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05/08/2003
Worm Survivors
Though we’ve had our differences with Russia on Iraq, we
certainly are indebted to them for supplying and now bringing
home our two astronauts after their extended stay on the
International Space Station. I imagine that even those spunky
astronauts and their Russian colleague must have had a few
butterflies in their stomachs on that unexpectedly bumpy ride
down to their landing in Kazakhstan nearly 300 miles short of
their target. Indirectly, the three of them were survivors of the
Columbia Shuttle disaster. Now we learn that there were other,
direct survivors of the tragedy. Searchers recovered a container
from Columbia containing moss cells and worms. When this
container was finally opened, the worms were found to be alive.
These sturdy worms are nematodes known as Caenorhabditis
elegans, or C. elegans for short. C. elegans is a tiny worm less
than a millimeter in length, barely discernible to the naked eye.
These weren’t the original worms loaded on Columbia back in
January. C. elegans typically lives for only about 10 days or so.
Hence, these were fourth or fifth generation worms, born on the
shuttle. I’ve mentioned C. elegans a couple of times in earlier
columns but have not given the tiny worm the attention it
deserves. There are thousands of papers published on this simple
creature. With less than a thousand cells and only a few hundred
neurons, C. elegans pales in complexity with us humans with our
billions of neurons in our brains.
Conveniently, C. elegans is transparent, allowing researchers to
observe the functioning of the different cells and also allowing
them to go in and manipulate or delete selected cells. A zap with
a finely focused laser and the cell is gone. They can also modify
the DNA in the cells. After doing their tinkering, workers can
then observe any changes in behavior and relate them directly to
the alterations they’ve made.
Normally, C. elegans lives in the soil and grazes on bacteria. For
experimenters, it’s easy to raise these worms by the thousands in
a Petri dish. Its short lifespan makes it very attractive for studies
on aging. You can starve C. elegans or change a gene and in
only a couple weeks you know if you’ve lengthened or shortened
the average lifespan. And, because you can have thousands of
worms in your experiment, the results are statistically significant.
Contrast this with the problem of trying to pin down definitively
the factors influencing the lifespan of us humans.
You might say, “Well and good, but what do studies on tiny
worms have to do with us?” Well, C. elegans was the first
organism containing more than one cell to have its genome
completely sequenced. Now, with our own human genome
99.9% sequenced, as announced only within the past couple
weeks, we find that we share more genes with C. elegans than we
might have expected.
You’ve no doubt seen or heard of all sorts of studies linking diet
and aging. Of great interest are the studies of what some might
call starvation, more scientifically called caloric restriction (CR),
and the increase in the lifespans of mice and other animals when
placed on relatively meager rations. Just watch the Today Show.
Very few of the centenarians that Willard Scott honors with their
pictures on the labels of those Smuckers jars are overweight.
There’s a compound called ubiquinone that turns out to be of
interest in connection with the aging process. Ubiquinone is a
compound that is found in all kinds of animal life and is
manufactured in our cells. Its ubiquitous nature accounts for the
name ubiquinone. It’s also called Coenzyme Q and there are
various forms. One of these is Coenzyme Q-10, which I’ve been
taking every day for the past few years. There have been a lot of
studies as well as a lot of controversy about the benefits of Q-10
but it seems to be agreed that it doesn’t usually do any harm. I
hasten to add that I’m not an M.D. and do not in any way suggest
that you join me in taking it!
You can understand that I perked up when I ran across studies of
Coenzyme Q and C. elegans. This worm normally feeds on
bacteria that themselves contain Q. One study that generated a
lot of attention came out of UCLA a year or so ago. Pamela
Larsen and Catherine Clarke took normal “wild” C. elegans and
fed the worms two diets. One was their normal diet of bacteria
containing Q. The other was bacteria that were Q-free.
Surprising to me was the fact that they found the worms fed on
the Q-free diet lived on average 60 percent longer than those fed
on the normal Q-containing diet! Well, the message is clear. If I
give up my Q-10, I’ll live to be about 120-130 years old!
Oh, were it so simple. For us humans there are so many other
factors entering into the aging process. Our genetic makeup is
certainly one of the key factors. This is also true for C. elegans.
There have been numerous studies on C. elegans in which genes
or combinations of genes have been silenced or otherwise
altered. These genes have names like sir-2.1, daf-2 or clk-1.
Whatever the names, by changing these genes or combinations of
them researchers have managed to more than double the average
lifespan of C. elegans. Think of the horrific state of affairs if our
own lifespans were doubled. The generational conflicts would
probably make the Iraq war look mild in comparison.
After last week’s column on equine libido and birthing problems,
I would be remiss if I neglected to mention the sex life of C.
elegans. Instead of males and females, with C. elegans there are
males and hermaphrodites. The hermaphrodites typically
fertilize themselves and lay around 300 eggs. After that self-
impregnation, they then welcome the advances of the male
worms to further multiply their egg output. Although we share
many genes with C. elegans, I think most would agree that our
arrangement of males and females is more suitable to our Homo
sapiens lifestyle.
And the sex life of C. elegans may have relevance to a heart
disorder that is responsible for the deaths of several thousand
young people a year. I found reference to this possibility in an
article on the Web site sciencedaily.com. The article deals with
the work of Luis Rene Garcia of Texas A&M University. Garcia
culls out the male worms from his collection of C. elegans and
then uses certain chemicals to alter their genes. There are four
genes in particular that interest him. It turns out these four genes
determine when the male C. elegans extends his sex organ.
The male worms with the altered genes were found to be in an
obviously horny state even when no females (hermaphrodites)
were present. This is totally out of character for the male C.
elegans and Garcia is looking to determine what mutations in the
DNA are responsible for the aberrant behavior. Some neurons
and/or muscles are obviously misfiring here. In his quest, Garcia
has found that one of the four genes is coded for a protein, two-
thirds of which resembles a protein that is involved in regulating
human heart rhythms. The heart disorder I mentioned is called
Long QT Syndrome and the victims of this disease are subject to
sudden death when a spontaneous arrhythmia occurs. It’s a long
shot but if Garcia can figure out what makes the male C. elegans’
neurons and muscles misfire, the answer might help solve the
misfiring of the heart in Long QT patients.
Finally, a follow-up on last week’s column. I went to a
Kentucky Derby party last Saturday and watched on TV as
Funny Cide, the gelding, beat out Empire Maker to win the roses.
A bunch of us males were in a group, trying to ascertain just
what made a horse a gelding. While we seemed to have the right
idea, all were uncomfortable with the thought of the procedure
and it took a gal in the group to come right out and say that the
horse was castrated. With all those potential stud fees, why in
the world would anyone do that? In case you missed it, I saw in
the paper that Funny Cide was born a “ridgling”, a horse born
with one or two undescended testicles. Funny Cide had one, and
was castrated after birth.
Perhaps you’ve heard about the putting down of Greyhounds that
consistently fail to be in the money in Greyhound races. With no
prospect of propagating his line, I can’t help wondering what
Funny Cide’s fate will be when his racing career is over. Will he
be retired to the equivalent of equine luxury or will he end up in
a glue factory? Let’s hope he gets the treatment befitting a
champion.
Allen F. Bortrum
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