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12/19/2002
A Clone Is Not a Clone?
A year drawing to a close always puts me in a reflective mood.
This was not a good year from a personal standpoint, with the
loss of my wife''s two sisters and of far too many friends and
acquaintances. Scientifically, however, it''s been a fantastic year.
The January 2003 issue of Discover magazine summarizes the
year with its selection of 100 top science stories of 2002.
Middle- and older-age women might well argue with Discover''s
number 11 ranking of the hormone replacement story that has
dominated the media recently. For them, it would probably rank
much closer to the top.
On the other hand, not too many women would relate to or care
much about number 66, which addresses the question as to why
we haven''t had more women walking in space (only six to date).
The simple answer is that the spacewalking suits were designed
for the heights and torsos of men. Those six women apparently
were tall enough and suit-ably proportioned.
Discover ranks cloning as the number 1 top story of the year,
specifically the proliferation in cloning, with the number of
successfully cloned species now standing at seven. There''s also
been fiddling with the genes in some of these clones. For
example, cows with human antibody genes were cloned in the
hopes that the cows will be a source of useful substances to fight
certain diseases. On the other hand, pigs were cloned without
certain pig gene(s) that lead to rejection if pig organs are
transplanted in humans. Of course, cloning got most publicity in
media reports of claims that human babies are being cloned or
possibly have been cloned.
Aside from ethical objections, the major scientific objection to
cloning humans is that the success rate of cloning is very low and
the chance of defective babies is too high. Number 33 in
Discover''s list concerns research aimed at finding out why the
success rate in cloning is so low. For example, only 4 percent of
the cloning attempts in cattle are successful. Hans Sch ler and
his group at the University of Pennsylvania found a possible key
to the failures. In cloning, what is done is to remove the nucleus
from one animal''s egg and introduce the nucleus from a mature
cell taken from another animal into the egg. For the cloning to
succeed, the transplanted genes have to function and develop in
the way they would perform in a natural embryo.
Previous work had shown that there''s a particular gene called
"Oct4" that prods the other genes into following the proper path
of development in the embryo. The amount of Oct4 and its
location is critical to the proper exercise of this guiding function.
Sch ler''s group found a couple of fundamental problems. One is
that, when mice were used in cloning experiments, the Oct4 gene
was either at the wrong location, in the wrong amount or even at
the wrong time around 90 percent of the time.
Furthermore, there are actually two copies of the Oct4 gene and
Sch ler''s group found that both of these copies of Oct4 are active
in natural embryos. However, they found that in cloned embryos
it seemed to be a crapshoot as to whether both Oct4 genes were
active. While these findings certainly should give pause to those
who would try human cloning, at the same time they give hope
that further understanding of the cloning process will make the
procedure more effective and reliable.
Jeff Wheelwright, author of Discover''s article on cloning,
expresses the opinion that cloning of humans is gathering
momentum and that we may well have to get used to it. For
those bothered by the possibility, he suggests first that we
consider a clone to be simply a "delayed identical twin".
Second, a clone is not a clone. This surprised me. He points out
that when the original nucleus is removed from the egg, some of
the so-called mitochondrial DNA remains behind. As a result, he
states that only 90 percent of the clone''s DNA is from the
individual being cloned. In this regard, Wheelwright points out
that a cat cloned this year was not the same color as its "genetic
parent".
I don''t expect that cloning will ever affect me personally, unless
it''s somehow related to stem cells and a medical breakthrough.
Discover''s number 46, however, was very interesting to me
personally. The story was titled "It''s Good to be Around Sick
Kids". I''m sure that most of you have seen or heard about recent
suggesting that kids need to grow up with some dirt to prime
their immune systems to fight various diseases, asthma being one
possibility. Now we have Marc Brisson, at the Public Health
Laboratory Service in London, saying that certain individuals
should deliberately expose themselves to children with chicken
pox. I am one of those individuals.
Like many of you, I''m sure, I had chicken pox as a child and,
unbeknownst to me, the Varicella zoster virus that caused the
disease went into hiding in my body. A few decades later, the
virus sprang to life and I came down with shingles, the first of
my three episodes of this malady. Here in the U.S., a vaccine for
chicken pox has been around for 7 years and, as with polio and
other scourges, the hope is to eliminate chicken pox entirely. Is
this mass vaccination a good idea? Brisson isn''t so sure. He
suggests that there could be 9 million more cases of shingles in
the U.S. over the next 50 years if chicken pox is eliminated.
Why? It seems that the immunity to chicken pox virus fades
over time. This allows the hibernating V. zoster to spring into
action as shingles. However, Brisson believes that exposure to
children with chicken pox gives the immune system a refresher
course, so to speak. The boost to the immune system keeps that
virus in hiding - no shingles. If so, and mass vaccination is a
success, it''s a case where older generations will suffer for the
good of their grandchildren. In the meantime, if you know of a
kid with chicken pox send him or her around. Shingles isn''t fun!
The number 2 story on Discover''s list is titled "Neutrino Mystery
Solved" by Maia Weinstock. I didn''t realize a connection
between that story, obviously not a biological topic, and number
40, "Finally, a Test for Alzheimer''s", but hear me out. William
Klink and Chet Mathis of the University of Pittsburgh, where I
did my graduate work, announced in July that when a certain
radioactive compound is injected into a patient, the compound
travels to the brain. If the brain contains the beta-amyloid
plaques characteristic of Alzheimer''s, the compound concentrates
in these plaques. This buildup can be detected using a PET scan.
If there are no plaques, the compound clears out of the body
quickly. This technique holds the promise not only of predicting
or diagnosing early Alzheimer''s but also of allowing the patient''s
condition to be monitored during course of any treatment.
Some 30 years ago, Raymond Davis, a worker at Brookhaven
National Laboratory and the University of Pennsylvania,
detected solar neutrinos. These neutrinos are the tiny particles
emanating from the nuclear processes in the sun and, as you''re
reading this article, zillions of them are passing through you.
Davis'' contribution was not so much in their detection but in the
fact that he was detecting a lot fewer neutrinos than should have
been coming from our sun. There was clearly something wrong.
However, I imagine because of the difficulty in detecting
neutrinos at all, there was skepticism that his measurements just
weren''t sensitive enough.
Davis'' finding led to speculation that neutrinos came in different
"flavors" and could transform from one to another in flight.
Experimental hints that this was indeed the case were found by
workers in Japan and Canada. This year, physicists at Sudbury
Neutrino Observatory in Ontario nailed it. They showed that the
electron-neutrino, the common garden variety that is generated in
the sun, does indeed transform to a large extent into two other
flavors called tau- and muon-neutrinos. Davis was right.
Not only that, but the existence of these different types of
neutrinos shows that neutrinos must have mass, be it ever so
small. Whether or not the neutrino has mass had been a subject
of speculation and controversy for many years. In October,
Davis shared a Nobel Prize for his work. Sadly, this recognition
came too late for Davis to fully appreciate it. A TV news
program last Sunday included a brief interview with Davis and
his wife. Davis is in the early stages of Alzheimer''s and his son
had to deliver Davis'' Nobel address. Let''s hope the PET scan
technique from Pitt will someday show that Davis'' plaques are
receding thanks to some medical breakthrough that makes
Discover''s list in the years to come.
Brian Trumbore has generously granted me two weeks off over
the holidays. The next Bortrum column will be posted on or
before January 8, 2003. Until then, thanks for putting up with
Bortrum''s ruminations over the past years and have a happy
holiday.
Allen F. Bortrum
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