Author: Ophelia Benson

One day in 1995, biologist Armand Leroi walked into Manhattan’s Strand Bookshop
and made a remarkable discovery. He came across a rather plain-looking remaindered
volume bearing the title Cancer Selection . The postdoc student had not heard of the book or its author, James
Graham. But, Leroi recalls: “I’m a sucker for odd theories of evolution, so
I bought it.” It was an impulse decision that was to have profound implications.
For buried in the book was a bold new idea that has become a muse to the young
scientist.

The book was lying on a table in front of him when I visited his South London
flat. Leroi, a reader in evolutionary developmental biology at London’s Imperial
College, is an articulate and rather intense man with a hint of an accent betraying
his Dutch origins. He says he knew the book was not a work by a professional
scientist: “In fact, Graham’s very frank about this. His whole thing is he’s
an outsider.” At this point Leroi reads aloud from the book’s cover blurb. “James
Graham began work on his theory in 1977 while working as a senior executive
in a large multinational corporation. He now devotes his full time to writing.
He is a member of Mensa” He pauses. “Well, these are obviously not standard
scientific credentials. And scientists who are members of Mensa don’t usually
advertise it.”

In 1995, Leroi read Graham’s book but then put it aside. He now credits it
as having spurred him and two colleagues at Imperial to reconsider a piece of
received wisdom in the field of evolutionary biology. Like the book, Leroi’s
paper in last month’s Nature Reviews Cancer is titled “Cancer Selection”. In it, he asks whether cancer may
have played a hitherto overlooked role in the evolution of complex animal life.

Biologists view events that are both common and life-threatening as among the
driving forces of evolutionary change. The occasional creature born genetically
endowed to cope more successfully with such an event has a greater chance of
surviving to reproduce and pass on whatever useful genes underpinned its good
fortune. Thus is evolution guided by the adaptive hand of natural selection.

Cancer is a common occurrence, and certainly a life-threatening one. But biologists
generally regard it as having no effect on evolutionary change because it mostly
afflicts people beyond their child-bearing years. As a result, cancer cannot
affect their chances of passing on any protective genes they may possess to
the next generation.

But not all malignancies are confined to the elderly: a minority of children
also develop lethal cancers. Leroi and his co-authors suggest that perhaps childhood
cancer mostly affects organs that have undergone recent and rapid evolution.
It is a radical proposal. In the first page of their paper is an acknowledgement:
“The idea that changes in morphology and life-history can expose animals to
an increased risk of cancer has been argued forcefully by James Graham in his
1992 book Cancer Selection .”

Graham – now in his early 70s and living in Lexington, Virginia – started to
think about cancer after reading The Selfish Gene
by Richard Dawkins. He had no particular knowledge of the disease.
What Graham knew about was manufacturing. He had spent much of his working life
in multinational corporations, and had become the chief financial officer of
a leading cosmetics company. From his industrial background he was well aware
that design improvements in a product often lead to an initial fall-off in the
quality of the manufactured goods. To retain the advantages of the improvement
while restoring the lost quality, adjustments have to be made to the production
process. Among living things, Graham reasoned, death caused by cancer might
play a similar role. It could serve to eliminate those individuals who inherited
a genetic programme unable to cope with any damaging side-effects associated
with change. Cancer, in other words, is evolution’s method of quality control.

Having received what he laughingly calls this “gift from the unconscious” he
began garnering the evidence. “I guess I went about it backwards,” Graham says.
“The typical scientist studies for years before he even attempts to deal with
evolutionary theory. I knew nothing when I had this idea.”

In a determined attempt to persuade others, Graham started writing to learned
journals, initially with some modesty. “I was looking for someone to come back
with intelligent comments about my inept efforts, and to advise me. That didn’t
happen. The reception I got was more like swatting a fly.”

He also wrote to evolutionary biologists. “I knocked on so many doors my knuckles
were bleeding. My dream was that someone would say to me, ‘Mr Graham, you’ve
got a good idea here. Why don’t we collaborate?’ I would have jumped at the
opportunity.” This didn’t happen either. Graham’s modesty began to evaporate.
One journal, Evolution , did take a more sympathetic view but an attempt to set up a collaboration fell through.

Eventually, he managed to get two severely pruned letters published in the Journal of Theoretical Biology .
“I then put on my PR hat,” Graham says. “I wrote a press release, and even hand-delivered
it to media people in Manhattan.” But there was still no serious consideration
from the scientific community.

