The China Study (8 page)

THE CHINA STUDY
40
cancer. A classic illustration of this difficulty is that countries with more
telephone poles often have a higher incidence of heart disease, and
many other diseases. Therefore, telephone poles and heart disease are
positively correlated. But this does not prove that telephone poles cause
heart disease. In effect, correlation does not equal causation.
This does not mean that correlations are useless. When they are
properly interpreted, correlations can be effectively used to study nu-
t r i t i o n and health relationships. The China Study, for example, has
over 8,000 statistically significant correlations, and this is of immense
value. When so many correlations like this are available, researchers
can begin to identify patterns of relationships between diet, lifestyle
and disease. These patterns, in turn, are representative of how diet and
health processes, which are unusually complex, truly operate. However,
if someone wants proof that a single factor causes a single outcome, a
correlation is not good enough.
STATISTICAL SIGNIFICANCE
You might think that deciding whether or not two factors are correlated
is obvious-either they are or they aren't. But that isn't the case. When
you are looking at a large quantity of data, you have to undertake a sta-
tistical analysis to determine if two factors are correlated. The answer
isn't yes or no. It's a probability, which we call statistical significance. Sta-
tistical significance is a measure of whether an observed experimental
effect is truly reliable or whether it is merely due to the play of chance.
If you flip a coin three times and it lands on heads each time, it's prob-
ably chance. If you flip it a hundred times and it lands on heads each
time, you can be pretty sure the coin has heads on both sides. That's the
concept behind statistical Significance-it's the odds that the correlation
(or other finding) is real, that it isn't just random chance.
A finding is said to be statistically Significant when there is less than
5% probability that it is due to chance. This means, for example, that
there is a 95% chance that we will get the same result if the study is
repeated. This 95% cutoff point is arbitrary, but it is the standard, none-
theless. Another arbitrary cutoff point is 99%. In this case, when the
result meets this test, it is said to be highly statistically significant. In the
discussions of diet and disease research in this book, statistical signifi-
cance pops up from time to time, and it can be used to help judge the
reliability, or "weight," of the evidence.

A HOUSE OF PROTEINS                            41
MECHANISMS OF ACTION
Oftentimes correlations are considered more reliable if other research
shows that two correlated factors are biologically related. For example,
telephone poles and heart disease are positively correlated, but there is
no research that shows how telephone poles are biologically related to
heart disease. However, there is research that shows the processes by
which protein intake and liver cancer might be biologically and caus-
ally related (as you will see in chapter three). Knowing the process by
which something works in the body means knowing its "mechanism
of action." And knowing its mechanism of action strengthens the evi-
dence. Another way of saying this is that the two correlated factors are
related in a "biologically plausible" way. If a relationship is biologically
plausible, it is considered much more reliable.
METANALYSIS
Finally, we should understand the concept of a metanalysis. A met-
analysis tabulates the combined data from multiple studies and ana-
lyzes them as one data set. By accumulating and analyzing a large body
of combined data, the result can have considerably more weight. Met-
analysis findings are therefore more substantial than the findings of
single research studies, although, as with everything else, there may be
exceptions.
After obtaining the results from a variety of studies, we can then be-
gin to use these tools and concepts to assess the weight of the evidence.
Through this effort, we can begin to understand what is most likely to
be true, and we can behave accordingly. Alternative hypotheses no lon-
ger seem plausible, and we can be very confident in the result. Absolute
proof, in the technical sense, is unattainable and unimportant. But com-
m o n sense proof (99% certainty) is attainable and critical. For example,
it was through this process of interpreting research that we formed our
beliefs regarding smoking and health. Smoking has never been "100%"
proven to cause lung cancer, but the odds that smoking is unrelated to
lung cancer are so astronomically low that the matter has long been
considered settled.

3........ ... .... _........ _....... ..
..
Turning Off Cancer
AMERICANS DREAD CANCER more than any other disease. Slowly and pain-
fully being consumed by cancer for months, even years, before passing
away is a terrifying prospect. This is why cancer is perhaps the most
feared of the major diseases.
So when the media reports a newly found chemical carcinogen, the
public takes notice and reacts qUickly. Some carcinogens cause outright
panic. Such was the case a few years ago with Alar, a chemical that was
routinely sprayed on apples as a growth regulator. Shortly after a report
from the Natural Resources Defense Council (NRDC) titled "Intoler-
able Risk: Pesticides in Our Children's Food,"l the television program
60 Minutes aired a segment on Alar. In February 1989 a representative
of NRDC said on CBS's 60 Minutes that the apple industry chemical was
"the most potent carcinogen in the food supply. " 2 , 3
The public reaction was swift. One woman called state police to
chase down a school bus to confiscate her child's apple.4 School systems
across the country, in New York, Los Angeles, Atlanta and Chicago,
among others, stopped serving apples and apple products. According to
John Rice, former chairman of the U.S. Apple Association, the apple in-
d u s t r y took an economic walloping, lOSing over $250 million. s Finally,
in response to the public outcry, the production and use of Alar came to
a halt in June of 1989.3
The Alar story is not uncommon. Over the past several decades, sev-
eral chemicals have been identified in the popular press as cancer-caus-
ing agents. You may have heard of some:
43

