The result? The older mice showed blood levels with increased levels of certain niche stem cells that had returned to youthful levels. One theory is that there actually exist cell signals in the young mice which activate pathways in the older mice to return to youthful levels.

You can read a full review of the paper here, however, the paper is currently under review at Nature and may be retracted. I will await the results with interest.

Mayack S.R. et al. Systemic signals regulate ageing and rejuvenation of blood stem cell niches. 2010(463):495-500.

What is the business plan of 23 and Me?

I think for most people it would seem like the business plan for 23 and me would be to simply charge you for the service. Currently you pay around $400 for the information, down from $1000 in 2007. But I don't think that is it the end of it, from here you could see the service making money in the following ways:

1. Being an affiliate for various pharmaceutics recommended specifically for you
2. Recommending or even selling diet and lifestyle plans just for you
3. Partnering or being an affiliate for other life tracking services, like the ZEO sleep monitor
4. Licensing their data-set for scientific studies or to accelerate pharmaceutical development

It is this last potential monetization opportunity that intrigues me the most, as I find it to be the most beneficial to humanity.

How 23 and Me can Accelerate Scientific Research

I recently read an article in Wired Magazine called: Sergey Brin's Search for a Parkinson's Cure. The article asserted that a lot of genetic data combined with survey data could be used to accelerate the accuracy of genetic testing, and the correlations found in the data would predict what science is already finding. The method was used and a paper was published on genetic causes of Parkinson's Disease. The method marks a shift from traditional scientific research which is painfully slow due the process of acquiring funding, review boards, internal politics, and a general lack of capital. Some would argue that review boards are good, and they are right, however, I don't think anyone wants to argue that the lack of good cures for cancer is a good thing. I am just saying that the scientific process could use a boost.

23 and Me provides an interesting prospect for that boost. They are having consumers pay them so they can collect a mountain of data, which in turn, provides value for the consumer and provides value for science. If this was put in the light of traditional research funding, it would take millions of dollars to get everyone's genome and survey data. The whole concept poses an argument for a sea change in biomedical research. Why aren't there more companies like 23 and Me providing tests for cooler proteins, like p16ink4a, which can measure your biological age. What would be even better at 23 and Me is to submit your data every month and track changes in gene expression over time. Now that would be really interesting.

I did some investigative reporting today. On what you may ask? Well basically what it would mean for me to be a PhD student in biostatistics. What it would mean in terms of what I could do, what the future challenges are for the field, and things like that.

What I found is that the PhD program would be course intensive at first, and from there it would move on to developing novel statistical methods. The novel part is important as it also counts for the "original research" requirement so often bandied about with that PhD (Doctor of Philosophy) thing. Yes.

But on the whole, the field of bioinformatics, biostatistics, what have you, appears to be one to me that is waiting for technology to happen. That is to say, the field is less likely to be advanced by nifty statistical methodologies that somehow can predict how the human genetic code is translated to create life, and is more likely to be advanced by cheaper more effective microchips and micropossessors which can capture all that cool RNA gene expression data which is working all the time in your body and making you, you.

Of course, this now brings on a daunting information technology job. One that demands high speed high capacity servers and brings a company like Google to mind in a hurry. But also, I must say, that it also appears to me to be an appealing entrepreneurial challenge, and one which could arguably have a greater impact on the field of genetic medicine than fancy statistical/computational techniques.

Of course, in fairness, I should also say that said techniques are yet vital, and that both should at least, develop at the same time.

The novel to me centers around a satire within a satire. The first one being that cloned humans who are created for the purpose of donating organs are subhuman, born into the world without reason, and bound to an unavoidable fate of donating organs till they die. I kept on wondering in my head why the characters didn't just try to make a run for it and escape their fate, till I remembered their whole situation paralleled the human condition with death. How as the use of technology grows in our society we are all becoming dehumanized. Or trans-humanized if you will. Anyway, it was a surprisingly deep novel. I strongly recommend it.

1. Find drugs which mimic the benefits of caloric restriction. This would be things like resveratrol, and work by Sitrus pharmaceuticals.

2. Looking for clues in the very old. Scientists can study a sample of the 1 out of 7 million people who reach the "supercentenarian" age of 110 with few bad health effects. Looking at their genes or other molecular markers can give us clues to new medicines.

Previous research has already shown that levels of p16INK4a increase exponentially with age, and recent research shows that inactivation of p16INK4a alleviates progeriod (early aging) symptoms in mice, suggesting that p16INK4a expression has an effect in the aging process.

The data used in this model of p16INK4a is taken from blood samples of 170 individuals. The level of p16INK4a was measured in blood cells of a limited lifespan, as such the model had to account for declines in p16INK4a due to apoptosis or immune clearance. Two models were created for the level of expression, the first which viewed the level of p16INK4a in a synthesis/degredation dynamic and the second which only accounted for p16INK4a loss after saturation. Both models are designed to account for the exponential increase in p16INK4a, even at an early age, leading into what is seen as an asymptotic "saturation" of p16INK4a expression. Despite some attrition, not all p16 senescent cells are cleared and many remain in the body for years.

The model also contained clinical factors which all had an effect on p16INK4a expression. Namely: smoking, exercise, and the rs10757278 genotype (Single nucleotide polymorphism). As found previously p16INK4a expression is considerably higher in those who smoke and levels of p16INK4a are considerably lower if those who exercise, but the exercise works only till age 65. The reason for this is not clear. Whether exercise loses its effect or the amount of exercise people attempt after age 65 drops considerably. The rs10757278 SNP reduces the level of p16INK4a but the exact mechanism is not known. The authors speculate that it is by activating other cell cycle control mechanisms p15INK4b and ARF which increases the death rate of cells inactivated by p16INK4a.

