• Dr. Robert A. Nagourney, MD

Pigment, Color and Cancer - The Need for Phenomics

An interesting story reported by National Public Radio on November 12 described the origins of color in biology. Andrew Parker, a biologist from London’s Natural History Museum, described the development of sightedness in living organisms.

Until 600 million years ago animals were sightless. Then predatory organisms developed vision and used it to pursue prey. From that point color became an integral part of biological existence. Colors could attract mates, serve as camouflage, protect against predators and attract other organisms such as pollinating bees.

One of the more interesting aspects of the discussion was the fact that vertebrates have no capacity to produce the color blue. Indeed green is also quite difficult. So how, one might ask, do butterflies, peacocks and people with blue eyes create the appearance of the color blue? The answer is quite interesting and may be instructive when we examine other biological phenomena.

Pigments, known as biochromes, are substances produced by living organisms that have the capacity to absorb or reflect light of specific wavelengths. Their chemical structure captures the energy of the light wave resulting in the excitation of electrons to higher energy states. Among the colors commonly found are heme porphyrins, chlorophyll, carotenoids, anthocyanins, and betalains. While it is comparatively easy for plants to produce a broad spectrum of colors, animals have a more limited palate. They can borrow pigments from other species, like the flamingo whose pink hue is borrowed from the shrimp it eats. It seems however, that blue and green pose unique problems and must be created through an ingenuous melding of chemical biochromes and what is known as “structural pigmentation.”

The wings of a bluebird or those of a Morpho butterfly use specialized structures that are capable of capturing light at just the right angle. In so doing, they selectively reflect light and combine specific wavelengths with chemical pigments to create the illusion of color. Blue butterflies and green parrots are, in reality, sophisticated illusionists.

So what of other biological phenomena, specifically cancers? Quite a lot it seems. We have come to think of cancer as a product of genetic information. Our linear thinking with origins in cancer biology dating to the 1950s has long held that biological phenomena reflect the presence (or absence) of genes. The principal known as Central Dogma dictated that DNA produced RNA, that RNA produced protein and that protein produced function.

Our tidy principles were dealt their first blow by the discovery of epigenetics and then by small interfering RNAs. Most recently noncoding DNAs have further clouded the picture. It seems that the behavior of cancers may be every bit as deceptive as the bright blue hue that we ascribe to our avian and insect brethren.

Like butterflies or birds, cancers cloak themselves in a mixture of genetic and structural elements. While their behavior may appear to reflect genetic aberrancies, it may be structural (e.g. micro-environmental) perturbations that confer their unique biology. One can no more grind up and extract a parrot’s wings to find blue pigment than can we grind up and extract the genetic information of cancer to recreate its complexity. This however has not prevented the reductionists among us from trying. Unfortunately for them, cancers are demonstrably more complex than their genetic makeup.

Like a bird or a butterfly we must witness the creature in its entirety to grasp its function and behavior. Genomic analyses conducted in a vacuum cannot define the complexity of cancer biology. To create successful cancer treatment outcomes, we need to determine cellular phenotype. And, the EVA-PCD assay is quintessentially phenotypic. This is why the functional profile resulting from the EVA-PCD assay can identify accurate targets and select therapies.