Challenging Conventional Wisdom on Cancer

From: janice matchett <janmatch@earthlink.net>
Date: Thu Aug 18 2005 - 13:36:55 EDT

"Here is the key point: cancer cells do not have the correct complement of
chromosomes. ... Some cancer cells may have as many as 80 chromosomes
instead of 46. They may actually have double the right number of
genes. ... I HAVE LEFT THE MOST DRAMATIC PART to the end. ......" [See below]

One comment:

"My solution: cut off all Federal funding and use the money to create a
"lottery" for the person(s) who finds the cause/cure.
This is just like the ulcer debacle. The poor man who finally figured out
the bacteria angle was vilified for years until the establishment was
dragged kicking and screaming into
reality." <http://www.freerepublic.com/focus/f-news/1465642/posts?page=3#3>3

<http://www.freerepublic.com/focus/f-news/1465642/posts>Challenging
Conventional Wisdom on Cancer (Is cancer caused by gene mutations?)
<http://www.freerepublic.com/focus/f-news/1465642//^http://www.americanprowler.com/dsp_article.asp?art_id=8588>The
American Prowler ^ | 8/18/2005 | Tom Bethell
Posted on 08/18/2005 12:31:18 AM EDT by
<http://www.freerepublic.com/focus/f-news/1465642//~nickcarraway/>nickcarraway
http://www.freerepublic.com/focus/f-news/1465642/posts

SCIENTISTS THESE DAYS TEND TO BELIEVE that almost any trait can be
attributed to a gene. The gene obsession, showing up in science journals
and on the front page of the New York Times, culminated in the Human Genome
Project. The human genome was sequenced, then that of the fruit fly, the
rat, the mouse, the chimpanzee, the roundworm, yeast, and rice. Computers
cranked out their mindless data. It has been a bonanza for techies and the
computer industry but the medical benefits have remained elusive.

Now they are talking about a Cancer Genome Project. It would determine the
DNA sequence in 12,500 tumor samples and is supposed to reveal
cancer-causing mutations by comparing the order of the letters of the
genetic code in tumor cells with sequences in healthy tissue. But there is
no single cancer genome, and the project will not improve our understanding
of cancer.

Cancer has proved resistant to every "breakthrough" and treatment hype, and
the new approach will only sustain the error that has dominated cancer
research for 30 years. Since the mid-1970s, leading researchers have
doggedly pursued the fixed idea that cancer is caused by gene mutations. I
believe it will prove to have been one of the great medical errors of the
20th century.

WHERE TO BEGIN? One place is a story in the Washington Post, a few months
back, headlined "Genetic Test Is Predictor of Breast Cancer Relapse." The
test "marks one of the first tangible benefits of the massive effort to
harness genetics to fight cancer," Rob Stein wrote. No real benefits yet? I
think that is correct. Two well-publicized genes supposedly predispose
women for breast cancer, but in over 90 percent of cases these genes have
shown no defect.

Genes that (allegedly) cause cancer when they are mutated are called
oncogenes. They were reported in 1976 by J. Michael Bishop and Harold
Varmus, who were rewarded with the Nobel Prize. Varmus became director of
the National Institutes of Health (NIH) under President Clinton; Bishop,
chancellor of the University of California in San Francisco, one of the
largest medical-research institutions in the country. The two scientists
had "discovered a collection of normal genes that can cause cancer when
they go awry," Gina Kolata later reported in the New York Times. About 40
such genes had been discovered. Normally harmless, "they would spring into
action and cause cancer if they were twitched by carcinogens." When
mutated, in other words. This was "a new era in research."

The following week, on October 20, 1989, Science magazine also reported the
award. The article claimed: "‚€¶the work of the Bishop-Varmus group has had
a major impact on efforts to understand the genetic basis of cancer. Since
their 1976 discovery, researchers have identified nearly 50 cellular genes
with the potential of becoming oncogenes." Their work was "already paying
off clinically."

