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01/09/2008

Genetic Breakthroughs

Since last we talked I became an octogenarian, having celebrated
my 80th birthday three days after Christmas. Last Friday I went
to the bank to make a deposit. The teller, a young African-
American man with dreadlocks, looked at my hat and said, “You
know, that style of hat is very popular among young people these
days.” I told the young man that he made my day by indicating
that, at age 80, I was “hip”! My wife was amused when I told
her the story, knowing that I am the most un-hip-like person.

Last week I also attended a meeting of our Old Guard group of
retired men. Our speaker was Donald Kent, a physician and
adjunct professor at Drew University, who spoke on the subject
of stem cells. His talk was very interesting, well organized and
delivered with authority and humor. I could say the same thing
about most of the talks at our Old Guard meetings but this one
was special. Kent is 94 years old! Obviously, this man is
blessed with a good set of genes.

Speaking of genes, the journal Science has come up with its
annual “Breakthrough of the Year”. For 2007, the winner is
“Human Genetic Variation”, as detailed in an article by Elizabeth
Pennisi in the December 21 issue of Science. It’s hard to believe
that it’s been almost seven years since the human genome was
decoded. Since then we’ve found that the number of genes in
our genome is significantly less than generally expected and that
the so-called “junk” DNA, the sequence of “letters” (A, G, C and
T for the base pairs), lying between the genes is far from being
junk. We’ve also begun to learn what genes distinguish us from
our primate cousins, as well as from the Neandertals. In other
words, we’re learning what it is that makes us Homo sapiens.

What Science is recognizing in 2007 is that we’re now starting to
answer the more personal question, “What in my DNA makes me
me?” There are zillions of possible ways that my genome can
differ from yours. With some 3 billion letters (base pairs) in the
human genome, one obvious way for my genome to differ from
yours is if one or more of the letters in your DNA differ from the
letters in mine. Say, for example, one stretch of letters in mine is
…ACGT… while in yours that same stretch is …AAGT… . The
A substituting for the C is called a SNP (pronounced “snip”) or
by its scientific name, “single-nucleotide polymorphism”.

There have now been studies on tens of thousands of individuals
for which portions of their DNA have been sequenced. This
partial decoding of their genomes has led to the identification of
genes linked to increased risk of various diseases such as
diabetes, Alzheimer’s, different cancers, heart disease, etc. In
addition to SNPs, whole genes can be missing, copied more than
once, out of the normal order in the DNA or other genes may be
inserted in the DNA. These so-called “copy-number” variations
were found to account for about 20 percent of the differences in
gene activity in one study. The other 80 percent of the
differences were associated with SNPs, just the single letters
being out of place.

Science also listed the breakthrough runners-up for 2007 and
second place went to “Reprogramming Cells”, notably stem
cells. Let me set the stage by using some of Don Kent’s lecture
to us old-timers. We begin with the sperm fertilizing the egg.
Soon after the sperm enters the egg, the cells begin dividing and
multiplying. One interesting stage occurs early on when the
embryo is a so-called “blastomere” consisting of only eight cells.
In a fertility clinic, at this stage they might take out one of these
cells and check it for genes indicating any complications such as
Down’s syndrome. The doctors and prospective parents can then
decide whether to implant that embryo.

After about a week, the embryo is a “blastocyst”. Kent likened
the blastocyst to a ping-pong ball, hollow but with a bunch of
cells lining the shell or membrane covering. These are stem
cells, which are termed “pluripotent”; that is, they can turn into
any type of cell in the body. These stem cells can be taken from
the blastocyst and therein lies the controversy that pits many fine
people against other fine people. As Kent put it, we would like
Mr. and Mrs. Smith – they pay their taxes, are very friendly and
participate in worthy community activities. They believe that a
fertilized egg at any stage is a human being with the rights of any
human being. We would also like Mr. and Mrs. Jones, just as
upright and laudable citizens as the Smiths. However, they
believe that at the blastomere and blastocyst stages the embryo
has no nervous system, no feeling of pain and is not as yet a true
human being. The Joneses say take the stem cells from the
embryo and use them for research towards a cure for disease.
The Smiths strongly object, saying this amounts to killing of a
human being.

