Wednesday, April 15, 2015

Personalized medicine starts to hit its stride

Image result for Epigenetics
The flexible genome [pic from]
I recently attended a conference at Harvard Medical School on big data and translational medicine.  Translational medicine is the discipline that links scientific discovery (bench insights) to patient care (at the bedside, hence the term that is sometimes used..."bench to bedside").  The general idea is that we never have a truly clean slate of health.  We are conceived, born, live our lives and eventually die.  During this time, we are in a constant state of change. While we have  a solid set of genes in our personal genetic code, they are under considerable pressure from other elements such as regulatory genes and epigenetic signals that are influenced by an individual's internal and external environment.  Some of the changes wrought by these elements are permanent and others are transient but either way, they affect the expression of the our genes in real time throughout our lives and constantly nudge us towards disease.  Add to the mix DNA repair mechanisms that also become less effective as we age, and the scene is set for our gradual demise from before we are even born. At any given time, we have a number of mutations and damaged physiological systems that do not constitute enough for overt disease.  Over time, these effects multiple and at some point we will experience a symptom or two and eventually, a diagnosis.  By the time the symptoms appear, the disease has become quite complex and pervasive, and because of this it is much more difficult to treat. If it could be caught in the earlier stages where there are fewer factors involved, and fewer compensatory systems triggered, it could potentially be nipped in the bud. This is one major goal of translational medicine- to identify the unique signals that show disease or disease risk at a stage where treatment is likely to be more targeted and more successful.

Everything above is old news, but the conference revealed exciting new directions for translational medicine.  For the first time, I have hope that personalized medicine is really starting to become a reality.  Large data sets are being collected, not by physicians or pharmaceutical companies, but by patients.  Over 95% of these patients are allowing their data to be used for massive projects that will attempt to connect early signs and symptoms with the risk of various chronic diseases.  Linking seemingly insignificant phenotypic changes to chronic disease development will eventually allow serious diseases to be detected before they become fully fledged and more entrenched.  For instance, already we know that slow blink rate is related to Parkinson's Disease and this can be used as a flag to look for additional symptoms in patients who are at risk of  Parkinson's.  Whether medicines can be developed and given to patients at these very early stages remains to be seen, but a critical step is incorporating some of these phenotypic or 'patient-reported-outcomes' (PROs) into clinical trials so that the more subtle signs associated with disease can be used to monitor effectiveness of treatments in early stages.  Big data is crucial here, and that patients are willing to share their data at such an unprecedented rate is remarkable.  I have had ideas about epigenetic disease triggers, PROs as trial endpoints, and very early disease intervention for many years, and to see it start to come together as translational medicine is absolutely thrilling to me.
I believe we are on the edge of a precipice and that this science will now begin to accelerate on a logarithmic scale.  Astra Zeneca just signed a nice deal with PatientsLikeMe, which is a strong indication that personalized medicine is about to go mainstream.  I can't image a more exciting time to be in healthcare.  Now, if we can also figure out the economics of the system and make that work in favor of the patient versus the insurers, we would be firmly on the path to better health for all.

Sunday, February 24, 2013

The probiotic...glow?

