More Recent Article on Dr.Brewer's Cancer Research
By Frederick I. Scott
Recent science news announcements and symposia brought to mind the remarkable utilitarian findings of a researcher whose work spanned the disparate disciplines involved to produce and substantially validate practical solutions to problems. These problems are now being addressed expensively in fragments, promising only the possibility of more research.
Dr. Keith Brewer, a physicist, served for some
time in his research career as Chief of the Mass Spectrometer
and Isotope section of the National Bureau of Standards (now the
National Institute of Standards and Technology, Gaithersburg,
MD). Among the studies he
conducted beginning in the early 1930s, the examination of the
ratio of potassium isotopes 39K/41K in a wide range of living
and nonliving materials proved most fruitful, particularly in
the study of cancer initiation.1 He found that ratio to be constant
at 14.200 to at least five
significant figures in ocean water, for example, down to at least
6000 ft. In embryonic and very young rapidly growing tissues,
however, he noted a tendency for the lighter isotope to be enriched,
giving values of 14.35 ± 0.05. In very old tissues, he
measured ratios as low as
13.75. In cancer tissues, the ratio remained close to 14.35, irrespective
of the age of the subject.
He found that when potassium ions bombard a membrane across which a strong potential is imposed, the lighter isotope concentrates with a separation coefficient proportional to the square root of the ratio of the heavier to lighter mass. With this finding he determined that the14.35 ratio in cancer and embryonic cells corresponded to single-stage enrichment. He showed that in solution the K atoms associate with 5-7 molecules of water. In the presence of other polar molecules, the number of atoms associated with the ion depends on the polarity of the molecules. The bombarding ions tend to carry all or part of their associated masses with them into the membrane, as determined by the solubility of the associated molecules in the membrane material.
When equilibrium conditions exist between the
membrane and the surrounding solution, he observed no isotope
effect, indicating that
equilibrium conditions prevail in normal cells, since little if
any isotope effect occurs in normal cells. Enrichment of the heavier
isotope, 41K, occurs by another mechanism not pertinent here.
Questions raised by these findings led Dr. Brewer to a study of the cell membrane and eventually to publication of a series of papers with Dr. Richard A. Passwater (Consultant in Gerontology, Ocean Pines, MD), on the subject of the physics of the cell membrane.2-6 The major constituents of the cell membrane are phospholipids; proteins contribute to the structure. The lipids are so disposed that the polar phospho groups constitute the outer walls. These polar groups are characterized by oxygen atoms connected to phosphorus by double bonds, i.e., P|O. The very electronegative oxygen atom (compared to the P atom) disposes the two electron pairs, connecting the atoms much nearer to the O atom than the P atom. The moderately-intense negative intrinsic field surrounding the |O group exerts a repulsive force between the |O groups resulting in a relatively uniform distribution of them over the surface. Thus, membrane surfaces may be classified as base exchangers, since the |O groups are powerful electron donors.
In the unexcited or ground state, the surface is only a mild electron donor, hence it attracts only cations high up in the Hofmeister series. (This series is the same as the ionization potential series ranging from ionic cesium [Cs+] at 3.87 V at the top down through rubidium [Rb+] at 4.16 V; potassium [K+] at 4.138 V; sodium [Na+] at 5.12 V; lithium [Li+] at 5.363 V; calcium [Ca+] at 6.09 V; to magnesium [Mg+] at 7.61 V.) Thus, only K+ ions, with the exception of Rb+ and Cs+ ions, can be attached. The instant an ion strikes the electron donor group and becomes attached, it finds itself in a powerful electric gradient of at least 105 V/cm to be drawn rapidly through the membrane in about 10-8 sec.
In the excited state, one of the electrons
in the electron pair is raised from the ground state to some high
energy level in the singlet or
triplet energy series. In this state the bond becomes strongly
electronegative, a powerful electron donor, transforming the membrane
surface to accept almost any cation in the Hofmeister series.
