In the movies, suspended animation rarely leads to a pleasant awakening - in the 1973 Woody Allen movie "Sleeper," main character Miles Monroe wakes up after 200 years in suspended animation to find himself in a world ruled, presumably thanks to the marvels of 22nd century biotechnology, by an evil dictator consisting of a disembodied nose.

But Seattle-based startup Ikaria Inc. hopes to harness a related state, reversible hibernation, for happier endings.

Ikaria's chief technology officer, Kevin Tomaselli, distinguishes reversible hibernation from suspended animation. While suspended animation is complete metabolic stasis, in hibernation, metabolic, heart and breathing rates are depressed by about 90 percent to 95 percent, but still active.

Tomaselli told BioWorld Today that Ikaria is "trying to capitalize on something that is pervasive and conserved throughout the animal kingdom, but poorly understood: namely, metabolic flexibility under injurious conditions."

Ikaria, which is named after a Greek island renowned for the healing qualities of its waters and home to the mythical Icarus, entered the limelight last week with a paper in the April 22, 2005, issue of Science and a Series A financing.

In the Science paper, Ikaria co-founder Mark Roth, who also is a member of the basic sciences division at the Fred Hutchinson Cancer Research Center, and his colleagues at the Hutchinson Center and the University of Washington at Seattle, reported they were able to induce reversible hibernation in mice for up to six hours. The mice showed a sharp drop in breathing and metabolic rate. Additionally, their body temperature was no longer homeostatically maintained, instead following ambient temperature; Roth and his colleagues recorded drops in body temperature to as low as 11 degrees Celsius. After revival, the mice showed no deficits on several behavioral tests. Roth called the observations "the widest range of metabolic flexibility that anyone has ever seen in a non-hibernating animal."

The key to the scientist's success was to expose the animals to hydrogen sulfide, a molecule that competes with oxygen to bind to cytochrome C oxidase. That competition disrupted the final step of the electron transport chain, the body's way to generate energy.

The basic idea is to bring oxygen demand down when supply is disrupted. "If oxygen supply is limited and demand is not, then that's a deleterious situation," Tomaselli said. "But if you can reduce demand, then you can buy time."

Buying time can be useful in two categories. For one thing, it can be used to preserve and extend the shelf life of cells, tissues and organs; Tomaselli called their limited shelf life "one of the main constraints in the procurement and delivery of organs for transplantation."

For therapeutic use in patients, a drug to reduce oxygen demand could be useful in situations such as cardiac arrest, stroke, heart attack and trauma, particularly trauma with major blood loss. Along that route, it could also be useful in surgery in which blood loss is severe.

The loss of homeostatic control of body temperature that accompanies reversible hibernation also could be useful to lower the temperature of patients with dangerously high fevers. Ikaria's Tomaselli compared oxidative phosphorylation, and the ensuing production of ATP and heat, to a furnace, and the addition of hydrogen sulfide to "throwing the breaker while keeping the pilot light lit. So core body temperature is less homeostatic, and temperature falls." In patients with high fevers, reversible hibernation could be used to reduce body temperature to a level that would still be elevated, but not life-threatening.

Tomaselli said the company hopes to both have products for organs and tissues on the market and to enter clinical trials for therapeutics within a five-year time frame.

Ikaria was co-founded by ARCH Venture Partners, the Fred Hutchinson Cancer Research Center and Mark Roth, with funding for the Series A coming from ARCH Venture Partners, Venrock Associates, 5AM Ventures, Aravis Ventures and the Washington Research Foundation.

So far, Tomaselli is the only senior management that has been announced by the company. Board member Robert Nelsen, managing director and co-founder of ARCH Venture Partners, told BioWorld Today that Ikaria's current number of employees is undisclosed, but that "we have made additional hires, and our biggest focus right now is probably hiring scientific and developmental folks, as well as a CEO."

Nelsen also declined to disclose the amount of the Series A funding beyond saying that it is in the "double-digit millions." He said that while the company will probably raise additional capital at some point, they also intend to enter corporate partnerships and write applications for certain grants.

Between these funding sources, if and when there is a need to raise money, Nelsen said "it will be more of a question of how much money to take, and under what terms, than of an availability of funds."

That also is due to the fact that despite the sci-fi sound of reversible metabolic hibernation, "there are more near-term applications than with your normal concept company. The interaction between practicality and the head-shaking, fall-out-of-your chair aspect of this is unique."