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Carl Zimmer Carl Zimmer is the author of several popular science books and writes frequently for the New York Times, as well as for magazines including The New York Times Magazine, National Geographic, Science, Newsweek, Popular Science, and Discover, where he is a contributing editor. Carl's books include Soul Made Flesh,, Parasite Rex and Evolution: The Triumph of An Idea. His latest book is Smithsonian Intimate Guide to Human Origins. Please send newsworthy items or feedback to blog-at-carlzimmer.com.
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The Loom
March 15, 2004
The Accidental TumorEmail This EntryPrint This Entry
Posted by Carl Zimmer

For over two centuries, opponents of evolution have searched for examples of natural complexity that could have only been created by design. Reverend William Paley was fond of the eye, with its lens, retina, and other components all beautifully fine-tuned to work with one another. These days, the Intelligent Design camp tries to invoke blood clotting cascades or the flagella that bacteria use to move around in the same way. (See here for some refutations of these arguments.) Ironically, one of the most successful, intricate examples of complexity in nature is something creationists never mention: a tumor.

Cancer cells grow at astonishing speeds, defying the many safeguards that are supposed to keep cells obedient to the needs of the body. And in order to grow so fast, they have to get lots of fuel, which they do by diverting blood vessels towards themselves and nurturing new vessels to sprout from old ones. They fight off a hostile immune system with all manner of camouflage and manipulation, and many cancer cells have strategies for fending off toxic chemotherapy drugs. When tumors get mature, they can send off colonizers to invade new tissues. These pioneers can release enzymes that dissolve collagen blocking their path; when they reach a new organ, they can secrete other proteins that let them anchor themselves to neighboring cells. While oncologists are a long way from fully understanding how cancer cells manage all this, it's now clear that the answer can be found in their genes. Their genes differ from those of normal cells in many big and little ways, working together to produce a unique network of proteins exquisitely suited for the tumor's success.

All in all, it sounds like a splendid example of complexity produced by design. The chances that random natural processes could have altered all the genes required for a cell function as a cancer cell must be tiny--too tiny, some might argue, to be believed. And surely the only way that a cell could become cancerous naturally would be for all the genes to change at once. After all, what good is it for a cell to be able to increase blood flow towards itself if it can't grow quickly? Getting so many genes to change at once makes an impossibility an absurdity. By this sort of reasoning, you'd conclude that cancer is the work of a supernatural designer.

And yet, despite all its appeals, creationists don't like to bring up cancer. Perhaps that's because they prefer to use the warm and fuzzy examples of complexity in nature instead of the pain-causing, life-ending ones. I'm no theologian, so I'll leave the religious implications of all this to others. But as a science writer, I do want to talk about what this means about creationism and evolutionary biology as sciences. Creationists say that they want to be taken seriously as scientists. But one mark of important scientific ideas is the important new scientific research it generates. Cancer is a case in point. Creationism in any of its flavors has never led to an important hypothesis about cancer. Evolutionary biology, on the other hand, is generating a wealth of new ideas about potential ways to fight cancer.

Martin Nowak of Harvard University and his coauthors offer a nice roundup of these ideas in a paper appearing in this month's Nature Reviews Cancer. (Nowak has posted a pdf of the cancer paper here, on his publications page. His other papers are worth checking out, too. He's done brilliant work on the evolution of everything from HIV to human language.)

Nowak and his co-authors argue that you can't understand cancer unless you recognize it as an evolutionary process. As cells divide, they mutate on rare occassion (roughly one out every 10 billion cell divisions). Most of these mutations will kill a cell, so that the genomes in most of the new cells in your body are identical to the old ones. But a few of these mutations can allow a cell to divide more quickly than its neighbors. They begin to outcompete the ordinary cells for resources, becoming even more common. These cancer cells continue to mutate, so that there's lots of genetic variation in a growing tumour. In a few cases, these mutations make cells better adapted to a cancerous existence, and the offspring of these cells come to dominate the tumor. As the tumor matures, new kinds mutations may be favored--ones that let it metastatize, for example, or withstand the abuse of chemotherapy.