44                           THE CHINA STUDY
• Aminotriazole (herbicide used on cranberry crops, causing the
"cranberry scare'" of 1959)
• DDT (widely known after Rachel Carson's book, Silent Spring)
• Nitrites (a meat preservative and color and flavor enhancer used in
hot dogs and bacon)
• Red Dye Number 2
• Artificial sweeteners (including cyclamates and saccharin)
• Dioxin (a contaminant of industrial processes and of Agent Or-
ange, a defoliant used during the Vietnam War)
• Aflatoxin (a fungal toxin found on moldy peanuts and corn)
I know these unsavory chemicals quite well. I was a member of the
National Academy of Sciences Expert Panel on Saccharin and Food
Safety Policy (1978-79), which was charged with evaluating the poten-
tial danger of saccharin at a time when the public was up in arms after
the FDA proposed banning the artificial sweetener. I was one of the first
scientists to isolate dioxin; I have firsthand knowledge of the MIT lab
that did the key work on nitrites, and I spent many years researching
and publishing on aflatoxin, one of the most carcinogenic chemicals
ever discovered-at least for rats.
But while these chemicals are Significantly different in their proper-
ties, they all have a similar story with regard to cancer. In each and ev-
ery case, research has demonstrated that these chemicals may increase
cancer rates in experimental animals. The case of nitrites serves as an
excellent example.
THE HOT DOG MISSILE
If you hazard to call yourself "middle-aged" or older, when I say, "Ni-
trites , hot dogs and cancer," you might rock back in your chair, nod
your head, and say, "Oh yeah, I remember something about that. " For
the younger folks-well , listen up, because history has a funny way of
repeating itself.
The time: the early 1970s. The scene: the Vietnam War was begin-
n i n g to wind down, Richard Nixon was about to be forever linked to
Watergate, the energy crisis was about to create lines at gas stations and
nitrite was becoming a headline word.
Sodium Nitrite: A meat preservative used since the 1920s.6 It kills
bacteria and adds a happy pink color and desirable taste to hot
dogs, bacon and canned meat.

TURNING OFF CANCER                            45
In 1970, the journal Nature reported that the nitrite we consume may
be reacting in our bodies to form nitrosamines. 7
Nitrosamines: A scary family of chemicals. No fewer than seven-
t e e n nitro sa mines are "reasonably anticipated to be human car-
cinogens" by the U.S. National Toxicology Program.8
Hold on a second. Why are these scary nitrosamines "anticipated to
be human carcinogens"? The short answer: animal experiments have
shown that as chemical exposure increases, incidence of cancer also
increases. But that's not adequate. We need a more complete answer.
Let's look at one nitrosamine, NSAR (N-nitrososarcosine). In one
study, twenty rats were divided into two groups, each exposed to a differ-
e n t level of NSAR. The high-dose rats were given twice the amount that
the low-dose rats received. Of rats given the lower level of NSAR, just
over 35% of them died from throat cancer. Of rats given the higher levels,
100% died of cancer during the second year of the experiment. 9- 11
How much NSAR did the rats get? Both groups of rats were given
an incredible amount. Let me translate the "low" dose by giving you a
little scenario. Let's say you go over to your friend's house to eat every
meal. This friend is sick of you and wants to give you throat cancer
by exposing you to NSAR. So he gives you the equivalent of the "low"
level given to the rats. You go to his house, and your friend offers you a
bologna sandwich that has a whole pound of bologna on it! You eat it.
He offers you another, and another, and another . . . . You'll have to eat
270,000 bologna sandwiches before your friend lets you leave. 9 , 12 You
better like bologna, because your friend is going to have to feed you this
way every day for over thirty years! If he does this, you will have had
about as much exposure to NSAR (per body weight) as the rats in the
"low" -dose group.
Because higher cancer rates were also seen in mice as well as rats, us-
ing a variety of methods of exposure, NSAR is "reasonably anticipated"
to be a human carcinogen. Although no human studies were used to
make this evaluation, it is likely that a chemical such as this, which
consistently causes cancer in both mice and rats, can cause cancer in
humans at some level. It is impossible to know, however, what this
level of exposure might be, especially because the animal dosages are
so astronomical. Nonetheless, animal experiments alone are considered
enough to conclude that NSAR is "reasonably anticipated" to be a hu-
m a n carcinogen. 9