I have pondered the validity of probiotics many times over the past couple of years, wrestling with the boundless enthusiasm of Jamie Lee Curtis versus the seeming lack of solid scientific data.  I learned at the Digestive Disease Week conference in San Diego last year, that one would have to eat about 6 probiotic yogurts a day to get enough of the beneficial little beasties within to make much of a difference to the symptoms of, say, irritable bowel syndrome (IBS).  At the conference there were several vendors hawking probiotics and even a 'Probiotics for Dummies' booklet.  I remained sceptical.
Since that conference I have read quite a bit on gut bugs, more correctly known as the gastrointestinal microbiome.  Overall, we have ten times more bacteria in our bodies that we have actual cells, and a hefty chunk of those are in our lower intestines.  So what difference would adding a few more possibly make?
Well, aside from the assertions regarding internal effects, a new paper has suggested probiotics may have a more visible benefit that may even confer an evolutionary benefit.  Researchers from Greece, Canada and MIT in the US, noticed that the fur of mice being fed probiotic yoghurt for studies on intestinal effects became unusually lustrous as the experiments progressed.  They followed up with a separate study on the effects of the probiotic yoghurt on the fur and indeed found daily consumption of the yoghurt with the probiotic microorganism Lacotobacillu reuteri (L. reuteri)  resulted in thicker skin and more lustrous fur, that was in part related to an effect on the immune system. To be sure it wasn't the yoghurt itself that was responsible, in a separate group of mice the investigators supplemented the diet  with the L. reuteri bug in drinking and found the same effect.  What's more, they also found increased acidity in the mucous membranes of the animals which they associated with increased fertility. The investigators thus concluded that the 'healthful glow' imparted on the animals from eating the probiotic yoghurt ( or drinking the 'good bug' in water) was an external display of fertility. Studies in humans are sure to follow, faster than you can say Activia. In the meantime, I am off to see what's in the 'fridge....

Levkovich et al. Probiotic Bacteria Induce a ‘Glow of Health’. PLoS One. 2013; 8(1): e53867.Published online 2013 January 16. doi:  10.1371/journal.pone.0053867

Tuesday, January 1, 2013

That was 2012.

A new year, a new resolution to blog more.  Of course, it never translates into me being more productive.   However, I am starting with a new blog post to kick off the year and as part of it I thought I would review what I learned in 2012 and what I am excited about for the coming year.  My major discovery last year was the world of epigenetics, acquired through a writing opportunity to cover the COST conference on Personalized Medicine that took place in Cyprus last June.  The conference was definitely the highlight of my work year and I hope to do it again this coming year if the follow-up goes ahead. The conference was designed to bring together practitioners of diverse disciplines to discuss personalized medicine from a number of perspectives and I was lucky enough to interview many of the participants and write up the summary of the conference.  Physicians, physiologists, engineers and philosophers were just a smattering of the perspectives represented. The field of epigenetics (the study of heritable influences on the genome, caused directly or indirectly by  environment and experience) was new to me, and I talked to as many 'experts' as I could about it and I came away convinced that the next major breakthroughs in medicine will be in epigenetics.  I also came away feeling that the most significant current hurdle we must address as scientists and physicians is overcoming our inability to put the complexity of our current health environment into manageable and communicable frameworks. We will only be able to do this if we start to think about problems holistically and top down, rather than from a reductionist perspective which by definition, is bottom up. The Parmenides Institute in Munich is at the forefront of this quest and on my wish list for 2013 is a visit to see Prof Albrect von Mueller at the institute to learn about the work and the tools being developed to expand cognitive reach in children and adults.
In mid 2012, I started a new job as scientific director of a medical communications agency; while I loved freelancing, I needed a regular income to pay for college and for health insurance.  I miss the freelancing lifestyle, but the new job is fun too.  I traveled quite a bit and already have much more planned for 2013. I also learned more than any normal person ever needs to know about the GI system. This coming year we have plenty of other areas of interest in the offing, including my favorite, neuroscience.   I am also exploring new business opportunities with a few friends, and I'll have more on that over the next few months.
In August last year, I wrote an invited editorial for the Personalized Medicine journal on crowdsourcing science and am following up with something similar in a cancer journal in the first quarter of 2013.  Crowdsourcing has its place in research but I think it needs to be used carefully. I'm looking for good examples in cancer at the moment if anyone has anything they'd like to share.  I will place a link on the blog when this one is published later in the year.

I'm always positive about the new year even though I don't much care for New Year's Evening festivities.  I like to look forward, and this year is no different. This year I'm going to work towards a few more publications as well as getting some of my less nerdy works published.  I hope to explore some academic connections and play my role to get the new business going.  With some luck and hard work, I might even finish the book I started 18 months ago. 

