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09/01/2015

Be Careful What You Breathe

 CHAPTER 60   Smoke and Genes 
 
Washington and California are on fire and the Mideast is or was experiencing a scorching heat wave with temps ranging up to 120 F and heat indexes in one Iranian town reaching 164 degrees Fahrenheit! I can't help thinking of the millions of refugees from the conflicts in the Mideast out there in tents. How appropriate the editorial by Marcia McNutt in the July 3 issue of Science. McNutt is the editor-in-chief of Science and the title of the editorial is "The beyond-two-degree inferno".   The two-degree inferno is the world expected if we don't manage to stem the rising tide of global temperature to less than two degrees Celsius above preindustrial temperatures. Quoting the editorial: "The time for debate has ended. Action is urgently needed." I couldn't agree with her more. 
 
In her editorial, McNutt points out that, while the European Union, China and California are all pushing hard to reduce carbon emissions, India hopes to double coal production by 2019 to meet its energy needs. And who would have expected a scientist like McNutt citing a pope, Pope Francis, as the most visible champion for mitigating climate change?! What a difference from the days of the persecution by his church of scientists such as Galileo and others for proposing such things as the Earth revolving around the Sun.
 
For the past month or so, I've been expecting emails from NASA with more spectacular pictures of Pluto and its moons from the New Horizons mission. However, NASA says that the spacecraft is in a period of relative R&R, returning data at a relatively slow pace on various other objectives of the mission. Actually, to me the most interesting recent email from NASA doesn't deal with outer space but with the situation back here at home, specifically the rising sea levels around the world due to the global warming cited in McNutt's editorial. A NASA release dated August 26, 2015 titled "NASA Science Zeros in on Ocean Rise: How Much? How Soon?" discusses the results of 23 years of satellite observations by NASA and partners on how sea levels have been behaving as a result of climate change.
 
Overall, since 1992, the average sea level around the world has risen 3 inches. This may not sound like much but the scenario envisioned by NASA and its partners calls for a rise of 3 feet in the next century or so. About a third of the rise in sea level is simply due to warming of the oceans; water expands on heating. Another third arises from the melting of the huge ice sheets in Greenland and in Antarctica, while the other third or so is due to melting of mountain glaciers around the world. 
 
Naively, I would have thought that the rise in sea level would be uniform around the globe. Not so. In fact, it seems that the sea level has actually fallen off the west coast of the United States! This unexpected behavior, unexpected by me at least, is caused by natural cycles in ocean currents such as the Pacific Decadal Oscillation (PDO), one of a number of recurring patterns of climate variability associated with our oceans. As NASA puts it, the PDO and associated lower sea levels are hiding the effects of global warming showing up elsewhere. So, those of you living on the West Coast, don't be misled; your time is coming!
 
I started this column mentioning that California and Washington are burning and, as I write this, crews of firefighters from nearby New York and as far away as New Zealand and Australia are helping fight those horrible blazes. Thinking of all the smoke filling the air from those fires reminded me of an article in the September 2015 issue of Discover magazine by Melissa Pandika titled "Something in the Air". Pandika cites an American Lung Association 2015 State of the Air report as finding four out of five of our metropolitan areas having the highest short-term and year-round particle pollution (essentially, soot) as being in California's Central Valley, with the Fresno area topping the list. Most of the pollution there is apparently due to exhaust from diesel trucks, cars and tractors. This is also an area where a large number of migrant workers Pandika begins her article describing driving from Palo Alto to Fresno with Kari Nadeau, a pediatrician specializing in asthma. As they near Fresno a truck ahead of them emits a big cloud of black smoke, another contribution to the area's pollution.
 
Nadeau is an eminent authority on allergies and asthma based at Stanford University. She found that patients were coming to Palo Alto from Fresno and that typically those patients had more severe symptoms of the disease than her patients from Palo Alto. One of her special interests is a type of immune cells known as regulatory T cells, T-regs. These cells are like policemen, with their function being to keep another type of cell, the T helper cell, under control. T helper cells perform a valuable service in that they jog the immune system into action responding to potential invaders. However, if the T helpers become too active and proliferate they can make the immune system too active and end up producing all the symptoms of asthma.  So, if the T-regs don't do their job the T helper cells get out of control and asthma is the result. 
 
