Our experiences don't just last a lifetime.....

Lasting Epigenetic Influence of Early-Life Adversity on the BDNF Gene.

Roth TL, Lubin FD, Funk AJ, Sweatt JD.

Department of Neurobiology and the Evelyn F. McKnight Brain Institute, University of Alabama-Birmingham, Birmingham, Alabama.

Biol Psychiatry. 2009 Jan 14. [Epub ahead of print]

This is an interesting study which again shows inheritance of acquired characteristics.But there is more to it. Read on.......

“In this study, researchers found that rats raised by stressed mothers that neglected and physically abused their offspring showed specific epigenetic modifications to their DNA. The abused mice grew up to be poor mothers, and appeared to pass down these changes to their offspring. Previous research has shown that bad rat mothering can be passed down through this kind of DNA modification--but those changes are thought to be triggered specifically by maternal behavior. In this study, researchers also had healthy mothers raise the offspring of stressed mothers, and found that the problems were only partially fixed. That suggests that the changes were not due to their neonatal experience but were already there when they were born.”

- From: "A Comeback for Lamarckian Evolution? – Technology Review (published by MIT) Wednesday, February 04, 2009.

Also read a mini-review by the author of this paper published in Biological Psychiatry.

The results of the papers discussed in my last two posts suggest that childhood experiences could make lasting impressions on the individual. This may be due to epigenetic modification of DNA. These DNA modifications have a profound effect on adult behavior of these individuals. In addition, these researchers claim that the offspring of these individuals too have the same DNA modifications. This can occur in two ways: First, a hormone or some other factor (a gene altering factor) produced by individuals exposed to these stimuli can alter genes in the germ cells, probably by DNA methylation (or other epigenetic mechanisms). This is particularly important in females because they are born with all the eggs that they will ever have (spermatogenesis in males, on the other hand, is an ongoing process and occurs during in the entire adult life of the male). Second, the hormone/gene altering factor may not affect germ cell directly, but may affect the DNA methylation pattern of the fetus as it develops in utero.

In either case, the hormone/gene altering factor is a throw back to Darwin’s theory of Pangenesis. Pangenesis, which was Darwin’s take on Lamarckism, was based on the idea that somatic cells would, in response to environmental stimulation, throw off 'gemmules’ which traveled around the body (though not necessarily in the bloodstream). These pangenes were proposed to be microscopic particles that supposedly contained information about the characteristics of their parent cell, and Darwin believed that they eventually accumulated in the germ cells where they could pass on to the next generation the newly acquired characteristics of the parents. Thus, it seems like the days of Lamarck and his theory of inheritance of acquired characteristics are back. The next challenge is to find this factor or hormone that brings about inheritable epigenetic changes. It is unlikely that the same hormone is responsible for specifically modifying a wide variety of genes. We are probably looking at a family of related “messengers”. It is also highly improbable that we are going to discover a totally novel class of such agents. It is more likely that certain known molecules have this additional function. The stage is set for a landmark discovery and it will come sooner rather than later.

At this point, I would like to draw your attention back to my first post on Lysenko. Lysenko’s research was on improving crop yields by propagating desirable acquired characteristics in plants. His research was thrashed as “not having a rational basis”. Today we know that there is a rational basis for his theory. I am not suggesting that Lysenko was right (only time will tell). However, what I am suggesting is that the rational basis for anything in science is based on existing knowledge. What is thought to be impossible today may become possible tomorrow. We should never be too hasty to dismiss anything as a scientific impossibility.

Transgenerational rescue of gene defect - Lamarckian style!

Transgenerational Rescue of a Genetic Defect in Long-Term Potentiation and Memory Formation by Juvenile Enrichment
Junko A. Arai, Shaomin Li, Dean M. Hartley, and Larry A. Feig
The Journal of Neuroscience, February 4, 2009, 29(5):1496-1502; doi:10.1523/JNEUROSCI.5057-08.2009
URL: http://www.jneurosci.org/cgi/content/abstract/29/5/1496

In an interesting experiment, scientists at the Tufts University School of Medicine, Boston, and Rush University Medical Center, Chicago, demonstrated that exposure of mice that have a genetically engineered defect in long term memory, to two weeks of an "enriched environment" (that includes exposure to novel objects, elevated social interactions and voluntary exercise) enhances memory not only in these "enriched" mice but also in their future offspring even if the offspring never experience the enriched environment. The transgenerational transmission of this effect occurs from the enriched mother to her offspring during embryogenesis.

What this research article is hinting at is that acquired characteristics - like habits, phobia etc. can be inherited. This was previously believed to be an impossibility. For example, if a parent has a particular learned skill, his offspring cannot be expected to be born with the same skill. This is because the skill is an acquired characteristic and such characteristics are not inheritable. At least that was what was previously accepted and this research challenges that premise. If this phenomenon is indeed true in humans, this would mean that a person's childhood experiences could influence behavior, not only in the same person as he/she grows up, but also in his/her offspring who have never been exposed to such experiences.

