Archive for the 'Cancer' Category

25
Jan
11

big, big health bills down the road

The other shoe dropped today. The first one dropped a couple of weeks ago when the Journal of the National Cancer Institute (JNCI) published: “Cancer Care Costs in the United States: 2010–2020.”
The estimated total cost of cancer care in the United States in 2020 is expected to be $158 billion assuming the most recent observed patterns of incidence, survival, and cost remain the same. This represents a 27% increase from 2010 due only to the projected aging and growth of the US population, according to a study published online January 12th in The Journal of the National Cancer Institute. However, the authors also note the cost of cancer care could rise even more quickly under some reasonable assumptions such as a 2% annual increase in costs of the initial and final phases of cancer care. […] Under a different scenario of continuing trends in cancer incidence, survival, and costs of care, the total cost of cancer care in 2020 is expected to be $173 billion, an even larger increase (39% from 2010).
That was shoe #1. Shoe #2 slammed to the floor when I read on physorg.com today: “Cost to treat heart disease in United States will triple by 2030.”
“Despite the successes in reducing and treating heart disease over the last half century, even if we just maintain our current rates, we will have an enormous financial burden on top of the disease itself,” said Paul Heidenreich, M.D., chair of the American Heart Association expert panel issuing the statement. […] Between 2010-30, the cost of medical care for heart disease (in 2008 dollar values) will rise from $273 billion to $818 billion, the authors predicted. “We were all surprised at the remarkable increase in costs that are expected in the next two decades,” Heidenreich said. “We need to continue to invest resources in the prevention of disease, the treatment of risk factors and early treatment of existing disease to reduce that burden.”
And, heck, there are more shoes to come. Some projections show Alzheimer’s disease increasing by 40% just between 2000 and 2025. The cost in dollars and in stress of that disease is huge. Just to round things out, an article in USA Today a couple of weeks ago put a big price-tag on obesity:

The total economic cost of overweight and obesity in the United States is $270 billion per year while the cost in Canada is about $30 billion a year, a new study shows. […] The $300 billion total cost in the United States and Canada is the result of: increased need for medical care ($127 billion); loss of worker productivity due to higher rates of death ($49 billion); loss of productivity due to disability of active workers ($43 billion); and loss of productivity due to total disability ($72 billion), said the Society of Actuaries (SOA).

That’s not even counting the long-term cost of obesity on the upcoming generation. A Stanford Medical Center publication lists among the effects of obesity: high blood pressure, diabetes, heart disease, joint problems, cancer, sleep apnea, metabolic syndrome, psychological problems…among other things. Some project that the current generation my be the first in US history to actually live shorter lives, on average, than their parents.
I worked 40 years in public health, 35 of them in a cancer organization. Never in my career did I hear a serious discussion of the economics of cancer, the aggregate cost of research and treatment, nor what, if any, unintended consequences might result in the bigger picture of healthcare in society. No one raised the question of whether surviving one disease just make people candidates for other problems just as dire. In the cancer community the goal these days is not to get rid of the disease entirely — a goal that it took a long time to realize isn’t feasible in the foreseeable future — but to make cancer a disease that no one dies from. So the result will be that cancer “survivors” will be shifted over to die eventually of something else: heart disease, maybe, or Alzheimer’s. Just as long as death isn’t from cancer, it’s a victory…of sorts.
My point is not that relieving the burdens of disease is an unworthy goal. But during the 20th century medicine fragmented into dozens of specialized professions, advocacy groups, and agencies, all pushing the envelope of what they want to achieve. It’s time for all concerned to step back and determine what expectations are realistic and what the consequences are. We’re now in a huge political hassle over the cost of future health care and who’s going to pay it. The data above indicate the price will be great. It’s time for well-intended advocates to include in their mission wrestling with the real-world issue of making their ambitions feasible with finite resources.
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11
Nov
10

Cancer reading of interest

I saw a review today in the NY Times of Dr. Siddhartha Mukherjees’s book, The Emperor of All Maladies. Supposedly it’s a “biography” of cancer. Evidently he recounts the changing historical conceptions of cancer and the efforts to deal with the disease. Since I worked in the field for 36 years I guess that qualifies as being a part of that history, or at least the recent part.

What interests me is that the reviewer, Janet Maslin, quotes the doctor as saying in the book:

Cancer is a flaw in our growth, but this flaw is deeply entrenched in ourselves…We can rid ourselves of cancer, then, only as much as we can rid ourselves of the processes in our physiology that depend on growth — aging, regeneration, healing, reproduction.

