A TRIPLE PLEASURE WORTH SHARING

I was invited by the Molecular Biology Institute and Biology Department at Indiana University in Bloomington to give a talk in their weekly seminar series. My host was Michael Lynch a well known molecular population geneticist whose work on mutations, evolution, and mutation rates is well known and appreciated among geneticists.  I gave the lecture on H J Muller, my mentor and Indiana University’s first Nobel laureate.  I had never used Power Point before and the day before my lecture I visited Lynch at his office in Jordan Hall.  He downloaded my disc onto his computer and showed me what I would have to do to move slides back and forth.  The lecture was in Myers hall where the Molecular Biology Institute is housed.  The auditorium holds about 300 people and at 4 PM it was packed.  I botched the moving of the slides from the computer to the large screen but fortunately Lynch came to my rescue.  But I was in full control in delivering the lecture which was rich in anecdotes.  Nedra said that I hadn’t lost my touch (she took my genetics course in the summer of 1958). Equally engaging was the question and answer period.  I showed two pages from my notebook for Muller’s course in Mutation and the Gene which I took in early 1955. I was interested in Muller since my high school days and when I took his course I wanted to see how he thought. So not only did I take notes on the “winning of the facts” as he called it, but his reasons for the course and the value of knowledge of the history of genetics.  My talk was well received and afterwards Nedra and I were invited to a dinner at a steak house where I enjoyed a margarita (which I shared with Nedra). It was delightful to have two hours of conversation and a superb filet mignon. I thanked my host because I felt rejuvenated.  It has been about 14 years since I have given a lecture to a large audience.  It carried me back to the endorphin rushes of lecturing in my Biology 101-102 course at Stony Brook University.  It gave me great satisfaction to discuss Muller’s life and the significance of his work in radiation genetics and evolutionary genetics and his efforts to help humanity. Muller denounced the racism, sexism, and class prejudice of the eugenics movement in the United States. He condemned (in Moscow in 1937) the attacks on genetics by a politically backed view of heredity whose advocate in that audience (T D Lysenko) Muller denounced as a charlatan.  During the Cold War, Muller was a leading critic of the abuses of radiation exposure.  It was also important, I felt to show his flawed personality, and I included a photocopy of his suicide note in 1932 in Texas when psychological depression made him feel unworthy of carrying on his career or life.  Fortunately he recovered and found positive outlets for the insecurities he harbored. The capstone of my pleasure was that I was giving this lecture at Indiana University where I had gotten my PhD working in Muller’s laboratory.

Review of latest book Mutation in Human Genetics

I was pleased to read Peter Harper's fine review of my book on the history of mutation. It appears in the journal Human Genetics July 2011. Harper is a medical geneticist who has written an excellent history of medical genetics. He is at the University of Cardiff, Wales, UK.

July 25 2011 First Review of my book on Mutation

Home » Genome Technology
A History of Mutation Shows How the Concept Has Changed Science
July/August 2011
By Christie Rizk

The word "mutation" means something different to a comic book enthusiast than
it does to a genetic researcher. But even as it pertains to science, the idea of mutation
has meant different things over time, changing greatly from how Darwin perceived it to
how it is used in the context of the genome.

It is this evolution of the concept of mutation that drives Elof Axel Carlson's new book,
Mutation: The History of an Idea from Darwin to Genomics. Carlson, a professor emeritus
at the State University of New York at Stony Brook, says most geneticists today
conceptualize 'mutation' as a change in an individual gene — an idea that dates back to
the work of Nobel laureate Hermann Joseph Muller in the 1920s. But that is not how it
always was. The term mutation itself has mutated and evolved to suit what researchers
have learned since the time of Darwin.

Beginning with Darwin and pre-Mendelian ideas of what mutation was, continuing through
the Mendelian aspects, work done by Thomas Hunt Morgan with fruit flies, and continuing
through to the ideas of mutagenesis, biochemical approaches to the study of mutation, and
mutation in relation to evolution, Carlson admirably straddles the very fine line between
losing the reader in overly detailed explanations or by being so vague as to say nothing
at all.

