People with heart disease have a reduced capacity to deliver molecular oxygen to their tissues. By contrast, people who are exercising are increasing delivery of oxygen to their tissues.

As an aside, during the height of the French Revolution, Antoine Lavoisier—usually credited with the discovery of oxygen—doubtlessly elevated his blood flow as he climbed the steps to the guillotine. But Lavoisier instantly suffered massive heart failure when his head was removed. Extremes of oxygenation, for sure.

Coming back to the present, many curent therapeutic interventions try to improve the ability of heart patients to perform sustained exercise by increasing the pumping function of the heart. Ergo, more oxygen delivered to tissues.

Another way to get the same result would be to get hemoglobin—the molecular carrier of oxygen—to release more of its oxygen even under reduced heart function. This now seems possible, thanks to new work on a relatively simple chemical compound: myo-inositol trispyrophosphate (ITPP).

Biolo et al. have shown that ITPP causes hemoglobin to more readily give up its oxygen payload (Proceedings of the National Academy of Sciences [2009] 106: 1926–1929). In experiments with mice undergoing severe heart failure, treatment with ITPP dramatically increased exercise capacity and oxygen delivery to tissues. Thus, ITPP is a real candidate to improve the lot of those afflicted with heart failure.

One also recognizes ITPP as a real candidate to improve oxygenation—and thus athletic performance—in healthy people. How different would this be from other performance-enhancing chemicals like, say, anabolic steroids?

You may not want to consult Alex Rodriguez on this one.

One of the oldest ideas in cancer treatment is to use the body’s own immunological defenses to ward off the nasty malignant cells. This works pretty well for microorganisms, viruses, fungi, and other hazards. Trouble is, tumors are self, and the body isn’t programmed to react negatively to its own offspring.

Clever scientists have responded to this dilemma by taking cells from the immune system (called dendridic cells) out of the body, activating them chemically to recognize the cancer cells, then placing them back in the host where they then should attack the tumor more voraciously. Works ok in mice, but, alas, not so well in humans.

New findings from a research group at Harvard show some progress in cutting this particular Gordian knot. Instead of taking the dendridic cells out of the body, Ali et al. create an infection-mimicking environment in the body, which activates the immune system. Then they show a cancer danger signal to this activated immune system, which—voila—produces a cancer vaccine response (Nature Materials 8 [February 2009], 151–158).

The magic in this experiment comes from chemistry, or course. The investigators used a polymer (poly[lactide-co-glycolide]) that could carry two kinds of additional molecules: one to activate the immune cells (so called cytokines) and the other to specifically announce the target cancer.

All the component molecules in this brew have already passed clinical safety tests, which should allow for rapid human testing. Good thing, since the concoction produced 90% survival in mice that otherwise would have died from their melanoma in 25 days. Of course, there is many a slip twixt mouse and man, but these results are nonetheless an encouraging advance in immunotherapy.

New drugs are routinely tested to see if assorted chemicals affect some biological activity of interest.

The test might be inhibition of bacterial growth, killing of cancer cells, or reduction of blood pressure in mice. The group of chemicals tested—often called a library—could come from the Sigma-Aldrich catalog, the samples that happen to be on your lab shelf, or a collection of structures related to previously known compounds with activity.

There is also combinatorial chemistry, which seeks to robotically generate hundreds of thousands of new structures for testing. One success of this method is the kinase inhibitor sorafenib for the treatment of kidney cancer. Other successes are hard to find, mostly because the multitude of compounds generated by such random syntheses doesn’t have much structural variety.

Progress on this front comes from a group of chemists at the University of Leeds. Building on the concept of “diversity-oriented synthesis,” Morton et al. report an ingenious new synthetic scheme that creates a broad range of basic molecular framework or scaffold structures, rather than just the decorative parts that hang off the scaffold (Angewandte Chemie International Edition 48:1 [2009], 104–109) .

The new approach yields many more novel products than earlier such schemes, with a higher amount of molecular shape diversity. It also lends itself to further modifications once lead compounds are discovered, and it contains relatively few steps, which makes large-scale synthesis more feasible.

A bigger problem remains unsolved: is it reasonable to expect small molecules to effectively and safely modulate the activity of complex biological functions mediated by interacting sets of macromolecules?

Time—and research—will tell. Maybe even in our lifetimes!

Way back in 2006 a group of clergy and scientists dreamed up the idea of Evolution Sunday.The idea was to get interested folk together to talk about the compatibility of science and religion.

Now that we are in 2009 and celebrating the 200th anniversary of Charles Darwin’s birth, the idea has expanded from a single day to Evolution Weekend. It appears to me from the Web site that lots of people and organizations are participating.

This is all to the good since whatever one’s religious views—or lack of religious views—scientific and spiritual disciplines both hold sway in the world. Both offer ways to understand things we find inexplicable. Both provide insights for advancing our basic humanity. Both are forms of belief, systems of philosophy, modes of investigation, pathways to discovery. Both connect us to the mysteries of the universe.

Reminds me of what Steven J. Gould once noted: “If there is any consistent enemy of science, it is not religion, but irrationalism.”