Personalized medicine starts to hit its stride

The flexible genome [pic from nature.com]

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.

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.