Essex had been transformed into Mister Sinister in 1859. By 1891 Sinister had moved to New York, and had taken the alias of Dr. Nathan Milbury, an alias based off of the manor of his wife's and one that he would use extensively through the years. Posing as an obstetrician, Sinister would have access to hundreds of mothers and babies, an abundance of generational genetic material to study. It was in 1891 that Sinister came across another pair of time traveling mutants from the future. The future X-Man Gambit and a shape changer called Courier. Using his scientific equipment, Sinister managed to replicate the shape shifting abilities of Courier. [Gambit (3rd series) #13]
This absorption of powers would go a long way to explain much of Sinister's abilities. Over the years he has demonstrated powers that lack description. Super human strength, invulnerability, various psionic abilities, teleportation, shape shifting, energy projection blasts and even surviving seeming obliteration. Sinister was one of the first beings altered by Apocalypse, but was by no means the last. While Apocalypse has given great power to each of his recipients Mister Sinister has seemed to be the most powerful. It would make sense that Sinister, with his extensive exposure to the genetic material of thousands of mutants, would have been able to incorporate many of those abilities into his already altered body. [Gambit (3rd series) #14]
During his quest for proper breeding and specifically the breeding of a mutant capable of opposing Apocalypse, Sinister would decide that the bloodline of the Summers family line would have the most merit. When he made this decision we currently don't know. However, by 1891 Sinister had already come across several members of the Summers line. During his employ of the Marauders in 1859 Sinister, still Essex, had employed a man named Oscar Stamp. Among the "freaks" caged in his laboratory Essex had imprisoned an apparently mute boy named Daniel. During the events leading up to and after his transformation by Apocalypse, the prisoners of Essex had been freed by the time-traveling Phoenix IV. Once freed Daniel traveled to America with his adopted father, Oscar Stamp. Upon arriving in the New World, Oscar and Daniel chose a new name. [Further Adventures of Cyclops & Phoenix #4]
By 1891 Sinister, posing as Dr. Milbury, had come into contact with this same Summers family, specifically the adult Daniel Summers. Whether Sinister knew that this man was the same mute boy whom he had imprisoned years before is doubtful, but still possible. Daniel had married a woman named Amanda Mueller. She had suffered from several miscarriages, but had managed to produce one son. After Amanda had been accused of several child-murders, Daniel had taken their son and departed.
After a passionate testimony by the reputable Dr. Milbury it Amanda was acquitted. It is unclear whether Amanda was indeed guilty of these murders and if she was, whether she was doing so at the behest of Mister Sinister. It is also unclear whether the multiple miscarriages that Amanda suffered were indeed accidental or an attempt by Sinister to study a fetus or premature child without having to explain of the disappearance of a child.
It is unknown how long Amanda Mueller's relationship with Sinister lasted, but it is known that she participated in genetic manipulation and genetic research during the time of Charles Xavier's adolescence. In a project called Black Womb, hidden inside the Alamogordo nuclear research facility, Amanda studied thousands of children, mostly mutants, inside of post-natal holding tanks. [X-Men Forever #4] Aided by Brian Xavier (father of Charles Xavier), Kurt Marko (father of Cain Marko "Juggernaut"), and Alexander Ryking, Amanda archived genetic material without altering it. [X-Men (2nd series) #12-13]
There can be little doubt that with this level of technology, unlimited funds, coupled with the study of, rather than the manipulation of, genetics, and finally her longevity (that of over a century of age) that Amanda was still carrying on the work of Mister Sinister.
Some time ago, during the time Jean Grey still lay at the bottom of Jamaica Bay, Mystique managed to procure classified government information. This information proved the US government's early involvement in Project Black Womb and its original purpose. Also proven was the involvement, at least as of 1946, of one Dr. Nathan Milbury. [X-Men Forever #2]
Amanda Mueller was not the only scientist interested in genetics who was visited by Sinister. In the late 1920s a young scientist in London named Herbert Edgar Wyndham dreamed of doing what Sinister had already accomplished: breaking the genetic code of human DNA. Wyndham would one day become the genetic manipulator known as the High Evolutionary, but in the late 1920s he was still quite mortal, working in the new field of genetics aside a colleague at the university, one Dr. Essex. [Uncanny X-Men #380]
While Herbert Wyndham was destined to become the genetics expert called the High Evolutionary, he did not become so on his own. By 1928 Wyndham had begun crude experimentations on lab animals with radiation exposure with little success. During a trip to an international conference on genetics in Geneva, Switzerland, Wyndham suddenly felt ill. Stumbling out into the street he met the hypnotic gaze of a man in a top hat and coat, shrouded in darkness. From this stranger Wyndham was handed a gift that should not exist in that time. [X-Factor Annual #3]
This mysterious benefactor who aids Wyndham on this and several other occasions, has never been seen again. While this is mere speculation it is quite possible, even likely, that Wyndham was aided by the maniacal Mister Sinister. Considering that Sinister worked closely with Wyndham at the university as Dr. Essex, that there were few people on the planet with the knowledge to give Wyndham the blueprint of DNA, that it is well within the motives of Mister Sinister to use others to help him in his work and that he does it again with Amanda Mueller at Project Black Womb odds favor this mysterious benefactor as being Mister Sinister.
Another one of Sinister's known bases of operations was the State Home for Foundlings in Nebraska. On the surface this orphanage seemed like any other, housing orphans and other underage wards of the state. Unknown to the staff and the world at large, the children who lived in the Orphanage were hand picked and often even orphaned by Mister Sinister. After identifying children with promising genetic potential, Sinister would have the parents suffer fatal accidents or other deadly fates. The children would then be transported to the State Home, where Sinister could watch and monitor their development. No doubt some of these children were originally identified from Project Black Womb. It is not known how long the orphanage was in use by Sinister, but during the last decade and a half or so the project as an orphanage was abandoned. What lay below, was not.
While above ground the State Home for Foundlings was an apparently average orphanage, below ground it was quite different. In his secret laboratory, hidden from the eyes of the world above, Sinister worked with machinery unlike any in the rest of the world. This machinery would serve as his laboratory, or more precisely his genetic workshop. While watching the children he had "recruited" above develop, he could attempt to study the effects of cross breeding with his equipment below. His ultimate goal, we would see later, would be to find that match which would lead to a progeny of untold power. Power that Sinister could bend to his will and purpose.
As it is not known how long Sinister used the orphanage, or how many children passed through its doors, it is impossible to determine how many mutants had their lives affected by this secret project. Doubtless the numbers are in the hundreds, but most likely, knowing the size of Project Black Womb, the numbers are in the thousands. Three lives were definitely affected by this facility. Two of these were mutants who were brought to the orphanage above, both of whom would play pivotal roles in the X-Men in the future. The third was not raised or even born in the home above, but was hatched in the laboratory below. (For more details on the events at the orphanage, check out the X marks the Spot entry about it : Orphanage, Nebraska)