Monthly Archives: March 2014
Influenza affects up to 15% of adults and 30% of children each flu season and early indications suggest we could be facing a severe season. The 2014 seasonal influenza vaccination is available from today…
Influenza affects up to 15% of adults and 30% of children each flu season and early indications suggest we could be facing a severe season. The 2014 seasonal influenza vaccination is available from today. So, what strains does it protect against and who should be vaccinated?
What is influenza?
There are two major types in humans – influenza A and influenza B, with the A strain causing more severe disease. Influenza B, however, causes a disproportionate amount of illness in children.
The virus also has many animal hosts including birds, pigs and horses. Genetic mixing between human and animal strains can cause new pandemic strains, to which humans have little or no pre-existing immunity. This susceptibility gives rise to rapid spread, high rates of illness and more severe disease.
Once new strains emerge in humans, they become established as seasonal variants in the population and tend to cycle over the years, with different strains dominating each year. The seasonal flu viruses we see now were once pandemic strains.
Seasonal influenza viruses mutate continually, so the vaccine needs to be updated annually to match the expected strains.
The commonly used vaccine (trivalent, inactivated influenza vaccine or TIV) covers three strains: two types of influenza A and a single influenza B strain. Protection is strain-specific, so the vaccine will generally only provide good protection against the included strains.
Each year the World Health Organization evaluates the data on circulating viruses and decides on which strains should be covered in the vaccine. Influenza is, however, unpredictable, and sometimes a strain which is not covered in the vaccine can emerge during the flu season.
In 2014 the vaccine includes:
- an A/California/7/2009 (H1N1) pandemic 2009-like strain (similar to swine flu)
- an A/Texas/50/2012 (H3N2)-like strain
- and a B/Massachusetts/2/2012-like strain.
Influenza vaccine is an inactivated product, so it cannot cause the flu. The vaccines are safe and effective, although one brand, Fluvax, is not approved for children under the age of five years because of an increased risk of febrile seizures.
There is now a quadrivalent influenza vaccine (QIV) available, which has the same strains as the trivalent plus protection against an additional influenza B strain. There are two major circulating lineages of influenza B, and research shows that the TIV matches the circulating B strain only 50% of the time. As such, the QIV offers greater protection against influenza B.
Should I get vaccinated?
The government recommends – and funds – the influenza vaccination for all people aged 65 years and older, Aboriginal and Torres Strait Islander people aged 15 years or older, pregnant women and anyone over six months of age with a medical condition that predisposes to complications of influenza.
These conditions include heart disease, respiratory disease, chronic illnesses including diabetes, kidney disease, asthma, immunosuppression and chronic neurological conditions. Children on long-term aspirin therapy should also be vaccinated.
Pneumonia is a common complication of influenza, so people in these at-risk groups, along with infants and over-65s, are also recommended to have the pneumococcal vaccine.
The rates of influenza vaccination for people aged 65 years and over are high, but people aged less than 65 years with medical risk factors are less likely to be vaccinated. Only 30-50% of people with risk factors get vaccinated each year.
Research shows the influenza vaccine can also protect against heart attacks. Given that ischaemic heart disease is the leading cause of illness and death in the world, the impact of influenza vaccine in preventing heart attacks could be significant on a population level.
The 2014 flu season
We often see the strain that dominated in the northern hemisphere in December-January appear in our winter. The major circulating strain in the United States this past winter was the pandemic H1N1 (swine flu) strain, which has a different pattern to usual seasonal influenza, in that it affects people aged 24 to 64 years more than people at the extremes of age.
Usually, other strains of seasonal influenza affect the extremes of age most – the very young and the very old. Others who are more at risk with the pandemic H1N1 are pregnant women, people who are obese, and Aboriginal and Torres Strait Islander people.
Flu seasons typically cycle between mild and severe epidemic years. The last severe influenza season in Australia was in 2009, the year of the pandemic swine flu, and we’ve have had mild to moderate flu seasons since.
This, coupled with the fact we’ve had an early start to the flu season in 2014 (with higher case numbers compared to the same time in previous years) suggests we could have a severe season in 2014.
Anyone in the groups recommended for vaccination on the National Immunisation Program schedule should get vaccinated as soon as possible.
The Top 10 Insights from the “Science of a Meaningful Life” in 2013
The past few years have been marked by two major trends in the science of a meaningful life.
One is that researchers continued to add sophistication and depth to our understanding of positive feelings and behaviors. Happiness is good for you, but not all the time; empathy ties us together, and can overwhelm you; humans are born with an innate sense of fairness and morality, that changes in response to context. This has been especially true of the study of mindfulness and attention, which is producing more and more potentially life-changing discoveries.
The other factor involves intellectual diversity. The turn from the study of human dysfunction to human strengths and virtues may have started in psychology, with the positive psychology movement, but that perspective spread to adjacent disciplines like neuroscience and criminology, and from there to fields like sociology, economics, and medicine. Across all these fields, we’re seeing more and more support for the idea that empathy, compassion, and happiness are more than you-have-it-or-not capacities, but skills that can be cultivated by individuals and by groups of people through deliberate decisions.
In 2013, the UC Berkeley Greater Good Science Center is now part of a mature, multidisciplinary movement. Here are 10 scientific insights published in peer-reviewed journals from the past year that we anticipate will be cited in scientific studies, help shift public debate, and change individual behavior in the year to come.
A meaningful life is different—and healthier—than a happy one.
The research we cover here at the Greater Good Science Center is often referred to as “the science of happiness,” yet our tagline is “The Science of a Meaningful Life.” Meaning, happiness—is there a difference?
New research suggests that there is. When a study in the Journal of Positive Psychology tried to disentangle the concepts of “meaning” and “happiness” by surveying roughly 400 Americans, it found considerable overlap between the two—but also some key distinctions.
Based on those surveys, for instance, feeling good and having one’s needs met seem integral to happiness but unrelated to meaning. Happy people seem to dwell in the present moment, not the past or future, whereas meaning seems to involve linking past, present, and future. People derive meaningfulness (but not necessarily happiness) from helping others—being a “giver”—whereas people derive happiness (but not necessarily meaningfulness) from being a “taker.” And while social connections are important to meaning and happiness, the type of connection matters: Spending time with friends is important to happiness but not meaning, whereas the opposite is true for spending time with loved ones.
And other research published in the Proceedings of the National Academy of Sciences suggests that these differences might have important implications for our health. When Barbara Fredrickson and Steve Cole compared the immune cells of people who reported being “happy” with those of people who reported “a sense of direction and meaning,” the people leading meaningful lives seemed to have stronger immune systems.
The emotional benefits of altruism might be a human universal.
One of the most significant findings to have emerged from the sciences of happiness and altruism has been this: Altruism boosts happiness. Spending on others makes us happier than spending on ourselves—at least among the relatively affluent North Americans who have participated in this research.
But a paper published in the Journal of Personality and Social Psychology suggested that this finding holds up around the world, even in countries where sharing with others might threaten someone’s own subsistence.
In one study, the researchers examined data of more than 200,000 people from 136 countries; they determined that donating to charity in the past month boosts happiness “in most individual countries and all major regions of the world,” cutting across cultures and levels of economic well-being. It was even true regardless of whether someone said they’d had trouble securing food for their family in the past year.
When the researchers zeroed in on three countries with vastly different levels of wealth—Canada, Uganda, and India—they found that people reported greater happiness recalling a time when they’d spent money on others than when they’d spent on themselves. And in a study comparing Canada and South Africa, people reported feeling happier after donating to charity than after buying themselves a treat, even though they would never meet the beneficiary of their largess. This suggests to the researchers that their happiness didn’t result from feeling like they were strengthening social connections or improving their reputation but from a deeply ingrained human instinct.
In fact, they argue, the nearly universal emotional benefits of altruism suggest it is a product of evolution, perpetuating behavior that “may have carried short-term costs but long-term benefits for survival over human evolutionary history.”
Mindfulness meditation makes people more altruistic—even when confronted with barriers to compassionate action.
In March, the GGSC hosted a conference called “Practicing Mindfulness & Compassion,” where speakers made the case that the practice of mindfulness—the moment-by-moment awareness of our thoughts, feelings, and surrounding—doesn’t just improve our individual health but also makes us more compassionate toward others. Coincidentally, just weeks after the conference, two new studies bolstered this claim.
The first study, published in Psychological Science, found that people who took an eight-week mindfulness meditation course were significantly more likely than a control group to give up their waiting-room seat for a person on crutches. This was true despite the fact that other people in the waiting room (who were secretly working with the researchers) didn’t acknowledge the person in need or make any gesture to give up their own seats; prior research suggests that this kind of inaction strongly deters bystanders from helping out, but that wasn’t the case when the bystanders had received training in mindfulness.
A few weeks later, another study published in Psychological Science echoed that finding. In this second study, which was unrelated to the first, people who had practiced a mindfulness-based “compassion meditation” for a total of just seven hours over two weeks were significantly more likely than people who hadn’t received the training to give money to a stranger in need. What’s more, after completing their training, the meditation group showed noticeable changes in brain activity, including in networks linked to understanding the suffering of others.