Maslin criticizes the statement as being an “oversimplification”. In what respect? I fully agree with the statement in that cancer comes from the errors inherent in our physiological cell processes or damage to those processes induced by outside influences. Cancer could only be eliminated if our cells ran perfectly for decades or were able to fix every error perfectly. Our cells do a heck of a job, but the reality is that over the long course of our lives errors creep in. I don’t think that overcoming flaws in basic processes can be done (although I don’t want to rule out amazing technologies that might be developed many decades out), so, as I’ve said before, goals and expectations about cancer need to get real.

There’s a kind of upside to the magnitude of the cancer problem. The fear of cancer had driven people to open up their wallets and the treasury to do a huge amount of bio-medical research. All of it contributes to the vast amount of knowledge needed to deal with many maladies and to understand our very nature. There’s still a long way to go. I sometimes wonder where we’d be in life knowledge and medicine without the terror of cancer. Human beings don’t seem very interested in knowledge if it doesn’t have a direct benefit to them.

p.s.: When I was working I’d whip out a credit card and order a book like this from Amazon immediately. Now, however, I’ve got a library card. I went online and placed a hold on the book. After 15 people ahead of me read one of the copies I’ll get hold of it and save the $16.95.

29
Jun
10

Uh-oh. In the minority…again

After my last post about the Australian scientist, Frank Fenner’s, apocalyptic prediction that humans would be extinct in 100 years — give or take a few — I decided to look around at how optimistic or pessimistic others are about the future. I didn’t have to look far. Today I ran across a survey by the Pew Research Center for People and the Press for Smithsonian.com about how optimistic Americans are about the next 40 years.

Well, Americans are plenty optimistic. The Pew summary starts: “Imagine a future in which cancer becomes a memory, ordinary people travel in space, and computers carry on conversations like humans.”

OK, I can do that! After all, I’ve been reading forecasts like that going back the the 1950s. Popular Science magazine did a lot of lists of what was going to happen and great drawings of people doing things like riding moving sidewalks. And, sure enough, 50 years later when I go to the airport there’s a moving sidewalk.

The other part of the survey intro is not so rosy, however: “Now imagine a darker future – a world beset by war, rising temperatures and energy shortages, one where the United States faces a terrorist attack with nuclear weapons.” Indeed, the survey is a mixture of up and down votes.

Many Americans see dramatic scientific and technological advancements on the horizon, with big developments in medicine, engineering, space travel and computers. However, despite the widely anticipated scientific breakthroughs – including the elimination of fossil fuels and gas-powered cars – the public foresees a  grim environmental future. Rising world temperatures, more polluted oceans and severe water shortages in the U.S. are seen as definite or probable over the next 40 years.

The survey is worth taking a look at. For my money, however, many of the questions frame the issues in such simplistic language that I wonder what people really intend with their limited answer choices. For instance, having been in the field of cancer public health for over 35 years I cringe when I see people were asked: “How likely do you think it is that…there will be a cure for cancer?” Seventy-one percent answered they thought definitely or probably cancer would be cured.

When I went to work for a cancer organization 36 years ago we had a slogan: “We’re going to wipe out cancer in your lifetime.” Today members of the cancer science and medical community are just happy that a sustained downward trend in cancer mortality is finally occurring. We stopped talking about “wiping out” cancer about 20 years ago. And oncologists are loath to even use the term “cure” when talking about outcomes for disseminated cancer. In fact, few people know it, but the goal of many in the cancer community these days is to make cancer predominantly a chronic disease rather than an acute, fatal disease. In other words success over the next few decades would be to enable the majority of patients with a wide range of cancer types to survive one or more bouts with the disease and die of something else. That’s a laudable goal, but it’s not anywhere near “wipe out.”

To think of cancer as one disease for which there will be a universal “cure” — that’s what the phrasing of the question implies — is kind of a throwback to the naive idea of several decades ago that cancer can be eradicated. It’s a basic misunderstanding of the disease. Unlike communicable disease, cancer is not something that attacks you from outside; it’s a malfunction of essential processes at the core of cellular life. I recall a breast cancer researcher who said every time a cell divides there’s a little risk of heading towards cancer.