And so it went. Researchers began to find more and more of these oncogenes;
then "tumor suppressor genes" were added. Now, in the Washington Post
article, we read that "researchers sifted through 250 genes that had been
identified as playing a role in breast cancer."

So, up to 250 genes are "playing a role." The Sanger Institute, which was
also involved in the human genome project, claimed recently that "currently
more than one percent of all human genes are cancer genes." The latest
figure is 25,000 genes in total for humans, so that is surely where the 250
"cancer genes" came from.

At the beginning, the oncogene theory posited that a single gene, when
mutated, turned a normal cell into a cancer cell. We have gone from 1 to
250, the latter "playing a role." This "multiplication of entities" --
genes -- is the hallmark of a theory that is not working. It's what
philosophers call a "deteriorating paradigm." The theory gets more and more
complex to account for its lack of success. The number of oncogenes keeps
going up, even as the total number of genes goes down. Six years ago some
thought humans had 150,000 genes in all. Now it's one-sixth that number.
How long before they find that all the genes "play a role" in cancer?

IT ALWAYS WAS unlikely that a single mutated gene would turn a cell into a
cancer cell. Mutations occur at a predictable rate in the body. As the
cells of the body number perhaps trillions we would all have cancer if a
single hit was sufficient. Then came the "multiple hit" theory. Three or
four, maybe six or seven genes would all have to mutate in the same cell
during its lifetime. Then, bingo, your unlucky number had come up. That
cell became a cancer cell. When it divided it just kept on and on dividing.

Meanwhile, the underlying theory never changed. The research establishment
remains in thrall to the idea that cancer is caused by gene mutations. It
was and is unable to lay its hands on the genes responsible, but it
believes they are in there somewhere.

There are several problems with the theory, but the most basic is this.
Researchers have never been able to show that a mutated gene, taken from a
cancer cell, will transform normal cells in the petri dish. They are unable
to show that the allegedly guilty party is capable of committing the crime.
They can transport these mutated genes into test cells. And the supposed
deadly genes are integrated into the cell's DNA. But those cells do not
turn into cancer cells, and if injected into experimental animals, they
don't cause tumors. That's when the experts said, well, there must be four
or five genes all acting at once in the cell. But they have never been able
to say which ones, nor show that in any combination they do the foul deed.

There is even a genetically engineered strain of mice called OncoMouse.
They have some of these oncogenes in every cell of their small bodies. You
would have thought they would die of cancer immediately. But they leave the
womb, gobble up food, and live long enough to reproduce and pass on their
deadly genes to the next generation.

I have a suggestion for Gina Kolata, who still works on these issues for
the New York Times. Why not try asking Varmus or Bishop exactly which
genes, either individually or in combination, cause cancer in humans or
anything else? I tried calling Bishop at UCSF a few months back but
couldn't get through. He will respond to the New York Times, surely. But
maybe not with a straight answer.

The desire to start over with a "cancer genome project" tells you they know
they are not even at first base. Dr. Harold Varmus, now president of the
Memorial Sloan-Kettering Cancer Center in New York, told the Times in March
that the new project could "completely change how we approach cancer."

Completely change? Maybe we do need a complete change. What about his
decades-old Nobel work? Was that a waste? In a way I think it was worse
than that, because when an erroneous theory is rewarded with the top prize
in science, abandoning that theory is difficult. The backtracking required
is an embarrassment to all.

JOURNALISM PLAYS A CRUCIAL ROLE. Especially in the field of medical
science, there is a big problem. It exists at all major newspapers and I
don't mean to single out the New York Times. Science journalists don't see
themselves as qualified to challenge the experts. If a reporter were to do
so, quoting non-approved scientists, top-echelon NIH officials would surely
complain to editors, and the reporter would be reassigned. The nation's
health would be said to be endangered.

