the art and observations of Ranjit S. Mathoda

Talking about slowing down or stopping aging seems like talking about magic, something unnatural, the substance of a movie, a sign of excessive fear of the inevitable, a foolish desire to avoid a promising afterlife, an attempt to sell something to the gullible, or just a short cut to losing all credibility. Aging is baked into our understanding of the world, into the structure of families, the unfolding of human history, the forms of our storytelling, and into how people decide upon their beliefs.

Yet because aging has been inevitable does not mean it will continue to be. David Hume once pointed out, “No amount of observations of white swans can allow the inference that all swans are white, but the observation of a single black swan is sufficient to refute that conclusion.” Human history has been filled with the white swan of aging, and it makes us doubt the black swan of a method to halt aging could actually exist.

There are reasons to believe that aging at the rates humans experience isn’t inevitable and could be modified. The first reason is that different species age at different rates. Charles Darwin explained that species evolved from common ancestors, through the pressures of selection and time. The rate of human aging may therefore be an evolutionary accident or due to selection pressures humanity could use its creativity to escape.

A second reason is that some human beings have diseases which cause them to appear to age significantly faster than normal (see wikipedia article on progeria). If the process of aging can be modified by a genetic abnormality in one direction, it could possibly be modified in the other direction.

A third reason is that aging has already been slowed down significantly in many creatures by severe caloric restriction. This appears to effect metabolism, which then effects the rate of aging. While caloric restriction has worked in even lower order mammals, large scale human studies have yet to be completed. Even if caloric restriction was shown to work in people it requires significant discipline while impacting lifestyle significantly.

These reasons provide potential means for exploring the processes of aging. A great deal of fruitful research has been done on aging in yeast cells. It is the current scientific understanding that inside a yeast cell a reduction in caloric intake causes a reduction in three enzymes (TOR, Sch9, and PKA) that are part of the metabolism process. Reductions in TOR in particular decreases the rate by which a cell creates new proteins and slows aging.

Now, in the April 18, 2008 issue of the journal Cell (see link), a team of researchers led by Brian Kennedy and Matt Kaeberlein have published research linking ribosomes, the protein-making factories in living cells, and Gcn4, a specialized protein that aids in the expression of genetic information, to the pathways related to dietary response and aging.

By studying different strains of yeast cells they found that mutations in the large subunit of ribosomes sometimes led to increased lifespan. They also tested diazaborine, a drug which interferes with the large subunit of ribosomes, and found that treated cells lived 50 percent longer than untreated cells. They also found that longer lived yeast strains with mutations in the large subunit of the ribosome produce an extraordinary amount of Gcn4, a specialized protein which helps transfer genetic information during cell growth. They then tried preventing the increase of Gcn4 to see if it would effect life span, and it did in fact lead to shorter life spans. The researchers have thus found three different ways to effect aging in yeast cells. (This is not the only research approach being followed; see my prior post)

The path from such research in yeast cells to a treatment for human beings will likely be a very long one. While it is possible that a means to short circuit the aging process without significant side effects may be discovered (as was discovered for creating a twin of a sheep; see my prior post), it is far more likely to take decades, or a century.

Yet there could come a time when denying someone anti aging treatments is considered cruel and unusual. Perhaps some people born today will live to see that time. If so, they may be the only people living to have once thought of aging as natural and inevitable. They may have great difficulty in convincing anyone that aging was anything other than a disease, waiting for a cure.

Shinya Yamanaka of Kyoto University has created a new technique that by inserting four genes into a mouse skin cell reprograms it so it appears to be an embryonic stem cell. This technique has already been verified by other teams of scientists.

This is huge news.

This means that rather than have a controversy over extracting stem cells from fetuses, and rather than have issues over the scarcity of organs for transplantation, it’s likely a matter of time before you will be able to grow a replacement body part from your own skin cells.