Progress is being made these days, but the lengthy process of testing new approaches not to mention the enormous costs associated with recent cancer treatments means that there a huge obstacles besides the disease itself to having a big impact on the population. So, the last day I was in my office when I retired six months ago, I found myself reassuring some young staff who were just starting their careers that there would still be a big cancer problem for decades to come. In other words, they’re not going to have to change careers because a sudden “cure” arrives.

The Pew survey suggests to me that the public is finally adjusting to the reality that dealing with cancer will take much longer than anyone could imagine a few decades ago. The figure showing that in 2010 71% of respondents expecting a cure is down from 81% in 1999. A drop in the number of people expecting a cancer cure in the next 40 years may not be “pessimism” but a more realistic assessment of the situation instead.

I think people who have in-depth information about any of the questions asked in the Pew survey would have questions about interpreting what the answers mean. While surveys like this tend to suggest optimism is good and preferable to pessimism, the fact is that skepticism often reflects a grasp of reality.

Among the other opinions expressed by the survey group are:

  • In 40 years computers will converse like people.
  • Artificial limbs will work better than natural ones.
  • Most of our energy will not come from oil, coal and gas.
  • The world will get warmer.
  • We’ll have a major energy crisis.

These findings reflect the subjects’ attitudes and aspirations than they are an analysis of the future. Most of the challenges to be faced during the 21st century will be massive processes not seen in the history of the Earth. There’s really no precedent for the confluence of forces unfolding in our time.

One final thing. Forty-one percent of the respondents to the Pew survey expect Jesus Christ to return to Earth some time in the next forty years. That would make moot the dire speculation by Fenner that the human species will become extinct in the next 100 years wouldn’t it?

14
May
10

Paging Dr Nano…

I’m kind of obsessed with the nanoscale world because it’s the scale at which basic living systems start. The macromolecules of cells — the building blocks of organisms — are really doing meaningful processes down at the nanoscale.

Nanotechnology — the technology of things designed and engineered down to the molecular and atomic level — is beginning to show signs for remarkable devices not far from going on the market. And one of the first, robust markets for nanotech is going to be medical nanotechnology, especially for cancer. I’ve been watching this for a few years years now.

I recently stumbled across a nanotechnology newsletter I hadn’t seen before: Nanowerk. It’s a European site focused on technology developments in European countries. Every country with healthy science and technology resources is steaming ahead with nanotech R&D in anticipation of huge future development. The newsletter circulates 10 to 20 briefs per day.

An article from May 4 really got my attention. It’s titled: “Informatics moves into nanomedicine,” and reports on research recently published in Pediatric Research. There are what I think are some interesting assertions about the near future of the field.

…some nanoparticles and nanodevices have already been approved or are about to be approved by the United States Food and Drug Administration, including, for example, superparamagnetic nanoparticles to detect metastases in some types of cancer or new devices that combine microfluids or nanosensors to detect tumours.

These applications of nanomaterials open up new prospects for personalized medicine, the authors add, indicating that classical clinical studies need to be redesigned to adapt to the advances taking place in genomics, proteomics and pharmacogenetics. “The introduction of nanoparticles that can target different molecules or groups of atoms with high precision can significantly advance the personalization of clinical procedures”, the article says.

But the statement that blew my mind is:

The possibility of biomolecular devices acting not only in vitro but also in vivo within diseased human organisms is also opening up new prospects, where biomolecular automata could even intervene to intelligently deliver drugs to the diseased regions of the human body just where they are needed.

In this respect, the authors note that research on a “Doctor in a Cell” is already in progress. This is a genetically modified cell that can operate in a human body. It contains a biological computer that can process and analyse external biological signals, emit a diagnosis and deliver the desired molecular therapeutic signal to treat the patient.

The doc-in-a-cell is “already in progress“?! Not exactly the Fantastic Voyage, but close enough to get me excited!

13
May
10

Walgreens blinks

Well, that didn’t take long!

On Tuesday I blogged about Walgreens announcement they were going to start selling a OTC genetics testing kit. I say were… Today they announced that they’re putting that idea on hold. As I predicted, the move started a firestorm and in just two days it was hot enough to get the big retailer to back off.

The FDA and a bunch of doctors and genetics experts piled on and put the brakes on the project.

“These kits have not been proven safe, effective or accurate and patients could be making medical decisions based on data from a test that hasn’t been validated by the FDA,” said agency spokeswoman Erica Jefferson, in an earlier statement Wednesday.