The same basic dynamics of evolution by natural selection that can alter a species are at work in the cells of a tumor. Obviously, however, the two cases of evolution are not identical. The mutations that alter a species are the ones carried down in sperm and eggs from one generation to the next; the mutations to cells in the rest of the body (the soma) are irrelevant. Cancer, on the other hand, is all about somatic evolution. And while ordinary evolution can last for billions of years, each case of somatic evolution ends with the death of the body in which it takes place.

That said, though, Nowak and his colleagues show how evolutionary dynamics can tell us a lot about how cancers get started and spread. One crucial fact about cancer is that the evolutionary arena where it gets its start is a microscopic one. Our organs are generally composed of millions of little compartments, each containing a few thousand cells. Colon cancer, for example, begins in so-called "crypts" that line the intestines. Normally the crypt is in a delicate balance. A single stem cell at the base of the crypt divides every day, producing a fresh colon cell. The older cells move up towards the surface of the intestines to make room, dividing themselves as well. The oldest cells near the top of the crypt die off in an intricate self-destruct sequence of biochemistry.

The evolution of cancer cells has a different trajectory depending on the size of their compartment. In a big compartment with lots of cells mixing together, natural selection will favor cancerous mutants, which will quickly spread--and possibly spread to neighboring compartments. In a small compartment like a crypt in the colon, supplied by just a few stem cells, cancer may grow more slowly because the cells are more likely to self-destruct before they can cause much trouble. (In fact, the architecture of our tissues overall may be adapted to keeping cancer in check this way.)

Another factor in the spread of cancer are the genes themselves. For example, one common sort of mutation found in cancer cells causes the cells to do a bad job of repairing their DNA. At first, this seems like a very dangerous mutation for a cancer cell to have, since it means that the cell risks mutations to the many genes that it needs to stay alive. Nowak and his colleagues find, however, that bad repairs have a benefit that makes them worth the cost. To understand why, bear in mind that each of our cells has two copies of each gene, inherited from mother and father. In order for cancer to progress, both copies of certain genes have to get knocked out in a cell. This is a remote possibility for most cells, but, according to Nowak's calculations, not for ones that have become genetically unstable. (Genetic instability, Nowak's work also shows, is responsible for cancer's extraordinary capacity to evolve protection against drugs.)

Nowak's work is elegant and fascinating, but as he admits, it's just the beginning of an understanding of how cancer evolves. (He's not the only one pursuing it--this article in the March 15 issue of The Scientist describes how other scientists are pursuing similar lines of research.) It's worth pursuing further, because it may make it possible to predict precisely particular cases of cancer will progress, and help reveal which line of attack will work best.

It will be interesting to see how the members of certain state boards of education react to this kind of medicine. Will they hold off on chemotherapy until they find out what insights their creationist friends have gotten about cancer? If they do, they'll be waiting a dangerously long time.

UPDATE 3/24/04: Welcome to readers visiting from Phenomena News. The editors at PN ask, "Diverting blood vessels? How does he know that it is not a way by the body to try to fight the tumor?" Oncologists actually have a lot of evidence indicating that it is the tumor, not healthy cells, that send signals out to blood vessels to stimulate growth. The cancer cells need the extra blood to grow rapidly. And some of the most promising research on curing cancer involve blocking blood vessel growth around tumors. Kill the blood supply, and you kill the tumor.


Category: Evolution


COMMENTS
Steve on March 15, 2004 07:17 PM writes...

Aside from a tiny number of crazies perhaps, of course they won't wait to see what the creationists come up with. They'll simultaneously consume the benefits from the science, and attack the basis of the science. Abstract notions like consistency either aren't important to them or aren't understood by them. Here's a personal example of something similar. I knew a guy who was absolutely sure that prayer can heal illnesses. I asked him if it would substitute for the medicine the doctor gives you. You have to do both at the same time, of course, he told me.

