internal and external conflicts
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Consider the past
Mary speaks with a terrible fatalism, claiming that nothing they are can be helped: past sins and mistakes have fixed their present and future irrevocably. The past also takes the form of old hurts that have gone unforgiven. We hear the same arguments again and again in this play, as the Tyrone's dredge up the same old grievances. Letting go is impossible, and so the Tyrones are stuck.
Although the four Tyrones live under the same roof this summer, there is a deep sense of isolation. Family meals, a central activity of family bonding, are absent from the play. Lunch happens between acts, and dinner falls apart as everyone in the family goes his separate way. Mary's isolation is particularly acute. She is isolated by her gender, as the only woman of the family, and by her morphine addiction, which pushes her farther and farther from reality.
Drug and alcohol abuse
Mary's morphine addiction is balanced by the men's alcoholism. Although the morphine is perhaps a more destructive drug, alcohol does its fair share of damage to the Tyrone men. It is Tyrone's great vice, and it has contributed to Mary's unhappiness. Drunkenness has been Jamie's response to life, and it is part of why he has failed so miserably. And Edmund's alcohol use has probably contributed to ruining his health.