He completed a National Science Foundation Postdoctoral Fellowship mentored by Paul Licht at the Department of Integrative Biology at the University of California, Berkeley until 1975.
He has challenged the Organizational/Default doctrine of sex determination, extending it to sexual differentiation of the brain and arguing for its replacement with an Ancestral (female)/Derived (male) paradigm.
[2][3][4] Crews discovered the important principle that sexual behavior, gamete production, and steroid hormone secretion could be dissociated, in his studies of the red-sided garter snake (T. s. parietalis).
It was his work with this species that provided the first demonstration that the activation of sexual behavior could be independent of sex steroid hormones, depending instead upon increasing spring temperature.
[5] The desert grassland whiptail lizard (A. uniparens), presented an opportunity to study first-hand how the neuroendocrine substrates underlying sexual behavior can evolve.
Of particular note is the revelation that the male-typical sexual behaviors which parthenogenetic females display turn out to be under the control of the postovulatory surge of progesterone rather than androgen, which the parthenogens do not produce.
This discovery in the parthenogenetic lizard led Crews to extend his work to genetically modified mice and rats, demonstrating that progesterone is not a “female-specific” hormone but plays a critical role in sexual behavior in males.
Today we recognize both sexes as organized and the question now becomes how the activation of a conserved network of genes leads to a binary response (ovary or testis).
Using the leopard gecko (E. macularius) as the animal model system, Crews determined how the experience of temperature during a narrowly defined period of embryogenesis affects the total phenotype of the adult organism, accounting for much of the variation observed among individuals in morphology, growth, endocrinology, neural activity, and neuroanatomy.
[10] This type of work calls attention to the need for researchers using genetically modified animal models to consider the context in which the phenotypes emerge.
[11] This was the first demonstration that endocrine disrupting chemicals (EDCs) can promote a transgenerational alteration in the epigenome that influences sexual selection, and possibly affect the viability of a population and evolution of the species.
His most recent work demonstrated that ancestral exposure to EDCs alters how descendants perceive and react to life challenges, in this case stress experienced during adolescence.
[14][15] Specifically, he established that environmentally induced epigenetic transgenerational inheritance alters brain development and genome activity to modify stress-induced behavioral responses exhibited by F3 males.
Taken together this work has generated a new perspective on the old question of ‘inherited vs experienced, ancestral vs acquired, or nature vs nurture’ and promises to shed new light on health management strategy.
Crews founded Reptile Conservation International in 1992 based on his discovery that application of estrogen to turtle and gecko eggs skews the sex distribution toward females.
His work is also frequently seen in film and television programs and has been featured in several articles and texts in the philosophy of science (e.g., Writing Biology by Greg Myers).