The brain activity capable of formulating such dreams, rare among literate people in later eras, conforms to the bicameral mentality hypothesized by Julian Jaynes as dominant into the second or first millennium BCE. Framing the dream experience varies across cultures as well as through time. Dreaming and sleep are intertwined. Dreams occur mainly in the rapid-eye movement (REM) stage of sleep—when brain activity is high and resembles that of being awake. Because REM sleep is detectable in many species, and because research suggests that all mammals experience REM, linking dreams to REM sleep has led to conjectures that animals dream. However, humans dream during non-REM sleep, also, and not all REM awakenings elicit dream reports. To be studied, a dream must first be reduced to a verbal report, which is an account of the subjects memory of the dream, not the subjects dream experience itself. So, dreaming by non-humans is currently unprovable, as is dreaming by human fetuses and pre-verbal infants. Subjective experience
Preserved writings from early Mediterranean civilizations indicate a relatively abrupt change in subjective dream experience between Bronze Age antiquity and the beginnings of the classical era.In visitation dreams reported in ancient writings, dreamers were largely passive in their dreams, and visual content served primarily to frame authoritative auditory messaging. Gudea, the king of the Sumerian city-state of Lagash (reigned c. 2144–2124 BCE), rebuilt the temple of Ningirsu as the result of a dream in which he was told to do so.
Side effects
Common side effects include:
Nausea
Bone marrow suppression, including
Decreased white blood cell count causing increased risk of infection
Decreased platelet count causing increased risk of bleedingLess common side effects include:

Severe allergic reactions
Pulmonary fibrosis (scarring of lung tissue) including fatal outcomes (usually only with prolonged use)
Hair loss
Interstitial pneumonitis
Rash
Itching
Irreversible bone marrow failure due to melphalan not being withdrawn early enough
Cardiac arrest

Mechanism of action
Melphalan chemically alters the DNA nucleotide guanine through alkylation, and causes linkages between strands of DNA. This chemical alteration inhibits DNA synthesis and RNA synthesis, functions necessary for cells to survive. These changes cause cytotoxicity in both dividing and non-dividing tumor cells. Tumor cells spend less time in resting phases than normal cells so at any given time, they are more likely to be metabolically active than most normal host cells. The rationale behind incorporating an alkylating function in a molecule resembling a primary cellular metabolite was to get a greater safety margin by fooling tumor cells into taking up the toxin preferentially. Synthesis
4-Nitro-L-phenylalanine (1) was converted to its phthalimide by heating with phthalic anhydride, and this was converted to its ethyl ester (2). Catalytic hydrogenation produced the corresponding aniline. Heating in acid with oxirane, followed by treatment with phosphorus oxychloride provided the bischloride, and removal of the protecting groups by heating in hydrochloric acid gave melphalan (3). Society and culture
Legal status
On 17 September 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for melphalan.