The smell of cancer

What Does Cancer Smell Like?

By VERONIQUE GREENWOOD Published: November 19, 2013

Excerpt:  Diseases can subtly alter people’s fragrance. In the normal course of metabolism, thousands of waste products are swept out in our breath, blood and urine, or simply released into the air above the skin. Metabolic disorders, like diabetes, interfere with the way the body breaks down nutrients and thus make that exhaust especially stinky. People with phenylketonuria (or PKU) tend to smell musty. A faulty or missing digestive enzyme makes people with trimethylaminuria (or TMAU) smell fishy.

My comment to the NYTimes (buried among 18 others published at 10:34 on 11/21/13): The link  to the smell of cancer may be clearer by starting with what’s known about the molecular mechanisms of nutrient-dependent pheromone-controlled reproduction in yeast.

The same model organism is used to manufacture new fragrances and in the development of pharmaceuticals, as reported here last month in “What’s That Smell? Exotic Scents Made From Re-engineered Yeast”

“..rather than spit out alcohol, the yeast spits out these products,” said Jay D. Keasling, a co-founder of Amyris…” — reported by Andrew Pollack.

Bringing in the physicists should help others to address the thermodynamics of intercellular signaling and stochastic gene expression in typical and atypical organism-level thermoregulation, since the molecular mechanisms of controlled cell proliferation are conserved across species from microbes to man.

There must obviously be typical and atypical odors associated with different cells types, since that is where physics, chemistry, and molecular biology meet.

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Addendum: Earlier this year I addressed the issue of fish odor syndrome mentioned in the NY Times article in the context of nutrient-dependent species-specific pheromone production that links the conserved molecular mechanisms from mice to humans. After detailing the synergy required for choline metabolism by the liver to result in a species-specific pheromone signature, I put the technical details into the context of something that might more readily be understood

Excerpt: “One clown asked another: ‘Do I smell funny to you?’ Adults with ‘fish odor syndrome’ are not likely to think that question is funny. Mice do not think about whether their brain development or their natural odor production is determined by diet. Yet, without thought, nutrient-dependent and pheromone-controlled chromatin remodeling is responsible for transgenerational epigenetic inheritance involved in species diversity (Kim et al., 2008; MacDonald & Roskams, 2009; Nadeau, 2009; Riccio, 2011; Tammen, Friso, & Choi, 2013). This suggests that questions about the adaptive evolution of species diversity (Papasaikas & Valcarcel, 2012) are not likely to be answered outside the context of the molecular biology common to all species (Shapiro, 2010).”

Questions about atypical cell proliferation in cancer are now being addressed in the same context of alternative splicings, which was addressed in the “molecular epigenetics” section of our 1996 Hormones and Behavior review article: From Fertilization to Adult Sexual Behavior.  Indeed, it was Teresa Binstock who forwarded to me the notices on both articles that appeared in the NY Times on Oct 20, 2013 and on Nov 19, 2013. In 1996, she wrote:

“Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”

It now seems likely that if other researchers had paid attention to this information about epigenetics and sex differences, more progress might have been made in the context that links nutrient-dependent pheromone-controlled adaptive evolution to sex differences and to other differences in cell types via the physics, chemistry, and molecular biology of all species. If not for the theory of mutation-initiated natural selection, which is what today’s students are still being taught, cancer research might have been based on accurate representations of  what is now known about RNA-binding proteins and how the epigenetic “landscape” is linked to the physical landscape of DNA in the organized genomes of all organisms.

Teaching professors the scientific truth about epigenetics might help them to abandon mutation-driven evolution. This would help their students make the progress that will be required to limit or cure cancers that involve  epigenetic effects on different cell types. Instead, we currently have people like Jay R. Feierman, the M.D. /Ph.D moderator of the human ethology yahoo group who wrote:

“It is very sad for me to see that when several different people on this group, all with doctorate degrees, tell you that you are not correct, you don’t consider that they might be telling you something helpful. Instead, you respond with arrogance and ignorance. I’ll add my voice to the other people on this group who have told you that you are not correct in terms of your understanding of what “variation” means in Darwinian biological evolution and what is doing the selecting. Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding Darwinian biological evolution. I think all of us are trying to be helpful to you. However, our efforts are in vain if you continue with arrogance and ignorance of this topic.”

For more than 15 years, Teresa Binstock, Milton Diamond, and I have understood more about the causes of variation in different cell types of different tissues in different organisms than what most people understand today.  I first met Jay R. Feierman at a conference in 1995, and for more than 15 years he appears to have learned nothing about anything. He still thinks that “Random mutations are the substrates upon which directional natural selection acts. — as if natural selection enabled selection for cancer.