Michael Menaker

Michael Menaker (May 19, 1934 – February 14, 2021), was an American chronobiology researcher, and was Commonwealth Professor of Biology at University of Virginia.

His research focused on circadian rhythmicity of vertebrates, including contributing to an understanding of light input pathways on extra-retinal photoreceptors of non-mammalian vertebrates, discovering a mammalian mutation for circadian rhythmicity (tau mutation in golden hamsters), and locating a circadian oscillator in the pineal gland of bird.

He wrote almost 200 scientific publications.

Menaker grew up in New York City and attended Swarthmore College.

After graduating from Swarthmore College in 1955 with a B.A. in biology, Menaker went on to Princeton University.

In the lab of Colin Pittendrigh, the father of research on biological clocks, Menaker studied the endogenous circadian rhythm of bats (Myotis lucifugus).

He graduated from Princeton University with a Ph.D. in 1960, and continued postdoctoral studies in Donald Griffin's lab at Harvard University.

As he continued to study bats, his interest shifted from circadian rhythms to hibernation patterns.

When Menaker joined faculty at University of Texas at Austin in 1962, he transitioned to studying circadian rhythms in the house sparrow (Passer domesticus) and the golden hamster (Mesocricetus auratus).

In 1968, Menaker provided evidence for the existence of extra-retinal photoreceptors that were sufficient for photoentrainment by measuring rhythmic locomotor behavior as the output signal of the house sparrows (Passer domesticus) circadian clock.

He demonstrated that photoentrainment could occur in the absence of optic neurons, evidence for the presence of an extra-retinal photoreceptor(s) coupled to the House Sparrow circadian clock.

In this experiment, bilaterally enucleated house sparrows were exposed to an artificial light-dark cycle.

They were kept in constant darkness to determine their free-running period and subsequently allowed to entrain to light cues.

Locomotor activity was recorded through observing perching behavior of the sparrows.

He tested three possible confounding variables for entrainment: (1) temperature fluctuation, (2) post-enucleation retinal fragments remaining in the eye, and (3) ectoparasites that might transfer light information through their movements in the birds' skin.

To study the effects of temperature on circadian rhythms, Menaker exposed the enucleated sparrows to an electroluminescent panel.

Menaker treated sparrows with Dry-Die, an anti-parasitic agent, to eliminate any possible effects of light transferring by ectoparasites.

Since the sparrows did not entrain during tests of temperature fluctuation and the sparrows remained entrained 10 months after enucleation, a point at which any excess of the functional retina would have degraded, Menaker ruled out these possible confounding variables.

Menaker's lab concluded the sparrows were able to entrain to environmental light cues.

These results demonstrate that retinal light receptors are not necessary for photoentrainment, indicating there is an extra-retinal photoreceptor(s) contributing to circadian locomotor activity.

Menaker's findings in enucleated sparrows were consistent with Aschoff's Rule, and he concluded that the retinae and the extra-retinal receptor(s) both contribute to the photoentrainment process.

In 1979, Menaker and Natille Headrick Zimmerman expanded on Menaker's previous work with house sparrows, by exploring the influence of the pineal gland and hypothalamus on circadian rhythms.

They transplanted the pineal tissue of one sparrow into the anterior chamber of the eyes of an arrhythmic, pinealectomized sparrow.

Prior to the transplantation procedure, the donor birds were entrained to a 12:12 light:dark photoperiod cycle.

This allowed them to compare the onset of activity, measured by perching patterns, of the donors before pineal transplantation and the recipients after transplantation.

Upon receiving pineal tissue transplantation, previously arrhythmic sparrows experienced the reestablishment of rhythmicity.

In fact, their reestablished circadian oscillations resembled the circadian oscillation pattern for locomotor activity of the donor sparrows.

The 20% of the sparrows who had successful transplantations showed temporary arrhythmicity in constant darkness for a period of 10 to 100 days, which was not always evenly distributed in the 24-hour day; the sparrows, however, eventually became rhythmic once again.

Menaker concluded the pineal gland is a driving oscillator within a multi-component system.

Menaker has held academic positions at the University of Texas, University of Oregon, and more recently, at University of Virginia, where he has been the Commonwealth Professor of Biology since 1987.

He served as Chairman of the Biology Department at Virginia from 1987 to 1993.

He has mentored several experts in the field of chronobiology, including Joseph Takahashi, Chair of the Neuroscience Department at University of Texas Southwestern Medical Center; Heidi Hamm, Chair of the Pharmacology Department at Vanderbilt University; and Carl Johnson Professor of Biological Sciences at Vanderbilt University.

He has authored almost 200 papers and maintained grant funding to support his research for over 60 years.

In 1988, Martin Ralph and Menaker serendipitously came across a tau mutant male golden hamster in a shipment from their commercial supplier, Charles River Laboratories, that was observed to have a circadian period significantly shorter than what is characteristic of that breed.

These golden hamsters are recognized for their narrow range of periods with a typical mean of 24 hours.

Thus, rather than overlooking this abnormal male hamster, Menaker conducted breeding experiments to produce homozygous tau mutants with a period of 20 hours and heterozygous tau mutants with a period of 22 hours.

The pattern of inheritance from this shortened tau indicated the genetic cause of this phenotype was isolated to a single allele, providing a genetic approach to the determination of the biological mechanism.

This accidental forward genetic screen yielded the first specimen that could be studied for genetic insight into mammalian circadian mechanisms.

The first major finding with this strain was that the oscillator had to be located in the suprachiasmatic nucleus (SCN).

To test this conclusion, Menaker and colleagues conducted experiments whereby the SCN from a tau mutant hamster was transplanted through a neural graft to a wild-type hamster with an ablated SCN.