The celebrity "solution"

Talk show host Tom Snyder has died of “CLL complications” and coach Bill Walsh may have done the same (some news reports saying he had CLL, others just "leukemia.") Not long ago the passing of journalist Ed Bradley brought the “good cancer” into the public eye, however briefly.

Whenever a celebrity of sorts comes down with chronic lymphocytic leukemia there are patients who get a little excited, hoping that we have at long last found the poster boy for our cancer (I say “boy” since most of the celebs with CLL seems to be men, at least that we know of.) Michael J. Fox has become associated with Parkinson’s Disease, Lance Armstrong with testicular cancer, and so on. There is a perception among some patients that having a "name" will gain our Rodney Dangerfield leukemia the respect it so richly deserves, after which bucketfulls of money will rain down from the sky, magically translating almost overnight into a cure.

Now, if Oprah or Bill Gates or Bono or Bill Clinton were to come down with CLL, we might actually see something like that, or at least the money part. But pending such an A-list victim, I think we have to be a little more realistic here. Having a celebrity speak for us could backfire, especially if the celebrity is old and male, which just confirms the perception that CLL is an old man’s disease that people die with and not because of.

Tom Snyder shunned the role of CLL spokesman. I remember when he announced two years ago on his website, Colortini, that he had CLL (see excerpt at end of this post). There was much excitement on the ACOR CLL list and he was bombarded with helpful tips, suggestions, and not-so-subtle proddings that he could do us all a lot of good if he decided to actively speak about his disease. Snyder said very little as time went on, other than to announce on his website before shutting it down that he had decided to “follow the protocols of Dr. Michael Keating” to treat his CLL. So I presume that he had RFC or the like.

That he managed to die of CLL complications within two years of diagnosis and treatment is unusual, and we should not jump to conclusions about his treatment choice or approach to the disease. But the fact is that a celebrity is no more capable of making the right choices about CLL than you or me; if anything, used to getting “the best” and feeling public pressure to do what is “expected,” they may not be quite as capable of thinking outside the box. (Add to this the fact that many celebrities are not too bright, and many really are as shallow as they appear. I have this on good authority from Marilyn, whose father is a retired Hollywood publicist.)

I believe it is thoughtfulness -- and thinking outside the box -- that we need if we are to get closer to a control and cure. Sure, it would be nice to have more money -- especially money that did not come with strings attached from drug companies -- but another area that needs attention is the culture of research. This is true of the cancer community in general.

Here is where I urge you to read Why We’re Losing the War on Cancer by Clifton Leaf, an article that appeared in Fortune a few years ago. (PDF here, if you prefer that to html.)

On the plus side, it is good to hear Leaf say, “The few dramatic increases in cure rates and patient longevity have come in a handful of less common malignancies -- including Hodgkin's, some leukemias . . ."

That's as far as he goes with anything that might be CLL-specific, but the way research is conducted affects us as well as everyone else, and that’s where, Leaf argues, some changes in the “cancer culture” may pay off.

Here's a taste of the article:

“So why aren't we winning this decades-old war on terror -- and what can we do now to turn it around?

“That was the question I asked dozens of researchers, physicians, and epidemiologists at leading cancer hospitals around the country; pharmacologists, biologists, and geneticists at drug companies and research centers; officials at the FDA, NCI, and NIH; fundraisers, activists, and patients. During three months of interviews in Houston, Boston, New York, San Francisco, Washington, D.C., and other cancer hubs, I met many of the smartest and most deeply committed people I've ever known. The great majority, it should be said, were optimistic about the progress we're making, believing that the grim statistics belie the wealth of knowledge we've gained -- knowledge, they say, that will someday lead to viable treatments for the 100-plus diseases we group as cancer. Most felt, despite their often profound misgivings about the way research is done, that we're on the right path.