“Our findings,” write the authors of the second study, “support the possibility that compassion and altruism can be viewed as trainable skills rather than as stable traits.”
Meditation changes gene expression.
Are genes destiny? They certainly influence our behavior and health outcomes—for example, one study published in 2013 found that genes make some people more inclined to focus on the negative. But more and more research is revealing how it’s a two-way street: Our choices can also influence how our genes behave.
In 2013, a collaborative project between researchers in Spain and France and at the University of Wisconsin found that when experienced meditators meditate, they quiet down the genes that express bodily inflammation in response to stress.
How did they figure this out? Before and after two different retreat days, the researchers drew blood samples from 19 long-term meditators (averaging more than 6000 lifetime hours) and 21 inexperienced people. During the retreat, the meditators meditated and discussed the benefits and advantages of meditation; the non-meditators read, played games, and walked around.
After this experience, the meditators’ inflammation genes—measured by blood concentrations of enzymes that catalyze or are a byproduct of gene expression—were less active. Blood samples from the people in the leisure-day condition did not show these changes.
Why does this matter? The researchers also looked at their study participants’ ability to recover from a stressful event. Long-term meditators’ ability to turn down inflammatory genes, it turns out, predicted how quickly stress hormones in their saliva diminished after a stressful experience—a sign of healthy coping and resilience that can potentially lead to a longer life.
This is good news to people who come from a family of stress cases who are stress-prone themselves: There are steps you can take to mitigate the impact of stressful events. Hard as it may be to find time or get excited about meditating, mounting evidence suggests that it can offer more concrete advantages to a healthy life than the leisurely activities we more readily seek.
Mindfulness training improves teachers’ performance in the classroom.
For educators grappling with students’ behavioral problems and other sources of stress, new research suggested an effective response: mindfulness.
Although mindfulness-based programs are not uncommon in schools these days, they’ve mainly been deployed to enhance students’ social, emotional, and cognitive skills; only a handful of programs and studies have examined the benefits of mindfulness for teachers, and in those cases, the research has focused largely on the general benefits for teachers’ mental health.
But in 2013, researchers at the University of Wisconsin’s Center for Investigating Healthy Minds broke new ground when they studied the impact of an eight-week mindfulness course developed specifically for teachers, looking not only at its effects on the teachers’ emotional well-being and levels of stress but also on their performance in the classroom.
They found that teachers randomly assigned to take the course felt less anxious, depressed, and burned out afterward, and felt more compassionate toward themselves. What’s more, according to experts who watched the teachers in action, these teachers ran more productive classrooms after completing the course and improved at managing their students’ behavior as well. The results, published in Mind, Brain, and Education, show that stress and burnout levels actually increased among teachers who didn’t take the course.
The researchers speculate that mindfulness may carry these benefits for teachers because it helps them cope with classroom stress and stay focused on their work. “Mindfulness-based practices offer promise as a tool for enhancing teaching quality,” write the researchers, “which may, in turn, promote positive student outcomes and school success.”
There’s nothing simple about happiness.
Who doesn’t want to be happy? Happy is always good, right?
Sure. Just don’t be too happy, OK? Because June Gruber and her colleagues analyzed health data and found that it’s much better to be a little bit happy over a long period of time than to experience wild spikes in happiness. Another study, published in the journal Emotion, showed how seeking happiness at the right time may be more important than seeking happiness all the time. Instead, allowing yourself to feel emotions appropriate to a situation—whether or not they are pleasant in the moment—is a key to long-lasting happiness.
In a study published earlier in the year in the journal Psychological Science, Sonja Lyubomirsky and Kristin Layous found that not all research-approved happiness practices work for everyone all the time. “Let’s say you publish a study that shows being grateful makes you happy—which it does,” Lyubomirsky recently told us. “But, actually, it’s much harder than that. It’s actually very hard to be grateful, and to be grateful on a regular basis, and at the right time, and for the right things.” She continued:
So, for example, some people have a lot of social support, some people have little social support, some people are extroverted, some people are introverted—you have to take into account the happiness seeker before you give them advice about what should make them happy. And then there are factors relevant to the activity that you do. How is it that you’re trying to become happier? How is it that you’re trying to stave off adaptation? Are you trying to appreciate more? Are you trying to do more acts of kindness? Are you trying to savor the moment? The kind of person you are, the different kinds of activities, and how often you do them, and where you do them—these are all going to matter.
The bottom line might be that if happiness were really that simple, we’d all be happy all the time. But we’re not, and that appears to be because there is no rigid formula for happiness. It’s a state that comes and goes in response to how we’re changing and how our world is changing.
Gratitude can save your life.
Or at least help lessen suicidal thoughts, says a study published in the Journal of Research in Personality.
Across a four-week period, 209 college students answered questions to measure depression, suicidal thoughts, grit, gratitude, and meaning in life. The idea was to see if the positive traits—grit and gratitude—mitigated the negative ones. Since depression is a large contributing factor to suicide, they controlled for that variable throughout the study.
Grit, said the authors, is “characterized by the long-term interests and passions, and willingness to persevere through obstacles and setbacks to make progress toward goals aligned or separate from these passionate pursuits.” It stands to reason that someone with lots of grit wouldn’t waste much time on suicidal thoughts.
But what about gratitude? That entails noticing the benefits and gifts received from others, and it gives an individual a sense of belonging. That should make life living—and, indeed, the researchers found that gratitude and grit worked synergistically together to make life more meaningful and to reduce suicidal thoughts, independent of depression symptoms.
As the authors note, their study has huge clinical implications: If therapists can specifically foster gratitude in suicidal people, they should be able to increase their sense that life is worth living. This new finding adds to a pile of new research on the benefits of gratitude. Saying “thanks” can make you happier, sustain your marriage through tough times, reduce envy, and even improve physical health.
Employees are motivated by giving as well as getting.
Over the past two decades, work satisfaction has declined, while time spent at work has significantly increased. Not a good combination!
Would paying people more money help? Some studies have shown that rewarding employees for their hard work and late nights at the office with a bonus will make things a little better and quiet dissatisfaction. But in September, through the collaborative research of Lalin Anik, Lara B. Aknin, Michael I. Norton, Elizabeth W. Dunn, and Jordi Quoidbach, we learned that employee bonuses might have the most positive effects when they’re spent on others. The researchers suggested an alternative bonus offer that has the potential to provide some of the same benefits as team-based compensation—increased social support, cohesion, and performance—while carrying fewer drawbacks.
Their first experiment focused on broad, self-reported measures of the impact of prosocial bonuses on an employee’s job satisfaction. They were either given a bonus to spend on charity or were not given a bonus at all. Those who gave to charities reported increased happiness and job satisfaction. The second experiment was conducted in two parts—both focused on “sports team orientation” by looking at the difference between donating to a charity or a fellow employee—and attempted to see if these improved actual performance. In the first part of the experiment, these participants were given $20 and told to spend it on a teammate or on themselves over the course of the week. In the second part of this experiment, they were instructed to spend $22 on themselves or on a specified teammate over the course of the week. Both of these experiments found more positive effects for givers than those who spent the $22 on themselves.
This collaborative research indicates that prosocial bonuses can benefit both individuals and teams, on both psychological and “bottom line” indicators, in both the short and long-term. So when you receive your bonus this year, you might want to think twice before buying those pair of shoes you’ve been dying for, instead consider spending it on someone else—because, according to this research, you’ll probably be much happier and more satisfied with your job.
Subtle contextual factors influence our sense of right and wrong.
An out-of-control train will kill five people. You can switch the train onto another track and save them—but doing so will kill one person. What should you do?
A series of experiments published in the journal Psychological Science suggests that on one day you’ll divert the train and save those five lives—but on another you might not. It all depends on how the dilemma is framed and how we’ve been thinking about ourselves.
Through the train dilemma and other experiments, the study revealed two factors that can influence our moral decisions. The first involves how morality has been defined for you, in this case around consequences or rules. For example, when researchers asked participants to think in terms of consequences, some readily diverted the train, thus saving four lives. On the other hand, those who prompted to think in terms of rules (e.g., “thou shalt not kill”) let the five die. But that factor was influenced by another that depends on memory and whether your past ethical or unethical behavior is on your mind—a memory of a good deed might make you more likely to cheat, for example, if urged to think of consequences. It’s the complex interaction between those two factors that shapes your decision.
That wasn’t the only study published during the past year that revealed how susceptible we are to context. One study found that people are more moral in the morning than in the afternoon. Another study, cleverly titled “Hunger Games,” found that when people are hungry, they express more support for charitable giving. Yet another experiment discovered that thinking about money makes you more inclined to cheat at a game—but thinking about time keeps you honest.