I’m having deja vu. That’s pretty much the same thing that happened when 23andMe and other gene testing companies went public back in ’07. Of course, some of the concerns expressed are not trivial.

The proliferation of consumer-marketed genetic tests has troubled many public health officials and doctors who worry that the products are built on flimsy data.

“The problem with all of these products is they’re based on incomplete, invalidated data and we don’t know what the impact on consumers will be,” said Dr. Muin Khoury, director of the National Office of Public Health Genomics at the Centers for Disease Control and Prevention.

The biology of how DNA variations actually lead to certain diseases is still poorly understood, although a number of public and private institutions have been racing to find answers.

That’s true. One of the themes of this blog is the unexpected complexity of genetic expression that has been uncovered during the past decade. Genetics scientists have been rocked back on there heels to the point of having to rethink some of the earlier assumptions in the field.

It seems that both the public and scientists have held some simplistic assumptions about how genes work. Scientists are making new discoveries nearly every day. So experts say with almost every breath these days: “Genes are not destiny!” Yep, the biology of what happens to us over time is much more complicated than that. So one of the most intriguing questions is: Why aren’t our genes destiny? If our state of being is an interleaving of genetic (internal) influences and environment (external) factors, how do they come together in the organism? That’s a deep issue that will take much more time to plumb. It’s one of those areas where scientists say: “It’s not fully understood.” (That’s science-speak for, “Duh!”)

My thought is that this is an opportunity to bring the public up to date and let them know the puzzle has 1,000 pieces, not 500 as first thought. We have been getting a trickle information about genetics for a couple of decades through media, but that volume is about to increase to a torrent. So where is the effort to help the public have a solid source of up-to-the-minute information? The federal government‘s agencies all have web sites with bits and pieces of the necessary information, but all-in-all the information on genetics is fragmented in a thousand places of variable currency and veracity.

So here’s my wild appeal: As a mainstay of our so-called health care reform effort, let’s extend the charge to our health and scientific agencies (NIH, CDC, NSF, DOE, NLM, etc.) to include making available to the public coordinated, up-to-date, evidence-based information on human biology, health maintenance, medical and scientific frontiers, and a realistic perspective about the circuitous route by which scientific progress is made . Make this available through state-of-the-art communication technology, i.e., the internet and its future derivations. Every citizen, doctor, blogger, teacher, or mom should be able to access reliable information on anything they hear about health in a few swipes of their smartphone. This is a big job and will take money. Surely in the billions budgeted for health care reform in coming decades this would be worthwhile. And this could be an international effort both in information gathering and in paying for it. Health research is global and the findings apply to all of us. The US isn’t going to go to Mars by itself, so why don’t we throw in with all the nations facing the same health issues?

Learning is a process. Walgreens accommodation to the regulators may eventually turn out to be part of something positive.

11
May
10

another volley in the healthcare revolution

The Washington Post is reporting today that a company called Pathway Genomics on is going to start selling through Walgreen’s 6,000 drugstores an over-the-counter kit for testing certain genetic traits.

Beginning Friday, shoppers in search of toothpaste, deodorant and laxatives at more than 6,000 drugstores across the nation will be able to pick up something new: a test to scan their genes for a propensity for Alzheimer’s disease, breast cancer, diabetes and other ailments

The test also claims to offer a window into the chances of becoming obese, developing psoriasis and going blind. For those thinking of starting a family, it could alert them to their risk of having a baby with cystic fibrosis, Tay-Sachs and other genetic disorders. The test also promises users insights into how caffeine, cholesterol-lowering drugs and blood thinners might affect them.

Yeow, that’s going to set off a firestorm! A couple of years ago when companies like 23andMe began to offer tests to consumers the California and New York public health departments and the FDA tried to shut them down. They issued “cease and desist” orders and threatened to charge them with violating various violations of business practice laws. In fact the kerfuffle has already started.

The Food and Drug Administration questioned Monday whether the test will be sold legally because it does not have the agency’s approval. Critics have said that results will be too vague to provide much useful guidance because so little is known about how to interpret genetic markers.

The medical profession is conservative with good reason: lives are at stake. But in all this, in my opinion, is also a component protection of professional prerogatives. Professions in any field don’t give ground to the ordinary person easily.

