Pigment, Color and Cancer

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 o220px-Lightmatter_flamingo2f 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 cobrilliance-clipart-canstock1498651mplexity. 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.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

5 Responses to Pigment, Color and Cancer

  1. sthompson218 says:

    I always appreciate your blog posts. I would like to share them through twitter if you could add social media sharing for that (and facebook and linkedin at the same time).

  2. Paul Blystone says:

    Dear Dr. Nagourney

    For years I have always asked people:

    “How come there is no blue food?” They would mention blueberries…but blueberries are really more toward the purple spectrum if you look at the stain they make.

    Theory: Plants depend on light…so perhaps the surface allows more spectrum manifestations. Humans surface is mainly determined by race and melanin. Not much need for greater spectrum manifestations.

    General point is that surface matters…..including cancer surfaces.

    I will try to remember my chemistry and physics form college. As you point out, color can be determined a couple of ways. The most common is that molecules absorb certain wavelengths and emit or allow to pass through others. The second is through a grating mechanism…whereby wavelengths are not so much absorbed..but cancelled out.

    I believe cancer uses multiple tricks. Genetic mutations are central to all cancers, but surface manifestations hold the key to treatments. Some cancers do manifest specific surface characteristics from a genetic flaw, such a Philadelphia mutation…which might be tackled via Gleevec. Others are not so simple, particularly solid tumor cancers.

    I believe that immunotherapy is the next wave of treatment advances. If you can kill cells while in the presence of leukocytes that learn from the kill, then a lasting memory effect might take place.

    I have always been a proponent of your EVA-PCD test. I wonder if you could add a platform for testing cells against immunotherapy responses?


    Paul Blystone

    • Paul

      Many interesting points raised. Color as we perceive it is the combination of pigments, whose chemical makeup allow them to selectivity absorb certain wavelengths and reflect others while “structural” elements “bend” light. For both it is the reflected wavelengths that we then see. A “blue” pigment” absorbs in the red and yellow ranges while a blue feather bends those spectra, so the blue spectrum returns to our eyes. Sunlight contains all white light spectra, so the color we see is indeed the absorption (or cancellation) of certain white light components. Colored materials do not “create” light. Human coloration is a mixture of heme, caratenoids and melanin. The yellow hue that very anemic patients manifest is actually caratenoids coming to the fore as heme diminishes.

      The observations in the blog reflected my belief that we need to look beyond the “informatics” of cancer to the “functionality” of cancer, a blending of pigments and structure, as it were. Color or for that matter human life is more than the sum of genetic elements. If, for example, you “extracted” the constituents of a butterfly’s wing, you would find the pigment chemicals and a collection of alpha helices and beta-pleated sheet protein structures (those that make up the structural elements of the final color). But unless you assembled those proteins in exactly the right configuration together with just the the right pigments, you would not see the color blue.

      One point. Cancer is not only the product of abnormal genes (mutations) being used normally but may reflect normal genes (wild type) being used abnormally. This is not unlike the color blue emanating from a “non-blue” structure. Similarly, our pursuit of mutations (genomics) may not truly define the abnormal process.

      I am in complete agreement that immune therapy is a brilliant area and we hope in the future to develop better means to predict outcomes for patients who are candidates for the newest classes of checkpoint regulators like PD-1.

      Thank you for your thoughtful input.

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