Overall, I plan to write much more this year (as I do every year!), but this year, I MEAN it.  Ha, ha. We'll see

Sunday, April 15, 2012

Smart parents raise smart kids-right?

Smart parents raise smart kids, but not for the reasons we all might think.  Making them do their homework, impressing on them the importance of reading, studying, paying attention in class, and generally being committed students, all give our kids the best chance at being smart-right?  Well, it turns out yes, and no.  While all the tricks we parents think we must teach our kids help them make the most of what they've got, what they end up having appears to be as much to do with what we gave them at conception, than whatever we've done for them since.
A large group of scientists running a project with the intriguingly mysterious name, Project ENIGMA, have discover that intelligence is probably affected by our genes to a greater degree than previously thought.  The researchers, from all across the globe pooled their resources and their data to look for correlations between DNA and specific brain disorders (the usual- dementia, depression, Parkinson's, schizophrenia, etc).  While they came up with some interesting data on the diseased brain, what they inadvertently uncovered was a connection between DNA and brain size, and even more curiously, between DNA and intelligence as measured by standardize IQ tests.  IQ tests look for a certain type of intelligence so the data has to be viewed with that in mind, but it appeared that a variant in a gene called HMGA2 may be able to explain differences in individual intelligence.  The difference in the HMGA2 was in one DNA letter only; at one point in the gene, the base thymine (usually represented as T), was replaced by a cytosine base (C).   People that had the letter C instead of T at a certain location on the gene were more likely to have a larger brain and score higher on the IQ tests.
This finding isn't really an answer to the question of inherited intelligence, but rather the starting point for many questions.  Correlation is not the same as causation and the size of the brain, the high IQ score and the genetic change, may all be linked by something else in the brain not yet found.  However, the association is interested and the methodology used by Project ENIGMA even more interesting.  Because it is difficult to obtain enough tissues in any one lab, to conduct thoroughly sound statistical analysis on genetic variations that only occur in a certain percent of the population, the researchers banded together to pool their brains, literally.  All the brain samples and data from each of the participating labs were used to look for associations between genes, brain size, disease risk and IQ test ability.  Without the collaboration, the project would not have been possible. The nature of the work and the extent of the collaboration has attracted hundreds of financial contributors that has ensured the success of the work.
So does this mean we should kick back as parents and let nature take its course?   Not at all.  Intelligence is only useful when harnessed appropriately, and usually (with notable exceptions), that happens through the cultivation of good study habits and the development of some level of self- discipline. When I was doing my PhD, someone told me that it would require one third pure hard work, one third organizational skills and one third smarts.  I never forgot that, and found it to be just about spot on not only for my PhD, but for pretty much every piece of work I've done since. Intelligence is only part of the picture.

[JOURNAL REFERENCE-Jason L Stein et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 2012; DOI: 10.1038/ng.2250]

Sunday, April 1, 2012

Another slice of cake?

I'm watching CBS 60 minutes with Dr Sanjay Gupta telling us how sugar is poisonous and speaking to a doctor who is recommending that men eat less that 150 calories worth of added sugar per day, while women eat less than 100.  The report is interesting; the effects of just s sip of soda stimulates the same part of the brain as hard drugs like cocaine, and continued consumption of sugar lead to a tolerance similar to that experienced by drug addicts. In other words, the more  you eat, the more you are driven to eat.  The chemical at the heart of this is not picky.  However we get dopamine to release from brain cells, be in sex, drugs or rock and roll or now... sugar, we are driven to need more.   OK, so we eat a lot of sugar. So what?  As long as we reduce our fats, red meats, bacon, chips etc, we are basically OK- correct?  As long as we control our weight somewhat, and lay off the chips we should be fine- right? Not even remotely.  A study being discussed on the show, took young adults and carefully controlled their diets for a period of time while monitoring their physiology and biochemistry.  They had blood drawn and were scanned throughout the study period which had them eating a non-added-sugar diet for the first few days of the study, followed by a diet with 25% of their calories in the form of sugar; still a relatively low amount of sugar by American standards (on average we consume about a third of a pound a day).  Blood samples were drawn every 30 minutes and the added- sugar consumers showed significant increases in small dense LDL cholesterol (the bad kind that clogs the arteries) within two weeks of eating the diet with 25% sugar.   For those old enough, you might remember that in the 70s the government restricted fat in the diet.
There was a short term benefit, likely due to increased awareness of dietary causes of disease and the number of people who reduced their intake of saturated fates.  However, the effect was not sustained.  Doctors not he show suggested we have replaced that fat with carbohydrates, and refined sugar in particular.  As one researcher pointed out, food without fat tastes like cardboard, so the food industry upped the sugar content to keeps palates satisfied.  Now, cardiovascular disease is back on the increase and our children may be the first generation to have a lower life expectancy that their parents.