The bottom line is that our sense of right and wrong is heavily influenced by seemingly trivial variables in memory, in our bodies, and in changes within our environment. This doesn’t necessarily lead us to pessimistic conclusions about humanity—in fact, knowing how our minds work might help us to make better moral decisions.
Anyone can cultivate empathic skills—even psychopaths.
In daily life, calling someone a “psychopath” or a “sociopath” is a way of saying that the person is beyond redemption. Are they?
When neuroscientist James Fallon accidentally discovered that his brain resembled that of a psychopath—showing less activity in areas of the frontal lobe linked to empathy—he was confused. After all, Fallon was a happily married man, with a career and good relationships with colleagues. How could he be beyond redemption?
Additional genetic tests revealed “high-risk alleles for aggression, violence and low empathy.” What was going on? Fallon decided he was a “pro-social psychopath,” someone whose genetic and neurological inheritance makes it hard for him to feel empathy, but who was gifted with a good upbringing and environment—good enough to overcome latent psychopathic tendencies.
This self-description found support in a study published this year by Swiss and German researchers, which showed education levels and “social desirability” seemed to improve empathy in diagnosed psychopaths. Another new study found that empathy deficits don’t necessarily lead to aggression.
It seems that psychopaths can be taught to feel empathy and compassion, though they have a disability that makes developing those skills difficult. When a team of researchers looked at the brain activity of psychopathic criminals in the Netherlands, for example, they discovered the predictable empathic deficits. But they also found that it made a difference in their brains to simply ask the criminals to empathize with others—hinting that empathy may be repressed rather than missing entirely in people classified as psychopaths. For some, at least, it may help a great deal to lift that repression.
Psychopathy remains an intractable mental illness and social problem—this year’s studies of treatment did not reveal a magic bullet that would turn psychopaths into angels. But we can take heart in the fact that if they can develop empathic skills, anyone can.
We now know that there’s much more to pain than simply what is happening in the painful body part, and attention has turned to the role of the brain. But not even this mysterious organ can tell us everything…
We now know that there’s much more to pain than simply what is happening in the painful body part, and attention has turned to the role of the brain. But not even this mysterious organ can tell us everything we need to know about pain, at least not yet.
You may wonder why the brain is part of the discussion about pain at all. After all, we’re not talking about a brain disease such as Alzheimer’s or stroke.
But we think that the brain is actually the best place to look when trying to understand pain; after all, pain is a purely subjective experience.
The problem is that pain cannot be “seen”. While a flinch, a limp, or a grimace may provide us with clues, ultimately we only know that someone is in pain if they tell us they are.
Just as not all pain arises as a result of an injury to a body part, not all injuries cause pain.
The brain interprets sensory information from the body according to the present context; incoming messages are evaluated concurrently with past experiences, memories, thoughts, and even how the painful body part is perceived. The same injury may cause us pain one day, and no pain the next.
Critically, pain is only experienced if the brain concludes, from this complex interplay, that there’s potential for harm or danger to the body.
And many researchers around the world are investigating the function of the brain, or its activity, with different neuroimaging tools.
The most common of these tools is a functional magnetic resonance imaging (fMRI) scanner. New technologies like this provide us with exciting opportunities if we use them to answer important questions, using rigorous methods.
Recent advances in statistical methods have led a US research team to find the answer to a very important question – can we see pain in the brain?
These researchers have discovered a neurologic signature of physical pain that is highly sensitive. These patterns of brain activity predicted pain with over 90% accuracy (positive predictive value) in the group of people scanned.
But can a brain scan tell the whole pain story?
Despite this being perhaps the closest we’ve ever come to “seeing” pain, there are some things about the study we should keep in mind.
The research used a particular type of stimulation – placing hot thermodes on the skin of the forearm – to produce pain in healthy pain-free participants.
One can assume that the study participants knew they were involved in an experiment, that the pain they were experiencing was going to be short-term, and that the experiment could be stopped if needed.
A major issue then is just how generalisable these findings are. Would we see the same neural signature for pain if we were to scan the brain of someone with a 30-year history of low back pain? Would we capture the complex interplay that has led to the construction of pain in that person, at that time?
This leads to question of whether it is, in fact, worth embarking on a quest to find an objective measure for something that is so fundamentally subjective. It may not be valid or useful to search for a biomarker for pain as we would for cancer or heart disease.
And there’s another, very significant, issue to consider.
Identifying a brain-based pain signature has been promoted as a step forward in understanding the pain experience of people who cannot communicate their pain. But we should take a very cautious approach to putting this into practice.
It’s not uncommon, even though we know so much about the disconnect between tissue injury and pain, for chronic pain sufferers to be accused of feigning pain simply because no pathology can be seen on an X-ray.
We must avoid simply moving these errors of interpretation from scans of the back to scans of the brain, or people suffering pain will continue to be mistrusted.
To this end, the lead author of the US study rightly warned against the use of a neurologic signature for pain as a “lie detector”.
The lack of an objective measure for pain is often seen as a barrier to understanding pain. But pain provides neuroscientists with a remarkable opportunity to investigate how the brain construes a complex experience.
By identifying a neural signature, the US study discussed above has made significant progress towards seeing pain in the brain. Research like this moves us forward on the fascinating road towards understanding pain and brain function.
But answers to questions about a complex and subjective experience are likely to come from more than the identification of a neural signature.
I Had My DNA Picture Taken, With Varying Results
Kira Peikoff, 28, had her DNA tested by three direct-to-consumer companies, and the results didn’t agree.
By KIRA PEIKOFF
Published: December 30, 2013
I like to plan ahead; that much I knew about myself before I plunged into exploring my genetic code. I’m a healthy 28-year-old woman, but some nasty diseases run in my family: coronary heart disease, rheumatoid arthritis, Alzheimer’s and breast cancer.
Pathway found that Kira Peikoff had an average genetic risk of psoriasis, top, while 23andMe assessed it as higher than average, and Genetic Testing Laboratories as low.
Readers shared their thoughts on this article.
So I decided to read the tea leaves of my DNA. I reasoned that it was worth learning painful information if it might help me avert future illness.
Like others, I turned to genetic testing, but I wondered if I could trust the nascent field to give me reliable results. In recent years, a handful of studies have found substantial variations in the risks for common diseases predicted by direct-to-consumer companies.
I set out to test the tests: Could three of them agree on me?
The answers were eye-opening — and I received them just as one of the companies, 23andMe, received a stern warning from the Food and Drug Administration over concerns about the accuracy of its product. At a time when the future of such companies hangs in the balance, their ability to deliver standardized results remains dubious, with far-reaching implications for consumers.
My experiment ran into hurdles from the start. After I ordered 23andMe’s saliva test kit, which for $99 promised a report on more than 240 health conditions and traits, it turned out that I could not legally send it in; the New York State Health Department forbids any labs that lack a state permit to accept specimens from a health-related test. Luckily, my in-laws mailed it from their home in New Jersey.
Then I learned that the other two companies I planned to approach were no longer offering genetic testing. Additional research led me to two more: Genetic Testing Laboratories and Pathway Genomics. G.T.L. charged $285 for a report on 25 disease risks, and required a professional sample collector to draw blood; Pathway charged $399 for a report on 24 disease risks. (In 2010, Pathway planned to sell its saliva test kit at Walgreens, but abandoned the idea after the F.D.A. challenged the sales. Now Pathway requires a doctor to order a kit on a patient’s behalf.)
After my tests had been sent, I braced myself for the revelations about my DNA. It took about two months to receive all the results, and when I did, the discrepancies were striking.
23andMe said my most elevated risks — about double the average for women of European ethnicity — were for psoriasis and rheumatoid arthritis, with my lifetime odds of getting the diseases at 20.2 percent and 8.2 percent. But according to Genetic Testing Laboratories, my lowest risks were for — you guessed it — psoriasis (2 percent) and rheumatoid arthritis (2.6 percent).
For coronary heart disease, 23andMe and G.T.L. agreed that I had a close-to-average risk, at 26 to 29 percent, but Pathway listed my odds as “above average.”
In the case of Type 2 diabetes, inconsistencies on a semantic level masked similarities in the numbers. G.T.L. said my risk was “medium” at 10.3 percent, but 23andMe said my risk was “decreased” at 15.7 percent. In fact, both companies had calculated my odds to be roughly three-quarters of the average, but they used slightly different averages — and very different words — to interpret the numbers. In isolation, the first would have left me worried; the second, relieved.
Medical ethicists and other experts have a different kind of worry about results like these: a lack of industry standards for weighing risk factors and defining terminology.
“The ‘risk is in the eye of the beholder’ standard is not going to work,” said Arthur L. Caplan, director of medical ethics at the New York University Langone Medical Center. “We need to get some kind of agreement on what is high risk, medium risk and low risk.”
Several other problems may account for my discrepancies. The genetic testing that these three companies offer is premised on reading segments of DNA called SNPs (pronounced snips), for single nucleotide polymorphisms. But these segments, which have been linked to diseases in research studies, vary among people.
