Welcome to Ray Firestone’s blog site. I am a chemist, retired from 43 years in Big Pharma, but still engaged in research. The objective of this blog site is to post ideas and proposals regarding science, industry and wherever else I feel I have something worthwhile to say. Your feedback is welcome. You can reach me at
BLOG 1: “SPIKES” IN NUTRITION
Since time’s beginning until one or two centuries ago, our bodies never had to contend with taking in more of any nutrient than our stomachs can hold. But now we can buy pure sugar, vitamins, minerals and other substances found in Nature. As a result, we can and do ingest many of these compounds in unnaturally large amounts, producing huge “spikes” in blood concentration which can be harmful. The recent spate of articles decrying many natural nutrients when taken in super-natural amounts warns against all food supplements, but when they are taken in ways that avoid spikes, supplements can be valuable.
BLOG 2: THE CHIMP-HUMAN GAP
Since Darwin’s time our view of inheritance has matured greatly. No longer can we say that we are nothing more than the sum of our individual genes. The effects and interactions among genes are more complex than that. We differ from chimpanzees in only ~1% of our genomes, raising the question of how such a small genomic difference can give rise to such a profound species difference. We don’t know yet, but several interesting proposals have been made.
Symmetry-allowed cycloaddditions may but not must be concerted, i.e. the two new bonds may or may not form simultaneously in a singe transition state. The Woodward-Hoffmann Rules, however, have since 1965 assumed such a powerful position in chemistry that most chemists believe that allowed cycloadditions are concerted, Q.E.D. In this paper I show beyond any doubt that at least 88 examples of symmetry-allowed cycloadditions – Diels-Alder and 1,3-dipolar cycloadditions – proceed stepwise through diradical intermediates, and furthermore that no example of such cycloadditions has been proven to be concerted.
In recent years, several publications have bemoaned the increasingly poor performance of Big Pharma in innovative research. I propose, based on my own experience there, that the reason lies in the deterioration in the relationship between management and creative researchers.
BLOG 5: COST OF CANCER CHEMOTHERAPY
Antitumor drugs are toxic to the patient as well as the tumor, so they must be directed toward the tumor and away from normal body cells. One way of targeting to tumors is to attach the drug to a monoclonal antibody that preferentially binds to the cancer cells. Several new antibody-drug conjugates have been approved by the FDA, causing great excitement. However, antibody conjugates are inherently very expensive, and the cost of treatment, even when it delays death by only months, can be about$100,000. Few patients can afford this. I have tried to cut costs by dispensing with the antibody, joining the drug instead to a small peptide that deactivates the drug, and releases it in active form only after contact with an enzyme (Cathepsin B) secreted by the cancer cells themselves, and nowhere else in the body. This works, but many obstacles remain before there can be human trials. Our first paper is presented here.
BLOG 6: DARK ENERGY
Dark Energy is a mysterious force that opposes gravity on a cosmic scale. It was invented to explain an unexpected phenomenon in the deepest past. I hold that it is unwise to adopt a hypothesis contrary to what is perhaps the most well-supported theory we have, on the basis of one rather imprecise observation when there are other more plausible explanations.
BLOG 7: THEORY AND EXPERIMENT IN SCIENCE
Physical science rests on physical data. This principle has held sway since the Enlightenment, although before that people were often persecuted for espousing, from experimental data, ideas that contravened accepted dogma. Now, modern times have brought with them some reversal of post-enlightenment attitudes.
The ages of the Earth and the Universe are both finite, and can be determined with reasonable precision: the Earth’s from the decay of radioactive elements in rocks, and the Universe’s from its rate of expansion as shown by the velocities of separation of heavenly bodies.
BLOG 9: EVOLUTION AND DARWINISM
Evolution and Darwin’s theory are often conflated, but they are separate concepts. Evolution certainly occurred, but natural selection is only a theory, albeit the best one we have. Its stochastic aspect is what disturbs some people.
BLOG 10: ROOTS OF MORAL BEHAVIOR
All societies have rules for moral behavior. Are they inborn via natural selection? Do we learn them from God or from other people? My view is that we learn them during our lifetime, driven by experiences in which we imagine ourselves in other peoples’ places while witnessing moments of discomfort, pain or fear on their part.
There is a recent trend toward relaxing the health standards for people over ~70 for weight, blood pressure and LDL. Recent studies find no increase in mortality when weight rises from BMI 22 to 27, BP rises from 140 to 150, and LDL rises to >100. I hold that these conclusions are fallacious because the studies make no distinction between robust and frail cohorts of the old.
Blog revised November 1, 2017
The title reaction, to date studied only by quantum mechanical calculations, has been described as concerted by two groups, despite their detailed reaction coordinates’ showing a stepwise pathway with a diradical intermediate. Concert is declared because the delay between formation of the two bonds is only ~13 fs. Herein, I show that concert is impossible because (1) diradical intermediates have been intercepted many times; (2) 13 fs is a calculated, not an experimental number; (3) concert cannot explain the rate similarity between ethylenic and acetylenic dipolarophiles; (4) The Born-Oppenheimer Principle contradicts their analysis; (5) intramolecular vibrational redistribution, which must precede bond formation, takes 500-1000ps; and (6) experiments show that actual thermal bond formation times are in the ns, not ps range.
BLOG 13: SUICIDE BY PROXY
Sometimes someone wants to end his own life but cannot do it himself, because he lacks the courage, or fears damnation, or wants some particular person to do it. This situation has often been depicted in fiction, but sometimes so subtly that the reader must infer what is not actually said. In reality (as distinguished from fiction), suicide by proxy is now a well-known entity encountered by the police, for example, who recognize there are times — and they are not infrequent — when desperate people seek death at the hands of law enforcement officers and others.