So the sugar in our diet does as least as much harm to our cardiovascular health as fat, and maybe more. But the story doesn't end there.  Obvious effects of increased sugar are obesity, metabolic syndrome, and diabetes, and all of these diseases have peripheral effects.  Less obvious is the effect of sugar on some cancers. Because sugar stimulates increases in insulin, it also catalyzed the growth of certain types of cancers.  Almost a third of common human cancers contain insulin receptors that circulating sugar latches onto and triggers the tumor cells to take up the glucose to use for cell growth.  Basically the tumor cells highjack our blood sugar and uses it to feed itself and grow.  Exactly whether the sugars in the blood cause the tumor to begin or just nudge it along once it has become established makes no difference.  Sugar is good news for cancer, and bad news for us.

There is much more to the sugar story that I'll save for other blogs but as we think about how to balance our diets, it's worth thinking about the role of the food industry in our food choices.  Since I still have the TV on, I'm catching a few ads I haven't seen before.  In one, Con Agra is encouraging us to buy their products and is promising one meal for a hungry child for ever specially marked package we buy.  This sounds incredible and I am sure there is good will behind the gesture. Certainly, there are too many hungry kids in America today. However, the foods that Con Agra is asking us to buy includes Snack Paks, frozen chicken nuggets, Chef Boyardee and others, all of which are high in sugar.  We buy and eat a package of processed food that will go a little way towards poisoning us (some might think that's too strong a word but based on what I have read and hear, I don't think so) and in return Con Agra will feed a child.  Does this make anyone wonder exactly how they will be feeing that child?

And finally, as I complete this blog, I just saw a fantastic commercial on the TV with a diverse group of vibrant people stripping open their coats and cardigans to unveil bright red shirts with 'I'm unique', I'm A Vailable, I'm a dreamer....etc, as they run, walk, dance, around some city. It seemed like such a positive commercial, celebrating all that is good in the world- courage, difference, creativity.  Imagine my disappointment when I realized what the ad was for.   Dr Pepper.  Ugh.