Sure enough, Nadeau found that the T-regs in the Fresno patients generally were not functioning as strongly as in her Palo Alto patients. She then joined forces with an epidemiologist, Ira Tager, who had been studying how pollution was affecting the lungs in patients in Fresno. With blood samples from Tager's patients, Nadeau concentrated on a particular gene known as Foxp3, a gene associated with the development of T-reg cells from immature T-cells. Here comes the interesting part and to set the stage I'll go back to a column I posted on May 1, 2013 (see archives). I won't go into detail here but a main thrust of the column was on work showing that, if a methyl group (a group consisting of a carbon atom and three hydrogen atoms, CH3) attaches to a gene, the gene typically stops making the protein it normally produces. 
 
When Nadeau looked at the Foxp3 genes from the Fresno asthma patients, those with asthma did indeed have more methyl groups than Fresno residents without asthma. Children in Palo Alto without asthma had the fewest methyl groups associated with Foxp3 genes. The conclusion - the Foxp3 genes tagged by methyl groups were not making the T-reg cells needed to control the T helper cells and asthma was the result. Nadeau and Tager went further in that they also concluded that secondhand smoke could also play a role in altering the gene and producing asthma. Even more worrisome, as I discussed in my earlier column, is the possibility that the methylation of genes can be passed along to the children and even grandchildren of an asthmatic mother! 
 
How things have changed over the past few decades. Back in the day, I recall how there was the feeling that once the code of our DNA was deciphered, we would be in great shape to understand pretty much everything about how our DNA operates. Then all those billions of CGAT "letters" in our DNA were found and it turned out things were much more complicated than expected. "Junk" DNA turned out not to be junk, folding of the DNA affects which genes are active, methyl groups turn off genes while other groups may activate genes, etc., etc. I've said before that I'm in awe of researchers who work in this field. We often hear the term "rocket scientist" in connection with complex science or engineering. While I am obsessed with the achievements of NASA and other entities involved in outer space exploration I am even more impressed with those biochemists and others who work on DNA, genes and the utterly complex chemistry that goes on in living creatures such as ourselves.
 
Having just taken a jab at rocket scientists, I must close on a sad note, the passing of a dear friend of 65 years who was a rocket scientist. In my last two columns, I noted the passing of three individuals who played important roles in times of my transitioning from one phase of my life to another. I didn't think there would be any other such "transitional" figures in my life but then I learned of the passing of Stanley Tannenbaum in a retirement home in California. Stan worked in the rocket lab across the way from the building where I worked in Cleveland at NACA Lewis Flight Propulsion Laboratory (now NASA John H. Glenn Research Center at Lewis Field) when I arrived there in 1950.  After the birth of our first child, my wife and I moved into a rental house that we shared with Stan and his wife Pauline. The Tannenbaums helped us in transitioning to parenthood and I learned some aspects of home maintenance from Stan. I remember he and I in the basement repairing a broken down washing machine while listening to Richard Nixon's famous "Checkers" speech when he was running for vice president on the ticket with Dwight Eisenhower.  It was in September of 1952.
 
In November, the day after casting the first vote of my life for Eisenhower, our family moved to New Jersey, where I joined Bell Labs. Later, the Tannenbaums also moved to New Jersey, where Stan continued rocket-related work at what was then Reaction Motors, later Thiokol. We resumed our friendship and would get together for dinners or an occasional round of golf. In 1965, we sold our house and bought another one in a town more conveniently located to Bell Labs. However, that summer we were without a place to stay until the owners of our new home moved out. The Tannenbaums graciously offered their newly refurbished basement as a home for a month during this transitional period. With their four boys and our two boys it was a lively place. We were blessed to have such good and true friends. Both Stan and Pauline, who died a few years ago, had great senses of humor and they were great role models when it came to love of family and raising four fine young men. Stan, the next time I hear of or see a rocket headed out into space I'll raise a glass to my good friend, the rocket scientist.      
 
Next column, hopefully, on or about October 1. 
 