The use of the model allows for a way to predict molecular aging on the basis of genetics and lifestyle factors. The authors conclude stating they will work to create a better model as the amount of their data increases.

Denis Tsygankova, Yan Liub, Hanna K. Sanoffb, Norman E. Sharplessb, & Timothy C. Elston (2009). A quantitative model for age-dependent expression of the p16INK4a tumor suppressor PNAS, 106 (39)

Specific organ functions rely on differentiated cells. How differentiated
cells are replaced is a fundamental question in biology
with important implications for regenerative medicine.

So begins a recent paper in Cell which has shown heart cells in rodents can be stimulated to proliferate, thus repairing any damage. Typically the heart stops proliferating or regenerating shortly after birth, so any event that causes death the heart cells, like a heart attack (myocardial infarction), is currently quite irreversible. Past research on heart cell regeneration focused on trying to manipulate stem cells to differentiate into new heart muscle cells(cardiomyocytes). The breakthrough in this paper was to focus on healthy differentiated heart cells and see if any proteins could stimulate them to start dividing and repair the damage.

The scientists (Kevin Bersell, Shima Arab, Bernhard Haring, and Bernhard Kühn) tested the signaling protein, neuregulin1 (NRG1)) which is known to stimulate heart cell growth in prenatal development and even in fetal tissue. The results showed that neuregulin1 stimulated proliferation in 30% of the heart tissue as compared with 1% proliferation in control groups.

The finding  represents a major breakthrough in regenerative medicine. The protein, neuregulin1, is administered via injection, creating a noninvasive method of heart tissue repair. Kühn, one of the major investigators of the paper, is already looking for profitable potential therapies.

Bersell, K., Arab, S., Haring, B. & Kuhn, B. (2009). Neuregulin1/ErbB4 Signaling Induces Cardiomyocyte Proliferation and Repair of Heart Injury Cell

As I read the article, I found myself asking a lot of questions, that seem obvious but that I rarely think about. Questions like: How exactly does my body repair a cut on my skin? How does it know to do it? What does it have in reserve? Why doesn't it use the same mechanism to keep my skin from looking wrinkled and scathed? How do scars form?

A sample passage:

In the skin, there are stem cells that exist within the bulge of the hair follicle and also in the basal layer of the epidermis. We still don't know whether all of the cells within the basal layer can behave as stem cells or whether only a few stem cells exist that are scattered within this layer. It's an open question of where along the lineage to differentiation is the point of no return where a stem cell becomes irreversibly committed to terminally differentiate. In the skin the point of no return has definitely passed in the dead hair cells or in the enucleated squames [squamous cells] that are sloughed off the skin. But can an epidermal cell that has exited the basal layer and begun its journey to the body surface go backwards under certain circumstances and become a stem cell again?

To answer this question, we need to have a firmer grasp of the key features of a stem cell that determine stemness.

What I suddenly realized reading the article is that all these questions of regeneration are very unknown, and the medical potential of finding out is huge, and beyond that, it would be hugely satisfying as a human to really understand how the mechanics of my body works. I would love to make a working molecular model of a human one day. (In computer simulation of course) ;)

As for the potential of stem cells? Well some wikipedians have put together a good image for that:

In the early 1880s the imminent German biologist August Weismann took it upon himself to re-evaluate the problem of heredity and found that the recent research of the era came to serious odds with Darwin's suppositions. The main change that Weismann proposed was that the body(or soma) is not responsible for governing the material of heredity(the germ line), but rather, that the germ line governed the soma, and then like any good aristocrat, isolated itself from the trials of the plebs as much as possible.

The net result of such a thought leads one to conclude that while the soma is vulnerable to damage over time, the germ line somehow remains untainted as it is passed down from generation to generation.

Another interesting result of Weismann's finding is how often great thinkers have to come along and pull together current research to create a paradigm shift in the central dogma of the time...and perhaps more to the point, how important it is to have a central dogma to be overthrown.

Could Weismann have really reached his conclusions about the germ line had it not been for Darwin's earlier (flawed) work? We can understand the appeal of Darwin's somatic-driven logic: sexual reproduction is not reached until later in life, the somatic cells seem to come first, where else could germ line material come from? Thanks to the scientific method, observational data eventually proved Darwin's logic wrong...however, it was perhaps Darwin's incorrect theory which most prompted the search for observational data in the first place.

We see a similar situation in the history of cell theory where Theodore Schwann adamantly advocated that cells originated from a kind of Spontaneous generation of sugars in the body. Again, the theory has appeal, spontaneous generation is still our current explanation for the origin of life on earth. However, as microscopes improved and the process of cell division that we now call mitosis became elucidated Schwann's work got set aside as an artifact of thought, and a new central dogma took its place.

This leaves us with two appealing questions:

1. What current theories do we have today that will eventually succumb to observational evidence?
2. What theories can we propose to challenge scientists to find observational evidence disproving our thoughts?

The theory I would like to suggest is that the stem cells of our body have the ability to fully regenerate every organ and system within the body. As the MIT tech review reported today such work at Fate Therapeutics is already underway. I can't wait to see what they come up with.