# Lea (1946/1955) — *Actions of Radiations on Living Cells*, "The Target Theory"

*D. E. Lea, **Actions of Radiations on Living Cells**, Cambridge Univ. Press (1st ed. 1946; 2nd ed. 1955,
reprinted 1962). Ch. III "The Target Theory" + Ch. V "Genetical Effects of Radiation." Operator drop (image-only,
504 pp.) 2026-06-12; **whole book OCR'd 2026-06-13** (`ocrmypdf --force-ocr`) → searchable
`papers/lateral/lea1946_actions-of-radiations-on-living-cells_2nd-ed_OCR.pdf` (PDF/A) + full `-layout` sidecar
`…_2nd-ed.txt` (24,708 lines). Locators below are `.txt` lines in that sidecar; the Ch. III quotes were also
re-checked against a clean 300-dpi tesseract pass (book p = PDF p − 25). CLOSE-READ 2026-06-13.*
**Grade: [CONFIRMED-primary]** (whole book OCR'd; target-theory + gene-mutation dose chapters close-read).
Register **H31**. Wishlist §🔵 row 2. The **single-hit / no-threshold origin** Mantel & Bryan (1961, their
ref 12) borrowed.

## What it is
The canonical statement of the **target theory** (*Treffertheorie*): some biological effects of radiation —
above all **gene mutation** — follow from a *single* ionization in a single target molecule (the gene). One hit
suffices; therefore the dose-effect relation is **exponential with no threshold** — any dose, however small,
carries a proportional probability of a hit.

## Verbatim (OCR of 2nd-ed. pp. 69–73; lightly cleaned)
- The applicable class: "Biological effects of radiation to which this theory is applicable are those in which
  the effect studied is due to the production of ionization by the radiation in, or in the immediate vicinity
  of, some particular molecule or structure. **Thus the production of gene mutation by ionization of the gene
  molecule, or of chromosome breakage following the passage of an ionizing particle through the chromosome,**
  are actions… to which the target theory is applicable." (p. 69)
- The single-ionization class: "**One class of action to which we apply the target theory is the class in which
  the biological effect is believed due to a single ionization.** We interpret in this manner the inactivation
  of viruses… the production of gene mutations… and the killing of bacteria." (p. 72)
- The no-threshold survival/effect curve (Ch. III, on the exponential law): the numbers killed by successive
  equal increments of dose "are not equal, but **each increment of dose kills the same *proportion***" →
  exponential survival, "−dn/n = dD/D₀, where D₀ is the dose required to score an average of **one hit** per
  organism." (book pp. 73–75)

## Verbatim — the empirical no-threshold result for gene mutation (Ch. V; full sidecar, lightly cleaned OCR)
*Now reachable thanks to the whole-book OCR — the quantitative Drosophila data (Muller; Timoféeff-Ressovsky &
Zimmer) that the single-hit theory rests on:*
- **Mutation yield ∝ dose:** "**mutations [is] proportional to the dose and independent of the intensity**"
  (sidecar l. 8650); "In view of the **proportionality of mutation rate to dose**, the simplest way of expressing
  mutation rate is by stating [the rate per r]" (ll. 8567–8568). A straight line fits the points (~60,000 F₂
  cultures); the slight high-dose curvature is only because yield cannot exceed 100% ("at no dose, however high,
  could the yield exceed 100%"), **not** a low-dose threshold (ll. 8665–8676).
- **Independent of dose-rate (the single-quantum signature):** the sex-linked-lethal yield per 1000 r "**does
  not vary by more than a few per cent, if at all, for nearly a millionfold variation of intensity**" — from
  0.009 to 2700 r/min (ll. 8679–8684). Dose-rate independence = each mutation is one ionizing event, with no
  accumulation/recovery and hence no threshold.
- The single-hit reading stated outright: the effect is attributable "to **one ionization, and … not the
  cumulative effect of several**" (l. 5028; cf. ll. 4941–4962).

## Why it matters
- This is the **deepest root in the dossier's no-threshold lineage.** The whole edifice — "no safe dose" for
  genotoxic carcinogens, the linear-at-low-dose default (Crump 1976, H26), the "virtually safe dose" (Mantel &
  Bryan 1961, H11), the "acceptable risk / permissible dose" substitution (NBS Handbook 59, H29) — rests on the
  premise that a *single molecular hit* can initiate the effect. Lea is where that premise is laid down, in
  physics, for gene mutation.
- It supplies the **two-pole framing's scientific spine**: the no-threshold *science* (Lea → Delaney's
  "no safe dose" absolutism) was, for genotoxic agents, *right* — which is exactly why the round-number
  *threshold* devices (Frawley's de minimis, the 10⁻⁶, the HC5) are answers to a question the science says has
  no safe-dose answer. Mantel & Bryan cite Lea (their ref 12) as the target-theory source.