So, we ask the question: Are acquired characteristics inheritable?

It has been accepted for some time now that acquired characteristics are not inheritable. Proponents of the theory of inheritance of acquired characteristics, like Lysenko (discussed in last week's post) have been discredited and their research thrashed as "unsound science", if not fraudulent science. The theory of inheritance of acquired characteristics, however, is not Lysenko's creation. It was proposed more than 200 years ago by Jean-Baptiste Lamarck and was once widely accepted. Over the next century, publication of Darwin's, and then Mendel's theories led to the general abandonment of the Lamarckian theory of evolution in biology. However, recently Lamarckian evolution has made a comeback of sorts. \

Lamarckian views of evolution are based on two principles:
1. Use and disuse - Individuals lose characteristics they do not require (or use) and develop characteristics that are useful.
2. Inheritance of acquired traits - Individuals inherit the traits of their ancestors.

These principles could be exemplified in the giraffe. Giraffes, while stretching their necks to reach leaves high in trees, strengthen and gradually lengthen their necks. These giraffes have offspring with slightly longer necks. While this example is appealing in its simplicity, there is no evolutionary evidence for this having happened. The theory gained wide acceptance because Darwin and Mendal put forward their theories only after Lamarck's death in 1829.

In any case, Lamarck's views were not completely dead at any point of time. There were many famous scientists who prescribed to Lamarckism in part or in full. These included William McDougall and Ivan Pavlov. William McDougall was a researcher at Harvard who studied the abilities of rats to solve mazes. He found that offspring of rats that had learned solve the maze solved them faster even though they were not exposed to the maze earlier. McDougall attributed this to some sort of Lamarckian evolutionary process. At around the same time, Ivan Pavlov, who was also a Lamarckist, claimed to have observed similar phenomena in animals being subjected to conditioned reflex experiments. He claimed that with each generation, the animals became easier to condition. The claims of McDougall and Pavlov were never proven to be true.

In the first few months of this year, scientists have published research that has shown that Lamarckian type inheritance of acquired characteristics is possible. The actual mechanism underlying these patterns of inheritance is still mystifying to scientists, but the answers seem to be around the corner as we continue to better understand the phenomenon of Epigenetics. More about epigenetics and neo-Darwinism in my next post.

Genetics, society and ethics - The Lysenko Affair

This first week, lets start of with a real life story you may or may not be aware of. I thought I will start with this because it illustrates two most fundamental principles of science.

At the peak of its powers, Soviet Russia supported several scientific endeavors aimed towards improving society and the doctrine of communism itself. The Lysenko affair involved one such Soviet attempt to meddle with science in an effort to promote its communist manifesto. Trofim Denisovich Lysenko was a biologist who believed acquired characteristics could be inherited, a fundamentally erroneous theory in genetics. His Soviet masters, however, liked the idea. Stalin and later, Krushchev aggressively pursued "Lysenkoism" and put Lysenko in charge of their crop yield improvement programmes. Lysenko's gain was Vavilov's loss. Nikolai Vavilov was an eminent genetics expert who did not prescribe to Lysenko's views. Vavilov was imprisoned and later died in prison. For the better part of 30 years, genetics in Russia went down a blind alley. It was only after Krushchev's reign ended that Lysenko's pseudoscience was recognized and abandoned.

This is one example of political influence of scientific research that led to great loss for society. Political interest in science, however, is not always a bad thing. The Human Genome Project would never have proceeded at the speed and efficiency with which it did, if it were not for political and societal backing. The Lysenko affair should remind us that "science, to be effective, must be in a climate of open inquiry and free expression of ideas". The message here is that politicians must support research done in an open scientific atmosphere by researchers who have no vested political interest. The scientific method must not be subverted by political bullies. This is the first principle I wanted to discuss - the independence of science. The second priciple will be discussed in my next post.

Acknowledgment:
Priniples of Genetics, 7th edition, Robert H. Tamarin.

The sunrise post

Statutory warning: This is a blog for the intellectuals, especially those with an inclination towards biochemistry, genetics and molecular biology.

Hello there,
That was probably a scary beginning with the statutory warning and all. You probably feel like you're looking at a cigarette packet or something.

Anyway, this is a blog for people who take science seriously. Even though it's meant primarily for those of you who have an academic background in biochemistry and molecular biology, I would like to believe that, over time, the posts here will be of broader relevance. The fact is that life is fascinating and mysterious. Everyday research shines a beam of light that only reveals greater mysteries and takes one on a trip that gets more exciting and fascinating by the day.

What I propose to do through this blog is to post a research article and discuss its background, importance and relevance. Through this, the I hope the reader, not only keeps abreast with what is new and cracking in the world of research, but also gains knowledge and understanding of the basic principles of science being discussed in the article.

So, here goes.......