All this contrasts with the far greater freedom that journalists enjoy in
the political arena, including defense and foreign policy. About 35 years
ago, leading newspaper editors decided to chart their own course and form
their own judgments. The context was the Vietnam War, more specifically the
Pentagon Papers. A big report critical of U.S. policy was leaked to the
press, and the Nixon administration went to great pains to suppress it.
National security was invoked, judicial restraining orders were issued, but
eventually the "public's right to know" trumped "national security." The
material was published.

That was the background from which Woodward and Bernstein and the Watergate
investigation emerged a year later. And we were the better off for it. The
real danger, then and now, was that of unchecked government power. And we
are seeing that exercised in the realm of medical science, where we do not
have a press that dares to think independently.

HOW DID THE IDEA TAKE ROOT that gene mutations cause cancer? Well, in the
1920s researchers bombarded fruit flies with X-rays and mutant flies
resulted. Humans exposed to large X-ray doses a hundred years ago proved to
be at high risk for skin cancer and leukemia. It was convincingly shown
that X-rays produced both mutations and cancers.

Working at the NIH in the 1960s, the biochemist Bruce Ames used bacteria to
detect the mutagenic properties of various substances. Some carcinogens
proved to be mutagenic, hence the gene-mutation theory of cancer. Robert A.
Weinberg, who directs a cancer research lab at MIT, says that by the 1970s
he and others had come to believe that "Ames was preaching a great and
simple lesson" about carcinogens: "Carcinogens are mutagens."

Some are, but some of the best known are not. Neither asbestos nor coal
tar, found in cigarettes, are mutagenic. They are carcinogens but they
don't affect the DNA -- the genes. But there was one more crucial discovery
still to be made. Or rather, rediscovery.

Robert Weinberg later claimed that a mutation in a single gene indeed had
transformed a cell in vitro. But it turned out that the cell-line, one that
had been provided by the NIH, was already "immortal," or cancerous. It did
not have the right number of chromosomes.

Normal cells have 46 chromosomes -- 23 each from mother and father. Such
cells are "diploid," because their complement of chromosomes is doubled. In
case you never took biology, genes are segments of DNA strung along the
chromosomes. The largest chromosomes, such as Chromosome 1 or 2, include
several thousand genes each. Sometimes babies are born with one extra copy
of the smallest chromosome, and because it is in the germ line this defect
is in every cell of the body. Such babies have Down syndrome. Having an
extra chromosome is serious business.

Here is the key point: cancer cells do not have the correct complement of
chromosomes.

Their "ploidy" is not good, so they are said to be aneuploid. Cancer cells
are aneuploid. This defect arises not in the germ line, but in the grown body.

Cells divide in the course of life, by a process called mitosis, and
sometimes there is an error in the division. The chromosomes do not
"segregate" properly (do not end up equally in the two daughter cells) and
an extra chromosome may be hauled off into one of the new cells. Such
over-burdened cells will usually die, but sometimes the error repeats and
magnifies and increases. The cell just keeps on dividing, its control
mechanisms overridden by the abundance of extra DNA in the cell. A tumor
forms in that part of the body, and that is cancer.

Some cancer cells may have as many as 80 chromosomes instead of 46. They
may actually have double the right number of genes.

The aneuploid character of cancer cells is the first thing that Theodor
Boveri and others noticed when they began to look at cancer under the
microscope, 100 years ago. Leaving unresolved the question of what causes
aneuploidy, early researchers thought that this was surely the genetic
cause of cancer. Mutation didn't enter into it. But gradually the early
research was buried. In the last generation, textbooks on the cell and even
textbooks on cancer have failed to mention aneuploidy or its bizarre
chromosomal combinations. Weinberg wrote two books on cancer without
mentioning aneuploidy. Overlooking what was plainly visible in the
microscope, researchers worked for years with those defective, immortalized
cell lines, assuming that their extra chromosomes were unimportant.

An analogy suggests the magnitude of the error. Cells today are compared to
factories, so let's think of an automobile plant. A cancer cell is the
equivalent of a monster car with (let's say) five wheels, two engines, and
no brakes. Start it running and you can't stop the damned thing. It's
hazardous to the community. The CEO wants to know what's gone wrong so he
sends underlings into the factory. There they find that instead of the
anticipated 46 assembly lines, there are as many as 80. At the end of the
process this weird machine gets bolted together and ploughs its way out the
factory door.