Scientists have identified about 10 million SNPs within our three billion nucleotides. But an entire genome sequencing — looking at all three billion nucleotides — would cost around $3,000; the tests I took examined fewer than a million SNPs.
“Imagine if you took a book and you only looked at the first letter of every other page,” said Dr. Robert Klitzman, a bioethicist and professor of clinical psychiatry at Columbia. (I am a graduate student there in his Master of Bioethics program.) “You’re missing 99.9 percent of the letters that make the genome. The information is going to be limited.”
Companies choose which SNPs to read. By comparing the technical reports provided with my results, I found that my tests sometimes relied on different SNPs to assess the same condition, like coronary heart disease. Each test studied four to 15 markers, with almost zero overlap, though two tests reached similar conclusions about my odds.
In the case of rheumatoid arthritis, though, the tests examined the same five markers, plus a few others, and delivered contradictory interpretations.
This is a very long and detailed piece, that may not interest some of you. However, the issues it presents need to be understood, especially by women, so it is worth wading through this article. Perhaps, do it in a few sittings, with a cup of green tea in hand and a comfortable sofa 🙂
Breast cancer causes and treatment:
where are we going wrong?
Colin B Seymour
Medical Physics and Applied Radiation Sciences Department, McMaster University, Hamilton, ON, Canada
Correspondence: Colin B Seymour
Medical Physics and Applied Radiation
Sciences Department, McMaster
University, Hamilton, ON L8S 2C1,
Abstract: This discussion paper seeks to provoke thoughts about cancer research in general, and why breast cancer in particular is not yet “curable”. It asks the question – are we looking at the disease in the right way? Should we regard cancer as a progressive state, which is part of aging? Should we tailor treatment to “reset” the system or slow progression rather than try using toxic and aggressive therapy to kill every cancer cell (and sometimes also the patient)? The thesis is presented that we need to revisit our fundamental beliefs about the disease and then ask why we cling to beliefs that clearly are no longer valid. The paper also questions the role of ethics boards in hampering research and discusses the concept that breast cancer is an industry with vested interests involving profiteering by preventive, diagnostic, and therapeutic players. Finally, the paper suggests some ways forward based on emerging concepts in system biology and epigenetics.
There is a perception that cancer research generally, and breast cancer research specifically, is not progressing as fast as might be hoped from the investment in research. The National Cancer Institute cancer trends progress report for the US for 2011/2012 shows that the incidence of and death rates from breast, colon, and prostate cancers are stable. It calculates that women have a one in eight risk of developing breast cancer, although there is an increased probability of the cancer occurring between their 50th and 70th birthdays. Other reports show slight decreases in mortality (approximately 2% per year) but stable incidence rates.1–3 However, the worldwide incidence is increasing by approximately 3% per annum and deaths by 1.8% per annum.4 This suggests that while improved detection and treatment in developed countries may be reducing mortality somewhat, we are perhaps missing something big in how we try to prevent and treat breast cancer in the global context. This paper intends to provide a broad overview of cancer research approaches to determine if there are any particular reasons for this relative lack of progress. We do not claim to be breast cancer experts, and that is why we feel we can contribute an “out of field” perspective.
It could be suggested that because current approaches are not working as well as might be expected, alternative approaches should be considered. Although this might sound reasonable, there are now a large number of organizations heavily invested in the status quo. It has been noted, with irony, that more people benefit from breast cancer than suffer from it. Without impugning in any way the motives of any individual researcher, it could be that
research structures and funding bodies are stifling innovative research by funding irrelevant but easily publishable work on the minutiae of a gene transcription pathway in a genetically sensitive mouse, rather than human based, but necessarily messier, research.
Causes of breast cancer
If a new “big picture” approach to breast cancer is to emerge, it is necessary to step back from the gene-dominated approaches to causation and examine what might cause this cancer at the gross level and what issues there are in establishing preventative or delaying techniques rather than aggressive treatment approaches. There are well known causes of breast cancer, such as the “Western diet” and the fact that Asian women have a reduced incidence until they come to reside in the West,5–7 smoking,8–10 and radiation exposure.11–13 There is also an ongoing controversy concerning the old idea dating back to 1943 that breast cancer may be caused by a handful of known oncogenic viruses.14,15 The candidate viruses are mouse mammary tumor virus, human papilloma viruses, Epstein–Barr virus, and bovine leukemia virus. The latter may explain the East–West breast cancer issue via consumption of cow’s milk and meat, but the evidence is very limited. It is possible that these viruses may collaborate with each other. The viral breast cancer hypothesis has a long history, with past failure to establish sound evidence of causation. This has dramatically changed because of the availability of new laboratory techniques discussed in the cited reviews. While diet, smoking, and control of oncogenic viruses are the subject of health education and guidance, radiation is not controlled to reduce risk; in fact, medical use of radiation represents the greatest radiation exposure to humans and, in our modern world, the risk of getting breast cancer may increase due to increasing elective or imposed medical radiation exposure. The female breast is, according to the International Commission on Radiation Protection, a very radiosensitive tissue.16 While “safe” doses are generally determined as those that will not harm the most sensitive tissue, they depend on models using “reference man”, ie, an ideal hermaphrodite body shape and epidemiologic data from the atomic bomb survivors of Hiroshima and Nagasaki.17,18 These approaches estimate safe doses based on old and outdated radiation biology while ignoring modern research, which could mean the “safe” dose is not so safe or even positively beneficial. It is important to know because exposures, particularly in the low-dose exposure region, are increasing. Mammograms (which involve breast irradiation) are offered on an annual basis to women over 50 years in spite of controversy about their effectiveness, the anxiety caused by false positives, and the potential risks of radiation exposure in sensitive individuals.19–24 Computer axial tomography scans have grown in popularity as elective tests during annual physical examinations. In the US, it is estimated that 90 million scans will be performed this year and a “wellness scan” is a common gift. This is very big business for medical doctors and hospitals as well as for producers of instrumentation. However, members of the public, who intensely fear very small environmental releases of radiation, do not seem aware that the wellness scan involves a whole body radiation dose of 3–20 mGy or more, depending on the specific test and the competence of the technician. In some cases, this is more than the annual dose limit for the general population.25–27 There has been a lot of publicity about the risks of these scans for children, but there could also be an enhanced risk for females developing breast cancer.28–31 Another new exposure, which is not so elective, is the use of backscatter X-ray machines as screening devices in airports. Again, they are said to be harmless, but that perception is based on the models referred to above and not on real data. The true risk will only emerge as the big human experiment with these machines progresses. Already there are concerns about skin cancer risk as the X-rays are low energy and do not penetrate far, but the breast is just under the skin and therefore at risk. As security paranoia increases, so may the energy of X-rays used, to enable more and more detail to be seen and to enable body cavities to be “searched”. This is already done in diamond mines in parts of Africa.
Clonal origin from a mutated gene
A concept which has probably delayed progress in breast cancer treatment, among others, is the idea that cancer has a
clonal origin, ie, that a mutation occurs in a cell causing it to be initiated and to give rise ultimately to a cancer.32–34 In the 20th century, this idea dominated to the extent that all other ideas were rubbished and unfundable; the Weinberg model35,36 and the Knudsen model37 were beautifully documented and very reductionist, in keeping with the times. In the field of radiation carcinogenesis, the idea that radiation could promote cancer was ignored, as were the concepts of microenvironmental influences, signaling mechanisms, and adaptive or inducible responses. Now there is a more enlightened view of carcinogenesis that admits the importance of these “nontargeted” effects,38–41 but unfortunately the idea that cancer could be a system level “response” to environmental influences (both at the tissue and organism levels) is still not widely accepted, and the invention of the “cancer stem cell” has merely replaced the older (identical) view of the clonal origin of cancer with all the consequent reductionist approaches to “treatment”, ie, eradication of the faulty aberrant culprit.
It is interesting to look at the history of conceptual approaches to the origins of cancer and how these led to the types of treatments used. Back in 1940, Haldane42 remarked that,
“When only physical and chemical methods are employed, only physical and chemical facts are forthcoming. The whole is not to be understood by the sum of its parts any more than an architectural masterpiece is to be comprehended by the chemical and physical analysis of the stones of which it is built”.
Hyman,43 a taxonomic zoologist also argued for a system level approach, saying,
“All recent particulate theories in biology derive from that biological theory called the mechanistic or physicochemical explanation of life and this is in turn developed from the materialistic physics and chemistry of the 19th century according to which the universe consists ultimately of matter moving through space. This means that all vital phenomena can be explained fully in terms of physics and chemistry. Physicochemical investigation has achieved an illusory success by neglecting such matters as correlation, organisation, adaptation, evolution and psychic properties or by inventing special particulate theories for them. However, the synthesis of physicochemical facts about parts of an organism cannot reconstruct the living being”.