In the embryonic cell, the membrane permits
essentially all K+ ions striking the electron donor group (|O)
to pass through into the
cytoplasm, as illustrated clearly by the isotope abundance ratio,
showing that these isotopes pass through the membrane in proportion
to the ratio in which they bombard the surface. So, too, with
cancer cells. But what mechanisms or materials triggered or caused
the excited state? These observations and the further work they
engendered, eventually led Dr. Brewer to propose and test a mechanism
for
interrupting the cancer process.7
The isotope effect for potassium, which transports glucose into the cell, and for calcium, which transports oxygen into the cell, means that glucose can readily enter cancer cells but that oxygen cannot. In the normal cell the glucose, upon entering the cell, reacts with the oxygen in the cell to be burned to carbon dioxide and water with the liberation of heat. Absorbed on the membrane surface, the heat raises the P|O radicals to an energized state, permitting them to attach more Ca++ ions. Thus, the oxidation within the cell, primarily that of glucose, determines the amount of oxygen entering the cell.
Dr. Brewer postulated carcinogenic materials,
primarily polycyclic in nature, and an energized state of the
membrane, resulting possibly
from prolonged irritation, create the condition in which glucose
can enter the cell but oxygen cannot. In the absence of oxygen,
the
glucose undergoes fermentation to lactic acid, dropping the cell
pH to 7 and eventually to 6.5. In the acid medium, changes in
the DNA and RNA effect the loss of control and chromosomal aberrations
may occur. Changes in the various cell enzymes produce toxic compounds
that kill the cells within the main body of the tumor, leaving
a thin layer of rapidly growing cells surrounding the dead mass.
The acid toxins leaking out of the tumor mass poison the host
and give rise to the pains generally associated with cancer.
Based on the ready uptake of cesium and rubidium
(which cannot carry glucose across the membrane) by the cancer
cells, Dr. Brewer
devised a therapy aimed at depriving the cell of glucose and supporting
the system with antioxidants and other nutrients. Tests with mice
and humans affirmed the efficacy of the therapy in preliminary
trials. In a most remarkable finding, all pains associated with
the cancer disappeared within 12 to 24 hr, except in a few cases
where morphine withdrawal required a few more hours. Rapid shrinkage
of tumor masses occurred with side effects of nausea and diarrhea
reported by some patients depending on the general condition of
the digestive tract.
While Dr. Brewer continued his studies and
supported work at the University of Wisconsin (Plattville, WI)
until his death, no further
exploration of this promising approach seems to have occurred.
Dr. Brewer's rationale and experimental findings seem so much more promising both theoretically and practically than some highly touted and expensive research proclamations in the news that one wonders about the perspicacity of the grantees and grantors - until one realizes that oftentimes researchers are in the business of research, not of problem solving.
References
1. Brewer AK. Cancer: Some comments on the
physics involved. Am Lab 1973; 5(11):12-23 and references therein.
2. Brewer AK, Passwater RA. Physics of the cell membrane: Part
I The role of double-bond energy states. Am Lab 1974; 6(4):59-74.
3. Brewer AK, Passwater RA. Physics of the cell membrane: Part
II Fluorescence and phosphorescence in cell analysis. Am lab 1974;6(6):19-29.
4. Brewer AK, Passwater RA. Physics of the cell membrane: Part
III The mechanism of nerve action. Am Lab 1974; 6(11):49-62.
5. Brewer AK, Passwater RA. Physics of the cell membrane: Part
IV Further comments on the role of the double bond. Am Lab 1975;7(1):41-50.
6. Brewer AK, Passwater RA. Physics of the cell membrane: Part
V Mechanisms involved in cancer. Am Lab 1976; 8(4):37-47.
7. Brewer AK. The high pH therapy for cancer tests on mice and
humans. Pharmacol Biochem & Behavior 1984; 21 Suppl 1:1-5.
Mr. Scott is Editor, American Clinical Laboratory.