But today's gene mutation theorist is someone who says: "That's not it. The
extra assembly lines are irrelevant. What is happening is that three or
four of the tens of thousands of workers along the assembly lines are not
working right!" In the analogy, genes along the chromosomes correspond to
workers along the assembly lines.

Any CEO would fire the lunatic who thought a few errant workers, and not
the bizarre factory layout, had caused the mayhem. But in the realm of
cancer research, those who do say that are rewarded with fat grants, top
posts, and awards. That's a measure of what has happened to cancer research.

I HAVE LEFT THE MOST DRAMATIC PART to the end. The man who rediscovered the
old work on chromosomes and cancer and has drawn attention to it ever
since, supported by investigations of his own, is none other than Peter
Duesberg of U.C. Berkeley. He was already in the dog house at NIH for
saying that AIDS is not an infectious disease and that HIV is harmless. All
his grants were cut off in retribution. But as a member of the National
Academy of Sciences he could still publish in respectable journals. So for
the last seven years he has been drawing attention to the cancer matter.
The NIH is pursuing the wrong theory, he says. Talk about persona non
grata! No more grants for him! (And he has not received any.)

A researcher at the University of Washington who became controversial at
NIH in an unrelated field warned Duesberg that "in the present system of
NIH grants, there is no way to succeed." No matter how much they prate in
public about thinking outside the box and rewarding "high-risk" proposals,
"the reviewers are the same and their self-interest is the same." In the
cancer field, grant proposals are reviewed by, and won by, proponents of
the gene mutation theory.

Wayt Gibbs published a good article about Duesberg's cancer findings in the
Scientific American (July 2003). And this response is beginning to emerge
in journals like Science: Er, well, there's nothing new here.‚€¶ We have
always known that aneuploidy is important in cancer. (Yes, but it was
forgotten and then buried beneath the paper mountains of new research.)
There is a quiet search for a "political" compromise: Can't we say that
both gene mutation and aneuploidy "play a role" in the genetics of cancer?

A leading cancer researcher, Bert Vogelstein of Johns Hopkins, told me some
time back that "at least 90 percent of human cancers are aneuploid." More
recently, his lab reported that aneuploidy "is consistently shown in
virtually all cancers." A few years ago, Varmus from Sloan-Kettering did
answer my e-mail query, writing: "Aneuploidy, and other manifestations of
chromosomal instability are major manifestations of many cancers and many
labs have been working on them." But, he added: "Any role they play will
not diminish the crucial roles of mutant proto-oncogenes and tumor
suppressor genes."

But why not? Maybe aneuploidy is sufficient.

At the end of May, Duesberg was invited to speak at NIH. His topic:
"Aneuploidy and Cancer: From Correlation to Causation." About 100 people
showed up at Building 10. The Genetics branch of the National Cancer
Institute (NCI) is interested in aneuploidy, and well aware of the
political sensitivities. But I am told that the director of the NCI, Andrew
von Eschenbach, a political appointee, is not particularly interested in
aneuploidy. He should be, though, because he is a cancer survivor himself
and in speeches calls for "eliminating the suffering and death from cancer
by 2015."

Duesberg challenged the audience to prove him wrong. He is looking for
diploid cancer: a solid tumor with the correct complement of chromosomes.
He is not much interested in the compromise solutions -- "a bit of both
theories." Prove me wrong, he says. A woman in the audience did suggest
cases of tumors that looked diploid, but Duesberg knew the literature here
and immediately referred her to a more recent study showing that these
tumors, on closer microscopic inspection, proved to be aneuploid.

Maybe in the end he will show that in order to achieve a real breakthrough,
it's important not to be funded by the NIH. If so, we will all have learned
a very expensive lesson.
Received on Thu Aug 18 13:38:09 2005

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