While these quotes did not address cancer specifically, they do point to the need to adopt a system level approach to the development of a cancer, which takes into consideration the microenvironment, including the very important microvasculature that supports the growth and division of the cells, and the surveillance systems that permit the cancer to develop. The vasculature is a really important target because the tumor cannot survive without an oxygen/nutrient supply.44–48 Many millions were invested in antiangiogenesis drugs, but these failed to show any beneficial effects in humans.49–51 However, a new understanding of the processes of vasculogenesis and angiogenesis is emerging, suggesting that “out of field” elements coming from the bone marrow are capable of signaling regeneration of the vasculature in the treated tumor area.52–55 The fundamental idea that the tumor bed was important in allowing the tumor to develop was first suggested in the early 1900s as a “seed and soil” hypothesis.56,57 This suggests that this field should be revisited for breast cancer treatment. To quote Denis Noble,
“Inspecting genome databases alone will not get us very far in addressing these problems. The reason is simple. Genes code for protein sequences. They do not explicitly code for the interactions between proteins […].”58
Similarly, inspecting data from genetically predisposed mice or mouse models with abnormal immune function is unlikely to answer questions about human breast cancer in human populations. At the practical level of improving cancer survival rates, possibly the most important new concept is that of Loeb,59–61 who formulated the concept of the “mutator phenotype”. This idea suggests that in a precancer host human, conditions in the microenvironment permit a greater than normal level of random mutations, allowing instability to occur. It is important to focus on the word “phenotype” because this implies change at the level of the tissue and not that an individual gene mutation has started anything. The gene mutations come after not before the system level change. This idea is of course well accepted in evolutionary biology where the concept of stress-induced or environment-induced mutagenesis is well established.62–64
Aggressive therapy works
One of the fundamental issues of medicine is that it is an empirical science. It does not have a strong theoretical base. Advances in treatment are usually developments of existing treatment. Clinical trials are between the existing treatment and the proposed new treatment, but there is never a “no treatment” control arm. However, if the existing treatment causes damage that is later attributed to the disease process,and the proposed new treatment does as well, illusions of an effective treatment are perpetuated. It could be that the “miraculous cures” or “spontaneous remissions” (depending upon your point of view) are attributable not to alternative treatment, but effectively to no treatment.
William Osler, one of the fathers of modern medicine, famously remarked that “One of the first duties of the physician is to educate the masses not to take medicine”.65 It could be argued that this is an explicit recognition of the body as a self-correcting system. He continues “The desire to take medicine is perhaps the greatest feature which distinguishes man from animals”. Again, it could be argued that there is recognition that pharmaceuticals can do more harm than good, and by corollary, a wait and see approach might be better. This approach is currently being used in prostate cancer management,66 where patients are segregated into those with “indolent disease” where active surveillance but no treatment is preferred, those with intermediate disease where standard treatment is given to control local disease, and those with aggressive metastatic disease in whom individualized therapy is being tried. Trials are currently underway at Princess Margaret, Toronto, and at other major hospitals (R Bristow, Princess Margaret Hospital, personal communication, May, 2013). This personalized approach is aimed at identifying the response/nonresponse signatures and identifying those with “noisy” or unstable genomes predisposing to successful tumor evolution, and treating accordingly.67
In the breast cancer field, the established idea seems to be that breast cancer is a disease that needs treatment. Perhaps we need to adopt the ideas in the preceding paragraph and think of it instead as a process, like aging. A different conceptual model can then be used. Aging is a natural biological process, and it could be argued that cancer is too. If cancer is a natural process, the question is reformulated, so it is no longer why certain people get cancer, but why the majority of people do not.
The utility of the model is that it is no longer necessary to seek a cure, because there may only be one for symptoms not for cause. Instead, the emphasis would be on control and delay. The advantage of this conceptual framework is that it could avoid many of the treatments that “cure the disease but kill the patient”. If cancer is a process, interference with the process could make the situation worse, as happens with many tumors that recur in more aggressive form after treatment. If the Loeb “mutator phenotype” hypothesis is correct, less treatment could equate to more effective treatment.68 In a relentless, and probably unrealistic, attempt to rid the body of all cancer cells, highly toxic chemicals and immunosuppressives are often used. Apart from the fact that this approach challenges evolutionary and adaptive mechanisms in the host to enable survival of the cancer, the quality of life of the patient plummets, until the disease drops below “detectable levels”. If the tumor biomarker level becomes detectable within 5 years, the patient has had a relapse; after 5 years a cure is declared.
One major issue is the confusion between knowledge and belief. Cancer treatment is often based upon belief rather than knowledge. A belief-based system is often unwilling to confront its uncertainty or lack of knowledge. To quote Osler, “The greater the ignorance, the greater the dogmatism”.69 Curing cancer has become in some ways a crusade, a battle of faith not of science. It has become a battle to kill the tumor without killing the patient, without consideration of whether that is the best treatment strategy. Perhaps the patient could survive with the tumor, in the same way we survive with intestinal flora.
In an article appearing in the UK Daily Telegraph on May 20, 2013, Lord Saatchi estimated 15,000 deaths occurred every year because of cancer treatment.70 He told the House of Lords “What we do know is that the cancer drugs do such damage to the immune system that the patient is helpless to resist fatal infections like E. coli or MRSA or septicemia”. He also said the Office for National Statistics under World Health Organization guidelines only recorded “the single underlying cause of death”.
It is therefore very difficult to determine how many patients die during cancer treatment primarily because of the treatment. It is also difficult to have reasoned discussions about this, because of the lack of objective data.
There is violent debate about the efficacy of screening (apart from the radiation issue and the problems of false positives and false negatives). Mammography screening is statistically proven to reduce mortality as discussed earlier;19–24 however, the matter is rather more complex. See, for example, the New York Times article by John Allen Paulos published in 200971 or the New York Times editorial published at about the same time,72 both of which suggest that there is more controversy than the peer-reviewed medical statistics papers would have one believe. A Norwegian study published in The New England Journal of Medicine24 also suggests that the situation is complex. The idea is simple: if the disease is diagnosed at an early stage, the treatment will be simpler and more effective. Both of these claims need to be analyzed in turn, but first the definition of cancer needs to be examined. Recently, there has been a large increase in the diagnosis and treatment of ductal carcinoma in situ. It has been treated, with no recurrence, and would seem to validate the screening program. However, there are now calls to re-examine the definition of cancer, and ductal carcinoma in situ would no longer be defined as cancer or warrant treatment. The economic costs of this overtreatment have been calculated to be substantial. Not as readily apparent is the fear engendered in the population, and cancer phobia may be linked to the more documented radiation phobia. Breast cancer is one of the fears of modern women, and some undergo preventive mastectomies and even oophorectomies if they carry the BRCA 1 or BRCA 2 gene. This fear is fed by charities encouraging regular screening, which often feature young and attractive models with babies in their advertisements.
Similarly, there is an argument that screening just alters where on the disease progression timeline it is encountered. If the natural history of cancer progression is 15 years, and it is detected early, regardless of whether the tumor is cured or not, the patient will survive 5 years and be “cured”. This concept of “5-year survival” has possibly influenced the screening program. Again, it should be noted that screening is a big industry with unproven benefits, like the annual flu vaccine!
Linear hypothesis of dose effect
There is a prevailing wisdom that cause–effect relationships are linear, ie, “increase the dose/activity and you will also increase the effect”. However, there is ample evidence that effects are not related to cause in any simple manner. Rather, the system is very complex, allowing for nonlinear, nontargeted, and chaotic elements, including the emergence of unpredictable responses determined by epigenetic influences layered onto an underlying genetic background.73,74 In relation to the breast, it is part of the reproductive system, and is unique in that it only becomes fully formed in early life after puberty. Breast tissue changes with hormonal fluctuation during the menstrual cycle and during pregnancy. It is therefore one of the tissues where genetics will be secondary to epigenetics. The cancer-susceptible genes are just that, and susceptibility will vary with epigenetics. This can also be used to explain the observed differences between parous and nulliparous women. This could explain the links between smoking and cancers not directly linked to the respiratory tract, but would also indicate there may be links, although not necessarily causative, with birth control pills. Any lifestyle choice could potentially alter cancer risk. Another interesting point is that epigenetics allows hormetic effects to be considered. In the U-shaped hormetic dose–response curves, the same substance can have both stimulatory and inhibitory effects depending upon concentration.75,76 The menopause then resets the risk, as it were. As Russo and Russo77,78 remarked, “These changes resulted in a similar appearance of the architecture of the breast of parous and nulliparous women after the fifth decade of life”. After menopause temporal changes in all groups remain similar, and only earlier patterns are different.
Why do we believe invalid things?
