Tuesday, March 4, 2014

SCIENTISTS BORN IN MARCH



Alexander Graham Bell [1847-1922],Scottish and later American, was born on March 14. We know him for the telephone but he was the first to recognize founder effects in genetics (hereditary deafness) and complex inheritance (supernumerary breasts in sheep). On the down side, he was a founder of the American eugenics movement.  Joseph Priestley [1733-1804] was born in England on March 13. He discovered air was not an element but composed of several gasses.  He isolated carbon dioxide (and made soda water as a beverage), discovered oxygen, and helped launch the Unitarian movement that stressed reason and not faith.  His home, laboratory, and church were burned by a mob in Birmingham and he then emigrated to the US. For March 14 Albert Einstein [1879-1955] is the most illustrious of the month, with his contributions that revolutionized our sense of the physical world through relativity, the photon theory of light, the cause of Brownian motion, and the equivalence of mass and energy. Also on March 14 we have Paul Ehrlich [1854-1915] , the physician who developed synthetic chemotherapy for infectious diseases (salvorsan for syphilis) and introduced the lock and key model of immunology. Caroline Herschel [1750-1848] was born on March 16.  She studied comets and mapped stars using telescopes invented by her brother. William Roentgen [1845-1923] was born on March 27.  He discovered x-rays and applied them to the detection of hidden objects and established medical radiology as a field. Rene Descartes [1596-1650] was born on March 31.  He was a philosopher and mathematician. His dualism was a major way scientists did science (separating the known or material world from the scientifically unknowable or spiritual world which at best was separate from the material world. He also developed analytical geometry which combined algebra and geometry and showed their conversion.  

Sunday, March 2, 2014

X-RAY TREATMENT FOR RINGWORM IN 1927 REMINDS US OF RADIATION ABUSES


Nedra and I saw a documentary “Hole in the Head” at the Monroe County Public Library on an act of radiation abuse carried out in 1927.  About 15 children, all African American, from a small town, Lyles Station, in southwest Indiana were taken by bus to the nearby general hospital at Princeton, Indiana.  There each had radiation treatment for ringworm. The children felt ill going home, some vomiting. Their hair fell out and in some grew back in patchy ways.  One, Vertus Hardiman, the subject of the film, had severe burns from the radiation and his scalp never quite healed.  He wore a cap or wig the rest of his life.  Despite this over dose of radiation, Hardiman lived into his mid 80s. He never married. His last three years were painful as bone cancer eroded his cranium leaving a gaping hole into his brain. The author of the documentary, Wilbert Smith, described the procedure used on the children as an experiment, but it is not clear for what purpose it was done or who designed it.  Smith compared it to the syphilis experiments carried out in the South in the 1930s-60s which deceived patients who thought they were being treated for tertiary syphilis.   The unit of measurement, the roentgen, was roughly described (but not named) in 1908 and made international in 1928.  The measurement of dosage for medical purposes was physiological until 1928. The number of seconds of exposure before skin reddened was called a threshold dose (or other names). Treatments were based on multiples of the threshold dose. The Victoreen dosimeter (which I used in Muller’s laboratory) was not invented until 1925 (by Otto Glasser and Hugo Fricke, both in the US) and marketed by Jack Victoreen in Cleveland in 1928.
              The treatment of ringworm by radiation began in 1897 in Germany. It was introduced to the US in 1903. The Kienbok-Adamson method of dividing the scalp into five target regions was proposed in 1907.  A London studied in 1910 claimed “in the hands of experts no danger is incurred.” Dose estimates for treating ringworm vary from 340-660 roentgens.   A 2003 study of 2224 x-rayed children followed for about 39 years contrasted 1380 who were given topical treatments (medications). In the x-ray group there were 16 intracranial tumors, 2 thyroid cancers, and 8 leukemias.  In the topical treated group were 1 intracranial tumor, no thyroid tumors and 1 leukemia.  After 1959 x-ray treatment ceased and was replaced by topical application of an antifungal medicine, griseofulvin.
              Muller had a folder of news clippings which I looked at in the Lilly Library at IU when I wrote his biography.  The abuses of radiation were numerous.  Medical uses included straightening out bow-legs in children, shrinking “enlarged” thymus glands (the alleged cause of chronic respiratory infections), curing plantar warts on the soles of feet, and inducing ovulation in infertile females by 100 r doses of x-rays to the ovaries and pituitary (the Kaplan treatment of the 1920s). Chiropractors at 4H fairs in Indiana had “straightest spine contests” using x-rays.  Shoe stores had fitting of children’s shoes with fluoroscopes.  When I married Nedra in Rochester, Indiana the shoe store on Main Street was called Taylor’s X-Ray Shoe Store.  During WWII those working in shipyards examined steel plate welds for imperfections using x-rays and protection of workers was spotty.

