Allan M. Maxam (source code)

= Allan M. Maxam
{c}

\b[<Allan M. Maxam>], with <Walter Gilbert>, developed a chemical approach to <DNA sequencing> reported in 1977. Their primary paper describes partial cleavage of terminally labeled DNA at selected bases, then size separation of labeled fragments by <polyacrylamide gel electrophoresis>.<A new method for sequencing DNA by Allan M. Maxam and Walter Gilbert>[PNAS 74, pp. 560–564, original full byline and Abstract]{ref} <Maxam-Gilbert sequencing> converts chemical selectivity into a position-dependent pattern along a pre-existing strand.

The word partial is central to the measurement logic. Different molecules contribute fragments ending at different positions, while a common labeled end supplies a reference. Extensive repeated cleavage of one molecule can remove information about more distant sites, because only the fragment still containing the label is visible in the corresponding readout.

An original probability model illustrates the tradeoff without prescribing experimental conditions. Suppose the number of relevant breaks in one molecule follows a <Poisson distribution> with mean $\mu$. Then
$$
P_0=e^{-\mu},\qquad P_1=\mu e^{-\mu},\qquad
P_{\ge2}=1-e^{-\mu}(1+\mu).
$$
At stipulated $\mu=0.2$, about 81.9 percent have no break, 16.4 percent have one and 1.75 percent have multiple breaks. At $\mu=2$, those fractions are about 13.5, 27.1 and 59.4 percent. More cleavage does not translate monotonically into a more interpretable set of singly terminated fragments. Actual sequence-dependent chemistry need not follow this simplified independent-break model.

The measured gel is also not the sequence itself. Reading requires calibrating fragment size, identifying the labeled end and comparing the base-selective channels. Overlapping bands or an incorrect orientation can corrupt an otherwise real chemical signal. Maxam's contribution demonstrates how a carefully designed molecular measurement can expose sequence information that bulk composition alone cannot recover.