Monday, January 9, 2012

Staying sane in the world today

Fish House play against a moving back wall at The Workshop in Mystic, CT
After reading this in Fast Company I think I may be a Genfluxer.   I usually dislike labels but I"m happy to adopt this one.  Genfluxers are comfortable with ambiguity, recognize that the future is inherently unstable, and wallow in chaos like pigs in muck.  That describes me pretty well and according to the article I am in good company.  Pete Cashmore, who runs Mashable is in there- he is a hero of mine.  Beth Comstock and Susan Peters  are shaking it up at GE. Baratunde Thurston is digital editor at The Onion and is a quintessential GenFluxer according to the article.   Social media and the Internet have created a fast-changing world that challenges many traditional notions of how work gets done. Knowledge Management (KM) was a discipline of sorts that grew up in the same time frame of Fast Company magazine and as I read the article I reflected on what it means to know what you need to know in the current environment.   Never before has it been so easy to gather information.  Just typing in a term into a search engine will get you a plethora of hits and comprehensive overview of your topic.  Some have suggested that the ease of information gathering has a down side in that you get what you ask for. And little else.  Serendipity is more elusive when you look for something directly, versus scanning through a magazine shelf and happening upon an interesting snippet that sheds new light on a particular problem.  A recent article in Intelligent Life magazine on the loss of serendipity in the digital sums it up nicely. Knowing what we know and don't know has perhaps never been easier, but the challenge now lies in asking the right questions and in not being too comfortable with your answers.  What seems right one day, may indeed be quite wrong on another depending on context.  Being open-minded and ready to shift perception based on emerging information is critical in today's environment.  For better or worse, we can no longer sit back and feel accomplished in our understanding.  I, for one, am comfortable with that although sometimes it feels easy to get left behind. Really, though, it may not be being left behind that is important thing to worry about. Rather, being too caught up with every changing view and losing sight of the big picture may be the greater danger.  That seems to me to be a recipe for burnout.  For individuals and companies wishing to keep their footing in the rapidly swirling environment, it seems that cultivating an open mind, getting comfortable with ambiguity, and being somewhat brave, may be the best approach to staying sane and, with luck (yes luck), finding success.

Friday, December 30, 2011

In 2012 I will be thin.... or will I?

The end is nigh.  Or so it seemed a year or two ago.  Now, it seems that the end of the world has gone off the boil and the race for the 2012 Republican nomination is eclipsing all talk of Armageddon.  As we begin this new year, millions of people are starting to act on new year's resolutions that will involve eating better, exercising more and possibly being nicer.  Working harder may factor in, and earning more is a no-brainer.  All of these will last at most a month or two and by Valentine's day the gyms will be empty and the larders stocked once again.   We humans are so predictable.  We love new beginnings but we are terrible at sustaining behavior change, especially if involves some effort, and getting fitter surely does.  Today on NPR, I heard Tara Parker-Pope (try saying that 10 times after a few beers) talking about her struggle with weight.  Tara is a health writer so for her to admit to weight issues is big and brave but the personal touch she brings to this story makes it convincing.  Her story, The Fat Trap, in this week's New York Times magazine and a telling  Q&A about it on line today, reports from the scientific literature on the memory of fat cells and their quest to keep themselves full.  She discusses the evidence that once a person becomes fat, their body will always try to maintain that weight despite all efforts to become slim.  A slim person who has once been fat will gain weight much more easily than someone of the same weight who has never been fat.  If this is true (and the article is compelling), then perhaps we should be less judgmental about people who start the fitness resolutions and then seem to give up so soon.
Researchers have shown that when women lost a significant amount of weight, even one year later, their levels of certain hormones were abnormal- ghrelin that stimulates hunger was unusually high, and peptide YY that usually suppresses hunger was below normal.  The cards were stacked against thee women even after they were no longer overweight.  A 2010 study found a number of gene variants that correlate with higher body-mass index.  One variant, known as FTO is carried in about 65% of Europeans and Africans, and up to 44% of Asians.  Whether we have one or two copies of this gene appears to correlate with weight and it seems that it may play a role in how we eat.  Genes, however, are likely only part of the problem.  Food cues are another.  We live in an environment that is saturated with food messages, images and cues to eat high fat, high sugar foods.   For people who have lost weight, their emotional response to food may be greater than slim non-dieters.  They also burn less energy than their non dieting counterparts for a given amount of exercise.
From all the data, it seems it's a hopeless situation, but Ms Parker-Pope feels it's better that she knows what she is up against and I feel the same way.  One of the surest ways to fall off the wagon is to have one day's blowout and then feel so bad you never get back on it.  Knowing that there are forces at work that your thin friend may never have to deal with, might actually strengthen the resolve to stick with the diet or the exercise plan.  Most importantly though, it seems we should not become overweight to begin with.  This underscores the value in educating children about balanced eating.  We need all the help we can get to maintain a healthy focus on food, diet, and exercise in the current world of information overload and dietary excess.  It's difficult enough to know what to eat and how much as an adult.  To teach our children to eat when they are hungry and to exercise as much as they can seems the responsible thing to do as a parent even though it's difficult with every other ad on TV being for some sugary or greasy snack.  For all of us, eating to satisfy hunger and getting out there and walking to work when we can, is a healthy prescription that we shouldn't sweat over, but just do our best whatever our biological odds.

