After making short work of the latest double homicide brought to him from Detective Bell (Jon Michael Hill), Sherlock Holmes (Jonny Lee Miller) is offered employment by a philanthropist (Dennis Boutsikaris) who wants Holmes' to find the murderer he believes gave him the incurable illness which is slowly destroying his mind before eventually killing him. After initially turning down the potential client, Holmes has second thoughts when the police arrest the man for the murder of his driver (Steven Hauck).
After taking home his payment (a rare bee), Holmes and Watson (Lucy Liu) head to a genetics lab where they talk to the president of the company (Gibson Frazier) and one of the medical researchers (Jennifer Lim) who inform the detective with enough money and skill someone could theoretically do what the philanthropist suggests. Given the names of seven scientists with the skills necessary Holmes sets out to finds a possible killer in Norway who was recently handsomely paid by one of the client's sons (Christopher Sieber).
Watson's apprenticeship begins in earnest as Holmes asks for her opinion at crime scenes and sends her to a seedy dry cleaners to pick up his sweaters with the ulterior motives of seeing what Watson can glean from the experience. When the scientist they talked to earlier that day turns up dead shortly after agreeing to help on the case Holmes becomes sure that they are on the right track, even with the dead woman's fiance (David Furr) gives the police a far simpler reason for her murder in a convict (Albert Jones) with a longtime beef with the victim whose blood was found at the crime scene.
Gathering six of the seven geneticists whose names the researcher gave Holmes before she died the detective discovers an alternative explanation for the convict's blood being found at the scene which only a top-shelf geneticist t could accomplish. After proving the fact to Captain Gregson (Aidan Quinn), Holmes and the Captain sit down to talk with the victim's fiance with the means and motive to commit, and then frame someone else for, the crime.
Despite solving one murder, Holmes is no closer to solving his original case until he discovers two more wealthy philanthropists have been hit with the exact same rare debilitating heredity disease (once again with no trace in their family's medical history). This leads Holmes to the man (Tom Galantich) responsible for it all, with a very personal motive to force funding into research for the disease he inflicted on others - he's suffering from it himself.
"Possibility Two" gives Holmes' an unique puzzle to solve that keeps the detective and audience guessing for most of the show. The late twists involving the other victims is a nice touch that points the case in an entirely new direction. Holmes' unique teaching methods get Watson to make her own collar, with the help of Detective Bell, and begin her training as a detective in earnest.
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