Sunday, February 15, 2009

Epigenetic change during pregnancy

Regular readers of this blog will know that I have commented on epigenetic change before. Epigenetics is rapidly emerging as a significant contributor to our understanding of the ways in which our genes influence both behavior and disease.

Briefly, epigenetic changes to genes do not result in mutations, alterations in the gene sequence, but they do result in changes in the way a gene is translated into protein. In other words, epigenetic changes alter the phenotype (observed characteristic) of the person without changing the genotype (the actual gene they carry).

In a paper out this week researchers from the University of Cincinnati reported that children with in utero exposure to polycyclic aromatic hydrocarbons (PAH – common car pollutants) were more likely to develop early onset asthma (by age 5) and this was linked to epigenetic change in a gene associated with the development of asthma (ACSL3). Living in urban environments has always had certain risks associated with it, but as the earth’s population continues to immigrate into urban centers, we must attempt to anticipate the genetic and epigenetic changes that will result.

Since it was first described, epigenetic change has fascinated me. Certainly its association with disease is important, but even more interesting is its association with behavior. Can exposure to environmental stimulus modify behavioral norms? The early answer appears to be yes, but time will tell. Since exposure to pollutants can affect later disease in children, one wonders whether other behavior in pregnant women can affect disease and behavioral outcomes in their children. In addition, we now believe that epigenetic can be passed on to offspring – do the choices (whether chemical or behavioral) of either parent affect children in epigenetic ways that go beyond and yet reinforce decisions about child-rearing. Perhaps so…

These are profoundly interesting questions both on the personal level and on the level of community and the human race as a whole. One wonders what affect increased urbanization will have on the very structure of the human DNA. Are certain behavioral norms that are more common in cities than in rural communities being reinforced at the epigenetic level? If they are, will these traits become ever more engrained in the fabric of what it is to be human? Then, what affect will new behavioral norms have on our understanding of religious doctrines as expressed through the centuries of church tradition? Is there a genetic underpinning for what many have called the loosening of behavioral standards in some Christian traditions? Though we cannot prove it (yet), the idea is thought provoking.

Friday, February 6, 2009

Want your sequence?

New Scientist is reporting today that the cost of a complete genome sequence has dropped to a mere $5000. This announcement will lead to profound breakthroughs in genetics research - particularly in our understanding of the SNP's genomics scientists say will be necessary for use to design personalized therapies.

We will be able to know - for a relatively modest cost - the exact DNA sequences for thousands of disorders and diseases. Perhaps we will finally be able to understand the contribution of genetics to complex human behaviors.

In addition to complete genomic sequences, at least three more breakthroughs are necessary before we can take full advantage of our genetics:
  1. A computational breakthrough that can not only map the differences between genomes with billions of letters, but also cull out the significant differences in the coding sequences.
  2. A way to map epigenetic modification in genome-wide analysis. Carrying a gene is not enough, it must be expressed to contribute to a person's phenotype.
  3. A database of human disease that contains what is now considered to be private information for comparison to genetic information.
When mapping technology gets down into the $100's of dollars range, look for a push for large scale enrollment in a genetic disease database.

Friday, January 9, 2009

Self-replicating RNA

Yesterday, NPR reported on an interesting experimental system developed at the Scripps institute in La Jolla, CA. The article, published this week in Science describes the creation of a set of self-replicating RNA molecules.

While this may sound a bit bland to the casual observer, it is a significant breakthrough for evolutionary biologists. For many years biologists have theorized that the earliest molecules of "life" must have been RNA rather than DNA. Their speculations were fueled by the fact that RNA molecules make much better enzymes than DNA molecules - therefore, they must have evolved first. It has been postulated by many that the earliest "life-like" molecules must have been self-replicating RNAs of some kind. Interesting theory, but the evidence was lacking. No one had been able to show that simple RNA molecules could be self replicating in the absence of proteins and DNA; until now.

Tracey Lincoln and Gerald Joyce were able to create short, simple RNA molecules that were capable of replicating themselves indefinitely. Are these molecules alive? Do they represent the earliest form of life on planet earth? No, not yet. Single, self-replicating RNA molecules do not display several of the characteristics of life and are therefore not alive. They cannot acquire and process energy and they cannot respond to their environments - Not life.

But Lincoln and Joyce did not stop there. They were able to design about a dozen different self-replicating RNA molecules. The next question - could they compete for limited resources and if they did, would they evolve to be more competitive. The answer - YES! Several of the molecules were more efficient than others at gathering building blocks and they were able to out-compete the others. Even more interesting, some of the molecules were able to mutate to become more competitive and these altered replicators were able to reproduce themselves.

