He Won His Battle With Cancer
By Bill Saporito/Philadelphia
Got cancer? It's all the rage. Actress Christina Applegate, Senator Ted Kennedy, Olympic swimmer Eric Shanteau, columnist Robert Novak are just the highest profile of the 1.4 million Americans who will get a diagnosis of cancer this year. Walk into the oncology waiting room of a hospital and you'll find it hard not to notice the crowd--or the balding heads, the yellow faces, that gaunt prisoner-of-war look of those who are well into their chemotherapy. You stare blankly across the room at the others staring blankly back, everyone silently asking the question: Am I going to make it? When you're facing that kind of primal question, you say to yourself, "Well, at least I'm not alone." And that is precisely the problem. You are not.
Although it's uplifting to talk about living with cancer, dying with cancer is the more honest reality. Cancer is overtaking heart disease as the No. 1 killer in the U.S.: An estimated 565,650 Americans will die from it this year alone, according to the American Cancer Society. Because the incidence of cancer increases with age, the nearly 80 million baby boomers now crossing into their 60s will probably drive the number even higher. At current rates, 1 in 2 men and 1 in 3 women will eventually have some form of cancer diagnosed. (Why the gender disparity? Men smoke more.) For the record, the cancer community includes me; five years ago, I was treated with chemotherapy and major surgery.
For an increasing number of cancer activists, researchers and patients, there is too much death and too much waiting for new drugs and therapies. They want a greater sense of urgency, a new approach that emphasizes translational research over basic research--turning knowledge into therapies and getting them to patients pronto. The problem is, that's not the way our sclerotic research paradigm--principally administered by the National Institutes of Health and the National Cancer Institute (NIH/NCI)--is set up. "The fact that we jump up and down when cancer deaths go from 562,000 to 561,000, that's ridiculous. That's not enough," says Lance Armstrong, 36, the cyclist and cancer survivor turned activist through his Lance Armstrong Foundation (LAF).
A new and more radical approach is being taken by groups like the newly formed Stand Up to Cancer (SU2C), which plans to finance research designed to deliver big leaps and home runs rather than the incremental improvements that are more typical of mainstream science. The new focus for funding grants, said Dr. Eric Winer, chief scientific adviser to the Susan G. Komen Breast Cancer Foundation, in a conference address, is results: "What we want to see is research that is going to change the number of women that are diagnosed with, or more importantly, die of, breast cancer within the foreseeable future." Others, like the Multiple Myeloma Research Foundation (MMRF), are trying a no-nonsense business model to speed drug development.
Doctors and scientists understand the frustration and the fear, and they don't necessarily mind the nudge. "We do need to change. Something needs to be done differently," says Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research at MIT. "We have a lot of new insight, and we need to have a whole new collection of drugs, a new armamentarium."
Some Advances, Much Pain
Aren't we making a lot of progress? Absolutely. In a lot of places. When you adjust for age (since cancer is over-represented in the elderly), fewer people are getting cancer, and those who get it are surviving longer. We are benefiting from improved surgical techniques as well as more refined chemotherapies and radiation strategies that use lasers and robots to target cancer cells. Cracking the genomic code is leading to new drugs, geared to individual dna, that disrupt the very mechanism of cancer. "The rate of discovery has been phenomenal," says Dr. Harold Varmus, CEO of Memorial Sloan Kettering Hospital in New York City, a former NIH director and a Nobel-winning researcher in lung cancer. "We feel we understand some of the basic principles. We understand the tissue environment."
Some of the latest weapons in Big Pharma's arsenal result from that understanding. Gleevec, for instance, treats one form of leukemia by zeroing in on the Philadelphia (Ph) chromosome, that part of the genome that directs bone marrow to keep making abnormal white blood cells. Because of drugs like Gleevec and therapies such as bone-marrow and stem-cell transplants, there are 12 million people walking around today who are classified as survivors.
But cancer isn't one disease; it's dozens of them, each with different mechanisms that make the fight diabolically difficult. The most pernicious forms of cancer--among them, pancreatic, lung and brain--are still nearly invincible. Survival rates in rare forms of cancer aren't budging much, either. And the cancer arsenal is still heavy on the blunderbuss--blasting the body with harsh chemotherapy and radiation that take a huge toll on healthy as well as diseased tissue. Nor has the national health-care system done a great job of prevention and early detection. Worst of all, many people don't have access to care. Overall, the death rate from cancer dropped just 5% from 1950 to 2005, the latest available data. During the same period of time, deaths from heart disease dropped 64%.
The Problems with Research
It's not that cancer research funded by NIH/NCI or Big Pharma is somehow second-rate. "The last 30 or so years of concerted effort have led to a tremendously rich understanding. This is not a waste of time," says Jacks of MIT.
