Are cancers newly evolved species?

Jul 26, 2011 By Robert Sanders
Are cancers newly evolved species?
A karyograph is one way to display the number of copies of each chromosome in a clone of cells from an individual or a cancer. Here, the karyograph shows the chromosomes of 20 individual cells (represented by black lines) of a normal human male. Each cell has precisely two copies of 22 chromosomes and one copy of each sex chromosome, demonstrating that human cells have a fixed and stable karyotype

(PhysOrg.com) -- Cancer patients may view their tumors as parasites taking over their bodies, but this is more than a metaphor for Peter Duesberg, a molecular and cell biology professor at the University of California, Berkeley.

Cancerous tumors are parasitic organisms, he said. Each one is a new species that, like most , depends on its host for food, but otherwise operates independently and often to the detriment of its host.

In a paper published in the July 1 issue of the journal Cell Cycle, Duesberg and UC Berkeley colleagues describe their theory that carcinogenesis – the generation of – is just another form of speciation, the evolution of new species.

"Cancer is comparable to a bacterial level of complexity, but still autonomous, that is, it doesn't depend on other cells for survival; it doesn't follow orders like other cells in the body, and it can grow where, when and how it likes," said Duesberg. "That's what species are all about."

This novel view of cancer could yield new insights into the growth and metastasis of cancer, Duesberg said, and perhaps new approaches to therapy or new drug targets. In addition, because the disrupted chromosomes of newly evolved cancers are visible in a microscope, it may be possible to detect cancers earlier, much as today's Pap smear relies on changes in the shapes of cervical cells as an indication of chromosomal problems that could lead to cervical cancer.

Carcinogenesis and evolution

The idea that cancer formation is akin to the evolution of a new species is not new, with various biologists hinting at it in the late 20th century. Evolutionary biologist Julian S. Huxley wrote in 1956 that "Once the neoplastic process has crossed the threshold of autonomy, the resultant tumor can be logically regarded as a new biologic species …."

Last year, Dr. Mark Vincent of the London Regional Cancer Program and University of Western Ontario argued in the journal Evolution that carcinogenesis and the clonal evolution of are speciation events in the strict Darwinian sense.

Are cancers newly evolved species?
In contrast to normal cells, cervical cancer cells (HeLa) have flexible chromosomes. The 23 normal chromosomes have between 0 and 4 copies, while the several dozen hybrid or “marker” chromosomes have between 0 and 2. The copy numbers differ in the 20 individual HeLa cells shown, but they are nearly clonal, varying around an average clonal number.

The evolution of cancer "seems to be different from the evolution of a grasshopper, for instance, in part because the cancer genome is not a stable genome like that of other species. The challenging question is, what has it become?" Vincent said in an interview. "Duesberg's argument from karyotype is different from my argument from the definition of a species, but it is consistent."

Vincent noted that there are three known transmissible cancers, including devil facial tumor disease, a "parasitic cancer" that attacks and kills Tasmanian devils. It is transmitted from one animal to another by a whole cancer cell. A similar parasitic cancer, canine transmissible venereal tumor, is transmitted between dogs via a single cancer cell that has a genome dating from the time when dogs were first domesticated. A third transmissible cancer was found in hamsters.

"Cancer has become a successful parasite," Vincent said.

Mutation theory vs. aneuploidy

Duesbeg's arguments derive from his controversial proposal that the reigning theory of cancer – that tumors begin when a handful of mutated genes send a cell into uncontrolled growth – is wrong. He argues, instead, that is initiated by a disruption of the chromosomes, which leads to duplicates, deletions, breaks and other chromosomal damage that alter the balance of tens of thousands of genes. The result is a cell with totally new traits – that is, a new phenotype.

"I think Duesberg is correct by criticizing mutation theory, which sustains a billion-dollar drug industry focused on blocking these mutations," said Vincent, a medical oncologist. "Yet very, very few cancers have been cured by targeted drug therapy, and even if a drug helps a patient survive six or nine more months, cancer cells often find a way around it."

Chromosomal disruption, called aneuploidy, is known to cause disease. Down syndrome, for example, is caused by a third copy of chromosome 21, one of the 23 pairs of human chromosomes. All cancer cells are aneuploid, Duesberg said, though proponents of the mutation theory of cancer argue that this is a consequence of cancer, not the cause.