I’ve had some experience with this. When I started in the cancer field 36 years ago we had two sets of printed literature: one set for the lay public and another for doctors and nurses. You were risking getting fired if you let a cancer patient get hold of the professional literature! The reasons then were the same ones physicians express now about internet information: “they (the public) won’t understand what it means; they will misinterpret it; they’ll suffer anxiety; they might make bad decisions about treatment.” But the internet irreversibly smashed the barrier to access to professional medical information. Doctors are still fighting a rear-guard action and complaining mightily about how it was better in the old days when they were the exclusive source of medical information. I’ve commented on that before.

I’m not dismissing the concerns. No doubt there will unfortunate incidents around these new tests. But what gets me is how unwilling the medical profession is to see the revolution of information that is underway and to rethink the medical paradigm. My pleas is for physicians to start — as a profession — to work on a more equitable and flexible basis with the citizens who want a greater and more equal role in their medical life. We’ll always have a doctor/patient relationship, but I think its going to be much different in the not far distant future.

The internet isn’t going away; instead it’s going to go much, much deeper into our health lives. And genetic tests are not going away either. Like it or not, deep personal knowledge about what lurks in our genes is on the way. Why isn’t the medical profession working with entrepreneurs, patients, futurists, and internet gurus to anticipate what’s coming and do something positive that works for everyone? There’s much, much work to be done, and soon. Without a collaborative movement of innovation and adaptation we’re going to suffer through repeated, time-wasting bouts of friction.

17
Apr
10

the paradigm for the genetics of complex diseases is changing

The structure of part of a DNA double helix

Image via Wikipedia

One of the themes of this blog is that living things are complex and making clinical gains from areas of research such as genetics is just plain hard. There’s been a lot of questioning of genetic research lately, but, as I’ve tried to point out, there are many factors other than plain ol’ DNA involved in finding the way genes manifest in disease. That basic situation got a better expectation this past week when two highly respected genetics researchers at the University of Washington, Mary-Claire King and John McClellan, published an essay in Cell titled, “Genetic Heterogeneity in Human Disease.”

For decades the basic genetics paradigm held that common diseases are caused by common variants (CDCV). That is, to look for genetic causes for cancers the reasonable thing would be to identify genetic variations (mutations) found most often in cancer cases. That makes sense, but it turns out that finding these common genetic variations is not enough to explain all the disease. King and McClellan say:

…from the perspective of genetics, we suggest that complex human disease is in fact a large collection of individually rare, even private, conditions…In molecular terms, we suggest that human disease is characterized by marked genetic heterogeneity, far greater than previously appreciated. Converging evidence for a wide range of common diseases indicates that heterogeneity is important at multiple levels of causation: (1) individually rare mutations collectively play a substantial role in causing complex illnesses; (2) the same gene may harbor many (hundreds or even thousands) different rare severe mutations in unrelated affected individuals; (3) the same mutation may lead to different clinical manifestations (phenotypes) in different individuals; and (4) mutations in different genes in the same or related pathways may lead to the same disorder.

There’s a huge idea here: Complex human diseases involve sets of complex genetic variations, so many, in fact, that each person’s case of a disease may have individual characteristics. We accept the idea that each individual is unique, but it’s perhaps surprising to think that your case of cancer, for instance, may bear individual characteristics.

The overall magnitude of human genetic variation, the high rate of de novo mutation, the range of mutational mechanisms that disrupt gene function, and the complexity of biological processes underlying pathophysiology all predict a substantial role for rare severe mutations in complex human disease. Furthermore, these factors explain why efforts to identify meaningful common risk variants are vexed by irreproducible and biologically ambiguous results.

Next-generation sequencing provides its own challenges. Whole-genome sequencing strategies detect hundreds of thousands of rare variants per individual (McKernan et al., 2009). Biological relevance must be established before a mutation can be causally linked to a disorder. The critical question is not whether cases as a group have more rare events than controls; but rather which mutation(s) disrupting a gene is responsible for the illness in the affected person harboring the variant. Variable penetrance, epistasis, epigenetic changes, and gene-environment interactions will complicate these efforts. It will be fun to sort out. [Emphasis mine.]
So, as I’ve remarked before, life is complicated. Living systems are the most complex things we know of in the universe, and we’re only now beginning to explore them in detail. We want results to save us now! But it’s going to be some time before we fully understand diseases like cancer and then a long time ’till effective therapies are widely available. Moreover, we have no idea what it’s all going to cost, and, as our recent rancorous debate on health care demonstrates, cost is no trivial matter.



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