It has been exciting to see the large number of books and articles written
for the general public grow in recent years. However, it is somewhat disturbing
to see even our fine weekly news magazine sometimes butcher their simplified
explanations of free radicals and antioxidant nutrients. In case you have
found some of these distortions confusing, I thought that it would help
if I called upon an old friend to help explain free radicals and antioxidant
nutrients. Although we corresponded in the early 1970's, we did not actually
meet until many years later.
Dr. William Pryor has been the leading expert on free radicals in biology
since the 1960s and has been explaining these subject to scientists and
writers alike for these many years. In 1966, when I first had a need to
study free radicals beyond that taught as "Advanced Organic Chemistry"
and what could be gleaned from the meager existing scientific literature,
I turned to Dr. Pryor's new book.
Since both Dr. Pryor and I have very busy schedules, it was no easy task
to find enough time to obtain these special explanations for you. It took
more than two years. Part of the following interview was conducted while
horseback riding and hiking up Big Mountain, near Whitefish, Montana, part
while panning for gold in the Sonora Desert, part while cruising to Bahamas,
and in between sessions at various scientific symposia. Yes, in order to
expand our understanding of the travels of electrons through our bodies
as part of the life process, it helps to have a mind not encumbered with
routine thoughts. Getting out into nature can be hard work, but you deserve
the most thoughtful answers to your questions.
It helps to have conditions just right to permit the mind to explore free
radicals. Professor William A. Pryor, Ph.D. (l) and Richard A. Passwater,
Ph.D. (r) discuss the mechanisms by which antioxidant nutrients protect
the body against free radical attack while appreciating the beauty of nature
from the top of Big Mountain, near Whitefish, Montana in June, 1992.
Dr. William A. Pryor is the Director and Boyd Professor of the Biodynamics
Institute of Louisiana State University in Baton Rouge. He has published
over 500 scientific reports and 25 books. He has served as editor of the
leading journal in the field, Free Radical Biology % Medicine and
the book series Free Radicals in Biology.
Passwater: Dr. Pryor, you became "THE" free radical expert
in the 1960s. At that time, I had become interested in free radicals in
biochemistry as a result of my experience and publications in fluorescence
spectroscopy and my laboratory studies on cross-linking agents and the aging
process. I had been investigating the aging process since 1959 by doing
in vitro experiments on UV-induced cross-linking of proteins in gelatin
gels. After I included fats in my experiments, I became very interested
in free radicals and lipid peroxidation. By the mid-1960s, I began in
vivo studies with small laboratory animals. At that time, there was
little organized in-depth knowledge of free radicals and there were no computerized
compilations of the scientific literature. Research areas were more fragmented
and it took years longer to come across related publications from other
That's how I became interested in free radicals and I am grateful to you
for your book and other discussions through the years. What caught your
interest in free radicals? Why weren't you focusing on something else?
Pryor: When I became a faculty member, I wanted to work in a field
that wasn't overrun. When I became an academician there were two very well
known English chemists, Professors Hughes and Ingold (Ingold was knighted,
so now it's Sir Christopher Ingold.), and several American chemists (one
of them was a UCLA professor named Saul Winstein) who were studying ionic
reactions. That was probably the most popular field for faculty members
to study when I became an academician. So I decided that was exactly what
I didn't want to do -- I didn't want to be a member of that herd. I wanted
to do something different that would be in a more unique area.
Passwater: Are you saying you were a radical?
Pryor: I wanted to go up the down staircase and I was fortunate enough
to start my career for a chemical company that gave me a great deal of freedom.
They were interested in sulfur as an oxidant -- sulfur is right below oxygen
in the periodic table and behaves a lot like oxygen. It turned out that
sulfur oxidation very often involved free radical reactions, so I became
interested in free radicals. I realized that there was no book that introduced
free radicals to beginning students. There was an excellent 1957 monograph
written by a Columbia professor named Cheves Walling called "Free Radicals
in Solution," but it was about 700 pages long and was very difficult
reading for students. So I wrote a book which was published by McGraw-Hill
Book Co. in 1966. It reduced radical chemistry down to its skeleton and
provided students with a way to understand how free radicals worked. In
other words, whenever they would hear about a new free radical reaction,
they would have a framework into which they could put that fact, and to
understand how radical chemistry worked.
That book (Free Radicals; McGraw Hill Book Co., 1966) was used in
a lot of universities to teach free radical chemistry to young students.
Passwater: Now in those days there was very little research with
free radicals in biological systems. Dr. Denham Harman developed the free
radical theory of aging in the mid 1950s but very few other scientists were
studying radicals. Drs. Al Tappel and Lester Packer come to mind, but there
were very few. Now there are thousands.
Pryor: After my book "Free Radicals" was published,
I thought I would be an organic free radical chemist for the rest of my
life. That book was published in 1966 but in 1968 I was invited to speak
at a conference on free radicals in biology organized by the American Institute
of Pathology at the Federation meeting in Atlantic City. When I got the
phone call to speak I said you have the wrong guy because I don't know anything
about free radicals in biology -- I am an expert on organic free radicals.