Are these collections of RNA molecules alive - no, at least not in the view of the authors of the paper in Science. They state quite strongly that their self-replicating RNAs are not alive. But they are a step toward that end. Others labs are working hard on creating artificial life and they will learn some significant lessons from the publication of this work. If life can be created in vitro, I suspect that it will be done in 20 years time.

What affect on Christian Faith? As regular readers of this blog will know - that depends on your view of origins.

The young earth folk will quickly point out that of course, created molecules can replicate and mutate... but they were created to do that. This data underscores the idea of a Creator. Of course in saying that they are ignoring their own basic premise that God created all systems complete and perfect. No need to change - change is bad, it leads to disease.

The old earth crowd/evolution will be quick to point out that this "proves" that RNA was at the heart of the earliest forms of life. These experiments demonstrate that RNA could have been there, but they do not definitively prove it is so.

So what should we do with this evidence. The prudent scientist will weigh it, watch it, and withhold judgment for now. The formation of self-replicating, minimally evolving RNA molecules is interesting, but not world-view shattering. This is one more bit of evidence in a long litany of evidence about how things might have happened. One of the maxims of science is that "what the evidence indicates now" may be altered by future experiments. So we wait. If this is another of the "black boxes" or solved mysteries that science is so fond of working at, then we should be careful to build our faith on something other than what we don't know now. Our faith should be built on faith in the living Triune God, and not on the mysteries in the creation that we don't understand.

Thursday, September 11, 2008

I was reading the blog of a friend of mine (Paul Kind) this morning and it started me thinking about the role of community in modifying behavior.

Here is a portion of his post:

"It seems to me that selflessness over selfishness is a near universal value. Every faith points us in this direction. Whether you follow the teachings of Jesus, Abraham, Muhammad, Siddhartha, or otherwise, selflessness over selfishness is at the core. It's trumpeted in politics, in the church, and in the workplace. And yet I imagine you would agree with me that so many of us have a long way to go in this quest.

Would it be accurate to say that the quest from selfishness to selflessness is at the core of every faith system?
Is this one of the main quests of life???"
(W)hat role can other people play in helping us along in this quest?

My response:

A different spin -

What if the naturalists are correct and there is a "selfish" gene and a mutated version of the same gene that I will call the altruism gene... Then, our natural tendency would be to get everything we can so we can spread our genes as far and wide as possible. He who has the most toys, fathers the most children, and wins a swim in the deep end of the gene pool.

But - in our present society altruism is seen as a virtue. Denying self holds a high place of honor. This would tend to favor the emergence of the altruism gene. The trouble is this: does personal altruism increase or decrease the ability of the individual to reproduce? Is the altruistic trait passed on, or genetically squelched out?

An individual who sacrifices themselves for the sake of others may be more likely to die before reproducing thereby reducing the tendency for altruism to be passed to his offspring. However, if the individual is part of a community that holds heroism and altruism in high esteem the trait may still be preserved. This is because of another mechanism that regulates the way genes are expressed known as epigenetic modification. The environment, or the local community, can increase the tendency toward certain behaviors by modifying gene expression. Notice the difference, the community is not changing the sequence of the gene for selfishness, simply altering its ability to be expressed.

Religion offers an opportunity to move away from our natural tendencies of selfishness and toward selflessness. In closely knit religious communities it is fairly common for an individual to sublimate their own needs to meet the needs of others. This tendency is reinforced constantly by the community ethos and conversation. These communities may cause epigenetic modification of the "selfish gene" thereby preventing, or at least decreasing, its expression.

As with most complex human behaviors it is imprudent, and probably unwise, to suggest that a single gene controls what a person does. Behavior is complex and likely controlled by genetic factors, brain structure, experience, and a host of other factors. Still, the role of community and faith in shaping the genetic component of behavior is fascinating.

Christianity may offer the best path to selfless behavior because of its emphasis on the supernatural nature of the pursuit. I cannot claim to know how the supernatural intersects with the natural - God works in mysterious ways - but what if one of the ways he works is by drawing people into community, thereby affecting gene expression, and changing behavior. That would be a tremendously complex system to bring about a simple result... sounds a lot like biology to me.

Friday, August 22, 2008

Germs, cancer, and providence

The August 1, 2008 edition of the Journal of Immunology contains a fascinating article by the AAI’s new president, Olivera Finn. Dr. Finn has been a cancer researcher for more that 20 years, working on the mechanisms whereby the human immune system recognizes (or fails to recognize) tumors. She is the discoverer of MUC-1, a glycoprotein that is found in an altered form in many different kinds of cancers. Dr. Finn’s contributions to the science of immunology are impressive, but her article reveals a woman who thinks even more deeply about the roots of disease and wellness as they relate to immune system function throughout life.

