Archive for the 'Personalized Medicine' Category


Epigenomics in breast cancer

In my last post I talked about how empigenomics is a hot topic in understanding how genes get expressed in organismic development and how errant development can lead to disease. Well, here’s a specific case where epigenomics plays a role in a common form of cancer: breast cancer.

An article about research on — my favorite science news site — reports how epigenomics plays a role in breast cancer. The interesting thing is that, to understand it, you have to realize that there’s a kind of cellular double-back-flip involved. Let’s see if I can spell this out.

  1. There is a “signaling pathway” called tumor growth factor beta (TGF-beta) that gets over-expressed in some advanced cancers: in this case breast cancer.
  2. TGF-beta sustains the activity of an epigenetic molecule called DNA methyl transferase 1 when a cancerous cell divides and produces offspring cells. The combination of the two factors is key to sustaining the progression of the cancer because they block the expression of genes that have been turned off in the process of turning normal cells into cancer cells. In this case the “epigenetic environment” is essential to enabling the cancer promoting process to be passed on to new cancer cells.
  3. But if the TGFR-beta can be blocked it causes the methyl transferase — the epigenetic factor — to fade away. With the epigenetic factor reduced the offspring cells re-expresses normal genetics and retard the cancer characteristics.

In my last post on epigenetics I mentioned that epigenetics is ordinarily thought of as passing temporarily acquired factors from one generation of an organism to the next. But epigenetics happens also at the level of cell generations, and acquired, abnormal cancer characteristics need to be passed from one generation to the next for cancer cells to stay cancer cells through several generations as tumors grow.

So there you have it: epigenetics at work in cancer. But all this blocking and unblocking in order for cancer to be sustained opens up the possibility it can be disrupted by a drug and stop the disease.


Epigenetics: even Dr Oz is talking about it

A couple of days ago as I waited in line to buy a few groceries the cover of  Time Magazine among the tabloids caught my eye. The cover article was titled, “Why Your DNA Isn’t Your Destiny.” It turns out the article is about epigenetics, another one of the processes that produce options and variations in genetic impact. (A few days ago I mentioned RNA editing and how it affects gene expression.)

For a long time life scientists have debated whether some diseases or behaviors are a matter of “nature” or “nurture.” And if diseases — like various cancers — have a component of nurture (environmentally affected) how does that happen? Epigenetics is a kit of processes that modify how genes are expressed without permanently modifying the DNA that’s passed down generation after generation. Epigenetics is sort of the go-between of the nature v s. nurture conundrum. It’s another way genetics gets variability and complexity.

The odd thing about epigenetics is that things in the environment such as drugs or chemicals can change the chemical environment of DNA inside the nucleus of cells causing additional molecules (called methylation) to attach themselves to the DNA and change its expression. The result is cell characteristics that are different from unaffected genetic expression. Also these modifiers can be passed from parent to offspring, but they don’t change the DNA. The Time article says:

Can epigenetic changes be permanent? Possibly, but it’s important to remember that epigenetics isn’t evolution. It doesn’t change DNA. Epigenetic changes represent a biological response to an environmental stressor. That response can be inherited through many generations via epigenetic marks, but if you remove the environmental pressure, the epigenetic marks will eventually fade, and the DNA code will — over time — begin to revert to its original programming. That’s the current thinking, anyway: that only natural selection causes permanent genetic change.

Once again we find that the rather simplistic ideas that scientists had a few years ago about how genes turn into organisms needs to be further explored in light of this rather subtle process. All of these complicating factor might ultimately lead to disease solutions, but it’s going to take some time.

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Fireball gene machines

One of the themes of this blog — the ups and downs of the genetics revolution — just keeps on giving. Despite some skepticism about the efficacy of genetic research in finding solid diesease treatments, the likelihood of an avalanche of genetic data from sequencing seems inevitable. That trend is propelled by the furious competition of the last few years to build cheap, fast gene sequencers. The product development anticipates ubiquitous use of such information in biomedical research and in personalizing medical regimes. Two instances cropped up just this week:

  1. Illumina unveiled at this week’s JP Morgan investment conference an upgraded, updated version of its gene sequencing machine: the HiSeq2000 (in case you’re in the market). This $690,000 baby might even be tuned over the next year to bring the cost of sequencing a human genome to $2,500. Well, that’s enough for the Beijing Genomics Institute. They’re in for 128 of them! Geneticist Elaine Mardis, at Washington University in St. Louis says: “This really provides a platform that is going to propel studies of complex diseases like cancer and autism.”
  2. And, according to David Ewing Duncan on his FB page, in a stroke of one-upsmanship, Complete Genomics today promised a sequencing platform that will deliver the whole genome sequence for a mere $1,500. Remember, the so-called holy grail for human genomic sequencing is $1,000.

As Dr. Mardis suggests the availability of sequencers that can do the job so cheaply (ergo quickly) is going to shovel the coal to the fast-moving steam engine of genetics research. Skeptics would argue more data does not necessarily mean more useful results. I guess geneticists are adopting the attitude of the child in that old joke that has the punchline: “There’s got to be a pony in here somewhere.”


