Sometimes coincidences just jump out and tackle you. Yesterday, as I was perusing the New York Times, I came across an article entitled “Cancer’s secrets come into sharper focus” and I was hit with no less than five (5) amazing coincidences.
The first coincidence is that I was thinking about cancer, because two years ago, my dad died after a 15-month bout with pancreatic cancer. Ever optimistic, he tried every treatment he could in the hopes that if he could hang on a little while longer, a better treatment would come out. He was a firm believer in the possibilities of science, being a scientist himself. In the two years that have gone by since then, I have not read about a single promising new treatment for metastatic pancreatic cancer. And I keep my eye out.
The article agrees with me. We have based a large part of our cancer research on looking into the human genome for the explanation of what goes haywire in cancer cells, it says. And maybe that’s not the right approach, or at the very least, not the whole story.
This brings me to coincidence #2 – the article mentions a “landmark paper” entitled “The Hallmarks of Cancer” (published in 2000) by Douglas Hanahan and Robert Weinberg. It is the single most cited paper of all time in the scientific journal Cell. The coincidence is that Hanahan is now director of EPFL’s cancer center and I had Thanksgiving dinner with him and his family and some other biology types last year. I didn’t know he was, like, the Albert Einstein of cancer research. He seemed perfectly normal.
I read the paper (you can too, it’s not one of those pay-per-view scientific articles and it’s actually quite readable, for biology). It sums up six characteristics of all the various types of human cancers.
Briefly, in a cancer cell, a whole host of genetic things go wrong, which screws up the biochemical communications both inside and outside the cell. It’s like having a Republican Congress and President. The checks and balances don’t work any more. And like the bad kid in the class, cancer cells also co-opt normal cells and get them to do stuff they wouldn’t normally do, like create blood vessels and scaffolding for the tumor. Cancer cells also break cell rules and go AWOL, setting up outposts in other organs. All the different kinds of cancers act out like this. Very bad behavior.
Near the end, the authors write:
Two decades from now, having fully charted the wiring diagrams of every cellular signaling pathway, it will be possible to lay out the complete “integrated circuit of the cell” upon its current outline. We will then be able to apply the tools of mathematical modeling to explain how specific genetic lesions serve to reprogram this integrated circuit in each of the constituent cell types so as to manifest cancer.
Okay, so we sort all these signaling pathways out, we should be able to take a logical, physics-like approach to fixing the problem. Got it. Go get ’em!
Except that eleven years later (today), it’s still pretty much a mess. We know a lot more than we did about cellular signaling pathways and the “oncogenes” that encode the rogue proteins that screw them up. Problem is, there are just so many of them. It seems like every time I open Newswise there’s another press release about a new discovery of a gene or a signaling pathway and how it will lead to a “promising avenue for cancer treatment.” It’s like LA – around every corner, there’s another gang member. Can you neutralize them all? Not likely. If you take out Osama Bin Laden, does Al Quaeda die? Not likely. Same with cancer.
Now back to the NYT article. Coincidence #3: the author is George Johnson, who also happens to have written a book entitled Fire in the Mind in which he mentions my dad and the Santa Fe Institute (dad was President at the time). I once attended a science writing workshop in Santa Fe taught by George. He’s a really smart guy and I like him a lot. So I know the article is going to be good.
George went to the annual meeting of the American Association for Cancer Research in Orlando this spring, and sat in on a bunch of talks and interviewed some researchers. He found out that there are a few things they’re realizing we haven’t taken into account when looking at cancer. As usual, we humans have been pathetically self-centered. Remember the microbiome? Well, this is coincidence #4. I wrote about it back in this May 3 post. Ninety percent of the protein-encoding cells in our bodies are not our own cells. They’re microbes. You’d think we’d pay attention to what they might be doing.
I think I was quite prescient in my blog post when I said: “We thought disease was about us, about our genes. It could very well involve a batch of rogue bacteria.” You heard it here first, folks.
Scientists are finally getting around to thinking that all those microbes might have an effect on our cells’ biochemical surroundings and, hence, cancer.
“We are massively outnumbered,” said Jeremy K. Nicholson, chairman of biological chemistry and head of the department of surgery and cancer at Imperial College London. Altogether, he said, 99 percent of the functional genes in the body are microbial.
Problem is that we know squat about the microbiome. Add another decade to that estimate, Hanahan. This is gonna take some time.
Another thing George mentions is that we’ve handily ignored the large portion of our DNA that doesn’t code proteins, the “junk” DNA. Turns out that most of the genome is junk. Hey! Coincidence #5! I wrote about junk DNA back in April in my blog post about Craig Venter and the James Joyce estate.
These days “junk” DNA is referred to more respectfully as “noncoding” DNA, and researchers are finding clues that “pseudogenes” lurking within this dark region may play a role in cancer. “We’ve been obsessively focusing our attention on 2 percent of the genome,” said Dr. Pier Paolo Pandolfi, a professor of medicine and pathology at Harvard Medical School.
Have a little respect. The non-coding parts of our DNA may very well have a purpose other than providing space for clever quotations. In fact, I never bought the “junk” hypothesis. It doesn’t make any sense at all that 98% of our DNA would sit around just twiddling its thumbs. It’s like saying that unless you have a salaried job you are extraneous. What about changing diapers and paying bills and buying groceries? There’s a lot more to DNA than just bringing home the bacon (protein).
Problem is that we know squat about what the “noncoding” DNA does. Another decade, maybe?
The last thing he mentions isn’t a coincidence because I haven’t written about it on the blog yet. But George explains how little mini-strands of RNA roaming around the cell could interfere with messenger RNA’s delivery task. We don’t understand this too well, either.
I’d like to encourage you to watch this 5-minute video from the NYT, which sums it all up really well.
So, in short, not only does cancer suck, but it’s horrifically complicated and involves all kinds of stuff we know next to nothing about. We will probably never be able to cure it. But it would be really nice to figure out a way to live with it, like we live with the virus that causes warts.
One more thing I’ll throw out there — did you know that people who have Parkinson’s and Alzheimer’s Diseases have a lower risk for developing cancer? As if the body can only take so much insult. Why would that be?