We all accept that science is the acquisition and organization of knowledge. To quote EO Wilson, “Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe”.79 In an older meaning, “science” also refers to a body of knowledge itself, of the type that can be rationally explained and reliably applied.80 This implies that science is based on experiments and that “belief” has no place. However, we are human and are all guilty of having pet theories and strong beliefs. The problems arise when powerful people adhere to their beliefs rather than being objective. “Empires” are often built and become sustained by grant or industrial money, meaning that adherence to the sustaining belief becomes critical for survival and vested interest overcomes truth. Data or grant proposals which do not support the dominant paradigm are ignored or not funded. Thomas Kuhn81 in his classic book, Nature of Scientific Revolutions, defined three phases of a revolution: outright disbelief of data that do not fit; grudging acceptance in the face of overwhelming data from many sources; and establishment of a new dominant paradigm, with the contention that the results are obvious and were in the literature since time began (they probably were!). A more cynical commentary is that the ruling scientists need to die before anything will change. The first part of this paper discussed specific issues in relation to breast cancer, which may be fundamentally wrong. In this section, we discuss reasons why things are not really changing. If our contention that breast cancer is now an industry is correct, then it should be possible to “follow the money”.
Grant system and structure
To quote Einstein, “If we knew what we were doing it wouldn’t be called research”. However, like research ethics boards, grant-awarding bodies almost insist that the applicant has the results written before the research takes place, and allow for no deviations. This is a common misconception of the nature of research. The result is that the research funded is relentlessly prescribed, and of necessity reductionistic, predictable, and largely useless. A more enlightened approach would be to fund productive teams/individuals; ie, assume that good researchers do good research. We tend to confuse the ability to write a good proposal with the ability to deliver good research. A less prescribed approach would allow the researcher to test and develop hypotheses over time. This is an area in which some of the multiple funding research groups could usefully participate; ie, the establishment of an “effective research” policy program.
“Easy” mouse models
In the Hitchhiker’s Guide to the Galaxy, it is revealed that mice are the real controllers of the universe (and everything!). Certainly this seems to be true in science, where mice can be given, and cured, of any disease. Wildly inappropriate mouse models are used for human disease (presumably because the technology exists), and all kinds of cancer can be cured in mice. For example, the antiangiogenesis drugs which held such promise and did cure mice, did not work in humans.48–52 Similarly, it is surely a strange approach to curing a systemic disease in a human to knock out a specific gene in a mouse. Normally it is not even possible to have a homozygous knockout, reducing the relevance even more. Since everything in biochemistry is connected, altering one pathway using knockouts will impact everything else. Maybe these approaches might help us to understand the progression of disease, such as in the Vogelstein model,82 but a cure is not obvious from knowing one level of cause in a complex system. Obviously if the mouse model were either good or relevant it would have resulted in the cure of cancer. Perhaps we did not notice … or perhaps there is a vast support industry involved in mouse research, and it is a branch of science that is now too large to be delegitimized.
Ethical issues make useful experiments difficult
It should also be possible to point a finger at ethical review boards that make it almost impossible to obtain tissue directly from the patient that could form the basis of relevant research. There must be a way of obtaining human tissue for research purposes without having to know the exact nature of the research to be done. If the tissue is to be discarded anyway, there seems to be no compelling reason why it cannot be used for research.
To paraphrase Jane Austen, “It is a truth universally acknowledged that it is virtually impossible to get human tissue for research purposes”. Most of this difficulty is due to medical ethics boards that have a basic misunderstanding of ethics and wish to evade responsibility rather than accepting the more difficult challenge of establishing a fair and equitable system that allows unwanted tissue to be used for research purposes. Part of the problem has been caused by the proliferation of patents and the sensationalizing of the Henrietta Lacks case. There is though, in some jurisdictions, a move towards assuming that all deceased persons should be regarded as donors, although there does not seem to be a corresponding move to regard all operatively removed tissue as legitimate for research purposes. Patients have come to sense that any part of them has some commercial value, and would rather see excess tissue discarded rather than risk someone using the tissue and possibly getting rich. This “envy” does not encourage basic research, although presumably it would be permissible if the intention were to individualize treatment, which many hospitals are now advertising. However, it should be stated that usually the individual treatments are prescribed through genetic profiling. As an interesting aside, the proponents of this individualized response are now suggesting that there will never be “one cure” for breast cancer, and that large-scale clinical trials for breast cancer will conceal drugs working in a subset of the population, and that by corollary clinical trials may confuse the issue.
Models assume a linear dose–effect relationship
This is probably one of the most dangerous beliefs because it prevents us from looking at discontinuities in mechanisms. The history leading to the dominance of this paradigm is well documented by Naviaux75 and Calabrese.76 Briefly, it goes back to the time of Paracelsus, who in the 16th century said: “Alle Ding’ sind Gift, und nichts ohn’ Gift; allein die Dosis macht, daß ein Ding kein Gift ist.” (All things are poison, and nothing is without poison; only the dose permits something not to be poisonous).83 However, this idea which is clearly correct, lost favor when homeopathic doctors used it to justify their science,84 which was clearly an incorrect interpretation of what Paracelsus said. The linear dose–effect relationship became dogma when Hermann Muller, a radiation geneticist and Nobel Laureate, demonstrated in 1926 that radiation could cause mutations.85,86 His dose–response relationship was linear. This was interpreted to mean that radiation (or other toxins) had no safe dose at which they caused no harm. The idea of beneficial effects of low doses (hormesis or homeostasis) was also excluded. Contrary evidence discussed in Calabrese’s paper,87 which suggested nonlinear responses after low-dose exposure to radiation and chemicals, was ignored, leading to the current dominant paradigm that all substances have increasingly adverse effects with increasing dose. The protection agencies (both for radiation and environmental chemicals) assume a linear no threshold dose–effect relationship for regulatory purposes. In the cancer treatment field, this leads to the idea that “more is better” and marginalizes creative thinking about adaptive responses, immune stimulation, nonlinear tumor evolution, tissue level emergent responses, or other low-dose effects, which could possibly open up new treatment avenues.
Prevailing paradigms are supported by strong, senior people who peer-review, and multibillion dollar industries selling treatment
Both cynicism and conspiracy theory are, perhaps, features of modern life. As remarked earlier, the cancer industry is a multibillion dollar business, and it remains true that businesses are committed to making money for their shareholders. They are not obliged to act in the best interests of their customers.
Health has to be regarded as any other industry. Pharmaceutical companies have products to sell, and have an advantage over the automotive industry in that the patient (customer) has little choice, is emotionally vulnerable, and is not being sold the product directly, but indirectly through the prescribing physician. The physician is effectively acting as a salesperson for the pharmaceutical industry and using their position of trust. Very few patients query their physicians’ choice of drugs. This complex relationship has led to cynicism, and led to links with conspiracy theory, where there is active belief that cancer could be cured if there was not so much money invested in the status quo. To continue the automotive analogy, this is similar to the conspiracy belief that formulae to replace petrol by water were purchased and destroyed by major oil companies. Scientists are equally being sold drugs and research areas. Science into the mechanistic actions of existing drugs and optimizing the effect of existing drugs is encouraged. Drugs are only useful to the pharmaceutical companies as long as they are under patent. Nonpatentable drugs are very rarely given a trial, in part because there is no justification as far as the pharmaceutical companies are concerned as a result of the expense involved in jumping the requisite regulatory hoops.
What can we do?
Positive suggestions to move forward
It is easy to criticize, but necessary to suggest possible solutions. We suggest tackling the thorny issue of determining what we really know about cancer from what we think we know. This involves going back to human data from patient or epidemiologic studies. Nonhuman data should be treated with caution and evaluated critically in the context of what the human data show. As Alexander Pope said, “The proper study of man is mankind.” This is partly because nonhuman data derived from inbred tumor-prone, tumor cell-injected, or knockout rodent models are of limited relevance to outbred human populations within which cancers develop in a background microenvironment or system which is currently poorly understood. Also, animal experiments are largely designed to confirm and strengthen the current hypotheses, not to formulate or infer new hypotheses. As Einstein succinctly said, “The intuitive mind is a sacred gift and the rational mind is a faithful servant”. We have created a society that honors the servant and has forgotten the gift. This is certainly true in scientific research, but the prevailing dogma is so strong and passions so easily aroused, that it will be difficult to distinguish between that which is known and that which is believed.
The second challenge will be in reformulating the timeframe of disease, and accepting that screening may be of no benefit to the patient. There are arguments made in both sides of this very contentious debate, but again the major difficulty is to assemble the evidence that arises from fact not belief. This probably negates many epidemiologic studies where the data are analyzed to reinforce current models instead of offering competing explanatory narratives. Assuming the fundamental methodology is not flawed, these studies could be reanalyzed.
The third challenge will be to determine whether there is an intervention window between a primary tumor and metastatic growth that is susceptible to epigenetic factors. If the primary tumor could be dissociated from malignant spread, it would be possible to treat these as two independent processes, which might open therapeutic windows. Finally, the idea that aggressive therapy to eradicate every last tumor stem cell, or clonogen, is the only way to treat cancer, needs to be revisited. A more holistic therapeutic approach that works with the body and is mindful of biological principles of evolution and adaptation, is certainly worthy of consideration.
The authors report no conflicts of interest in this work.