Permalink to Comment
Mike on March 16, 2004 04:51 PM writes...

My favorite example, from the inorganic world, is the snowflake. What remarkable precision, symmetry, and variety. (It may well be that no two are the same, but I'm waiting for more evidence to come in.)

If you saw a microscope photograph of a snowflake, how could you help but ask, "Who made that?"

Permalink to Comment
Philip Skell on March 23, 2004 01:53 PM writes...

Excellent article, to which I will add the following observation.

The experimental contributors to this subject give credit to evo-bio, but fail to make clear what is the relation. Certainly there is no connection to the historical biology, the one lost in deep time, which is the miniscule base on which classical Darwinian Theory is built. The modern understandings of cancers came from modern experimentation, and not from tracing some vague notion into that lost past.

What is, confusingly, labeled evo-bio is, in this case, the modern recognition and elaboration of the adaptations which occur within these competing systems. The deep past contribute nothing to these studies, other than the triviality that, of course, every living organism must have had an ancestor.

Permalink to Comment
Kurt on March 23, 2004 04:53 PM writes...

The basic problem with creationsim is that it does not solve the intellectual problem that it is supposed to. The creationists argue that "irreducable complexity" requires the existance of an intelligent "creator". Yet, an "intelligent creator" is itself an example of irreducible complexity that would a previous "intelligent creator", and so on. The root issue of "irreducible complexity" never gets solved. Thats why creationism is quite disingeneous.

Permalink to Comment
Pat Bartholomew on March 23, 2004 10:46 PM writes...

You can't win this argument with a creationist. When I tried to explain carbon dating to a friend of mine, she had a very simple answer. "God made the rocks and minerals that way because he wanted to create pretty things."

So keep it warm and fuzzy and save your energy.

Permalink to Comment
Tadd on March 24, 2004 02:03 AM writes...

I love the post by Pat. Creationists are so brainwashed by religion they no longer have the capacity to cogitate on the subject of creationism. To me the complexity of life requires evolution. Without it we could not have the diversity and amazing adaptations life on this planet represents. Its hard to outsmart ignorance and argument will usually just lead to deadlocked opinions.

Permalink to Comment
hideki yukawa on March 24, 2004 12:29 PM writes...

I'm responding to the Update paragraph at the end of the article.

Avastin is the commercial name for the Genentech drug that recently went through Phase III clinical trials and was shown to significantly increase survival rate in colorectal cancer patients.

http://www.cancer.gov/clinicaltrials/results/bevacizumab-and-colorectal-cancer0601

What's special here is that Avastin is an 'anti-angiogenesis' drug. i.e. it was designed to suppress growth of new drugs.

So - the short story is that preventing new blood vessels helps kill cancer. So these new blood vessels were made by the tumor, for the tumor.

Anyway, I've given up arguing with creationists. I am too weak.

Permalink to Comment
Touchdown on March 25, 2004 11:38 AM writes...

God is always the wildcard. If He/She/It is omnipotent, then anything is possible.

Incidentally, creationists believe in a "Fall". This is perhaps the moment Intelligent Design introduced cancer cells into the world.

Permalink to Comment
Rob McEwen on March 25, 2004 11:50 PM writes...

The article you linked to that was supposed to refute irreducible complexity (IC) was pathetic.

When providing the most details and evidence, it took "cheap shots" at the weakest IC examples.

As it progressed to harder examples, it invoked more and more wishful thinking, more guesswork, more circular reasoning, and less hard science.

Finally, when it got to the best examples of IC, it leaned on the weight of its earlier stated pathetic arguments and evidence (or lack thereof) and continued to invoke guesses rather than hard science.

Also, several significant IC examples were left out.