              I don’t know if an experiment was going on Lyles Station, Indiana or what its intent was. What is clear, however, is that abuse of radiation through ignorance, over-confidence, wishful thinking, and incompetence was prevalent in the early history of medicine and radiation abuse still exists because those attitudes are difficult to control.

Saturday, March 1, 2014

SVANTE PAABO AND THE NEANDERTHAL GENOME

I much enjoyed reading Svante Pääbo’s Neanderthal Man: In Search of Ancient Genomes [Basic Books, 2014].  Pääbo is a founder of the field of palaeogenomics, which attempts to reconstruct and interpret the DNA of ancient and extinct organisms. Pääbo spent more than 20 years trying to work out the genome of first the mitochondrial DNA of Neanderthals and then the nuclear DNA of these cousins of our own species.  Pääbo uses a combination of memoir, log book, and narrative to give the year by year account of set-backs, new technologies, and constant rethinking of approaches to achieve these important contributions to human evolution and molecular biology.  Unlike Watson’s Double helix   account of the structure of DNA, Pääbo has a different challenge.  He knows that the cells of Neanderthals were virtually identical to living cells of humans because they would have mitochondria, mitochondrial DNA, nuclei, and DNA (very likely with 46 chromosomes largely syntenic in their sequences of genes).  In Watson’s quest, the structure was the unknown.  In Pääbo’s quest, the differences in genes and variations of the genes was the quest.  For both there was the firm conviction, going back to H.J. Muller in 1926 that the gene was the basis of life. 
              Pääbo was born in Stockholm, his father, Sune Bergsgtröm, was a physiologist who worked out the structure and function of prostaglandins, molecules that acted like hormones at the cellular or immediate tissue level. For that work he received a Nobel Prize in 1982.  He carries his mother’s last name, because Karin Pääbo (a biochemist from Estonia) conceived him in an affair she had with Bergstrom.  The young Pääbo rarely saw his biological father and took solace in being a nerd-like scholar, infatuated with Egyptology, after his mother took him to visit Egypt when he was thirteen.    He also complicated his life as a gay activist in Stockholm (although he turned out to be bisexual).  He chose medicine as a possible option for a career but as his father’s fame became more apparent, he began thinking of working as a biochemist, and shifted to a PhD program.  His mentor worked out the DNA sequences of genes involved in antibodies. This rekindled Pääbo’s idea of working with mummies, using their DNA as a way to study ancient genes.
              Pääbo found a sympathetic curator in East Germany during the Cold War and began working with mummified tissue in his laboratory at Uppsala.  He did this independently of his dissertation research and showed his results to his mentor who was impressed and encouraged his career. The publications led to postdoctoral opportunities in Berkeley with Alan Wilson and eventually an appointment as head of a new department at a Max Planck Institute in Leipzig. As his publications grew in number, his access to samples of fossil bones increased when he switched from mummified tissues of Egyptians to his quest for Neanderthal DNA. These are not easy chapters for those without a science background.  They reveal the enormous challenge of identifying Neanderthal DNA as an entity separate from contaminating bacteria and the sweat, dandruff, and other excreta of modern human contamination, often by those who first retrieved the bones from caves and burial sites.  We learn how Pääbo relied on a team of students and employees whose work he supervised but who formed a weekly seminar of criticism of everyone’s work and what it signified.  Those brainstorming sessions led to more sophisticated controls, inventions of new procedures, search of the literature for new technologies, and deeper insights than any individually had conceived.  In most fossil Neanderthal bones it is rare for more than a few percent of the DNA to be Neanderthal. Proving to skeptical molecular biologists that the sequences they reported were Neanderthal and not artifacts of the past or present was stunningly difficult.  It is worth reading through those chapters to see how difficult this field was for a careful investigator. 