Key to Duesberg's theory is that some initial chromosomal mutation – perhaps impairing the machinery that duplicates or segregates chromosomes in preparation for cell division – screws up a cell's chromosomes, breaking some or making extra copies of others. Normally this would be a death sentence for a cell, but in rare cases, he said, such disrupted chromosomes might be able to divide further, perpetuating and compounding the damage. Over decades, continued cell division would produce many unviable cells as well as a few still able to divide autonomously and seed cancer.

Duesberg asserts that cancers are new species because those viable enough to continue dividing develop relatively stable chromosome patterns, called karyotypes, distinct from the chromosome pattern of their human host. While all known organisms today have stable karyotypes, with all cells containing precisely two or four copies of each chromosome, cancers exhibit a more flexible and unpredictable karyotype, including not only intact chromosomes from the host, but also partial, truncated and mere stumps of chromosomes.

Staining chromosomes with different dyes highlights the orderly nature of the normal human karyotype (left), that is, humans have precisely two copies of each chromosome with no leftovers. A bladder cancer cell (right) has extra copies of some chromosomes, a few missing normal chromsomes, and a lot of hybrid or marker chromosomes, which characterize cancer cells.

"If humans changed their karyotype – the number and arrangement of chromosomes – we would either die or be unable to mate, or in very rare cases become another species," Duesberg said. But cancer cells just divide and make more of themselves. They don't have to worry about reproduction, which is sensitive to chromosomal balance. In fact, as long as the genes for mitosis are still intact, a cancer cell can survive with many disrupted and unbalanced chromosomes, such as those found in an aneuploid cell, he said.

The karyotype does change as a cancer cell divides, because the chromosomes are disrupted and thus don't copy perfectly. But the karyotype is "only flexible within a certain margin," Duesberg said. "Within these margins it remains stable, despite its flexibility."

Karyographs display karyotype variability

Duesberg and his colleagues developed karyographs as a way to display the aneuploid nature of a cell's karyotype and its stability across numerous cell cultures. Using these karyographs, he and his colleagues analyzed several cancers, clearly demonstrating that the karyotype is amazingly similar in all cells of a specific cancer line, yet totally different from the karyotypes of other cancers and even the same type of cancer from a different patient.

HeLa cells are a perfect example. Perhaps the most famous cancer cell line in history, HeLa cells were obtained in 1951 from a cervical cancer that eventually killed a young black woman named Henrietta Lacks. The 60-year-old cell line derived from her cancer has a relatively stable karyotype that keeps it alive through division after division.

"Once a cell has crossed that barrier of autonomy, it's a new species," Duesberg said. "HeLa cells have evolved in the laboratory and are now even more stable than they probably were when they first arose."

The individualized karyotypes of cancers resemble the distinct karyotypes of different species,, Duesberg said. While biologists have not characterized the karyotypes of most species, no two species are known that have the same number and arrangement of chromosomes, including those of, for example, gorillas and humans, who share 99 percent of their genes.

Duesberg argues that his speciation theory explains cancer's autonomy, immortality and flexible, but relatively stable, karyotype. It also explains the long latency period between initial aneuploidization and full blown cancer, because there is such a low probability of evolving an autonomous karyotype.

"You start with a chromosomal mutation, that is, aneuploidy perhaps from X-rays or cigarettes or radiation, that destabilizes and eventually changes your karyotype or renders it non-viable," he said. "The rare viable aneuploidies of cancers are, in effect, the karyotypes of new species."

Duesberg hopes that the carcinogenesis-equals-speciation theory will spur new approaches to diagnosing and treating cancer. Vincent, for example, suspects that cancers are operating right at the edge of survivability, maintaining genomic flexibility while retaining the ability to divide forever. Driving them to evolve even faster, he said, "might push them over the edge."

Explore further: The accelerator of molecular motors: What drives peroxisomes to degrading pollutants

More information: Is carcinogenesis a form of speciation? (Cell Cycle, Vol 10, Issue 13)

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jamesrm
5 / 5 (3) Jul 26, 2011
A similar theory that I heard about maybe 10 years ago made me think that cancer is the last (nuclear) option of the immune system to a perceived threat, try like hell to evolve away to survive the threat?
emsquared
5 / 5 (7) Jul 26, 2011
This distorts the purposeful, basic concept of a species being at it's core a set of interbreeding organisms (sure there's asexual species, but cancer isn't even asexual it's just cell division with consequentially variable genetics). Cancer is not a biological species, it has no life history. You don't have to call cancer a species to fit genetic digression into our understanding of it's mechanisms. No, I'm quite comfortable with the accuracy of classifying cancer as cancer. Frankly this seems to me more an attempt at sensationalism then trying to progress a greater understanding.
Y8Q412VBZP21010
5 / 5 (1) Jul 26, 2011
Frankly this seems to me more an attempt at sensationalism then trying to progress a greater understanding.