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How do you know you are sick? No, really… Think about it. If you have suffered through another winter of coughs and sniffles, and you are about to be hit by the spring allergies, you will know the feeling of being tired and grumpy, where everything seems to hurt that little bit more and you wish everyone…
How do you know you are sick?
No, really… Think about it.
If you have suffered through another winter of coughs and sniffles, and you are about to be hit by the spring allergies, you will know the feeling of being tired and grumpy, where everything seems to hurt that little bit more and you wish everyone would just leave you alone.
What’s even worse is that your favourite foods and music don’t seem to cheer you up when you are that sick with the latest bug.
But how can being sick change how you act and feel? Your immune system is working overtime dealing with the bug. It must just be draining your batteries and that is making you feel so rubbish, right? Well, maybe a little, but actually not enough to make you feel the way you are. So how?
Everything you feel and think happens in your brain, so there must be a connection between the bug or the immune system and our brains… Bingo, that’s it!
Our immune system is constantly talking to our brain, keeping it updated on any changes to our health. So if we do get an infection our brains can change our behaviour to deal with the illness in the old tried and true way, with rest and recuperation (with a little grumpiness thrown in for good measure).
But the brain “talks” a neurotransmitter chemical language. Can the immune system “talk“ this same way to our brains?
So here is the curve ball: did you know your brains are actually more “immune” than “brain”?
Hang on, what about all the cool videos flying through the brain with all the wiring sparking and sending messages everywhere? There weren’t any immune cells there.
Well, despite the common perception, no one has that much air in their heads! That space is filled with immune cells, called glia. They actually outnumber the neuronal wiring ten to one. These immune cells are critical to the health and well-being of our brains. They also help translate the immune messages for our brain to tell us that we are sick.
How sick is the addicted brain?
This realisation that the immunology of our brains contributes to so many aspects of behaviour and cognition has led to paradigm shifts in the fields of psychiatry and mental health. A recent exciting development has been the discovery that changes in brain immunology contribute to drug addiction.
Now, of course dopamine is still the key reward neurotransmitter of the brain. But the immune system that surrounds the dopamine systems of the brain also seem to be very sensitive to drugs of abuse. So much so, that in preclinical studies it is possible to make rats like alcohol, opioids and methamphetamine a lot more, just by turning on the immune cells in specific brain regions.
This has significant drug addiction treatment implications. It means that treating drug addicts from a “brain” perspective might only solve part of the problem. The “other brain”, the brain immune cells, might need a little love and attention as well.
In fact, studies being conducted with the support of the National Institute on Drug Addiction (NIDA) in the United States have shown significant promise in treating opioid and methamphetamine addiction with brain immune-targeted treatments.
What does it mean for addicts?
Current drug substitution programs such as methadone maintenance programs provided in Australia are cutting edge, innovative and provide a world class health service to our drug addicted brothers and sisters.
But surprisingly, such programs are not widely available in many developed countries owing to negative political pressure that “you are just giving the junkies what they want for free” and “if they just tried harder they could just stop”.
But think about it; if your brain immunology is telling your brain you need your next fix, you have an uphill battle on your hands: ten immune cells to every neuron. That just isn’t a fair fight. This means that immune targeted therapies might be a much more politically palatable option in the future to compliment existing substitution therapy programs.
So where to now? When will we see an end to drug addiction with this new understanding of brain immunology?
Bottom line is, we don’t know. But at least now we can start to integrate the exciting developments in brain immunology with the many decades of neuroscience drug addiction research to provide hope to the hundreds of thousands of drug addicts worldwide that a cure could be in sight.
Mark Hutchinson is a panelist at the University of Adelaide’s public research forum this evening on Tackling Addiction.
Australians are getting heavier and, as a result, are more likely to suffer life-threatening illnesses such as heart disease, diabetes and strokes. But should we be worried about a bit of excess weight? After all, isn’t it better to focus on exercise so we can be healthy, whatever our size? Today’s…
Australians are getting heavier and, as a result, are more likely to suffer life-threatening illnesses such as heart disease, diabetes and strokes.
But should we be worried about a bit of excess weight? After all, isn’t it better to focus on exercise so we can be healthy, whatever our size?
Today’s Viewpoints: can you be healthy at any weight? Tim Olds argues we can; while Anna Peeters outlines why we shouldn’t give up on keeping our weight in check.
A study published earlier this month followed up 9,538 Americans born between 1931 and 1941. It asked a very simple question: who are the least likely to die?
The authors considered the weight status of the participants at age 51 or over, and how their weight changed in the subsequent 16 years or until their death. At entry into the study, they were classified as normal weight, overweight, obese, or very obese. In the intervening years they were classified as either increasing weight, staying stable, or losing weight.
So which group was the least likely to die? Not, as we might expect, the normal weight participants who were weight stable, or lost weight. It was overweight participants who remained overweight, followed by overweight participants who became obese. Apart from the very obese who became ever more obese, those most likely to die were normal weight participants who lost weight.
It seems counter-intuitive, but there has been a flood of studies among Americans, Norwegians, Canadians, Hispanics, Europeans and older Australians with similar findings: overweight people live longer.
Rather than worrying about getting fat, we should all relax a bit and focus on being healthy at any weight.
We know that excess weight and obesity lead to many chronic diseases, ranging from diabetes through to cardiovascular disease and cancer, to sleep apnoea and musculoskeletal disease.
We and others have shown that the overall impact of these health risks is more disability in old age. We also looked at middle-aged Australians and found that those who were even mildly overweight were at greater risk of disability later in life than those of a normal weight.
The results Tim discusses above are significant and reflect the importance of maintaining, not gaining, weight as we age. They also show the risks of unintentional weight loss as we age, usually a sign of losing muscle rather than fat.
As individuals, we should definitely focus on being healthy at any weight. But as a society we should not lose sight of the fact that most Australians are continuing to gain weight. The latest analysis of the Australian Diabetes Obesity and Lifestyle cohort, found young adults were gaining 0.5kg per year, or around 7kg over the 12 year study.
In this context, it would be irresponsible not to work together to improve our nutrition and activity environments, and prevent more weight gain.
Anna is quite right on two points, and here we can agree: adults everywhere are getting fatter (though this is not true of kids). And fatter people are more likely to suffer from a wide range of diseases, including diabetes, arthritis and cardiovascular disease.
Now let me ask another question. Which is more important: fatness or fitness? Should we spend limited health dollars trying to get people to lose weight, or to get active? I’ll argue here for physical activity.
First, people who are fat but active have a much lower risk of death than people who are fat but inactive. Second, people who are fat but active have about the same, or lower, risk of death than people who are lean but inactive. Third, if you exercise, you’ll be healthier even if you don’t lose weight
But does fitness trump fatness? A study published this month may help to answer that question. It followed 11,240 Americans for 12 years and calculated the percentage of deaths attributable to fitness, fatness, diet and smoking. The greatest contributor to deaths was low fitness (6-7%), followed by smoking (5%), diet (3%) and fatness (0%).
We have an epidemic of inactivity. Low fitness is a stronger predictor of overall mortality than fatness. Weight loss among overweight and healthy obese people is a failed concept both in terms of evidence and in terms of implementation.
So why on earth are we focusing so much on fatness, and so little on physical activity?
There is no debate about the importance of aerobic fitness for health, quality of life and survival. But fitness is a marker of your capacity for activity, not your current physical activity levels, and it’s also affected by sex, age, ethnicity, obesity, activity and poor health.
While Tim’s point that fitness matters more than weight is true, the same article also shows that weight matters more than physical activity.
But it should not be a competition. Healthy diet, activity and weight all work together to improve our fitness.
Tim mentions that obesity rates are no longer going up in kids. Well, in the US, the rate of childhood obesity is declining, thanks to strong government action to improve food and activity standards in children’s setting. This action came about to combat the obesity epidemic.
We need strong advocacy if we are to smarten up the food choices available to us in Australia.
The focus now needs to be on the healthy environments and behaviours, and obesity remains an important marker of our progress. If we normalise obesity we’re missing our chance to prevent premature chronic disease for our children, and our children’s children.
Yes, increasing activity and avoiding inactivity has the potential to improve health in everyone. But achieving that is just as hard as improving diet, or any combination of the two, which is the general aim of weight loss strategies.
Anna is quite right when she says the stabilisation and decline in obesity in kids is most likely the result of repeated messages at all levels. But kids are the low-hanging fruit of the obesity tree, because parents act as gatekeepers for their exercise and dietary behaviours. Unfortunately, parents aren’t as good at regulating their own behaviours.
Weight loss attempts by adults have a poor success rate. Take this 2005 Danish study which followed a large cohort of adults over six years. At the start, about 36% said they intended to lose weight. At the end of the study, 38% of those intending to lose weight actually had lost weight. That doesn’t sound too bad, until you know that 38% of those not intending to lose weight had also lost weight!
We also know that over the long term (i.e. years) only about 5-10% of those trying to lose weight maintian their weight loss.