              I have often argued in my books that the life sciences rarely work through paradigm shifts.  This book illustrates the incremental changes over 20 years – hundreds of them – that brought about the reality of a new field of science.  We like to believe in the Copernican moment, when a shift takes place and a new field or world view emerges. They are rare in all of science and most new science and theories we add to the field we call the life sciences, fall not into flashes of rare insight but into the hard work of identifying mistakes in our experimental designs, interpreting unexpected findings, identifying contaminating variables, and eventually building an edifice of evidence that meets all known challenges of one’s contemporaries.  That Pääbo has done.

Monday, February 17, 2014

ONE SIN PUNISHES ALL HAS HISTORIC ROOTS





        I have often been puzzled by the over-reactive response to injustice whether that behavior is justified or not.  In the Biblical tradition that comes about several times.  First is Adam and Eve’s sin of eating a forbidden fruit.  The punishment involves aging and death to all future humanity (along with wearying toil for men and the pain of childbirth for women).  A similar response for a single misdeed involves Ham laughing at his drunken naked father (Noah). All of Ham’s descendants will serve (presumably as slaves) his siblings’ descendants. During the era of 18th and 19th century slavery in the United States that was frequently used to justify slavery. It’s not just the Bible that does this.  In Greek mythology, Pandora’s curiosity in opening a forbidden box, unleashed all sorts of misery and disasters (only hope was left in the box). Back to the Bible again, God tells Moses to kill all Amalekites including their wives and children because they hectored the Jews as they left Egypt.  It is not just religion that practices overkill response.  Nazi ideology sought to kill all Jews for what?  Trying to make a living as doctors, lawyers, professors, or merchants thereby depriving “real” Germans from earning a living?  Death for people who lived there for 1000 years or more?  That genocidal mentality was seen among those who settled the western territories and starved, deported, or killed Native Americans leaving the few survivors in isolated reservations.  What was their crime? They wanted to live as their ancestors did on their hunting grounds or their own farmlands and European descendants who came to North America felt that the land was theirs because they were civilized and Native Americans were savages to be chased away. Fortunately humans are diverse and some choose diplomacy over war, some choose an appreciation for diversity rather than a wiping out of anything but sameness whether that sameness is religious creed, ethnicity, race, or political ideology. On a smaller level we see it in the response to anger.  Some choose a lawsuit and sue for damages.  Some individuals settle for a bar-room brawl. Some (in this age of easy access to guns) come back with guns blazing for insults (loud music, an insulting phrase, being “uppity,” not being deferential).  In a vague way we try to understand but not justify that overkill response if a person is psychotic as seems to be the case for our mass murders in schools, theatres, or churches.  But so many people end  up in court cases for attempted or realized killing of others and use rationalizations to defend their horrible actions (eating Twinkies did it;  spoiled by excess wealth; used stand one’s ground laws; self-defense; couldn’t stand it anymore; substance abuse weakened my judgment; loyalty to a gang’s ethical code, family honor demands it).   Most people, fortunately, do not respond with excess violence to their sorrows real or imagined. What we do not know is the brain physiology that allows one person to “lose it” and most people to find less violent ways to find justice.  Whether it is genetic, viral, epigenetic, hormonal, or induced during gestation by yet unknown factors we do not know.  That is a much needed area for basic research.

Saturday, February 15, 2014

MY MORNING CUP OF COFFEE



        I began drinking coffee when I was in high school.  My father was my alarm clock and at 6:30 AM he scratched my head and as I sat at the edge of the bed, he handed me a cup of his Swedish style coffee—with lots of cream and sugar.  I glugged it down and was fired up for the day.  At NYU, GIs from WWII taught me to drink coffee black and unsweetened and that I have done ever since. Coffee was cultivated in the Middle East but got its origins as a beverage in Ethiopia and it spread to Yemen. It got to Europe from Constantinople to Venice by Italian traders during the Renaissance. Coffee beans were smuggled out of the Middle East to India and later to Java (hence a cup of Java), and then to the Caribbean and South America. The first coffee houses in England began in 1637.  It was not until 1683 that coffee shifted from black and unsweetened to cream and honey in Vienna.  Coffee houses spawned the stock exchange and the Royal Society among other enterprises.  In 1773 our Boston Tea Party led to the American patriotic duty to drink coffee and shun tea. Coffee percolators were invented in 1818.  Decaffeinated coffee was invented in 1903.  Instant coffee was introduced in 1938. The coffee break was invented by a clever marketer in 1952 and the variety coffee house became nationwide with Starbucks in 1982.