Nevertheless, Graham persevered. “I was convinced I was correct, and if an
idea is correct it’s important.” As simple as that. And his conviction drove
him to the only remaining option: to publish himself. He did so under the imprint
Aculeus Press. Aculeus is Latin for needle or sting. The book received several reviews, not least in Nature
, whose critic wrote: “I, at least, like the idea.” But then silence.

Frustrated at years of being ignored by the scientific establishment, Graham’s
tone had, by this time, grown belligerent. Many biologists reading his book
would balk at the first chapter. Provocatively titled “Biology’s dirty little
secret” it dismisses conventional thinking about Darwinian evolution as “utter
nonsense” and an “intellectual error of the rankest sort”. Although the prose
is clear and readable it is also assertive, didactic and sometimes patronising.
The reader is constantly warned that all contrary views are foolish, absurd
or self-evidently wrong: “Unlike the old theory, mine is correct.”

Graham goes on to compare himself to Darwin (neither had been educated as a
scientist) and Friedrich Wegener of continental drift fame (as a meteorologist
not a geologist, Wegener too was an outsider). Thomas Kuhn’s classic The
Nature of Scientific Revolutions is wheeled out to remind us that people responsible for the “fundamental inventions
of a new paradigm have been either very young or very new to the field
whose paradigm they change”. (The italics are Graham’s.) He even
compares his method of work to Albert Einstein’s.

At this point it is difficult not to lose patience. “Its whole tenor as it
rails against the biological establishment is that scientists are just too thick,”
Leroi says. “They’ve missed it all. They’re stuck in their paradigms of conventional
Darwinian evolution. But James Graham is going to set them right.”

Happily for Graham, Leroi had the forebearance to judge the work on its merits.
“When I’d originally read Graham’s book, I thought there was something in it.
But I forgot it,” he admits. Then he moved to the UK and started working with
another evolutionary biologist, Austin Burt. “I can’t remember whether he was
in my office or I was in his, but we looked on each other’s bookshelves and
said, ‘Gosh, Cancer Selection , you’ve got it too’.”

It turned out that Burt had also picked up a remaindered copy of the volume
in Moe’s Bookshop, Berkeley, while in California as a postdoc.

An extraordinary chain of coincidences that began with two postdoc biologists
buying the same rare book on opposite sides of America has now brought them
together in London with a third colleague, Vassiliki Koufopanou, to pen their
own thoughts on cancer.

They accept Graham’s premise that the disease is ancient and ubiquitous and
can be a force in natural selection. “That idea is the central one,” Leroi admits.
Needless to say, Graham doesn’t stop there. He reinterprets the diversity of
animals in the light of his discovery, opining, for example, that snails evolved
shells to protect themselves not from birds but from ultraviolet light and hence
cancer. “You can apply this approach to any feature of the biological world,”
Leroi says, “and Graham does so, willy-nilly.”

Graham claims that cancer selection is not a but the driving
force in the emergence of complex animal life. “He believes that with good,
clear thinking one can arrive at an answer,” Leroi says. “But this isn’t enough.

Because something could be a certain way doesn’t mean that it actually is
that way. All those biologists who spend their time trying to test
evolutionary theory – well, he thinks they’re just number-crunchers who can’t
see the big picture.”

Nevertheless, spurred on by Graham’s reasoning, Leroi began to consider cancer
in children. It turns out that only a few of the body’s organs are particularly
susceptible to childhood cancer, such as the bones and the brain. Both incorporate
recent evolutionary novelties. “As Homo sapiens, we are famous for our big brains that have evolved so enormously
over the past few million years,” Leroi says. And then there’s our pubertal
growth spurt.

“Chimpanzees don’t have it. It’s possible that the osteosarcomas that kids
get in the bones undergoing the growth spurt are a consequence of this being
an evolutionary novelty.” Although admitting that the evidence is circumstantial,
Leroi also thinks it is persuasive.

Childhood cancer kills before the age of reproduction, and is therefore amenable
to selection. Yet it continues to exist. Why? Because natural selection has
not yet had the time to deal with it.

The possibilities for speculation are limitless. For example, one outcome of
evolution can be an increase in size. But bigger animals have more dividing
cells, and therefore more cells to turn cancerous. So why don’t elephants suffer
cancer more than mice? Maybe they do; maybe it’s the success of large animals
in developing better anti-cancer mechanisms that has allowed them to become
large.

As diseases go, cancer is seldom far from our attention. The thought that this
much-feared disease might have played a major role in shaping our evolution
is tantalising. But it took an outsider to see this possibility, and the chance
interest of an insider to draw it to our attention.

This article first appeared in the Times Higher Education Supplement.
Check out their web page here.