Instructor Notes — Chapter 16
IGF-1, Myostatin Inhibitors, and the Muscle-Building Peptides Advanced. Prerequisites: Chapters 14, 15, 5.
What this chapter is for
Chapter 16 is where the book's methodological argument stops being abstract. Chapter 2 asserted that mechanism is necessary and never sufficient; Chapter 5 built a rating system around it; Chapters 14 and 15 applied it to growth hormone. This chapter supplies the demonstration: a mechanism that is completely correct, a set of drugs that engaged the target exactly as designed, and a therapeutic program that failed anyway — at a link nobody had written down as an assumption.
If students take one thing from the chapter, it should be §16.6. Everything else is scaffolding.
Plan your time accordingly. A single session should spend roughly: - 10% on §16.1 (mostly review, but the loading-dominance point must land) - 20% on §16.2–16.4 (molecular material; some classes need more) - 20% on §16.5 (the trials; this is the setup) - 35% on §16.6 (the spine) - 15% on §16.7–16.9 (sarcopenia, the market, cancer)
Resist the pull toward §16.3. The animals are the most fun material in the chapter and will eat the session if you let them.
Prior knowledge to check
Before starting, confirm students can state:
- What "surrogate endpoint" means (introduced Ch 5, defined rigorously here).
- The replacement-versus-enhancement distinction from Ch 14.
- That "raises GH/IGF-1" is a surrogate claim, not an outcome claim (Ch 15).
- What happened to lean mass and to physical function on GLP-1 drugs (Ch 8 §8.8). This one is essential. If students cannot recall it, spend five minutes restoring it before §16.6, because the pairing does most of the pedagogical work.
Predictable misconceptions
"The trials failed, so myostatin isn't really a brake." No. The drugs worked at the level of tissue — mass went up. The mechanism was confirmed and the therapy failed. Students who collapse those two have missed the entire point, and the misconception is common because "the drug failed" is normally shorthand for "the drug did nothing."
"⚠️ is better than ❌." Usually, but not here. The ⚠️ on myostatin inhibitors for muscle disease is awarded because human data exists and disappointed. The claim's plausibility is lower than that of an unstudied claim, while its evidence base is larger. Expect confusion; it is productive confusion.
"More muscle obviously means stronger." The hardest one to dislodge, because it is grounded in real personal experience. The move that works is not asserting the counterexample but exposing the confound: training raises every rung at once, so everyone's lived evidence about mass is actually evidence about training. Let students arrive at that themselves if you can.
"Those trials were in sick people, so they don't apply to healthy athletes." Do not dismiss this. It is the strongest available counterargument and parts of it are correct. §16.8 gives three responses; make students produce at least one before you supply them.
"IGF-1 causes cancer." Overclaim. Equally, "there's no evidence of any link" is an underclaim. The chapter's five-part formulation (mechanism / association / confounding / acromegaly / GH receptor deficiency) is worth having students recite until they can do it without drifting in either direction.
"Follistatin-344 is a peptide." It is a protein, glycosylated, roughly 35–40 kDa. Chapter 1's size framework is doing real diagnostic work here, and this is a good place to reward students who remembered it.
Sensitive-material guidance
Assume some students in the room use, have used, or are close to someone who uses compounds discussed here. That assumption should change how you teach it, not whether you teach it.
- No moralizing, no sneering. The book's voice is explicit about this and the classroom should match. A student who has spent money on IGF-1 LR3 will stop listening the moment they feel judged, and they are precisely the student the chapter was written for.
- Do not ask students to disclose use. Not directly, not in a show of hands, not in an anonymous poll that the room can decode. If a student volunteers, receive it neutrally and move on.
- Never speculate about identifiable people. Not athletes, not public figures, not anyone's training partner. Claims are discussed by type.
- Redirect protocol questions. Students will ask about doses, sourcing, and stacking. The honest answer is that the book contains none of that by design, and that the questions belong with a clinician who can see their history. Say it once, warmly, and hold the line.
- The cancer material needs care. Some students will have family cancer histories. State the uncertainty precisely and do not dramatize it.
Teaching moves that work
Open with the photograph problem. Show — or describe — a Belgian Blue. Ask the room what it proves. Collect answers. Then hold those answers unresolved until §16.3's Hype Check. Students who committed publicly to "it proves the drug will work" learn more from the disanalogies than students who read them cold.
Teach §16.5 before §16.6, and let the failure sit. Do not rush to the explanation. Give students two or three minutes to generate their own hypotheses for why mass rose and function did not. Most rooms produce two of the four mechanisms unprompted.
Run the ladder as a physical exercise. Put mass / strength / function / independence on the board as four boxes with three arrows. Ask the room to attack each arrow in turn. This converts §16.6 from a reading into an argument students built.
Use the Chapter 8 pairing as the closer, not the opener. Its power comes from surprise. Set up the myostatin result thoroughly, then ask: "So a drug that raises lean mass doesn't help. What would you predict about a drug that lowers it?" Then give them Ch 8.
Assign Exercise D7 (write the press release, then annotate it) as a graded write-up. It is the single best diagnostic of whether §16.6 landed, because students cannot fake it — either they can see the surrogate doing the outcome's work in their own prose or they cannot.
Assessment guidance
- Quiz (22 items) is straight recall and comprehension; suitable as a pre-class readiness check or a post-reading gate. Items 17, 20, and 22 are the discriminating ones.
- Exercises Sections A–D are recall and comprehension; E is rating practice; F is dossier work; G is synthesis. For a single problem set, A2, B4, C4, D1–D5, E2, E4, and G1 give good coverage in about 90 minutes.
- † items are extended. Twelve of the 34 are marked. G4 and G5 make good take-home essays; E5 makes a good in-class debate prompt.
- Case Study 16.1 works best as a seminar. Case Study 16.2 works best as an individual write-up, because its central move — separating what evidence establishes from what it feels like it establishes — is a private, uncomfortable operation.