“Yet virtually all these experts offered testimony that, when taken together, describes a dysfunctional "cancer culture" -- a groupthink that pushes tens of thousands of physicians and scientists toward the goal of finding the tiniest improvements in treatment rather than genuine breakthroughs; that fosters isolated (and redundant) problem solving instead of cooperation; and rewards academic achievement and publication over all else.

“At each step along the way from basic science to patient bedside, investigators rely on models that are consistently lousy at predicting success -- to the point where hundreds of cancer drugs are thrust into the pipeline, and many are approved by the FDA, even though their proven "activity" has little to do with curing cancer."

In other words, we need to be thinking outside the box, making jumps and connections that might achieve genuine breakthroughs. Wars are won not only by slow and incremental attack; sometimes fortune favors the bold.

I wish we could send Dr. Keating and the other top dozen CLL experts in the world on a retreat and tell them, “Take your time, Money is no object. Forget your egos. Talk about the offbeat ideas you have been husbanding in the back of your mind, share your wish lists, sit around and drink too much Scotch and shoot the bull.”

And I would stick some creative thinkers from other disciplines in the room with them -- Steve Jobs-types, and our own Chaya Venkat -- to challenge their notions and light fires in their imaginations.

And then let’s set up a little private research center where the experts and the thinkers can come and work anonymously, creatively, crazily.

Would something come of it? We’ll never know until I win Powerball or Oprah starts noticing lumps in her neck.


EXCERPTS FROM TOM SNYDER'S BLOG

Below is an excerpt from Tom Snyder's blog discussing the discovery of his leukemia. I always liked Tom; he was pixilated, which the dictionary defines as "behaving as if mentally unbalanced; very eccentric. Whimsical; prankish. Slang Intoxicated; drunk." Here's to you, Tom; I hope they serve good martinis up there, and don't talk the Big Guy's ear off.

A cat scan turned up some interesting stuff. My spleen is enlarged, which the doctors say might be crowding my stomach in my abdomen, thereby causing some of the bloating I am experiencing. And judging by my white cell count and a variety of other factors including what was shown on the cat scan, I have been diagnosed with something called chronic lymphocytic leukemia. Jesus H. Christ! When I was a kid leukemia was a death sentence. Now, my doctors say its treatable! With pills or chemotherapy or a combination of both. Lemme pause here on this word treatable.

Four years ago they stuck a defibrillator/pacemaker in my chest because my heart disease was treatable! A year and a half ago a nearly torn tendon in my left leg was diagnosed as treatable. Then I came down with atrial fibrillation, but was told not to worry about that because it is treatable! I don't know how much more room I have in my aging carcass for this treatable shit! Anyway, my doctors assure me this is nothing to worry about, and I have to accept that, I guess. They say this kind of leukemia is not fatal, that people can live with it for thirty years. Notice, they don't say people will live thirty years. But they "can" live up to thirty years. Considering I will be sixty nine years old next month I ain't looking for thirty years, but fifteen more would be nice! I looked up chronic lymphocytic leukemia on the Internet and found a source that predicted people who are diagnosed early can live up to twelve years. Those who are not diagnosed early--and the website does not define "early"-- have a survival rate of about two years. I don't know if my diagnosis was early or late.

My doctors say this disease (which I'll refer to as CLL from now on) has a very slow rate of progression. I had more blood work done today to make certain this diagnosis is correct. The doctors will have the results of this in a week or so and then we will see what treatment they recommend. I am going to Northern California for about two weeks and I am not taking my leukemia with me. The doctors say that's okay with them.

The CLL mouse

One thing that CLL clears the head about is animal testing. When it comes to finding a cure or control for something that might kill you, touchy-feely considerations go out the window. It is entirely selfish, as well as specie-centric, to put mice through the tortures of laboratories for the benefit of man. It is also an effective way of testing new drugs, figuring out new targets for therapy, and of finding a quicker path to controlling or curing this damned disease.

I come from the background of the guilt-ridden meat eater, the wannabe vegetarian who thinks barbequed pork ribs are extraordinarily tasty and who must stare his own hypocrisy in the face every time he sees his reflection in the glass of the butcher's case. I am, like Homer Simpson, a prisoner of bacon.