Duesberg? A sensationalist? Who knew? BTW, check the comments on Duesberg on the RATE MY PROFESSORS website, they're -- ahhhh -- interesting.

It has been pointed out that if we regard a multicellular organism as a "metacolony" of cells, then there will always be an option for one line of cells to "cheat" and exploit the collective for its own advantage. But since that generally destroys the collective, it's quite literally a dead end. As Dawkins puts it, relative to his often-misunderstood "selfish gene" concept: "Nice guys finish FIRST."
that_guy
4.2 / 5 (5) Jul 26, 2011
This distorts the purposeful, basic concept of a species... ...this seems to me more an attempt at sensationalism then trying to progress a greater understanding.

gold star.

An individual cancer in no way meets any definition for species, as it has to be a perpetuating lineage composed of many related individuals that reproduce. We do not call people with down syndrome a new species, and we do not call sterile hybrids new species. Since virtually every cancer is a dead end, it does not meet the definition.

However, the few communicable cancers they mentioned do warrant the conversation, and frankly open up fascinating and disturbing possibilities.
Cave_Man
3.4 / 5 (5) Jul 26, 2011
This distorts the purposeful, basic concept of a species being at it's core a set of interbreeding organisms (sure there's asexual species, but cancer isn't even asexual it's just cell division with consequentially variable genetics). Cancer is not a biological species, it has no life history. You don't have to call cancer a species to fit genetic digression into our understanding of it's mechanisms. No, I'm quite comfortable with the accuracy of classifying cancer as cancer. Frankly this seems to me more an attempt at sensationalism then trying to progress a greater understanding.

It's this kind of close minded thinking that has prevented us from gaining knowledge, we consider different virus and bacteria as different species. Maybe you forget that all life on this planet started out as single celled asexual species and we are but a "cancerous" mutation of that.

Not to say we are parasitical except that we must eat other organic life forms, like cancer.
FrankHerbert
1 / 5 (6) Jul 26, 2011
I wouldn't go so far as to say all cancers are unique species but some definitely are. HeLa would be THE example. A human/virus hybrid.
Cave_Man
not rated yet Jul 26, 2011
I like first comment, seems plausible. I mean where do viruses come from? Considering they are just complex RNA fragments with coding proteins it would make sense that they are just mutations of existing organisms, like cancer only they developed independence to a higher degree (like the transmissible cancers mentioned in the article).

I mean how is a transmissible cancer even possible unless this theory is correct, we thought it was damage to our own cells that made it compatible enough to live in us but if cancer can be contagious in a small non-diverse population then we need to rethink much of out cellular biology when it comes to relating micro-organisms to macro-organisms, like how we deal with prevention of creating superbugs and the pathology of long term organism evolution.

At a rate of one generation per minute some bacteria can evolve at an unprecedented rate.
antonima
5 / 5 (1) Jul 27, 2011
One generation per minute?? I think you might be thinking of viruses. AFAIK 15 minutes is close to the lower limit.


However, the few communicable cancers they mentioned do warrant the conversation, and frankly open up fascinating and disturbing possibilities.


I agree, I have never heard of this before..
opens up the possibility for .. vampirism? The new cancer could be
1. Transmissible through saliva
2. Potentially anemia inducing
3. Could secrete hormones such as testosterone or epinephrine
Kedas
not rated yet Jul 27, 2011
New species, uhhhmm.
I guess we can't lure them out? :)
barakn
2.3 / 5 (3) Jul 27, 2011
The people arguing against this based on the definition of a species are basically ignoring how the vast majority of the prokaryotes reproduce.
that_guy
not rated yet Jul 27, 2011
The people arguing against this based on the definition of a species are basically ignoring how the vast majority of the prokaryotes reproduce.

I'd like to point out that many people are arguing on several points on the definition of a species.

