PROSTAGLANDINS: A CALL TO ARMS

Prostaglandins are infinitesimal, ephemeral, and powerful signaling molecules, self- regulating every cell in the body, a structure or function not regulated by prostaglandins yet to be discovered. Derived from essential fatty acids, prostaglandins signal within the cell, from cell- to- cell, tissue- to- issue, organ–to-organ, brain- to-body, and body to brain.  When prostaglandin metabolism is regulated, physiological processes function normally; when up-regulated, physiology becomes pathology.

In 1930 Rafael Kurzrok and Charles Lieb noted that semen can, paradoxically, cause uterine muscle to either relax or contract. In 1936, Ulf von Euler and Maurice Goldblatt isolated the active principles from the semen of boars, von Euler naming them "prostaglandins" out of the erroneous belief that they are manufactured exclusively by the prostate. In 1960 Sunne Bergstrom characterized the structure of prostaglandins, Bengt Samuelson their metabolic pathways, and in   John Vane showed that aspirin inhibits them, a discovery that stimulated worldwide interest. In 1982, Vane shared the Nobel Prize in physiology and medicine with Bergstrom and Samuelson.

Prostaglandins are synthesized, among others, by coral, algae, sponges, fungi, shellfish, fish, insects, reptiles, birds, vertebrates, mammals, primates and humans.  Enter, "prostaglandins" in a biomedical database, and you will find thousands of studies revealing their regulation of our physiology. Databases also contain copious evidence of the role of prostaglandins in many of our diseases. Prostaglandins are key factors in lactose intolerance and hay fever, as much as they are they are in depression, heart attacks, strokes, and cancer. 

In 1964, E.W. Horton reported that prostaglandins have powerful effects on the brain. Inspired by his study, pharmacologists, including my late colleague David Horrobin, showed that drugs that act on the brain, such as lithium and antidepressants, inhibit prostaglandins. All of the putative mechanisms of developing cancer are driven by excessive prostaglandin production. Cancer is accelerated replication of abnormal cells, and prostaglandins are responsible for developing abnormal cells, and for cell replication. In 1977 Horrobin showed that prostaglandins regulate nucleic acids (DNA and RNA).  Neglect or suppression of this study allowed genomics to become the prevailing paradigm, and dominate medical research.

In his “Against Method” Paul Feyerabend noted that suppressing a paradigm in preference to one politically favored could permanently damage society. In the nineteen-seventies-and-eighties, prostaglandins attracted substantial drug company investment, one of the companies referring to them as “Medicine’s New Frontier.”  With new technology that accelerates the production of DNA, venture capitalists, and the U.S patent office launched biotechnology and genomics, stampeding these companies into divesting from prostaglandins to buy  biotechnology and  genomics companies to secure their patents.

The premier medical journals have paid scant attention to prostaglandins, publishing many hundreds of articles in which they are not mentioned. The two prostaglandin specialty journals focus on high tech research with a narrow focus, rejecting low tech, clinical articles with broad implications. Medical school deans in both the US and UK vie for funding, with prostaglandins last on the list rather than first. Prostaglandins are biomedicine’s true standard with which to differentiate truth from untruth. Many laboratories continue to publish quality studies on prostaglandins, but more than enough was known about them thirty years ago to have warranted a paradigm shift .“Evidence,” now a buzzword, is often suppressed or hyped to the advantage of pharma, media, and politicians, both those in Washington and in medical schools.  When genomics was shown to be flawed, “epigenetics” was launched to search for factors regulating genes, deftly ignoring the fact that prostaglandins had been shown to be these factors. 

Prostaglandins determine tolerance or intolerance towards everything with which the body comes into contact, including stem and genetically altered cells. Medical research is largely based on the premise that DNA and RNA in the cell nucleus, and enzymes and proteins in the cell, whose structures are defined by DNA, are of overwhelming importance in disease. While significant, their practical importance has been exaggerated. Membrane lipids, which modulate the behavior of these entities, offer far more opportunities for practical therapeutic interventions. 

Trying to shed light on resistance to, or suppression of, advances is a key theme of the writings of philosophers and historians of science and medicine. I believe that the answer may be found in the teachings of Francis Bacon: a lack of ethics, and a lack of charity. Paul Feyerabend noted that the guardians of paradigm failures seldom concede to valid newcomers, to the extent that political intervention might hold the only hope of progress. With global warming and aging populations, we face alarming increases in infection and cancer rates, and the importation of tropical infections, with the suppression of prostaglandins imperiling our ability to manage them. We are amazed at how easily people lost their senses in signing up for the South Seas bubble, and the Dutch tulip mania. Unless we act quickly, posterity will view us as ruining healthcare by abandoning prostaglandins.