Saturday, July 6, 2013
UPDATE FOR A NEGLECTED BLOG
I’ve enjoyed reading a few blogs over the years but almost all blogs I’ve read end abruptly or sputter along with long intervals of silence. That includes me. Why does this happen? Partly it’s the lack of response to blogs. After putting these on line and getting zero response I begin to wonder if anyone is bothering to read these and if they aren’t, why should I continue? They are not diary entries meant just for my own record of my life. I suspect something like that goes on in the minds of the “sputtering” blogs I’ve read. There is also the tendency to shift ways of communicating. As a youth I wrote a lot of letters and I could even mail a letter in the morning to a friend in Brooklyn and he would receive it later that afternoon (those were the good old days of the US Post Office). Few poor people had phones during the great depression and for the few who wanted to contact someone who didn’t have a phone, they would call the local candy store public telephone and the proprietor would ask a child to run to the apartment of someone down the block and they would answer the call or call back from that phone.
In more recent times (the 21st century) people have Facebook but the comments are generally no more than one paragraph. Twitter (which I have not yet used, since I am an 81 year old Luddite and technophobe) is limited to fixed space so comments are pithy and filled with abbreviations. It’s a bit like stenography to me. Each new technology for communication has a way of eclipsing the older way of communication and the trend is to brevity of response and brevity of sharing ideas. Blogs do not have that limitation and allow more reflective pieces to be written. To my surprise, even my moribund Blog gets an occasional inquiry and I have used it to reconnect to distant relatives, to hear from colleagues I have not had any contact with for decades, and even one person doing genealogy who shares a relative of Nedra’s from the American Revolutionary War. So that has inspired me to equate writing a Blog with tossing a note in a bottle into the ocean and waiting for a response.
I left off in the Blog in 2011. Since then another of my books has appeared -- The 7 Sexes. Biology of Sex Determination. IU Press published it in February but so far no reviews have appeared. It is a history of how the components of our sexuality (seven of them) came to be known and how the past interpreted such things as hermaphrodites, same-sex orientation, gender roles, or how boys or girls came into being. I show how little we knew until recently. Sex hormones were virtually unknown until the 1920s. Fertilization as the union of a sperm and an egg came about in the 1870s. In older anatomies of the 1700s the ovaries were described as female testes. In antiquity it was almost pure guess work on what causes male or female offspring or how the sexual apparatus functions.
I have also written articles on the history of genetics for the journals GENETICS and Mutation Research Reviews. I’ve done lots of book reviews for the Quarterly Review of Biology. I continue to write and have about a dozen books unpublished that exceeds my output of published books (13). I am also doing a book on the history of the Unitarian Universalist Church of Bloomington and serve as their historian. That has been fun to do and I have followed the evolution of religion from animism to the present and compared it to the history of rationalism from antiquity to the present. I have identified eight different types of Unitarian ways of looking at religion. The UU Church of Bloomington started as a fellowship in 1948 and it helped integrate the IU campus and county which was segregated and racist then. It is now a large creedless church with about 500 members ranging from Wiccans to atheists with most being a more socially committed group who like discussing meaning in their lives and commitment to making the world a better place.
Nedra continues to do her volunteer work for Habitat for Humanity and she is involved in the local quilting guild. We enjoy IU theatre, its musicals, and occasional concerts.
Wednesday, October 19, 2011
Assessing low doses of radiation: background fact sheet
The discovery of x-ray induced mutations by H. J. Muller in 1927 led to the field of radiation genetics.
By 1944 the following was known:
1. X-rays induce gene mutations that are indistinguishable from those arising by natural means. Muller noted that in his 1927 X-linked lethal detection stock (ClB) that he also obtained X-linked visible mutations and he mapped them to the same locations as their previously found spontaneous alleles from 1910-1926.
2. X-rays induced a class of mutation not previously described, called “dominant lethals”. It was not known if these were point mutations like the recessive X-linked lethals until 1944 when G. Pontecorvo, using a stock designed by H. J. Muller, detected losses of chromosomes caused by aneucentric chromosomes. These were shown to arise from a single break in a chromosome that led to reunions of replicated chromosome fragments forming a potential acentric chromosome and a potential dicentric chromosome. McClintock had independently found such losses using maize and called this the breakage-fusion-bridge cycle.
3. X-rays induce a large number of chromosome breaks that lead to chromosome rearrangements (worked out for radiation induced chromosome rearrangements in the 1930s). This included inversions and translocations which could be detected genetically and confirmed cytologically.