As the NY Times reports:

If the technique can be adapted to human cells, it would let scientists use a patient’s skin cell to generate new heart, liver or kidney cells that might be transplantable and would not be rejected by the patient’s immune system.  …

The technique is much easier to apply than nuclear transfer, does not involve the expensive and controversial use of human eggs, and should avoid all or almost all of the ethical criticism directed at the use of embryonic stem cells.  …

It raises no serious moral problem, because it creates embryonic-like stem cells without creating, harming or destroying human lives at any stage, said Richard Doerflinger, a spokesman on stem cell issues for the United States Conference of Catholic Bishops.  …

Ever since the creation of Dolly, the first cloned mammal, scientists have sought to lay hands on the mysterious chemicals with which an egg will reprogram a mature cell nucleus injected into it and set the cell on the same path of embryonic development as when egg and sperm combine.  …

Last year Dr. Yamanaka and his colleague Kazutoshi Takahashi, both at Kyoto University, published a remarkable report relating how they had guessed at 24 genes that seemed responsible for maintaining
pluripotency in mouse embryonic stem cells.  …

When they inserted all 24 genes into mouse skin cells, the cells showed signs of pluripotency. The Kyoto team then subtracted genes one by one until they had a set of four genes that were essential. The genes are inserted into viruses that infect the cell and become active as the virus replicates. The skin cell’s own copies of these genes are repressed since they would interfere with its function. “We were very surprised that just four genes are sufficient to reprogram the skin cells,” Dr. Yamanaka said.  …

Dr. Yamanaka’s report riveted the attention of biologists elsewhere. Two teams set out to repeat and extend his findings, one led by Rudolf Jaenisch of the Whitehead Institute and the other by Kathrin Plath of the University of California, Los Angeles, and Konrad Hochedlinger of the Massachusetts General Hospital. Dr. Yamanaka, too, set about refining his work.

In articles being published in Nature and a new journal, Cell-Stem Cell, the three teams show that injection of the four genes identified by Dr. Yamanaka can make mouse cells revert to cells that are indistinguishable from embryonic stem cells.  …

An immediate issue is whether the technique can be reinvented for human cells. One problem is that the mice have to be interbred. Another is that the cells must be infected with the gene-carrying virus, which is not ideal for cells to be used in therapy. A third issue is that two of the genes in the recipe can cause cancer. Indeed 20 percent of Dr. Yamanaka’s mice died of the disease. Nonetheless, several biologists expressed confidence that all these difficulties will be sidestepped somehow.  …

Repairing the body with its own cells should in principle be a superior form of medicine to the surgeon’s knife and the oncologists’ poisons.

http://www.nytimes.com/2007/06/06/science/06cnd-cell.html?_r=1&hp=&pagewanted=all

Medicine will likely never be the same.

Next, by Michael Crichton.

This book is about the very strange biotechnology future that is approaching much faster than most people suspect. It is also about how this future may be governed by our current laws, which make little sense. For example, because the law doesn’t recognize your right to own your body parts, major medical institutions have more rights and incentives in your body parts than you do. I couldn’t agree with Mr. Crichton more on either his observations about the technology or the law. Unfortunately, I’m not sure a novel was the proper format for this book, as the story and characters seemed to have been forgotten in favor of the ideas being communicated.

The Way to Win: Taking the White House in 2008, by Mark Halperin and John F. Harris.

This book’s subtitle notwithstanding, it is actually an examination of how campaign masterminds like Bill Clinton and Karl Rove operate. To its credit the book does delve deeply into explaining the operational techniques and why some seemingly foolhardy policy positions are actually effective at moving a candidate closer to victory. It shows how better insights and superior execution of a campaign can catapult little known candidates over their rivals, to the heights of power.

It also shows in some detail what I’ve long suspected: that although their followers are often motivated by their hate for the leaders of the opposing political party, the leaders of successful campaigns often admire each other and copy liberally from each other whatever works.

The book fails to adequately address the most interesting question about the 2008 campaign: how the Internet effects fund raising, getting the message out, and turning out the vote on election day. The subject matter of the subtitle wasn’t quite addressed.

Rembrandt: the Painter at Work by Ernst van Wetering
Velazquez: the Technique of Genius by Jonathan Brown and Carmen Garrido

How exactly did Rembrandt and Velazquez create their paintings? What choices did they make in how to make their brush strokes, how to mix their paints, how to layer their paints, how to compose their creations?

Sadly, if these books touched on such matters, they did so in a rather oblique way only. What was very helpful in these books was their inclusion of pictures of both entire paintings and of closeups of portions of such paintings. From the pictures I learned alot.

An interesting project has begun to catalog every known species, Wikipedia style. That is, each species gets its own web page, with photos, video and sound recordings, and locator maps when possible, and is subject to the same public editing process practices on Wikipedia.

http://www.washingtonpost.com/wp-dyn/content/article/2007/05/08/AR2007050801803.html?nav=rss_education

I wonder if someone will eventually add the DNA sequence of each species…

Update, 5/9/07: A video showing what the encyclopedia of life will look like can be found here: http://www.eol.org/home.html