The book is a quick read. It doesn't seek so much to re-educate readers on what mutation
is, as it does construct a timeline of how scientists have perceived it through the past
couple of centuries. "The idea of mutation is rooted in our awareness of change over
time," Carlson writes in his preface. "In the life sciences, consideration of
change is essential to evolutionary biology and also, perhaps less obviously, to the
study of genetics. … Many scientists tend to be unaware of how their colleagues of many
generations ago conceived their field. Examination of this process … has the added
benefit of informing us about the way ideas help or hinder the development of a field of
science." Carlson's book presents a history of the concept of mutation, but also a
history of how science itself has changed because of that word's evolution.

The author also seeks to make the reader aware that, though the definition of the word or
the concept of mutation may have changed over time, these changes are the result of
"accumulation of incremental knowledge based on new techniques and
experiments," and that in the "SNPs of the introns and exons of today's genes,
there are still echoes of Darwin's fluctuating variations." In seeking to lend a
sense of history to a word that is used often in today's science, Carlson succeeds.

Blog March 17 2011 Japanese Reactor Disaster

Thoughts on the Japanese reactor disaster in response to a query from my daughter, Christina Carlson who lives on the West coast.

I have followed the catastrophe in Japan with deep interest. It confirmed my feelings that nuclear reactors are a bad idea. I have always felt that when a highly complex system with dangerous outcomes meet unanticipated stresses, it has a risk of failing. That happens when dams break, Titanics sink, and Chernobyl/3 Mile Island/ and Japanese reactors fail. Most industrial backers will shy away from the costs of a well designed reactor that anticipates 9.0 earthquakes and 30 foot tsunamis or a terrorist attack, say a jet slamming into a reactor.

That is my first impression of my take on this bad outcome. I am concerned that two days ago there was a report that one of reactors “may” have had a partial meltdown with a release of 400 milliSieverts per hour. Since that’s about 40 roentgens per hour, just one day’s exposure would be an LD-50 [mean lethal dose] dose in which half of those receiving such a dose (400-500 R or 4 to 5 Sv) would die of radiation sickness. Fortunately, the efforts to pour sea water every day are working to some extent because within an hour or so the emitted dose was back to a fraction of that rate (1-10 mSv/hr). So the workers in the nuclear reactors are not dying of radiation sickness the way the Chernobyl workers did where the release was on-going because they had no way to flood the reactor for weeks and eventually had to entomb it in concrete.

The third impression is more difficult for me to assess. Low doses do cause small amounts of mutational damage (but not radiation sickness) so worldwide the effect will be trivial like the Chernobyl disaster for the US or most of the world. The regions that got clobbered were in Ukraine and by wind drift to Lapland and other parts of Europe. I still remember how disturbed I was when you were in Berlin at the time and giving me the doses that were being measured and reported on German radio and TV in Germany. But, of course that was because thousands of roentgens per day were being pumped for about two or three weeks into the atmosphere. I don’t know if the Japanese will contain this faster than the Russians, but I am encouraged that the rate fluctuates. Every time they dump more sea water in, the radiation emission drops by orders of magnitude which is a good thing. What I can’t assess is the condition of the spent rods and their ability to be doused with sea water and the cracked reactor (s). There may be two or more with such cracks.

If I were in Japan and could afford to leave, I would, especially with young children. As far as living on the West coast, I don’t see any way it would be possible for such diluted radioactive debris to fall out on coastal cities in worrisome amounts. It would be similar to nuclear fallout from weapons testing at the worst and those tossed the radioactive debris into the stratosphere which the Japanese reactors can’t do.
A last thought. The potassium iodide [ KI] tablets are not very useful on the west coast because I131 or other isotopes will be minuscule in dilution hitting the west coast. Most of that KI risk comes from drinking milk of cows that eat grass that grows on Iodine contaminated soil. It would be easier to monitor the milk and not use it if it’s above a certain low level. The KI had it been used in Ukraine in the first few days of heavy radiation they could have saved lots of children from thyroid cancers.

