The DHARMA Initiative was a purely scientific experiment which, however, went seriously wrong due to unforeseen possessive effects on humans (the sickness) in one of the stations (Station 3) caused by powerful mystical forces. The forces were released by an accident of some sort (the incident), involving a certain numeric code (the Numbers). These same forces are behind the unusually strong electromagnetic fluctuations to the study of which the Station 3 was set up in the first place. Due to the flow of these forces into the Island, spirits were released that should have been kept at bay, misfortune was unleashed into the world outside the Swan, souls became possessed and strange occult phenomena came to pass.
Following the incident, possessed scientists continued with the scientific experimentation (including social and psychological experiments) but this time with a bizarre mystical twist. The main objective of these demonic experiments was to tempt the subjects into evil and thereby render them more vulnerable to demonic possession. Soon after the incident, however, the "unpossessed" scientists figured out -- by regularly typing the mystical code -- to keep these forces from pouring out into the world from another plane (Pandora's Box) and possessing their colleagues.
The damage however was already inflicted and a great deal of supernatural forces released. Over time only a handful of the unpossessed survived, forced to live in secret and to fend for themselves. Boat and plane crashes were orchestrated by possessed scientists in order to bring more “food” to these forces as well as to find someone capable and willing (e.g. Locke) to reopen the Pandora’s Box – this time for good. Certain strong-minded individuals (Jack and Kate), however, proved too resistant to be overcome by the shady forces and eventually managed to foil the sinister plan. Apart from Jack and Kate, the souls of every other survivor was "lost". Jack and Kate were the sole survivors.
In short, science met faith, and both Jack and Locke were proven right.
- There are some mystic elements - the Whispers, Charlie's and Claire's mystic dreams, animals and people appearing as "ghosts", people appearing as "possessed", Locke regaining the ability to walk, Jin apparently regaining his fertility.
- The Numbers seem to have a meaning that is mystical. The Lottery and the unlucky events afterwards are hard to explain scientifically.
- The Island seems to have some sort of "life" on its own.
- The scientific stations, the orientation movie and the DHARMA Initiative all point towards some sort of scientific involvement.
- The unusual electromagnetic fluctuations on the Island appear to be the only truly extraordinary observations about the Island prior to any scientific mission to the Island. Since many of the later events on the Island can be explained within the context of scientific experiment, those apparently mystical elements that cannot be thus explained could indeed be somehow connected to these electromagnetic fluctuations.
- The writers of Lost appear to have consciously presented in the persons of Jack and Locke a seeming contradiction between "a scientific" and "a mystical" explanation to the events on the Island. Hence, the viewer seems to be knowingly misled to choose between two apparently incompatible options while the truth appears to combine both elements. Most of the other Lost theories fail to harmonize these elements, leaning exclusively on one or the other premise.
- Jack does have the black and white stones, he could also be on a time loop like Desmond, but finally breaks it and passes away with Kate (or a different female) in the caves (Adam and Eve).
- It would be sort of the easiest explanation, basically the DHARMA Initiative and the Orientation Video speak the truth and the Numbers really are magic. But would that fit into the concept of Mindf***? Maybe it does.
- In podcasts, it was said, that the Numbers may not really have a mystical meaning and that there is an explanation for all that goes on (and it sounded like it is not a mystical one)
- Does not even mention The Others
- Locke "opened the box" by opening the Hatch, but on the other hand he follows the Station 3 protocol, seemingly preventing another incident. Hardly any other of the survivors can be said to be "good" or "evil". All have their moments...
- In the Santa Rosa Mental Health Institute (in a flashback), Hurley tells Leonard that he played the Numbers in the lottery and won. Leonard exclaims "No! You weren't supposed to use the Numbers! Now you opened the box!"
- Perhaps the instances where Pandora's box is alluded to are merely a literary reference. This seems to be the most likely explanation, as the show is full of them.