4. In general the induction of X-linked lethals is linear for doses of 100-6000 R.
5. In general the induction of translocations (as a measure of 2 breaks) was to the 3/2 power instead of the expected square. Muller believed this was associated with the practice of x-raying mature sperm (spermatids or spermatozoa) which tend to have most of the nuceloplasm removed from the nucleus and the chromosomes are pressed close to one another and they are highly coiled and compact. This leads to a single path of radiation producing more than one break. This happens less frequently when immature stages are used where the chromosomes are not compacted and when that is done the incidence of breakage approaches the square of the dose.
6. Attenuated doses (studied by SP Ray-Chaudhury at Edinburgh in 1939 for 400 R given in 30 minutes produced the same percent of x-linked lethals as 400 R given over 28 days). Muller argued that this meant individuals exposed to chest x-rays and practitioners not protecting themselves with shielding were at risk to radiation induced damage at low dose. Because 400 R given over 28 days is like getting a chest x-ray every minute [about 0.01R or 0.0017 R per second] . Most chest x-rays take about 1 second to administer. Thus a low dose of 0.0017R per second over 28 days yields 400 R over 28 days. The effects are cumulative and, as Ray-Chaudhury showed, the percent of induced mutations is the same as that received the acute dose.
Between 1944-1960 the following additional findings were added:
1. The breakage-fusion-bridge cycle was the likely cause of radiation sickness among the survivors of the blast effects of the atomic bombs in Japan. The tissues affected and their symptoms (blistering and reddening of the skin, pinpoint ulceration of the intestinal tract, petechiae or rashes of capillary bleeding inside tissue and in the skin, reduced red blood cell count, reduced white blood count, loss of hair, bleeding from the intestinal tract and vagina were all consistent with those tissues (skin, gut epithelium, capillary endothelial cells, and bone marrow) that had frequent cell cycles replacing tissues exposed to mechanical damage (skin gut and blood vessel lining) or that had high turnover (red and white blood cells). Long term survivors could expect cataracts and increased risk to cancers (usually 7 years for the leukemia to appear and about 25 years for the solid tumors to appear)
2. X-rays cause direct hits to genes causing point mutations and they cause conversion of water to peroxides that act as chemical mutagens and alter nitrogenous bases. Stone, Wyss, and Haas in 1949 showed that bacteria directly exposed to radiation gave only slight more mutations than unexposed bacteria placed on x-rayed food in petri dishes. This showed most of the bacterial mutations from radiation are peroxide induced. This would make a substantial amount of mutations induced by x-rays in humans as similar to effects of exposure to peroxides. Humans have about 70% water in their tissues.
3. Charlotte Auerbach in 1945 published her war-time results (classified as secret until the war ended) on chemical mutagens in fruit flies. She used mustard gas and found most of the mutations induced were fractional or mosaic. It was not until the double helix structure of DNA was worked out in 1953 that this was resolved. Fractional mutations receive one DNA strand with a chemically induced lesion and the complementary strand had the normal complementary base. These two lines of cells are present after fertilization—one leading to mutant expression and one leading to normal expression. In fruit flies the chances of such a mosaic having a gonad with mutant cells present is about 20%. Those progeny show full expression of the mutant.
4. The Watson-Crick double helix model of 1953 led to the study of chemical mutagens on viruses. Three categories were identified by Cricks laboratory and by Benzer’s laboratory in the early 1960s. Transitions were chemical alterations of one purine for another purine or of one pyrimidine for another pyrimidine. Transversions were mutant events in which an altered purine led to altered pyrimidine or the reverse. Frame shift mutations were associated with chemical mutagens that intercalated or inserted a ring shaped molecule, jamming the DNA and during replication leading to losses or gains of one or more pairs of nucleotides. Agents like nitrous acid, hydrogen peroxide, and formaldehyde produce chiefly transitions and transversions. Agents like proflavine or quinacrine (multi-ring compounds) acted as frame-shift agents.
5. In 1952 radioactive fallout was first reported by Japanese fishermen who were exposed to it during the US first H-bomb tests in the Pacific. They had severe radiation sickness.
6. In 1954-1963 there were numerous tests of radioactive fallout from USSR and US atmospheric testing. Barry Commoner studied baby teeth and showed that radioactive elements (especially strontium 90) from these weapons testing was falling on grasslands in the US and entering the milk supply of these children in the United States. The teeth would expose photographic film when these were allowed to rest on it for a day or more.
7. The sequencing of DNA became possible in the 1980s and by the year 2000 it could be extended to whole genomes. Any mutation can be identified (they are sometimes called SNPs or single nucleotide polymorphisms) and this opens up a possible way to look at Japanese atomic bomb survivors or their children to see what SNPs have been induced to control matched populations of nearby Japanese cities not exposed.