It was almost hilarious that the article expected Behe to "prove" that systems are irreducibly complex when it is actually up to the Darwinists to "prove" that the system is evolvable without evoking wishful thinking and circular reasoning.

hint: real life examples where a single mutation is the only change needed to allow a process to act in a new way is not good enough because these examples provided are no where near the complexity of Behe's best examples of IC, for example.

Permalink to Comment
Carl Zimmer on March 26, 2004 01:20 AM writes...

Rob, your argument doesn't make sense. Why shouldn't Michael Behe or other Intelligent Design advocates be expected to prove that systems are irreducibly complex? That's the whole *point* of their argument. Furthermore, coming up with a plausible evolutionary hypothesis can refute Intelligent Design, because it claims that no such hypothesis could ever be proposed. The only response from Intelligent Design advocates to these hypotheses is to call them wishful thinking. As far as I can tell, this merely means that we do not know every step in a process that tooks millions of years. But calling an evolutionary hypothesis wishful thinking is no defense of Intelligent Design. These hypotheses are consistent with what we know about how genes mutate and how genes in different species are related to one another. Intelligent Design, on the other hand, offers no insight into these facts whatsoever.

Even more puzzling is your reference to Intelligent Design's "weakest examples." If Intelligent Design cannot explain such examples, then what can? Evolution? So does Intelligent Design dip in here and there in the history of life, leaving evolution to handle these "weak examples"? Behe himself seems suggest that the evolution of hemoglobin from myoglobin is not a good example of Intelligent Design, offering no explanation for how it actually happened. According to evolutionary biology, it occurred hundreds of millions of years ago through gene duplication. So here we have an ancient, incredibly profound event--a classic case of macroevolution--handed over to the forces of evolution.

It's these sorts of inconsistencies that make the vast majority of biologists look at Intelligent Design as an absolutely useless concept.

Permalink to Comment
Rob McEwen on March 26, 2004 03:30 AM writes...

>"weakest examples"
By using this term, what I mean is simply that some examples used to demonstrate IC are more complex than others. Obviously, the more complex ones are the more powerful and the most difficult for Evolutionists to explain using Evolution as the framework. Using the phrase "Weakest examples" may have falsely given the impression that such examples might prove the opposite of IC... But nothing could be further from the truth because Behe NEVER said that EVERYTHING is IC.

I should have said "least complex examples of IC" instead of "weakest examples"

I simply noted that the article seemed most factual and observation-based when discussing the "least complex examples of IC" (which seemed like a cheap shot) and got more hypothetical and reliant on unproven assumptions of evolutionists as it moved on to the more advanced examples.

>hypotheses are consistent with
>what we know about how genes mutate...

Oh really? Are you familiar Dr. Lee Spetner and his book, "Not By Chance! Shattering The Modern Theory of Evolution"

Spetner graduated from MIT with a PhD in physics. Later, he studied mutations for years at the Department of Biophysics at John Hopkins University.

Basically, Spetner says that, in years of studying real-life mutations in a lab, the vast majority of non-neutral mutations delete or scramble DNA. Little to none actually add new genetic structures... and there are built in fire-walls which make it rare for a mutation (of any type) to gain momentum within a population.

Therefore, when you combine two rarities ("additive" mutations) with the "firewall" (my description) which makes mutations difficult to spread into the overall population... you get an extreme rarity.

Spetner is not saying that this is impossible... only that it is so rare that there is simply not enough time since the earth cooled for Evolution via mutations & natural selection to get the job done.

Also, when you have to wait a long time to get enough additive mutations to make changes (if there is even enough time or enough additive mutations), you end up with many more harmful mutations along the way that have to be factored in. In fact, it more sensible to say that natural selection weeds out the bad mutations more than anything else. But anytime that this happens... the supposed additive mutation would be "killed off" as well.... kind of like a storekeeper who loses a little bit on each sale... might make a tiny profit on one sale very decade or so... and then says, "don't worry, I'll make it up on volume."