They said that was just what they wanted. They wanted someone to teach them
about free radicals. Now free radical biologists are very well educated
about free radical reactions, but 1968 was essentially the beginning of
I went to that meeting and gave an introductory lecture on how free radicals
worked, but I rapidly realized that what everybody else was saying was a
heck of a lot more interesting that I was saying and I had better find out
something about free radicals in biological systems. So I expanded my reading
of the scientific literature on the subject and wrote a review article for
Chemical and Engineering News which they made into a feature article, called
"Free Radical Pathology."
Then I started a book series called "Free Radical Biology." In
1974, when I was organizing the first book for that series, the only scientists
I could find were those doing radiation biology -- the effects of radiation
on biological systems. But by the sixth volume of that series, I was inundated
with scientists doing all kinds of interesting free radical biology. In
fact, if you look at the six volumes of that series you can see the evolution
of free radical biology from rather esoteric things that aren't really of
concern to the practicing physician to interesting disease processes like
arteriosclerosis, heart disease, and cancer. You can see why the explosion
in interest in free radical biology has occurred.
For example, it was thought for many years that the most potent effect vitamin
E would have would be as a anti-cancer agent. However, it appears that vitamin
E is going to have a more important effect in reducing heart disease, than
in protecting us against cancer. Coronary artery disease appears to begin
by oxidation of the LDL particles to a fat-rich cell called a foam cell
that builds up in arterial walls and produces the occlusion of the artery.
Similarly, nitric oxide is interesting. It was always though of as merely
as a toxic component of smog. It's a free radical, but not a very reactive
one. My group had been studying nitrogen dioxide, which is the more reactive
nitrogen oxide in smog. Then it was discovered that nitric oxide is produced
in many types of cells in our body and controls all manner of reactions.
It controls smooth muscle cell contraction, for example. When heart victims
take nitroglycerin, it is because it releases nitric oxide which causes
the muscles in the artery bed to relax and reduces blood pressure.
Nitric oxide control also is involved in penile erection, and this is the
first new lead in some time in the treatment of impotency. Nitric oxide
is a key component in one nerve cell transmitting an electrical impulse
to the next. So, here in just a few short years we have gone from nitric
oxide being a relatively uninteresting toxic component of smog to being
a key component in biology.
Drug companies are actively involved in synthesizing new compounds that
will release nitric oxide, compounds better than nitroglycerine for example.
Passwater: The field of free radical pathology is rapidly expanding
into new fields of study. You must have some measure of this by the frequency
of which free radical research is quoted since you are the editor of the
journal Free Radical Biology in Medicine.
Pryor: Yes, I edit a journal called Free Radical Biology in Medicine.
I am a co-editor with Dr. Kelvin Davies who is head of biochemistry
and molecular biology at the Albany Medical School in New York. Dr. Davies
and I started this journal -- I started the review portion of it and Dr.
Davies started the fundamental scientific portion of it -- about ten years
The Institute for Scientific Information, which does computer ranking of
the importance of scientific journals based on the frequency with which
other scientists cite articles in those journals, now finds that we are
in the top twenty journals in the field of biochemistry and molecular biology
-- there are almost 200 journals in that field. Three years ago we were
in the top 50 and we have come up to the top twenty very fast. That's because
we've been careful to only publish high-quality articles in our journal,
but also it is because of the enormous interest in the field of free radical
I used to tell my students that they could very easily do a literature search
by coming to my office and I would tell them the most important person in
that field and I had a file on that person. I filed everything by author
and we could do a complete literature search in the five file cabinets I
used for this. Soon, however, my students then began doing computer searches
and turning up names I had never heard of doing things that were vitally
important. I rapidly began to realize this field had outgrown my knowledge
of the people in it.
The field has mushroomed to the extent there are so many bright young people
flooding into the field, M.D.'s and Ph.D.'s doing research on all manner
of conditions and diseases, that it is now beyond any one person's ability
to know and understand the entire field.
Passwater: It just goes to show how little science actually does
know about the chemistry of life. We have known about nitric oxide for over
a hundred years, but we had no idea that it was a neurotransmitter or hormone
until a few years ago. It was just two years ago that Science magazine called
it the "Molecule of the Year." It is increasingly appreciated
as a physiologic messenger and a major regulator in the nervous, immune
and cardiovascular systems. We are constantly learning of the effects of
free radicals and now we have a free-radical hormone.
Let's get to the basics. What are free radicals?
Pryor: All that a non-chemist interested in this subject has to understand
is that a free radical is an active part of a molecule. Readers who wish
a basic, but more technical description, can define a free radical as merely
a chemical species with an odd number of electrons.
Readers who have had basic science or chemistry courses probably are familiar
with drawings of atoms with various "shells" or layers of electrons.
These electronic shells consist of one or more electron orbitals. An electronic
orbital is merely a region in which there is a high probability of finding
an electron. These orbitals (or regions) are determined by the structure
of the species, but a common feature of all electronic orbitals is that
they hold a maximum of two electrons.