Allen F. Bortrum

 

 



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-09/01/2015-      
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Dr. Bortrum

09/01/2015

Be Careful What You Breathe

 CHAPTER 60   Smoke and Genes 
 
Washington and California are on fire and the Mideast is or was experiencing a scorching heat wave with temps ranging up to 120 F and heat indexes in one Iranian town reaching 164 degrees Fahrenheit! I can't help thinking of the millions of refugees from the conflicts in the Mideast out there in tents. How appropriate the editorial by Marcia McNutt in the July 3 issue of Science. McNutt is the editor-in-chief of Science and the title of the editorial is "The beyond-two-degree inferno".   The two-degree inferno is the world expected if we don't manage to stem the rising tide of global temperature to less than two degrees Celsius above preindustrial temperatures. Quoting the editorial: "The time for debate has ended. Action is urgently needed." I couldn't agree with her more. 
 
In her editorial, McNutt points out that, while the European Union, China and California are all pushing hard to reduce carbon emissions, India hopes to double coal production by 2019 to meet its energy needs. And who would have expected a scientist like McNutt citing a pope, Pope Francis, as the most visible champion for mitigating climate change?! What a difference from the days of the persecution by his church of scientists such as Galileo and others for proposing such things as the Earth revolving around the Sun.
 
For the past month or so, I've been expecting emails from NASA with more spectacular pictures of Pluto and its moons from the New Horizons mission. However, NASA says that the spacecraft is in a period of relative R&R, returning data at a relatively slow pace on various other objectives of the mission. Actually, to me the most interesting recent email from NASA doesn't deal with outer space but with the situation back here at home, specifically the rising sea levels around the world due to the global warming cited in McNutt's editorial. A NASA release dated August 26, 2015 titled "NASA Science Zeros in on Ocean Rise: How Much? How Soon?" discusses the results of 23 years of satellite observations by NASA and partners on how sea levels have been behaving as a result of climate change.
 
Overall, since 1992, the average sea level around the world has risen 3 inches. This may not sound like much but the scenario envisioned by NASA and its partners calls for a rise of 3 feet in the next century or so. About a third of the rise in sea level is simply due to warming of the oceans; water expands on heating. Another third arises from the melting of the huge ice sheets in Greenland and in Antarctica, while the other third or so is due to melting of mountain glaciers around the world. 
 
Naively, I would have thought that the rise in sea level would be uniform around the globe. Not so. In fact, it seems that the sea level has actually fallen off the west coast of the United States! This unexpected behavior, unexpected by me at least, is caused by natural cycles in ocean currents such as the Pacific Decadal Oscillation (PDO), one of a number of recurring patterns of climate variability associated with our oceans. As NASA puts it, the PDO and associated lower sea levels are hiding the effects of global warming showing up elsewhere. So, those of you living on the West Coast, don't be misled; your time is coming!
 
I started this column mentioning that California and Washington are burning and, as I write this, crews of firefighters from nearby New York and as far away as New Zealand and Australia are helping fight those horrible blazes. Thinking of all the smoke filling the air from those fires reminded me of an article in the September 2015 issue of Discover magazine by Melissa Pandika titled "Something in the Air". Pandika cites an American Lung Association 2015 State of the Air report as finding four out of five of our metropolitan areas having the highest short-term and year-round particle pollution (essentially, soot) as being in California's Central Valley, with the Fresno area topping the list. Most of the pollution there is apparently due to exhaust from diesel trucks, cars and tractors. This is also an area where a large number of migrant workers Pandika begins her article describing driving from Palo Alto to Fresno with Kari Nadeau, a pediatrician specializing in asthma. As they near Fresno a truck ahead of them emits a big cloud of black smoke, another contribution to the area's pollution.
 
Nadeau is an eminent authority on allergies and asthma based at Stanford University. She found that patients were coming to Palo Alto from Fresno and that typically those patients had more severe symptoms of the disease than her patients from Palo Alto. One of her special interests is a type of immune cells known as regulatory T cells, T-regs. These cells are like policemen, with their function being to keep another type of cell, the T helper cell, under control. T helper cells perform a valuable service in that they jog the immune system into action responding to potential invaders. However, if the T helpers become too active and proliferate they can make the immune system too active and end up producing all the symptoms of asthma.  So, if the T-regs don't do their job the T helper cells get out of control and asthma is the result. 
 