I am also convinced that animals have emotions. I have shared my life with cats and have seen it personally. I have no doubt that the same is true of dogs. There is a marvelous book called When Elephants Weep: The Emotional Lives of Animals by Jeffrey Moussaieff Masson. Masson provides compelling evidence that animals do have feelings, "higher" animals at least. (This includes -- shudder -- pigs.) How high are mice on the chain? Not so high that research on mice bothers me sufficiently to oppose it. If it is a matter of them or me, then until the mice rise up and destroy us, I believe using them in cancer research is necessary.

So it is with satisfaction that I read the news that Amy Johnson and the research team at Ohio State University have developed mice with, essentially, CLL. A report in the August 15, 2006 Blood online provides a tantalizing abstract as well as a comment by the renowned CLL expert Dr. John Gribben.

It is worth noting the abstract here, in full, emphasis mine:

"Drug development in human chronic lymphocytic leukemia (CLL) has been limited by lack of a suitable animal model to adequately assess pharmacologic properties relevant to clinical application. A recently described TCL-1 transgenic mouse develops a chronic B-cell CD5+ leukemia that might be useful for such studies. Following confirmation of the natural history of this leukemia in the transgenic mice, we demonstrated that the transformed murine lymphocytes express both relevant therapeutic targets (Bcl-2, Mcl-1, AKT, PDK1, and DNMT1), wild type p53 mutational status, and in vitro sensitivity to therapeutic agents relevant to the treatment of human CLL. We then demonstrated the in vivo clinical activity of low dose fludarabine in transgenic TCL-1 mice with active leukemia. These studies demonstrated both early reduction in blood lymphocyte count and spleen size and prolongation of survival (p=0.046) as compared to control mice. Similar to human CLL, an emergence of resistance was noted with fludarabine treatment in vivo. Overall, these studies suggest that the TCL-1 transgenic leukemia mouse model has similar clinical and therapeutic response properties to human CLL and may therefore serve as a useful in vivo tool to screen new drugs for subsequent development in CLL."

If words aren't enough, the graphics accompanying Gribben's comment include a telling chart showing how the mice developed drug resistance to fludarabine. Fludarabine has gone from the wonder drug to a necessary evil in CLL therapy as doctors have, over time, discovered its negative as well as positive effects. A mouse model such as this may be able to predict drug resistance in a matter of weeks or months -- sparing us human lab rats from having to discover it the hard way over a period of years.

In his comment, Gribben writes:

"While there is naturally great excitement in exploiting strains of mice with leukemia to test therapy, these models will also be invaluable to understand mechanisms of responsiveness and resistance to chemotherapy. Although the initial response rate to fludarabine of patients with CLL is high, eventually patients develop relapse with resistant disease. Here again, Johnson and colleagues have demonstrated the utility of this murine model since these mice demonstrate initial responsiveness to fludarabine in vivo, with resulting modest improvement in survival, but rapidly develop resistant disease. Much work still has to be performed to examine the mechanisms whereby such drug resistance occurs, and in particular whether there is eventual loss of function of p53 as occurs frequently with end-stage CLL. However, this model has sufficient clinical and therapeutic similarities to human CLL to believe that this will open up exciting new opportunities to screen new drugs and novel combinations in vivo and speed therapeutic development in this still incurable disease."

When I saw Dr. John Byrd at Ohio State in June, we discussed fludarabine and disease resistance. While it has been theorized that fludarabine may select for the p53 deletion, killing off all the other CLL clones and allowing the worst one to survive, Byrd emphasized that it has not been proven. Byrd told me that a nine-month study is underway comparing CLL mice receiving fludarabine with CLL mice receiving no treatment. Will the study show a greater incidence of p53 deletions in the fludarabine-treated mice?

Stay tuned. And say a little prayer of thanks for our furry friends with the enlarged spleens and extra-thick necks.