Passwater: Those definitions of a free radical are certainly adequate
for the lay person to understand what free radicals are and how they may
damage the body. However, since we also have quite a few readers who are
biochemists can you elaborate a little more? I am sure that our non-chemists
friends will bear with us for just a moment.
Pryor: Chemists use even a more technical definition of a free radical.
The lay person doesn't have to understand "how" free radicals
interact with other chemical species, nor do they have to predict the energy
used or released in such interactions. This is the job of chemists, and
we need more precise definitions and understandings.
It is helpful for chemists to consider a free radical as any chemical species
having one or more "lone" or "unpaired" electrons. When
an electron is by itself in an orbital, there is "extra" energy
available due to the magnetic field resulting from its spin. Normally, two
electrons are coupled or paired in an orbital and since their spins are
in the opposite direction, their magnetic vectors cancel each other.
The reason that the more basic definition is accurate is that all atoms
and molecules that have an odd number of electrons must have at least one
electron that is in an orbital by itself. However, this basic definition
doesn't take into account such things as di-radicals, which are chemical
species having two
lone or unpaired electrons, and atoms of the many elements, which are free
radicals because they contain lone electrons in orbitals even though the
total number of electrons may be even. All chemical species with an odd
number of electrons are free radicals, but there are some free radicals
that have an even number of electrons, but generally speaking those exceptions
are not the free radicals we generally deal with in biochemistry.
A few free radicals are stable molecules; nitric oxide, which we were just
discussing, is an example of a stable molecule being a free radical. The
nitric oxide molecule has an odd number of electrons so it is a free radical.
I hope that all of these technicalities don't confuse your non-chemist readers.
Passwater: If it does, all they have to do is remember your basic
definition that a free radical is the reactive part of a molecule. Since
you have given us a non-technical definition of a free radical, would you
also give us a non-technical explanation of how free radicals can be so
destructive in the body and be involved diseases?
Pryor: When you have a free radical produced in a chemical system
you generally get a propagation of damage. Envision a situation at a dance
hall where you have all couples dancing and then you admit a lone bachelor
-- what used to be called a "stag." Now this lone male is "reactive"
-- he really wants to dance -- so he reacts with "i. e., cuts in on"
a dancing couple. So now he has a partner to dance with but another odd
man is produced. Whenever you have an odd species and you throw it into
a collection of even species, there will always be odd species. In the case
with a free radical, which has an odd number of electrons, you will always
have some chemical species with an odd electron present until another free
radical comes along and couples with that first free radical to make a stable
species with an even number of paired electrons. So in the dance hall analogy,
it would take another woman, who would then partner with the odd man, and
then you would have all pairs again, and the dance would be uninterrupted
by this propagation of "cutting in."
Free radical damage propagation and "dancing uninterrupted" propagation
are similar because electrons also have a property analogous to the "sex"
factor of our dancers. AS we discussed earlier, electrons spin about their
axes, like the Earth spins on its axis to give us day and night. Electrons
also travel about the nuclei of atoms or travel in orbitals in molecules
much like the Earth travels around the Sun to give us yearly seasons. So
electrons in chemical species have spin and travel in orbitals. We describe
their spin vector property in Quantum Mechanics as being either "down"
or "up." It is much like the concept of being either "positive"
or "negative," and somewhat akin to our dancer analogy of being
either "male" or "female."
In order to pair up, free radicals must have opposed spins. In our dancers
analogy we used opposed sexes to represent this capacity to pair up. In
some circumstances, free radicals can keep track of their spin so that two
free radicals with an "up" spin cannot pair. It would take a free
radical having its extra electron with an "up" spin and another
free radical having its non-paired electron with a "down" spin
to form new stable species. So in the sense having ladies and men dancing
and having a spare man propagating "damage" and then taking a
woman coming in to even things out in a way makes chemical sense.
Passwater: In quantum mechanics, we describe the electrons within
a molecule or atom in terms of four quantum numbers. Each electron differs
from the other electrons in the atom or molecule by a given amount of energy.
The smallest difference in energy between electrons is due to their spin.
As you said electron spins can be described loosely as being "up"
or "down." Earlier you mentioned that when electrons in an orbital
are paired and thus spinning in opposite directions, the forces of the magnetic
fields generated are neutralized. When there is a lone electron, the molecule
or atom will have a magnetic vector and is said to be "paramagnetic."
People sometimes confuse radicals with ions. Ions are electrically charged
due to either an excess of electrons or protons. Radicals have magnetism
due to the lone electron's spin.
I have enjoyed your analogies for almost forty years now. Chemists have
the extensive background to understand orbital theory and quantum mechanics,
but it is indeed an art to be able to quickly explain complicated concepts
to those who haven't had the opportunity to study the appropriate background.
This is why the press used to come to you for background explanations --
it wasn't only because you were an "authority," it was because
you were the great communicator.
Dr. Pryor, let's pause here and resume the discussion of various types of
free radicals in Part II, and we'll save antioxidant nutrients for part
III. I am going to have fun and see if you can come up with even more analogies
to explain more about biologically important free radicals.
All rights, including electronic and print media, to this article are copyrighted
to © Richard A. Passwater, Ph.D. and Whole Foods magazine (WFC Inc.).