Studies have also shown that in the face of public health “weight scare” messages (such as the Measure Up ads), overweight people think that the messages don’t apply to them — only to really overweight people — while obese people simply pull down the shutters and block their ears.
Weight loss is a laudable goal, but we’ll end up with a healthier (and probably leaner) population if we shift the emphasis from weight loss to healthy lifestyle, and tell people that exercise and a good diet are more important and more achievable goals.
In Australia, more than six in ten adults and one in four children are overweight or obese. To deal with this we need to promote and facilitate healthier nutrition and activity, enable those at risk of further weight gain to maintain weight and manage weight and health complications in those living with obesity.
Clearly, advocating healthy lifestyles is one part of the solution, but education alone will not be sufficient. We need to enable those living with obesity to maximise their health and well-being, and access treatment.
We also cannot ignore the role of the environment we live in. So, instead of debating fitness versus fatness, we need to shift from a focus on individuals to a focus on society. Then healthy choices – both activity and diet – can become the easy choices for everyone.
If you’re anything like me, your medicine cupboard is chockers with various non-prescription pain remedies: liquids, pills, capsules, children’s painkillers, formulations that are “gentle on the stomach” and products that claim to target specific parts of the body.
So what’s the difference between these products, and how do you choose what’s best for different types of pain?
Paracetamol, aspirin and ibuprofen
According to the Bandolier league table of analgesics for acute pain, the three most common painkillers – paracetamol, aspirin and ibuprofen – are all reasonably effective.
By comparison, a 400mg dose of ibuprofen (two regular tablets or capsules) will produce 50% pain relief in two out of five cases of acute pain. Paracetamol at a dose of 1000mg (two of the usual-size tablets) will produce the same benefit in just over a quarter of cases, whereas aspirin at a dose of 600mg (two usual tablets) is effective in just under a quarter of cases.
The measure used to calculate these results is called the number needed to treat (NNT). This is based on a 50%-or-better reduction in pain due to the drug alone, in a clinical trial setting. This is a reasonably stringent requirement which translates to a pretty effective treatment in the real world, once you include placebo benefit and being able to use hot packs, ice or other first aid measures.
How do you choose between the big three?
It’s important to realise that these analgesic drugs are not diagnosis-specific. They no more target specific sources of pain than the fire sprinklers in a building target the fire.
They all act by interfering with important pain signalling molecules wherever they occur in the body. It may well be that there are more of these molecules being produced in areas that have been injured, but the image of a friendly drug floating through your system with a specific target in mind is completely fanciful. The drugs block these molecules wherever they find them.
Given there is little high-quality evidence on which to base your choice of over-the-counter analgesics for specific conditions, it makes sense to decide which potential side effects you want to avoid.
Sprains and strains
For musculoskeletal injuries such as sprains and strains, the site may be inflamed in the first few days after the injury, causing warmth, swelling, redness and difficulty using the injured area normally. If inflammation is clearly present you will probably find that ibuprofen or aspirin are better.
If you have pain but no inflammation, paracetamol is likely to be as good as the other two.
Rest, ice and immobilisation are likely to be more helpful than any medication for acute muscle or tendon injuries.
Acute back pain tends to respond poorly to most medications, including prescription drugs. If one of the big three seems clearly better than the others for your flareup of back pain you should stick with it, but for most people none of them are much help in the early stages of the pain.
For pain following a dental procedure or other minor surgery, ibuprofen has the edge in effectiveness, but at the expense of potential increased bleeding complications if you take too much.
Both aspirin and ibuprofen inhibit the stickiness of platelets in your blood and make it less able to clot.
Headaches represent a particular problem. True migraine headaches respond better to aspirin and ibuprofen than paracetamol.
Tension type headaches can respond to any of the three and are the commonest type of recurrent headache. But frequent use of paracetamol, especially in combination with codeine and doxylamine succinate, is associated with the phenomenon of rebound headache.
Aspirin and ibuprofen by themselves are less likely to cause worsening headaches, but produce more side effects on the kidneys and gastrointestinal tract with regular use. Combined with codeine, they are as bad as paracetamol.
The moral of the story with headaches is to avoid taking non-specific medications more often than a couple of times a week, and look for non-pharmacological ways of reducing the frequency of your headaches.
Period pain is an instance where there is some evidence to prefer ibuprofen or one of its anti-inflammatory cousins to aspirin or paracetamol.
As always, the duration of medication use and the dose should be kept as low as possible to get the job done.
Cold and flu
Cold and flu tablets mostly have paracetamol as the analgesic component, probably because of its ability to reduce fevers.
There is conflicting evidence that treating fevers due to acute infections is always a good idea. The system by which the body produces a fever is complex, and very strongly conserved throughout evolution, and there is still no clear demonstrated benefit for suppressing it. So save the paracetamol or aspirin for when the infection is causing symptoms such as headache or muscle pain which might warrant its use.
Painkillers for children
Paracetamol has some clear safety advantages in children. Aspirin use among children can trigger a nasty problem called Reye’s syndrome which has an unknown mechanism and is potentially fatal due to liver and brain damage. The occurrence of Reye’s syndrome in Australia has thankfully plummeted since aspirin was banned for use in children some years ago.
Ibuprofen, in recommended doses, does not seem to trigger Reye’s syndrome despite its mechanism of action being almost identical to aspirin. Ibuprofen, however, needs to be used with caution in children who have unpredictable asthma as it may trigger attacks.
Dosing of over-the-counter analgesics (and almost all other drugs) in children needs to be done very strictly in accordance with the recommendations on the label. Read them very carefully and follow the dose guidelines meticulously.
Fatal cases of liver damage in children have occurred with paracetamol where adult doses have been used inappropriately, and cases of kidney failure have occurred where the same has been done with ibuprofen.
No matter what the label may say, these drugs are not diagnosis-specific, so choose your over-the-counter painkiller based on the side affects you want to avoid as much as what your pain is.
Finally, it’s important to stick meticulously to the recommended doses on the label. These have been chosen after enormous research and experience to be the doses which best combine effectiveness with safety.
How to Choose a Multivitamin
U.S. News & World Report – Health, 11/11/2013
The most important thing to do when choosing a multivitamin is to determine where the ingredients come from. The answer to this question will tell you what the quality of the product actually is. You specifically want to know if the ingredients were sourced from whole foods or if they were created synthetically. Synthetic ingredients are manufactured in laboratories while the latter come from real whole foods. Vitamins work together synergistically in their natural state but not when they are synthetically isolated. This is an important distinction because it directly affects their ability to be absorbed and used in the body. This is the biggest reason you should choose a whole food–based multivitamin over a synthetic one. The main numbers you should be concerned with are: Recommended Dietary Allowance (RDA), Adequate Intake (AI) and Tolerable Upper Limit (UL). These values are collectively known as Dietary Reference Intakes (DRIs) and have been established by the Institute of Medicine of the National Academies.
How zinc starves lethal bacteria to stop infection
Monday, 11 November 2013
Australian researchers have found that zinc can ‘starve’ one of the world’s most deadly bacteria by preventing its uptake of an essential metal.
The finding, by infectious disease researchers at the University of Adelaide and The University of Queensland, opens the way for further work to design antibacterial agents in the fight against Streptococcus pneumoniae.
Streptococcus pneumoniae is responsible for more than one million deaths a year, killing children, the elderly and other vulnerable people by causing pneumonia, meningitis, and other serious infectious diseases.
Published today in the journal Nature Chemical Biology, the researchers describe how zinc “jams shut” a protein transporter in the bacteria so that it cannot take up manganese, an essential metal that Streptococcus pneumoniae needs to be able to invade and cause disease in humans.
“It’s long been known that zinc plays an important role in the body’s ability to protect against bacterial infection, but this is the first time anyone has been able to show how zinc actually blocks an essential pathway causing the bacteria to starve,” says project leader Dr Christopher McDevitt, Research Fellow in the University of Adelaide’s Research Centre for Infectious Diseases.
“This work spans fields from chemistry and biochemistry to microbiology and immunology to see, at an atomic level of detail, how this transport protein is responsible for keeping the bacteria alive by scavenging one essential metal (manganese), but at the same time also makes the bacteria vulnerable to being killed by another metal (zinc),” says Professor Bostjan Kobe, Professor of Structural Biology at The University of Queensland.
The study reveals that the bacterial transporter (PsaBCA) uses a ‘spring-hammer’ mechanism to bind the metals. The difference in size between the two metals, manganese and zinc, causes the transporter to bind them in different ways. The smaller size of zinc means that when it binds to the transporter, the mechanism closes too tightly around the zinc, causing an essential spring in the protein to unwind too far, jamming it shut and blocking the transporter from being able to take up manganese.
“Without manganese, these bacteria can easily be cleared by the immune system,” says Dr McDevitt. “For the first time, we understand how these types of transporters function. With this new information we can start to design the next generation of antibacterial agents to target and block these essential transporters.”
The research has been funded by the Australian Research Council and the National Health and Medical Research Council.