Finally, at the very least, the irreducible complexity examples that Behe refers to raise the bar of all the stuff evolution has to accomplish in this timeframe. Whatever you think you've proven regarding IC, you can't take the "complexity" out of "irreducible complexity"

Sure there are many examples of microbes and viruses gaining more complex DNA by horizontal transfer between them... but this cannot be used to explain evolution because these transfer DNA that was ALREADY in existence.

Also, there are a handful of examples where a single mutation gives an organism a benefit by adding a function ...but often, this addition also removes another function... thus making it a controversial topic as to whether DNA was truly added. (nylonase, for example)

Therefore, Carl, can you list for me examples actually observed in a laboratory or in nature which demonstrate mutations which "added" DNA without horizontal transfer, and which were sufficient to cause speciation? (If you can't find any sufficient to cause speciation... how about giving me the most extreme examples that scientists have observed.)

BTW, try to do better than "nylonase".

Permalink to Comment
Wesley R. Elsberry on March 26, 2004 11:54 AM writes...

There are several relevant resources that readers should check out on matters of "intelligent design" conjectures.

The TalkDesign web site hosts a number of critiques of "intelligent design" claims, including Behe's "irreducible complexity".

The TalkOrigins Archive is a web site with a large number of FAQs on both antievolution claims and straightforward explications of evolutionary biology. Of special interest to Rob will be the FAQs on speciation (1, 2) and macroevolution (Macroevolution, 29+ Evidences for Macroevolution
The Scientific Case for Common Descent
). There are even resources on the topic of evolving fitness and Lee Spetner.

I also have a page on evolutionary increases in information, which fills the request made by Rob nicely, IMO.

Also, check out the new weblog, The Panda's Thumb, at which I'm a contributor.

I'd like to make an observation on "intelligent design" in general. ID claims are aimed at obtaining a concession that evolutionary processes are insufficient to account for observed biological phenomena. After that, ID advocates hope that people will simply fill in with an "intelligent designer" of their preference to cover the gap. ID arguments are all of the negative variety: because evolution can't do this, you must accept that an "intelligent designer" did.

So, how do ID advocates wend their way toward finding evolutionary insufficiency? Do they identify phenomena with good evidential records of their origin and find that no natural mechanisms are able to cover the situation? No, they do not. ID advocates identify the systems that have the least evidence that can bear upon just how they might have arisen and whack on those. If evolutionary biologists don't have the evidence to work with, they certainly can't generate "detailed, testable pathways" that ID advocates like Rob claim it is their burden to produce. This is such a weak and pathetic strategy that the term I use for Michael Behe's arguments now is "God of the crevices". You see, Behe's claim to fame is to have taken the old young-earth creationist bleat of "what good is half a wing?" and bring it into the modern era of molecular biology, reborn as, "what good is half a flagellum?" Biochemistry, Behe says, is the basement floor, and there is no further place to go. Thus, the gaps Behe goes on about have a bottom, and are crevices.

Back in 2001, I was in a panel with William Dembski, and pointed out that the only way for ID to progress was to take up those case where there was evidence at hand. Things like the impedance-matching system of the mammalian middle ear and the Krebs citric acid cycle. Michael Behe was sitting in the audience at the time. Have ID advocates taken up those sort of systems for analysis? Not on your life.

"Intelligent design" advocates use Behe's "irreducible complexity" and Dembski's "specified complexity" as arguments to convince people to disregard theories which have some evidential support, and force acceptance of conjectures with no evidential support. It's a good trick, that.

Permalink to Comment
ibrahim on May 26, 2004 05:44 PM writes...

i knw you like it.

Permalink to Comment


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Kieran suggests ” that people who subscribe to Intelligent Design theory need to have the perverse mechanics of childbirth explained to them.” Karl Zimmer goes one step further, and asks why they don’t embrace “one of the most s... [Read More]

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