Genetics backlash

Uh-oh. I ran across a couple of articles yesterday that are indicative of what I’d call a backlash about genetics that has cropped up over the last couple of  years. Let’s just say that after the enthusiasm generated by the Human Genome Project and the establishment of a number of personal genomics companies, the bloom is off the rose. After all the high expectations for genomics earlier this decade, there is a lot of disappointment right now.

David Freedman’s article in last month’s Fast Company is titled: “The Gene Bubble: Why We  Still Aren’t Disease Free.” (The term “disease free” in the title perhaps shows how exaggerated the expectations for miracles from genetics have become.) The article describes how biotech companies and investors were ardently hoping that decoding the human genome would lead to specific genetic markers that would provide shortcuts in the process of developing drugs for companies desperately seeking an alternative to the drawn-out, expensive process of testing huge numbers of compounds for drug candidates.

But, Freeman points out, that’s not how things have worked out so far. Only a handful of therapeutics have come forth that can be directly linked to genomic evidence, and many of the companies that were founded on the prospect of genetic paths to products have gone out of business, been bought up, or gone to other approaches. Instead what we’ve found is that virtually all complex diseases have many genetic associations, none of which is a keystone to the illness, and additional complex mechanisms are involved in gene expression.

Freeman quotes Bryan Walser, CEO of gene-discovery company Perlegen Sciences, as he sums up his perspective:

Gattaca got it totally wrong… In the movie, genes have 100% penetration,” meaning that if you have a flawed gene, it’s certain you’ll get the disease it’s associated with. For most major common diseases, he explains, specific genes are almost never associated with more than a 20% to 30% increased chance of getting sick. Indeed, the notion that a small number of genes represents a large component of the risk for a particular disorder has simply turned out to be untrue for almost all major illnesses. And the weakness of these correlations extends to other attributes as well. The gene most strongly linked to intelligence accounts for less than 0.4% of the observed variation, while the top six intelligence genes together predict 1% of the variation. A 2009 study of about 6,000 people came up with a technique for predicting a person’s height by looking at the 54 height-related genes; the results turned out to be one-tenth as accurate as averaging the heights of both parents and adjusting for sex, a technique introduced in 1886 by statistician Sir Francis Galton.

There’s a “we’ve been had” tone to this article, not unlike the backlash against the machinations on Wall Street in the last couple of years. Freeman lays the blame for overselling genetics projects on life science companies that wanted shortcuts to profits paid for by taxpayers and to scientists who wanted to sustain themselves on a pipeline of government research grants. That’s all a bit too conspiratorial for my tastes, and it’s a perspective that comes with the clarity of hindsight. The Human Genome Project and a lot of its proffered benefits also reflect the state of knowledge — or lack thereof — at the time they were proposed. The complexity we now see reflects a lot we’ve learned from tools and techniques of quite recent origin. As has happened a number of times in life science history, we’ve learned that the fundamental processes of life are a lot more complex that we imagined.

More about this matter in the next post.


Joining the iPhone throng

When my cell phone contract came up for renewal last July I was able to convince myself that ponying-up for an iPhone and the $30 monthly data plan made sense. Besides keeping up with the cool kids, I think “smart phones” are the next great pulse in digital evolution. Having a gateway in from the internet and out to whatever data stores you want with you 24/7 is a transition that’s as big as the invention of the PC or the internet itself. IMHO the mobile here and now digital interface is the paradigm that will shape us from now on.

So today Apple — without a lot of fanfare — announced the 2 billionth app download from its 85,000 app App Store to the more than 50 million iPhones and iPods out there. Joining the iPhone herd is not a novel move. Moo!

But the function most resonant with my background and interests is the health aspects of real-time mobile connection. The new phone coincides with my own efforts at a little better health behavior. I’ve already downloaded a number of “apps” to see how they can support my program. I’ll be working my way through the mini-programs in the Healthcare and Fitness category and a few from the Medicine category on the App Store. I’ll post more later on how this is working out for me.


Patient decision aids

dr-patientHey, I found out about something I hadn’t heard about before: patient decision aids. It appears to be a movement being developed out of Canada (you know, that awful bastion of socialized medicine) with some participation from the US. Anyway, the idea is to provide patients with a body of information about the situation they’ve been diagnosed with and a process for talking it over with their doctor and reaching a mutually satisfactory decision about what to do. In the context of our current debate about health care reform one outcome welcome by about everyone is curtailing over-treatment.

A white paper from Healthwise, a nonprofit that develops the tools, defines a decision aid this way:

Patient decision aids are tools to help people participate with their doctors in key medical decisions. These aids are useful when there is more than one medically reasonable option to diagnose or treat a health problem—particularly when the options have different costs, risks, or benefits that some people might value differently than others.

This is something I want to keep track of. It sounds like a piece of Health 2.0 And it sounds like an attitude of joint participation between patient and provider that most people these days are looking for.

Oh yeah, here’s an example for herniated disc. Ouch!!

Umm, Delicious Bookmarks


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