46                             THE CHINA STUDY
So, in 1970, when an article in the prestigious journal Nature con-
c l u d e d that nitrites help to form nitrosamines in the body, thereby im-
plying that they help to cause cancer, people became alarmed. Here was
the official line: "Reduction of human exposure to nitrites and certain
secondary amines, particular1y in foods, may result in a decrease in
the incidence of human cancer."7 Suddenly nitrites became a potential
killer. Because we humans get exposed to nitrites through consump-
t i o n of processed meat such as hot dogs and bacon, some products
came under fire. Hot dogs were an easy target. Besides containing addi-
tives like nitrites, hot dogs can be made out of ground-up lips, snouts,
spleens, tongues, throats and other "variety meats."13 So as the nitrite!
nitrosamine issue heated up, hot dogs weren't looking so hot. Ralph
Nader had called hot dogs "among America's deadliest missiles." 14 Some
consumer advocacy groups were calling for a nitrite additive ban, and
government officials began a serious review of nitrite's potential health
problems. 3
The issue jolted forward again in 1978, when a study at the Massa-
c h u s e t t s Institute of Technology (MIT) found that nitrite increased lym-
p h a t i c cancer in rats. The study, as reported in a 1979 issue of Science, 15
found that, on average, rats fed nitrite got lymphatic cancer 10.2% of
the time, while animals not fed nitrite got cancer only 5.4% of the time.
This finding was enough to create a public uproar. Fierce debate ensued
in the government, industry and research communities. When the dust
settled, expert panels made recommendations, industry cut back on ni-
trite usage and the issue fell out of the spotlight.
To summarize the story: marginal scientific results can make very big
waves in the public when it comes to cancer-causing chemicals. A rise
in cancer incidence from 5% to 10% in rats fed large quantities of nitrite
caused an explosive controversy. Undoubtedly millions of dollars were
spent follOwing the MIT study to investigate and discuss the findings.
And NSAR, a nitrosamine possibly formed from nitrite, was "reasonably
anticipated to be a human carcinogen" after several animal experiments
where exceptionally high levels of chemical were fed to animals for al-
m o s t half their lifespan.
BACK TO PROTEIN
The point isn't that nitrite is safe. It is the mere possibility, however un-
likely it may be, that it could cause cancer that alarms the public. But
what if researchers produced conSiderably more impressive scientific

47
TURNING OFF CANCER
results that were far more substantial? What if there was a chemical that
experimentally turned on cancer in 100% of the test animals and its rela-
tive absence limited cancer to 0% of the animals? Furthermore, what if
this chemical were capable of acting in this way at routine levels of intake
and not the extraordinary levels used in the NSAR experiments? Finding
such a chemical would be the holy grail of cancer research. The implica-
tions for human health would be enormous. One would assume that this
chemical would be of considerably more concern than nitrite and Alar,
and even more significant than aflatoxin, a highly ranked carcinogen.
This is exactly what I saw in the Indian research paper16 when I was
in the Philippines. The chemical was protein, fed to rats at levels that
are well within the range of normal consumption. Protein! These results
were more than startling. In the Indian study, when all the rats had been
predisposed to get liver cancer after being given aflatoxin, only the ani-
mals fed 20% protein got the cancer while those fed 5% got none.
Scientists, myself included, tend to be a skeptical bunch, especially
when confronted with eye-popping results. In fact, it is our responsibil-
ity as researchers to question and explore such provocative findings. We
might suspect that this finding was unique to rats exposed to aflatoxin
and for no other species, including humans. Maybe there were other
unknown nutrients that were affecting the data. Maybe my friend, the
distinguished MIT professor, was right; maybe the animal identities in
the Indian study got mixed up.
The questions begged for answers. To further study this question,
I sought and received the two National Institutes of Health (NIH)
research grants that I mentioned earlier. One was for a human study,
the other for an experimental animal study. I did not "cry wolf' in
either application by suggesting that protein might promote cancer.
I had everything to lose and nothing to gain by acting like a heretic.
Besides, I wasn't convinced that protein actually might be harmful. In
the experimental animal study, I proposed to investigate the "effect of
various factors [my italics] on aflatoxin metabolism." The human study,
mostly focused on aflatoxin's effects on liver cancer in the Philippines,
was briefly reviewed in the last chapter and was concluded after three
years. It was later renewed in a much more sophisticated study in China
(chapter four).
A study of this protein effect on tumor development had to be done ex-
tremely well. Anything less would not have convinced anyone, especially
my peers who would review my future request for renewed funding! In