary culture).

* Something else I don’t regret, and a common pitfall avoided: wasting a lot of time on “social” media, TV, and other forms of semi-addictive junk. I’ve made mistakes

* Being mean when I didn’t need to be, which is almost all of the time.

* Understanding that tact can, properly used, enable directness.

* Not looking into that thing on my tongue in July 2022, when I first noticed it, but that is very specific to me and probably not generalizable.

Reading through these, I realize that a lot of them are more about my generation than me as an individual: I made a lot of the same dumb mistakes a lot of other people made. When I was young, I thought I was different, and totally in control of my own destiny—and everyone else probably thought so too. And yet it turns out that I erred in extremely common, boring ways.

The Story's Story

Category Archives: Culture

“Woman-to-Woman-to…Huberman:” What journalism looks like from the inside

In which the squamous cell carcinoma tumors in my neck grow by 20% in two months

Food and friends, part 2: Edible food-like substances and the need to swallow again

The dead and dying at the gates of oncology clinical trials

Will things get better? Suicide and the possibility of waiting to find out

Why don’t schools teach debugging, or, more fundamentally, fundamentals?

On not being a radical medicine skeptic, and the dangers of doctor-by-Internet

Puzzles about oncology and clinical trials

“Please be dying, but not too quickly: a clinical trial story”

Regrets:

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