B. J. Hoffman 2026-11-05
B. J. Hoffman coauthored the 1983 cDNA library method with U. Gubler. Their procedure connected first-strand copying of messenger RNA with an enzymatic second-strand synthesis step, simplifying recovery of double-stranded DNA copies.[ref]
A simple and very efficient method for generating cDNA libraries by U. Gubler and B. J. Hoffman. Primary byline and Abstract
The paper establishes this collaborative contribution; it does not assign every laboratory step to an individual author.A particularly informative validation used a previously sequenced bovine transcript and tested the recovered copies by sequencing. The abstract reports faithful full-length products for that test.[ref]
A simple and very efficient method for generating cDNA libraries by U. Gubler and B. J. Hoffman. Abstract, known bovine preproenkephalin RNA comparison
Sequence comparison addresses what the method preserved, rather than merely showing that DNA material was produced.An original probability example separates two quality questions. Let mean that a recovered copy is full length, and mean that its sequence meets a stated correctness criterion. ThenIf a stipulated preparation has and , the fraction satisfying both criteria is 0.76. Multiplying marginal probabilities would require an additional independence assumption; the conditional expression does not.
For a cDNA library, a product can therefore have plausible length but sequence changes, or correct sequence over a shorter region while lacking an end. Validation should state which region was read and which criterion was tested. An illustrative 100-copy sample with 80 full-length products and 76 meeting both conditions has 95 percent correctness among the full-length products but 76 percent joint success across all recovered copies. These numbers explain the distinction and are not measurements from the original study.
C. A. Smith 2026-11-05
C. A. Smith is the first author, under that initial-only byline, of a 1990 study identifying a receptor for TNF-alpha. The team isolated a cDNA clone from a human lung fibroblast library by expression screening with radiolabeled ligand. The encoded integral membrane protein was predicted to contain 461 amino acids and a cysteine-rich extracellular region.[ref]
A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins by C. A. Smith and others. Science 248, pp. 1019–1023, Abstract and first-author byline
This connects a functional binding measurement with a candidate protein sequence.The experimental logic is to ask whether introducing a particular cDNA produces a new binding phenotype. A cDNA library contains many candidates, so selective expression and a detectable ligand can turn a molecular search into a recoverable signal. An appropriate negative control tests binding already present without the candidate. Recovering a binding clone does not by itself characterize every downstream biological response.
For an original model of specific binding, let free ligand concentration be and letwhere the second term represents a stipulated nonspecific component. At , the specific component is half of , but the total signal is larger by . Estimating binding affinity from uncorrected total signal would therefore confuse receptor occupancy with background association.
The study's sequence comparison also connected the receptor with other cellular and viral proteins.[ref]
A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins by C. A. Smith and others. Abstract, extracellular-region sequence similarities
Functional selection and sequence similarity provide complementary evidence: one tests binding in the assay, while the other suggests structural relationships. This scientific contribution is verified without expanding the author's initials or assigning a guessed personal biography. U. Gubler 2026-11-05
U. Gubler is first author, with B. J. Hoffman, of a 1983 method for generating cDNA libraries from small amounts of messenger RNA. The method combined first-strand synthesis with second-strand synthesis mediated by Ribonuclease H and DNA polymerase I.[ref]
A simple and very efficient method for generating cDNA libraries by U. Gubler and B. J. Hoffman. Gene 25, pp. 263–269, primary byline and Abstract
This contribution made information in an RNA population accessible through recoverable DNA copies. The published initial is retained without assuming an expanded identity.A cDNA library represents the RNA molecules successfully copied and recovered, rather than automatically representing every gene equally. Reverse transcription, second-strand synthesis and subsequent recovery can change representation. A useful library therefore requires more than a high total number of clones: rare transcripts and full-length products must also be considered.
An original sampling calculation isolates the rare-transcript question. Suppose a target transcript has probability in each independent recovered clone. The probability that examined clones contain no target isFor , this is about 0.448. Requiring at least 95 percent probability of finding one target givesso at least 299 clones are needed under the stated independent-sampling model. Copying bias that lowers the recovered target fraction changes that calculation even if the starting RNA fraction was known.
The primary method paper also tested fidelity against a known transcript sequence.[ref]
A simple and very efficient method for generating cDNA libraries by U. Gubler and B. J. Hoffman. Abstract, full-length sequence validation
Representation, product length and sequence agreement are distinct measurements. A large library can still undersample a rare transcript or contain truncated copies; neither conclusion follows from clone count alone.