Most cancers cannot carry on their lineage without the 'host' continuing. But the cancers kill the host. for a parasite like that to continue, it would have to be in some way independent of it's host, and capable of finding another host to exist as a species.

As I said, by the chromosomal number argument, anyone with down syndrome would be a new species...and that is ridiculous...
emsquared
3 / 5 (2) Jul 27, 2011
The people arguing against this based on the definition of a species are basically ignoring how the vast majority of the prokaryotes reproduce.

Asexual reproduction results in separate organisms, with separate life histories, new generations. Division of cells in asexual reproduction is binary fission - horizontal gene propagation, cancer I'm pretty sure is just mitosis - cell replication/division. There is a difference. Not to mention budding.

Cancer isn't a species in the classical sense, period. Not even HeLa. Separate from a victim, cancer has to be propagated on purpose. Cancer is not a parasite. It's not a separate organism. It's cancer.

@Caveman
There's a difference between close minded and denying a statement based on a fallible premise. I am not close minded. This study, and you, are misappropriating defined terms towards no productive end. Calling cancer a species doesn't increase our understanding of cancer, it only makes species a less meaningful more dilute term.
emsquared
5 / 5 (1) Jul 27, 2011
The transmittable cancers may have a valid argument, I don't know enough (anything) about them to say much one way or the other. It'd have to be cancer cells themselves that are transmitted and continue to propagate to consider it. Ultimately, for it to be able to be said that cancers evolve and are a species, IMO, the genetic changes have to make them more likely to reproduce - lead to a higher fecundity. Cancer (except maybe the transmittable ones) can't be said to have the biological characteristic of fecundity.

Part of my unwillingness to accept cancer as a species also comes from a desire not to confuse the public.

Go ahead and say cancers can have, distinct/stable genomes, that's true that's fine, but this doesn't make it a darwinian species.
FrankHerbert
1 / 5 (6) Jul 27, 2011
Cancer isn't a species in the classical sense, period. Not even HeLa. Separate from a victim, cancer has to be propagated on purpose.


HeLa survives outside of a host, does it not?

In fact, is HeLa not notoriously difficult to kill once it roots itself in a lab?

HeLa is also transmissible with great effort (implantation).
emsquared
not rated yet Jul 27, 2011
HeLa survives outside of a host, does it not?

I guess I was including media as a "host", but all I know about it is what I heard on NPR so I probably shouldn't have spoke there cause I really am not too well informed on it's properties.
malapropism
not rated yet Jul 27, 2011
A good article in general (notwithstanding the validity of the subject matter/researcher's opinion and resultant comments) but the statement that
all known organisms today have stable karyotypes, with all cells containing precisely two or four copies of each chromosome

is quite incorrect. Certainly this is true of all higher animals that I'm aware of but in the plant world, at least, hexaploidy and octoploidy (6 & 8 copies of each chromosome, respectively) and other multiples are not uncommon (I've personally seen up to 14-ploid; don't know what you'd call that and admittedly that high *is* a bit unusual). Nor are triploidy and aneuploidy although often, but not always, these are reproductively inviable. When these organisms are viable and produce offspring the karyotypes are most definitely stable and may carry forward the chromosomal variation.
*Edited to fix a typo.
ziphead
1 / 5 (1) Jul 28, 2011
Life happens.

If we have a new self-maintaining lifecycle, then I think by definition we have a new life form.
If we have a new life form, we need a name for it, hence a new species.

In that sense, it looks like the Devil Facial Tumor Disease ticks the required boxes.
Not so sure about HeLa, but some military research facility somewhere could make have already made it happen.

jamesrm
not rated yet Jul 28, 2011
Theres a bit on wikipedia about transmissible cancers

"Contagious reticulum cell sarcoma of the Syrian hamster,[4] can be transmitted from one Syrian hamster to another by means of the bite of the mosquito Aedes aegypti.[5]

A malignant fibrous histiocytoma was contracted from a patient by a surgeon when he injured his hand during an operation.[6]"

http://www.retrov...3/S1/S92
"that a single malignant clone of CTVT cells has colonized dogs worldwide. Thus the tumor has evolved into an independent parasite, which has long outlived its original host, possibly a wolf. CTVT represents the oldest known malignant cell in continuous propagation, and challenges the concept of increasing genome instability in cancer progression."

Someone once said
"There are more things in heaven and earth, Horatio,Than are dreamt of in your philosophy."