Sure enough, Nadeau found that the T-regs in the Fresno patients generally were not functioning as strongly as in her Palo Alto patients. She then joined forces with an epidemiologist, Ira Tager, who had been studying how pollution was affecting the lungs in patients in Fresno. With blood samples from Tager's patients, Nadeau concentrated on a particular gene known as Foxp3, a gene associated with the development of T-reg cells from immature T-cells. Here comes the interesting part and to set the stage I'll go back to a column I posted on May 1, 2013 (see archives). I won't go into detail here but a main thrust of the column was on work showing that, if a methyl group (a group consisting of a carbon atom and three hydrogen atoms, CH3) attaches to a gene, the gene typically stops making the protein it normally produces. 
 
When Nadeau looked at the Foxp3 genes from the Fresno asthma patients, those with asthma did indeed have more methyl groups than Fresno residents without asthma. Children in Palo Alto without asthma had the fewest methyl groups associated with Foxp3 genes. The conclusion - the Foxp3 genes tagged by methyl groups were not making the T-reg cells needed to control the T helper cells and asthma was the result. Nadeau and Tager went further in that they also concluded that secondhand smoke could also play a role in altering the gene and producing asthma. Even more worrisome, as I discussed in my earlier column, is the possibility that the methylation of genes can be passed along to the children and even grandchildren of an asthmatic mother! 
 
How things have changed over the past few decades. Back in the day, I recall how there was the feeling that once the code of our DNA was deciphered, we would be in great shape to understand pretty much everything about how our DNA operates. Then all those billions of CGAT "letters" in our DNA were found and it turned out things were much more complicated than expected. "Junk" DNA turned out not to be junk, folding of the DNA affects which genes are active, methyl groups turn off genes while other groups may activate genes, etc., etc. I've said before that I'm in awe of researchers who work in this field. We often hear the term "rocket scientist" in connection with complex science or engineering. While I am obsessed with the achievements of NASA and other entities involved in outer space exploration I am even more impressed with those biochemists and others who work on DNA, genes and the utterly complex chemistry that goes on in living creatures such as ourselves.
 
Having just taken a jab at rocket scientists, I must close on a sad note, the passing of a dear friend of 65 years who was a rocket scientist. In my last two columns, I noted the passing of three individuals who played important roles in times of my transitioning from one phase of my life to another. I didn't think there would be any other such "transitional" figures in my life but then I learned of the passing of Stanley Tannenbaum in a retirement home in California. Stan worked in the rocket lab across the way from the building where I worked in Cleveland at NACA Lewis Flight Propulsion Laboratory (now NASA John H. Glenn Research Center at Lewis Field) when I arrived there in 1950.  After the birth of our first child, my wife and I moved into a rental house that we shared with Stan and his wife Pauline. The Tannenbaums helped us in transitioning to parenthood and I learned some aspects of home maintenance from Stan. I remember he and I in the basement repairing a broken down washing machine while listening to Richard Nixon's famous "Checkers" speech when he was running for vice president on the ticket with Dwight Eisenhower.  It was in September of 1952.
 
In November, the day after casting the first vote of my life for Eisenhower, our family moved to New Jersey, where I joined Bell Labs. Later, the Tannenbaums also moved to New Jersey, where Stan continued rocket-related work at what was then Reaction Motors, later Thiokol. We resumed our friendship and would get together for dinners or an occasional round of golf. In 1965, we sold our house and bought another one in a town more conveniently located to Bell Labs. However, that summer we were without a place to stay until the owners of our new home moved out. The Tannenbaums graciously offered their newly refurbished basement as a home for a month during this transitional period. With their four boys and our two boys it was a lively place. We were blessed to have such good and true friends. Both Stan and Pauline, who died a few years ago, had great senses of humor and they were great role models when it came to love of family and raising four fine young men. Stan, the next time I hear of or see a rocket headed out into space I'll raise a glass to my good friend, the rocket scientist.      
 
Next column, hopefully, on or about October 1. 
 
Allen F. Bortrum