With President Bush on the side of the Smiths, the controversy
becomes a national issue. Well, in 2006 some Japanese scientists
found that, if they added four genes to cells in the tail of a
mouse, the cells had to all intents turned into stem cells capable
of forming all of the mice’s body’s cells including eggs and
sperm. They even used these “induced” stem cells to treat a
mouse form of sickle cell anemia.

Their work created quite a stir but there was doubt that this
approach would work for us humans. However, this past
November the Japanese team announced that they had used their
mouse recipe to make human skin cells into stem cells! Not only
that, but an American team reported that they had also succeeded
in turning skin cells into stem cells using a slightly different
recipe. Our 94-year-old Dr. Kent was quite aware of this work
and included it in his talk.

Naturally, this turning of skin cells into stem cells made
headlines in the media. If skin-derived stem cells were truly
equivalent to embryonic stem cells, the ethical and moral issues
would be resolved and the Smiths, Joneses and Bush would all
be happy, as I presume would all of us. But we can’t truly
celebrate until researchers determine the safety of using these
induced stem cells in treating actual diseases or injuries such as
those of the spinal cord. The problem of how to deliver the stem
cells also has to be solved. For example delivery by encasing in
a virus is one possibility that has been investigated but there’s
concern about the possibility of prompting the growth of
cancerous cells. Or could the stem cells themselves lead to
uncontrolled cell growth resulting in cancer? As Dr. Kent
summed up the current status of stem cells: “There are lots of
questions for which we don’t yet have the answers.”

Oh, you might be interested to know that my “hip” hat is over 39
years old. I’m not sure what type of hat to call it but it’s a
subdued brownish plaid-like hat with a relatively narrow brim,
turned up in back. I bought it in 1968 in Montreal, where my
wife and I were attending a meeting of The Electrochemical
Society. It was our first visit to Montreal, with its French
ambience. The joie de vivre was exemplified while I was
browsing in a department store and I couldn’t help noticing a
very attractive, nicely endowed young woman shopping nearby
wearing a completely transparent blouse and no bra! Strange
how one remembers certain things, isn’t it? I of course, being a
materials scientist, was wondering just what kind of fabric it was
that could be so transparent. Believe that and I’ll sell you a
bridge connecting Manhattan and Brooklyn!

Allen F. Bortrum



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-01/09/2008-      
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Dr. Bortrum

01/09/2008

Genetic Breakthroughs

Since last we talked I became an octogenarian, having celebrated
my 80th birthday three days after Christmas. Last Friday I went
to the bank to make a deposit. The teller, a young African-
American man with dreadlocks, looked at my hat and said, “You
know, that style of hat is very popular among young people these
days.” I told the young man that he made my day by indicating
that, at age 80, I was “hip”! My wife was amused when I told
her the story, knowing that I am the most un-hip-like person.

Last week I also attended a meeting of our Old Guard group of
retired men. Our speaker was Donald Kent, a physician and
adjunct professor at Drew University, who spoke on the subject
of stem cells. His talk was very interesting, well organized and
delivered with authority and humor. I could say the same thing
about most of the talks at our Old Guard meetings but this one
was special. Kent is 94 years old! Obviously, this man is
blessed with a good set of genes.

Speaking of genes, the journal Science has come up with its
annual “Breakthrough of the Year”. For 2007, the winner is
“Human Genetic Variation”, as detailed in an article by Elizabeth
Pennisi in the December 21 issue of Science. It’s hard to believe
that it’s been almost seven years since the human genome was
decoded. Since then we’ve found that the number of genes in
our genome is significantly less than generally expected and that
the so-called “junk” DNA, the sequence of “letters” (A, G, C and
T for the base pairs), lying between the genes is far from being
junk. We’ve also begun to learn what genes distinguish us from
our primate cousins, as well as from the Neandertals. In other
words, we’re learning what it is that makes us Homo sapiens.

What Science is recognizing in 2007 is that we’re now starting to
answer the more personal question, “What in my DNA makes me
me?” There are zillions of possible ways that my genome can
differ from yours. With some 3 billion letters (base pairs) in the
human genome, one obvious way for my genome to differ from
yours is if one or more of the letters in your DNA differ from the
letters in mine. Say, for example, one stretch of letters in mine is
…ACGT… while in yours that same stretch is …AAGT… . The
A substituting for the C is called a SNP (pronounced “snip”) or
by its scientific name, “single-nucleotide polymorphism”.