For the last few years there have been suggestions in the literature that exposure to infectious agents early in life is essential for the prevention of allergies later in life. The hygiene hypothesis implies that rearing children in an environment that is too clean might cause them to have more allergic illnesses in adulthood. In he paper, Dr. Finn extends the hygiene hypothesis to include cancer as well. In her work, both in vitro and in vivo, patients who had certain infections at a young age developed protective immunity against both the infectious agent and to a group of antigens called tumor-associated antigens. As adults these individuals had lower incidence of cancer.

Have you ever been confronted by someone who says: “How can you believe in a God when the world is full of disease and suffering?” What if it turns out that there are reasons for infection and disease that are part of an even larger plan we know nothing about? While I am not suggesting that I know the whole reason, research like this makes me wonder if we are just seeing the tip of some infinite rationale?

Even more intriguing is Dr. Finn’s penultimate paragraph where she suggests that there might be a very small subset of proteins that could comprise a “universal vaccine” capable of preventing all forms of infectious disease, cancer, and autoimmune disease. Her theory is intriguing, though scientifically mind-bending. It makes me wonder, is this a form of divine providence, heretofore unknown? Time will tell.

Saturday, August 16, 2008

Update from APA

For the first time since my wife completed her PhD I am a guest at a professional conference. It is really a terrific feeling seeing Kay in her element and respected for her work. But that is not the subject of this entry.

I attended an interesting talk yesterday afternoon on Rhesus monkeys. The researcher, Dr. Steven Sumi, has worked with a large colony of these animals for over 20 years. They are genetically similar to humans, as are most primates, but are not our closest genetic relative.

If you carefully observe these animals you will notice that there are several sub-populations within the larger family groups. The subject of this study was a population (5-10% in the wild) that is overly aggressive and prone to taking serious risks, including alcoholism and binge drinking. These little monkeys are mostly male, and - if their behavior cannot be corrected - are kicked out of the family and not allowed to return. Aggressive behavior is not welcome in these matriarchal family groups.

Tie to genetics - In humans several genes have been associated with risk taking behaviors, alcoholism, aggression, etc, including (but not limited to) an uptake transporter for the neurotransmitter serotonin (5-HIAA). According to Dr. Sumi there is a single nuceotide polymorphism (SNP) that causes the amount of the transporter to be dysregulated (lower than normal). (At this point I need to pause and point out that I am at a psychology meeting and not a neuroscience meeting. While the behavioral aspects of Dr. Sumi's talk were excellent, his presentation of the genetic and molecular data was rather weak. I suspect that he collaborates with a group of geneticists who do that aspect of the work.)

Back to the presentation - interestingly, the mutation in 5-HIAA that we see in humans also shows up in the Rhesus monkey... and only in the group that is overly aggressive! There seems to be a strong, positive correlation between the presence of the mutated 5-HIAA and aggressive, risky behaviors.

Left alone the correlative relationship of gene to behavior would be interesting, but watch this: if a baby monkey with the bad version of 5-HIAA is reared by an experienced mother with good mothering skills the effect of the bad gene can be completely reversed!!! This represents an excellent example of nurture overwhelming nature.

What's missing? Quite a bit actually. First, Dr. Sumi never intimated whether these animals were homozygous or heterozygous for the mutated 5-HIAA, so we have no way of knowing how much of a contribution was made by the mutated gene. As far as I can tell, no knock-in, knock-out, or RNAi experiments have been done on these animals to determine the full measure of gene involvement. I would suggest that this research needs to be expanded by the molecular biology community.

One last observation made by Dr. Sumi bears mention. The mutated form of 5-HIAA is only seen in the most widely dispersed and biologically successful primates: Rhesus monkeys and humans. He suggested that the reason this gene stays around in the gene pool is that it is necessary for our survival as a species.

Monday, July 28, 2008

One of my favorite places

I am sitting in a lodge on the side of a mountain in Grand Lake, Colorado and I must confess that this is one of my favorite places in the world. Partly for the scenery, but mostly for the community, solitude, and environmental ethic of this little corner of heaven. Shadowcliff lodge was founded several decades ago on the premise that a mountain resort could be built on sustainability principles. Since that time, they have endeavored to buy locally (as much as possible), recycle everything possible, use limited electricity (purchased from renewable sources), and limit the amount of water used. They have been very successful and this place has become a summer-time haven for like-minded people who enjoy the mountains.

So, I will be here for the next few days. Internet access is somewhat limited, but there is plenty to do. Adam, you would love it here.