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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