      Coffee comes from a red berry of the tree Coffea arabica. The berries are dried, the seeds removed and roasted and then the seeds are ground.  Coffee’s appealing qualities include its stimulation from caffeine that in many people represses drowsiness.  Caffeine is a purine (like adenine and guanine found in DNA) but it is only weakly mutagenic at high doses. At various times coffee was considered satanic (but Pope Clement VIII approved it in 1607) or equivalent to alcohol (and hence not permitted for early Moslems). It is still banned by Mormons (Latter Day Saints) and when I spent a semester as a visiting professor teaching at the University of Utah, those who drank caffeinated coffee were called “Jack Mormons.”  Most observant Mormon students drank decaffeinated coffee (such as Sanka) or ersatz coffee (such as Postum that C. W. Post made from roasted wheat bran and molasses). During World War II when coffee was rationed, I remember hearing on the radio Eleanor Roosevelt describe how she mixed yesterday's coffee grinds with Postum and a spoon of fresh coffee grounds to make coffee for Franklin. 

Friday, February 14, 2014

FEBRUARY HAS SOME NOTABLE BIRTHDAYS FOR SCIENTISTS



February 12 is Charles Darwin’s birthday (1809-1882) and this year I celebrated drinking my morning coffee in a glass cup engraved with my name and the occasion – Darwin Day 2007 where I gave a talk on Darwin at Rutgers University.  Darwin of course provided massive evidence for evolution and proposed a mechanism, natural selection by which environments selected among variations (later called mutations) and over time this led to species divergence and change. February 15 is Galileo Galilei’s birthday (1581-1585).  We honor him for his telescopic support for the heliocentric model of the solar system proposed by Copernicus.  His observations of the moons of Jupiter, the phases of Venus, the sunspots on our sun, and the presence of mountains and craters on the moons made modern astronomy possible.  February 16 is the birthday of Hugo de Vries (1848-1935).  We honor him as a rediscoverer of Mendel’s laws on the transmission of hereditary traits.  He also stimulated interest in mutations and attracted a new generation of geneticists to work in that field. February 19 is the birthday of Nicolaus Copernicus (1473-1543) whose heliocentric model of the solar system he first formulated as a privately circulated letter (the Commentariolus) and did not allow publication of his larger book until he was near death for fear of the repercussions of his ideas despite his being a priest.  February 28 is the birthday of Linus Pauling (1901-1994) a noted chemist who received a Nobel prize for his work on the chemical bond, his recognition and description of sickle cell anemia as a “molecular disease,” and his activism to bring about nuclear weapons testing restrictions (for which he added a second Nobel prize).

              Scientists of note are distributed across all twelve months.  This is a particularly nice group of my favorite scientists.

Monday, February 10, 2014

WHY BOOK DISCUSSION GROUPS MATTER



I first joined a book discussion group when I was in Los Angeles in 1961.  We were going to the Westwood Unitarian Fellowship and met Peter Gary, a Hungarian composer and Holocaust survivor.  He led a monthly book discussion group and we read books that were stimulating – classics, provocative novels, and non-fiction that enlightened us. In 1968 Nedra and I moved to Stony Brook, New York  and joined the Stony Brook Unitarian-Universalist Fellowship.  They had a book discussion group led by Ernie Kamperman, a dentist.  It used a similar format of books recommended by participants and lively discussions.  In both cases these were held in a host’s home (either Gary’s or Kamperman’s).  When Kamperman got ill and died in 1975, I kept the book discussion going for the next 30 years and they were rotated among a half dozen homes of participants. When we moved to Bloomington, Indiana in November 2009 and joined the UU Church of Bloomington, there was no book discussion group.  I volunteered to start it and so far we meet in our home which has a spacious living room that can hold 12 people comfortably. We pick books that are prize winners or nominees for Nobels, Pulitzers, National Book Awards or Booker Prizes.  We occasionally read a classic (like Tocqueville’s Democracy in America or Lessing’s Nathan the Wise).  The person who recommends the book starts the discussion by telling us why that book was chosen. The conversation for an hour is lively and we then have coffee and cake and discuss what we should read next, alternating a work of fiction and a work of non-fiction.  The result of some 50 years of reading at least a book each month outside my fields of genetics or history of science has been enriching.  I learn from others and see how differently we interpret the works we read. It is also nice to have a sustained discussion on ideas that matter in a world that has abandoned soirees and replaced them with full time pundits on television.