Radiation damage is proportional to dose. So a mSv is 0.1 R which is a chest x-ray dose (or for some machines, ten chest x-rays worth). The individual risk is very low of cancer and zero for any symptoms of radiation sickness. But a dose of 100 R or 1 Sv is very high and will cause symptoms of radiation sickness. But radiation decays inversely to the square of the distance so if you are several miles away from a 100 r release the amount getting that far will be in the small mSv range (about 1 to 10 mSv). What all this means is that anyone within a few feet of the reactor will be dangerously at risk if not heavily protected with lead shielding. The workers there are at high risk. But since no one should be in a radius of 12 miles or so, those outside that zone will be at relatively low risk unless a Chernoby-l like explosion heaves a plume into the stratosphere which drifts and rains down radioactive debris. That’s what I’ve been nervous about because of the unprotected spent fuel which is filled with radioactive isotopes.

Life Lines 15

AGING IS A MATTER OF HOW MANY MITOCHONDRIA YOU HAVE LEFT

Way back in high school you learned that the mitochondrion was “the powerhouse of the cell.” If you took a college biology course as an undergraduate you probably learned that the mitochondria in your cells are bacteria-like in size and have their own DNA and that their major function was to take small carbon-bearing molecules from your digested foods and burn them with the oxygen you breathe to produce chemically stored molecules, chiefly ATP. The mitochondria power the metabolic activities of the cell, tearing molecules apart and synthesizing more complex molecules from simpler ones. Each of your cells has about 1000 mitochondria and each mitochondrion has several dozen copies of its small circular DNA. There are about 60 genes in a mitochondrial chromosome. Most of those genes are involved in production of chemical energy and thus the “powerhouse” reputation that you may remember. If you multiply the number of your cells by the number of mitochondria per cell you get a staggering 100 quadrillion of them in your body (that’s a one followed by 17 zeroes). When they act collectively making ATP they produce heat. The warmth of your body reflects the activity of your mitochondria. That’s why you get hotter in the summer when you exercise and why you shiver and jump around in the cold to warm your body.

Unlike the genes in the nuclei of your cells that produce 99.99 percent of your body, the mitochondrial genes only function is this one essential function of producing the bulk of the energy you need to stay alive. They do so at a price. They lack repair enzymes so mutations accumulate faster in mitochondria than in your nuclear chromosomes. When you are young this is less of a problem because your cells are still dividing but when you are an adult most of your cells slow down and rarely divide. So the mutations accumulate and your cells do not replace worn out mitochondria. The business of making energy by burning small carbon-bearing molecules with oxygen also produces a lot of chemicals that damage DNA. Your mitochondria make hydrogen peroxide. Have you ever seen it bubble when you daub it on a sore? These reactive oxygens readily damage DNA. So here’s the problem. You begin to lose mitochondria as your cells age. That means less energy per cell. When the energy is too low the cell dies. So if I look at the 76 year old skin on the back of my hands I see wrinkles, as you do if you are also old like me, but because I am a biologist, I also see in my mind’s eye, the cells that have winked out on me like so many dead light bulbs over the years and those cells have not been replaced (because I am no longer a child or teenager). The dead cells in the lower layers of my skin reduce the mass of my hands and the covering skin wrinkles as it collapses into those numerous cavities. So now you know why you wrinkle when you get old. Dead mitochondria lead to dead cells that lead to wrinkles. But, alas, there is more. Because we get old eventually, our mitochondria are fewer in number per cell and thus we produce less heat for our body. So now you know why your grandparents need a warmer temperature in their apartments or homes and why they heap blankets on themselves or wear clothes around the house that younger people would take off or feel stifled. I think of my interview with Sir Julian Huxley in his home in London, and he sat with gloves on (the fingers cut off) and a shawl around his shoulders and a small blanket over his lap. His mitochondria were fading in his memory too and his wife had to keep correcting him. Those who long for extending their lives have a tough job when they begin to shift their attention from our nuclear genes and chromosomal telomeres and start looking at our disappearing