Sunday, October 30, 2011

Dreams are real

When I was young I had a recurring dream that I was in a small town in a desert and I had lost my parents.  The town was a colorful collage of dusty roads, bright tents and intense citizens cloaked in veils and robes, their faces hidden from me at all times.  I somehow knew it was a dream but was powerless to change the direction. I was always lost, always without parents, and never able to escape the desert.  Lack of control in dreams is the norm for most of us but not for a small number of people who can experience lucid dreams.  Whilst in the dream state, as recorded by brain activity showing Rapid Eye Movement phase (REM sleep- the phase that is associated with dreaming), lucid dreamers can respond to external commands and can direct the course of their dreams.  This is a learned skill that has recently been put to use to determine whether brain activity in dreamers correlates with movement in non-dreamers.  German scientists at the Max Planck Institute in Leipzig, in collaboration with scientists from the Charite hospital in Berlin, put sleepers into a magnetic resonance scanner and asked them to indicate when they were in a lucid dream state via eye movement.  The lucid dreamers were then asked to dream themselves clenching a fist while the researchers monitored their brain activity.  It seems the brain lit up in the same way as when the dreamers were awake and actually clenching a fist.

The major difference between dreaming and acting while awake seems to be the physical paralysis that accompanies the dream state that stops us from us from acting out the dream.  In some people this mechanism appears to be defective though.  People that develop Parkinson's Disease or a form of dementia called Lewy Body disease, sometimes suffer from sleep disorders where they appear to be acting out their dreams long before the actual disease appears.   These disturbed sleepers are usually unaware of their nighttime antics which can cause harm to their bed partners through punching and kicking. Violent nights that leave the sleeper oblivious can go on for up to 50 years before the Parkinson's or dementia reveals itself and occur in 60-80% of patients.  My own father who I have blogged about often, would throw himself out of bed or hit my mother with force during his sleep for about 10 years before he received his diagnosis of Lewy Body.   She would retreat to another room as an act of self-preservation on those nights where he was active, and complain to me that he was 'at it again.'  Never once did either of them mention it to the doctor, and I didn't know there was a connection with brain disease until much later, when other symptoms had started to appear. 

Now, the question of why this occurs in this at-risk population is a hot topic for research.  One has to wonder whether the sleep disorder is cause or effect of the final disease.   A quick review of the literature finds the jury out on the actual mechanism of the disorder but in the meantime, any regular violent night time behavior, particularly where the sleeper is unaware of the problem, warrants a check up at the very least.

Reference: Max-Planck-Gesellschaft. "Scientists measure dream content for the first time: Dreams activate the brain in a similar way to real actions." ScienceDaily, 28 Oct. 2011. Web. 30 Oct. 2011.

Tuesday, September 27, 2011

Hey, We're Number ... Uh ... 36! | Truthout

Hey, We're Number ... Uh ... 36! | Truthout

Genes, diet, and most of all access to good healthcare all contribute to the poor ranking of the US in life expectancy- number 36 according the United Nations, and number 50 from CIA factbook estimations. We spend far more than any other country on healthcare but there is so much disparity in quality and access that one person may die of a highly treatable condition while another exists for years on rounds and round of expensive cancer therapies with a very low quality of life. How we let this stand is an interesting question and perhaps relates to the 'haves' being the ones with the voice, but not realizing the plight of the 'have-nots'. Any comments on why we are not up in arms about these statistics?