There have now been studies on tens of thousands of individuals
for which portions of their DNA have been sequenced. This
partial decoding of their genomes has led to the identification of
genes linked to increased risk of various diseases such as
diabetes, Alzheimer’s, different cancers, heart disease, etc. In
addition to SNPs, whole genes can be missing, copied more than
once, out of the normal order in the DNA or other genes may be
inserted in the DNA. These so-called “copy-number” variations
were found to account for about 20 percent of the differences in
gene activity in one study. The other 80 percent of the
differences were associated with SNPs, just the single letters
being out of place.

Science also listed the breakthrough runners-up for 2007 and
second place went to “Reprogramming Cells”, notably stem
cells. Let me set the stage by using some of Don Kent’s lecture
to us old-timers. We begin with the sperm fertilizing the egg.
Soon after the sperm enters the egg, the cells begin dividing and
multiplying. One interesting stage occurs early on when the
embryo is a so-called “blastomere” consisting of only eight cells.
In a fertility clinic, at this stage they might take out one of these
cells and check it for genes indicating any complications such as
Down’s syndrome. The doctors and prospective parents can then
decide whether to implant that embryo.

After about a week, the embryo is a “blastocyst”. Kent likened
the blastocyst to a ping-pong ball, hollow but with a bunch of
cells lining the shell or membrane covering. These are stem
cells, which are termed “pluripotent”; that is, they can turn into
any type of cell in the body. These stem cells can be taken from
the blastocyst and therein lies the controversy that pits many fine
people against other fine people. As Kent put it, we would like
Mr. and Mrs. Smith – they pay their taxes, are very friendly and
participate in worthy community activities. They believe that a
fertilized egg at any stage is a human being with the rights of any
human being. We would also like Mr. and Mrs. Jones, just as
upright and laudable citizens as the Smiths. However, they
believe that at the blastomere and blastocyst stages the embryo
has no nervous system, no feeling of pain and is not as yet a true
human being. The Joneses say take the stem cells from the
embryo and use them for research towards a cure for disease.
The Smiths strongly object, saying this amounts to killing of a
human being.

With President Bush on the side of the Smiths, the controversy
becomes a national issue. Well, in 2006 some Japanese scientists
found that, if they added four genes to cells in the tail of a
mouse, the cells had to all intents turned into stem cells capable
of forming all of the mice’s body’s cells including eggs and
sperm. They even used these “induced” stem cells to treat a
mouse form of sickle cell anemia.

Their work created quite a stir but there was doubt that this
approach would work for us humans. However, this past
November the Japanese team announced that they had used their
mouse recipe to make human skin cells into stem cells! Not only
that, but an American team reported that they had also succeeded
in turning skin cells into stem cells using a slightly different
recipe. Our 94-year-old Dr. Kent was quite aware of this work
and included it in his talk.

Naturally, this turning of skin cells into stem cells made
headlines in the media. If skin-derived stem cells were truly
equivalent to embryonic stem cells, the ethical and moral issues
would be resolved and the Smiths, Joneses and Bush would all
be happy, as I presume would all of us. But we can’t truly
celebrate until researchers determine the safety of using these
induced stem cells in treating actual diseases or injuries such as
those of the spinal cord. The problem of how to deliver the stem
cells also has to be solved. For example delivery by encasing in
a virus is one possibility that has been investigated but there’s
concern about the possibility of prompting the growth of
cancerous cells. Or could the stem cells themselves lead to
uncontrolled cell growth resulting in cancer? As Dr. Kent
summed up the current status of stem cells: “There are lots of
questions for which we don’t yet have the answers.”

Oh, you might be interested to know that my “hip” hat is over 39
years old. I’m not sure what type of hat to call it but it’s a
subdued brownish plaid-like hat with a relatively narrow brim,
turned up in back. I bought it in 1968 in Montreal, where my
wife and I were attending a meeting of The Electrochemical
Society. It was our first visit to Montreal, with its French
ambience. The joie de vivre was exemplified while I was
browsing in a department store and I couldn’t help noticing a
very attractive, nicely endowed young woman shopping nearby
wearing a completely transparent blouse and no bra! Strange
how one remembers certain things, isn’t it? I of course, being a
materials scientist, was wondering just what kind of fabric it was
that could be so transparent. Believe that and I’ll sell you a
bridge connecting Manhattan and Brooklyn!

Allen F. Bortrum