The long-standing criticism, though, is that NIH/NCI is necessarily structured for caution, for limited returns based on individual scientists grinding it out in their labs--the three-yards-and-a-cloud-of-dust mentality. To get funding, individual researchers typically have to write grant proposals that demonstrate a reasonable expectation of success. "You have to have already done some of the stuff and then propose it, before they're going to believe it's the right thing to do," says Dr. Ray DuBois, executive vice president of M.D. Anderson Cancer Center and a cancer researcher. A proposal can take months to write, so a rejection means the loss of a scientist's productivity as well.
It can also mean that "lesser" cancers don't get as much attention. M.D. Anderson has a project to map the entire bladder-cancer genome. "It's not something that NIH is interested in because it's a little less common than other cancers," says DuBois. Using other funds, researchers identified a gene defect that correlates smoking and bladder cancer. "If you have that defect and you smoke, there's a 100% chance you'll get cancer," says DuBois. But the hospital is more likely to get support for work on lung cancer, a much bigger problem. So call it research triage.
Whatever optimism researchers have is tempered by the fact that money is tighter. Funding for the NCI has been flat during the past three years of the Bush Administration, at about $4.8 billion. "One of the things that happens when money gets tight is that everything gets more conservative," says Dr. Curtis Harris, an NIH cancer researcher.
What's more, the lean times come in a period when the cost of research has outpaced inflation, so there's a double hit. The NIH has a "pay line" of roughly 14%, meaning it hands out only that percentage of the total money requested. Just 1 in 10 grant proposals it considers "meritorious"--that is, worthy of funding--gets a payout.
There are opportunity costs to this system. Collaboration suffers as scientists guard their work to keep the money coming. Because the funding process favors experienced grant writers, young investigators can lose out. Such friction and lack of funds, some argue, are causing a brain drain to Singapore and other regions that are actively seeking to develop their biotech industries. "The incentives are totally misaligned. The repetitive nature of funding the same universities and the same people--all of these things add up to the stagnant position that we're in," says Doug Ulman, president of the LAF and chairman of the Director's Consumer Liaison Group at NCI.
The Politics of Cancer
No one in Washington is in favor of more cancer. But attempts to expand the NIH's budget or get separate funding from Congress have been stymied by internecine fighting among cancer groups. Armstrong tells of vice-presidential candidate Joe Biden's frustration at being besieged by cancer-site advocates--lung, breast, blood--and those for other terrible diseases, each unwilling to let dollars pass to another without an argument. "Within that group, you have a lot of fighting, hogging, people trying to elbow each other out," says Armstrong. The legislators' message to these groups is simple: Get your acts together.
Last year Armstrong persuaded the advocate community in Texas to play nice in support of a referendum to spend $3 billion fighting cancer over the next 10 years. The passage of the proposal was a huge victory in a spend-wary state, and perhaps it was a model for others. The program makes cancer prevention and screening key components, which saves the state money in the long run.
This year Armstrong has tried to make cancer an election issue. He got Senator John McCain to attend the Livestrong Cancer Summit earlier this year. McCain, a skin-cancer survivor, committed to increasing spending but not to a specific amount. Senator Barack Obama has committed to doubling the budget for fighting cancer as part of a broader reform of health care. Certainly the frail, failing Senator Ted Kennedy's dramatic speech at the Democratic Convention, coming in the midst of his battle with brain cancer, underscored the point.
Even with a new President inclined to increase spending, throwing money at the problem isn't the answer. "There is no strategic plan," says former Senator Bill Frist, a heart and lung surgeon before he entered politics. Frist voted to double NIH funds in 1998 but wouldn't recommend it again without a better road map. There are numerous federal agencies that cover cancer, for instance, and less than complete coordination among them.
Frist says the scientific and advocacy communities need to agree to a five-year "business plan" with specific targets and measurable goals. "If you put together a good long-term strategic plan, and it was supported by the scientific community," he says, "it would be funded." That is a goal of the Kennedy-Hutchison cancer bill, which could get to the Senate floor this fall. It proposes no less than a complete overhaul in cancer policy. "We need to integrate our current fragmented and piecemeal system of addressing cancer. Front and center in our current system are the troubling divisions that separate research, prevention and treatment," Kennedy said in a Senate hearing in June.
The New Paradigm
These are precisely the kinds of challenges that gave rise to Stand Up to Cancer, the advocacy group organized by CBS newscaster Katie Couric and eight other women, all of them connected to Hollywood, including Spider-Man producer Laura Ziskin, who has breast cancer. Says Couric, who lost her husband and sister to cancer: "It was clear to me and other people that this borders on the ridiculous. You ask yourself: What can be done?" SU2C has a scheduled Sept. 5 launch with an unprecedented three-network simulcast, hosted by Couric, Brian Williams and Charles Gibson. It features a roster of stars, including a performance by cancer survivor Melissa Etheridge and a film by Errol Morris (who produced Standard Operating Procedure, an acclaimed documentary about Abu Ghraib abuses). "I will make you laugh," says Ziskin, who produced the show. "I will definitely make you cry." But so, too, would any name-your-disease telethon.
