Dean's World

It would be embarassing if the government had been wasting its time and money all these years, wouldn't it?

It's never a waste of time to learn you are wrong.

I hate to be cynical but:
1)There is nothing in the news story that contradicts the idea that mutation of certain genes causes cancer. It mentions new possibilities for treatment and diagnosis.
2)It's well known that cancer cells have different structures. They look different. That's how biopsies work.
3)"The notion that genes cause cancer is quickly fading, although the theory still has its holdouts."
If that means what I think it means, I've seen a LOT of holdouts recently.

It seems like nice work, but I don't see how it contradicts the consensus, as opposed to adding to it. You seem to want to think the biology establishment is wrong. I think the amusing slip in "investigators have been looking at DNA structure instead of genetic causes of AIDS for a while now" suggests why ;)

this in no way contradicts what's out there. It's entirely possible that changes in DNA message and structure BOTH contribute to cancer.

I wasted enough time in a biochem class taught by cancer biologists to know that the structure of a DNA molecule, histone-bound or not, is dependent on the message of the molecule. C/G bases and A/T bases induce different amounts of twist (yes, that is the technical term) and there are even equations and models that help scientists predict the structure of a given bit of DNA message. This in addition to the changes that result further downstream (in the resulting protein).

So it's possible that changes in message lead to changes in structure, and (without having seen the paper) perhaps what Maniotis and colleagues have found is the mechanism (still unknown) by which these genetic changes have an effect.

Remember too, that we used to think that humans had a LOT more genes than the genome project has shown. The idea that structure plays a role is a natural consequence of the fact that SOMETHING must account for the diversity.

It's not surprising that young researchers look into new paradigms. That's how scientists make their own names. Look at what Baltimore and his coworkers did when they discovered RNA viruses. They took the Holy Grail dogma of genetics: DNA-> RNA-> Protein and turned it around. There was a hell of a lot of resistance to changing the dogma, and when they were proved right, they won the Nobel prize. This is how it works. Also why I will never win a Nobel Prize.

lol...nice point Maor about his little word slip.

I'm with Caltech, structure changes with sequence.

Obviously I haven't read the paper either, but the article makes it sound like it's not that big of stretch to say that the Genes DO matter...it's just that their effects are perhaps a little different (maybe just more complex).

I could easily see this article saying that the genes do indeed act as contributors, but that also their effect on DNA structure is a contributor as well.

And ya coulda fooled me that genes causing cancer is fading fast with a few holdouts.

Hank,

That looks like a good article...I skimmed it briefly. I have no doubt that cancer is one big orangic SNAFU. It seems to be nature's most complicated killing machine and I wonder if we'll ever really understand how all the different cancers work--probably not until I'm dead from one of them.

Cool stuff.

I'm familiar with Maniotis' work--it's a bigger challenge to the existing view of cancer than you guys seem to get. But whatever--You can read the paper when it comes out.

Elizabeth:

How did this 'radical new approach' popular among 'young researchers' ever get any funding, given that young researchers are too intimidated by the establishment to do groundbreaking work and funding isn't available to those proposing a paradigm shift?

The way it typically occurs: someone proposes that the existing theory (in this case, the theory that so-called "oncogenes" mutate to cause cancer) is completely wrong, and proposes a new way of looking at things. At first those who defend the reigning paradigm, who have all sorts invested in the current theory, dismiss or ignore it as irrelevant. The young turks chafe under it, debate it, find ways to sidle up to it, and wait until they are old enough, respected enough--and spot an opportunity, a crack in the armor.

It's a familiar story, isn't it? Most scientific theories seem to go through this, don't they? It's just a bigger deal now, what with huge multibillion$$ enterprises riding on so many theories.

It sounds like Maniotis and his colleagues have some interesting evidence about a specific mechanism at work in cancer persistence that hadn't been considered before, and not only are they getting funded, they're getting praised for thinking outside the box.

Heh. Except the ideas that got them started were first proposed--and roundly dismissed--back around 1988. It took about 10 years before anyone looked at it with any seriousness. By the late '90s, enough were taking it seriously that small amounts of funding started flowing to those who wanted to investigate it.

Luckily, in this case, no large monied interests were directly threatened by challenging the existing research paradigm. Just petty bureaucracies and the usual academic turf wars.

What does he think about AIDS?

Heh. He thinks the HIV/AIDS theory is hogwash. But we're not talking about that here, are we? ;-)

Perhaps this will clarify the point:

Obviously I haven't read the paper either, but the article makes it sound like it's not that big of stretch to say that the Genes DO matter...it's just that their effects are perhaps a little different (maybe just more complex).

The reigning theory for quite some time was that a few specific suspect genes would mutate to cause cancer. Unfortunately, as time went on, the evidence that they actually behaved this way got slimmer and slimmer--and it still pretty slim now.

What actually got this all started (since Elizabeth seems to have let the cat out of the bag) was an in-depth review that Peter Duesberg did (Duesberg got his greatest fame and acclaim as a cancer researcher, and it's still his real passion) in which he basically described everything wrong with the oncogene theory and all the problems and paradoxes it had. He proposed most of the oncogene research had turned up interesting stuff but had failed to do anything about what it was supposed to help: cancer.

He then proposed that a structural problem found in all malignant cells--aneuploidy--was the actual cause of cancer, and that the so-called oncogenes are completely innocent.

Now, whether he's right about all that or not, the fact is that while all this was dismissed, by the late '90s that particular paper was starting to be cited by other cancer researchers--and even cancer researchers who thought he was wrong thought he'd brought valuable insights that inspired new directions in research.

To hear Duesberg (and many of his friends in molecular biology) tell it, the only real difference between his views on aneuploidy and his views on HIV is that no one's bread and butter is directly threatened by questioning oncogene theory. Thus someone who questions it is not painted as a danger, a holocaust denialist, a lunatic, a crackpot, a conspiracy theorist, yadda yadda yadda--merely a scientist with insights worth listening to.

Draw your own conclusions. You can read more about Duesberg and aneuploidy right here.

By the way, in case you care: Maniotis does NOT believe that aneuploidy is what causes cancer. However, Duesberg's work suggesting that it was suggested all sorts of directions for his lab to work in.

I'll be happy to ask Maniotis any questions you'd like me to ask him.

Helpful analogy for folks:

1. Cell = Harvard University
2. Nucleus = Library on Campus
3. DNA = Encyclopedia Set (23 Volumes)
4. Chromosome= 1 Volume
5. Gene = Word
6. Nucleotide= Letter

Cancer= Words get all screwed up and start making nonsense:

Example:

The capital of England is London
Teh caxital of Engline si London
hTe csxitel fo Egnile si Landin

Hank,

Bad analogy. The DNA in cancer cells does not get all jumbled up. If it did the cell would die; end of story. Most of the genes/words are still there in cancer cells. Using your analogy it's more like all the punctuation gets jumbled up so that the meanings of the sentences change.

dale