Science Editor

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Currently, the only curative procedure for end-stage heart failure - a leading cause of death in Western countries - is an organ transplant. But even this last-resort surgery is curtailed by the chronic lack of donor hearts.

Experimental gene therapy for heart failure and chronic heart muscle diseases has been tried by many cardiac researchers for many years, but so far without signal therapeutic success. It's been limited by the short-term effects, myocarditis and low efficiency of gene transfer delivered by traditional viral vectors.

Now the August issue of Nature Medicine, released online July 22, 2002, reports: "Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV [recombinant adeno-associated virus] gene delivery." Its authors are at the University of California at San Diego Institute of Molecular Medicine.

They used the rAAV delivery vehicle to express human phospholamban (PLN) - a key heart muscle regulator - in a cohort of 59 cardiomyopathic hamsters. At 5 to 6 weeks of age, those rodents initially showed cardiac contractile dysfunction, followed by progressive cardiac dilation and heart failure. The gene transfer treatment protected contingents of the animals' heart muscle cells from plasma membrane disruption for 28 to 30 weeks.

"Our study," the journal article records, "describes a new in vivo protocol for the transcoronary [injecting the gene directly into the arteries] delivery of genes that holds considerable promise for the long-term molecular remodeling of the failing myocardium." It added: "Using this system, we have achieved high efficiency (over 60 percent of the ventricular muscle) and long-term expression (over seven months)."

The paper concludes: "Given that there is currently no therapy for end-stage heart failure aside from heart transplantation, future studies are warranted to translate these findings into larger animal models and the clinical setting."

Inhaling Air Deeply Into The Lungs Can Be Hazardous To Health; Aerosols To Blame

Air breathed into the lungs follows a direct, reversible in-and-out path. Right? Wrong, asserts a paper by physiologists at Harvard University. Their paper in the Proceedings of the National Academy of Sciences (PNAS), released online July 15, 2002, tells why in its title: "Chaotic mixing deep in the lung."

This contrarian finding is of more than theoretical interest, the authors point out. It also has significant practical implications. Chaotic pulmonary mixing may be a key to the deposition of aerosols (minute airborne particles), which are leading causes of many pulmonary diseases, such as lung cancer, bronchitis, emphysema and asthma. Infectious aerosols can be biological invaders - anthrax, tuberculosis germs and flu viruses - as well as inorganic particles - dust, cigarette smoke and asbestos.

The PNAS paper noted, "The long-term effects of particulate air pollution on public health are striking; they have been shown to be equivalent to a shortening of life expectancy of approximately two years in the U.S. - comparable to the deaths caused by all cancers."

The acinus or alveoli are sites of the smallest pulmonary pockets - where the gas exchange of oxygen for carbon dioxide between blood and air takes place. To simulate airflow in these pockets, the authors as a first step filled excised rat lungs with an ultra-low-viscosity, quick-setting white fluid, then ventilated the lungs with a blue liquid. The two-tone tracers quickly polymerized, preserving in the resulting gel a solid cast of the flow pattern.

Instead of a smooth fluid passage entering and exiting, the microscope revealed intricate blue-white swirling patterns, testifying to chaotic mixing.

Yeast Cells That Curb Calorie Intake Live Longer; How About Worms? Rodents? Primates? Humans?

New results overturn conventional wisdom that calorie restriction (CR) lengthens life span by slowing metabolism, thereby slowing generation of damaging reactive oxygen species. Researchers at the Massachusetts Institute of Technology in Cambridge have authored a paper in Nature dated July 18, 2002, titled: "Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration." To which a companion commentary adds the headline: "Don't hold your breath."

The MIT co-authors point out that CR extends life span in a wide spectrum of organisms, and is the only regimen known to lengthen the life span of mammals. They set up an in vivo model in baker's yeast wherein life span can be extended by limiting glucose.

More than 60 years ago a report appeared demonstrating that rats fed a diet containing 30 percent to 50 percent fewer calories live for four years instead of the normal three. Since then, CR has been shown to prolong the life of species ranging from one-cell yeast to roundworms and fruit flies. In yeast, the co-authors report, life span went up when they turned up the rate of respiration (oxygen metabolism) by a factor of three. It was this finding that challenged the traditional view that curbing calorie intake added to the length of life by decreasing metabolism and the associated production of harmful free-radical forms of oxygen.

These free radicals are a byproduct of the electron-transport chain by which mitochondria - power-plant organelles in every cell - generate energy during respiration. It's not yet known whether humans who cut down on calories live longer, but experiments in primates suggest they do. The commentary comments: "Prompted by the continuing stream of press reports about the CR experiments, a variety of optimists, hucksters and fanatics have started to promote CR and to practice it with the aim of living longer themselves - or at least transferring wealth from the rest of us. Considering how unpleasant it is to follow a low-calorie diet," the editorial concluded, "if the molecular pathway downstream of CR can be identified, perhaps CR mimetics' can be developed which will produce the anti-aging benefits but spare us the hunger."