It's what happens next that is different. SU2C will not distribute funds to research institutions. Instead, it will assemble dream teams of scientists across disciplines and institutions, and they will work collaboratively on projects designed to deliver a product of sorts--as opposed to an academic paper--within a defined time period. Says Ziskin: "They can only get funded if they can produce a treatment."
To vet and choose the projects, SU2C has recruited a high-powered scientific advisory committee chaired by Phillip Sharp, a Nobel Prize--winning cancer researcher at MIT. The selected projects will then be monitored by the American Association for Cancer Research. "What I hope to do is identify areas where we could accelerate progress, particularly in areas where there's need--ovarian, pancreatic, glioblastoma," says Sharp.
Additionally, 20% of the funds raised will go to higher-risk projects with potentially greater paybacks. It's a science version of throwing it long. "If you run the same play every time, you're not going to win the game," says Armstrong. One of SU2C's advisers was the late Judah Folkman, a famed cancer scientist whose pathbreaking theory that tumors grow via angiogenesis (creating their own blood supply) was resisted for decades. "There may be other Judah Folkmans out there," says Ziskin. "We don't want them wandering around for 40 years."
SU2C is not the only independent group shaking things up. The Multiple Myeloma Research Foundation used a pay-for-results funding model that has more to do with Silicon Valley than Big Pharma to support research that in four years got four new treatments to patients--Thalomid, Velcade, Revlimid and Doxil. That's about six years faster than the decade it usually takes for such drug development and rollout. Multiple myeloma is a rare cancer of the bone marrow that sickens about 20,000 Americans each year--precisely the uncommon form of the disease that often falls into the research cracks. The MMRF benefited from the aggressive work of founder Kathy Giusti, a multiple-myeloma survivor and former pharmaceutical executive. When she and her group first raised enough money to start funding research, she faced a feeding frenzy of research applicants. "They will do what they have to do to get grant money. They're desperate," she says.
The MMRF made sure it got the most from its grant dollars by adopting an enforced-collaboration model in 2004, linking work at four cancer centers into a consortium managed by PricewaterhouseCoopers and providing them all with patients, tissue samples and a set of targets and goals. "The odds of a cure coming from one center are nil," Giusti says. "You need a mutual fund to fight cancer." From not having a single drug in the pipeline, the MMRF now has 30, half of them in clinical trials. The average lifespan of a multiple-myeloma patient has been extended by three years, to seven.
If the MMRF model works for a single, specialized cancer, it's not clear that a group like Stand Up to Cancer--which is casting a far wider research net--will show the same results. But clinicians say it's worth trying. "There needs to be a mechanism whereby we can bring groups of people together from different institutions in one group," says DuBois, who is part of SU2C's scientific panel. At the same time, there is hope that the 20% of grants SU2C is setting aside for outside-the-box research will yield something semimiraculous.
The strategy is often compared to that of the Manhattan Project, which produced the first atom bomb, or the Apollo program, which put astronauts on the moon. Some worry that it oversimplifies things. "This isn't an engineering problem," says the NIH's Harris. "It's a problem in which we know only parts of the solution."
But more communication among scientists is always better than less, and besides, there may be more engineering to beating cancer than people realize. MIT, which knows a thing or two about designing things, is building a $100 million research center that will put together biologists and chemists with engineers skilled in such arts as nanofabrication. "We are going to breed a group of people who are totally aware of the cancer problem and totally aware of the modern tools and computational powers of engineers," says Sharp.
MIT plans to make dream-team proposals, which Sharp views as a chance to loose the forces of science on the particularly diabolical forms of cancer. One of MIT's strategies is to build nanomolecules that, when injected into the body, can hunt for cancer cells, bind to them and deliver therapies directly to the bad cells; or to build nanomolecules that could locate abnormal genes and silence them. "It's MIT," says Sharp. "We shake and bake."
None of this absolves the rest of us from our own behavior. Think of all those fools standing in front of office buildings and restaurants grabbing a cigarette. Think of our national epidemic of obesity, which researchers believe has many links to cancer.
Cancer has become a little too familiar to us, too much a part of our social fabric. We embrace it with runs and walks and swims and bike rides that bring people together to raise funds and hopes and share their grief. "It's tough. We are a very optimistic organization, and all of our materials are about living every day to the fullest and living strong and fighting cancer. But at the end of the day, if you look at what's happened, some would argue that we haven't been that successful," says LAF's Ulman.
At a Livestrong ride, run and walk in the Philadelphia area, some 5,000 people took part on a beautiful summer day to raise $3 million for the LAF. "These aren't fun runs," says Armstrong. "They are very emotional, tearful times." Some participants had cancer; some were survivors. And most of those who rode by bore on their backs the names of dead relatives, a rolling graveyard passing through the placid Pennsylvania countryside.