8. Evelyn Witkin discovered there are repair enzymes in cells. These can repair single stranded breaks, double stranded breaks (the most common from x-ray direct hits), thymine dimers (the type formed by exposure to ultraviolet light), and mismatched pairing. When double strand breaks occur and are repaired it is possible for the wrong bases to be inserted in the patched region. These would be expressed as gene or point mutations. There are human genetic disorders with defective repair enzymes. Such disorders (Louis-Barr syndrome, Bloom syndrome) are characterized by frequent cancers and an early death. Bacteria lacking catalase (an enzyme that inactivates hydrogen peroxide) have higher spontaneous mutation frequencies and higher induced radiation mutations.
Concerns about experimental design
Any geneticist doing experiments on dose-response effects has to know this very complex background to designing a low dose experiment and to guard against errors that would obscure what is being tested or the interpretation of the results. Here are some of the difficulties of doing low dose experiments:
1. In fruit flies it is difficult to do experiments that are below 100 R because the scale has to be very large. In general the lower the dose the larger the scale of exposed and control populations are needed. In a fruit fly mutagenesis experiment this is usually done by examining vials of flies that descend from the F2 of P1 exposed flies. If the P1 is a normal male and the F1 is a heterozygous fly containing a marked chromosome and the exposed sperm, each F1 vial set up tests one sperm from the exposed male. If the control rate is about 1 X-linked lethal per 2000 flies examined then the control group of several thousand vials has to differ from the low dose exposed group of several thousand vials being tested. For a control rate of 1 in 2000 the statistical expectation range is 1-12 out of a test using 2000 vials for the control. Thus if a low dose of 50 R is done for an experiment involving 2000 vials for the exposed there may be an incidence of 13. This has a range of 6-18. Since the lower range of the induced overlaps the higher range of the spontaneous range, these are not significant. A tray of vials may contain 100 vials and this mean 20 trays of controls and 20 trays of experimental. A more likely experiment anticipating these low number statistical fluctuations would have to use more vials, say 4000 controls and 4000 vials of the experimental or a total of 80 trays so that the two ranges do not overlap. That’s a lot of work. Before 1957 grant support was mostly private. Sputnik changed that to NSF and NIH money on a large scale. This is one reason why there were so few large scale experiments testing low doses before the Cold War. The USSR did not have atomic weapons until 1952 so the issue of fall out and radiation protection was not as elevated. For this reason it could not have been a fall-out issue that motivated Muller. Whatever Muller’s views were on radiation safety they long predated the World War II use of atomic weapons. He was raising concerns about radiation safety as early as 1928 when he gave a talk on x-ray induced mutations at Waco, Texas and cautioned physicians that they should protect themselves and their patients by using lead shielding. Bentley Glass, who attended that lecture, said physicians walked out in protest.
The issue of hormesis
Hormesis was introduced in 1888 by Hugo Schultz. It asserts that low doses of toxic agents may have beneficial effects by boosting an immune response (or some other beneficial mechanism in plants and organisms lacking an immune system) to the agent. Edward Calabrese is a major supporter of hormesis in a wide range of agents, including carcinogens, mutagens, pharmaceutical agents, and radiations. He has extended hormesis to a study of low dose linear curves for toxic agents and radiations and he has extended hormesis to the presence or absence of threshold doses for radiation. Calabrese is not a geneticist. He received his PhD in 1973 for a study of metabolism in black blow flies from the entomology department at UMass Amherst. The next year in 1974 he received a D.Ed. degree with a dissertation on logo therapy. Logo therapy is the psychiatric system worked out by Viktor Frankl using meaning and purpose to achieve mental health particularly in stressful situations (Frankl survived the Holocaust concentration camps).
Calabrese through a press release accused Muller of being a liar and a bully in getting federal and international agencies to accept the thesis that there is no threshold for the linearity of radiation dose-effect curve (which presently runs from about 100 R to 12,000 R for fruit flies). Muller relied on the work of Ray-Chaudhury for the attenuated doses as a reason to exclude a threshold dose and to uphold the extrapolation of the linearity curve. An attempt by Curt Stern to use 50 R was done with Ernest Caspari and a letter and manuscript draft was sent to Muller shortly before he left for Stockholm to accept his Nobel prize in 1946. Calabrese claims that Muller was upset over the apparent below expected response to the 50 R exposure. This to Calabrese is deceit despite the fact that most scientists do not cite unpublished work and despite the fact that Muller wrote to Stern some of his first impression objections to the interpretation of the results. When the paper was published both Stern and Caspari acknowledged a low probability (about 1%) of the results being consistent with the linearity hypothesis and they discussed what problems were involved in their experimental design.
It is disappointing that Calabrese did not treat this as a dispute in science (they are common). Instead he chose to make a conspiratorial case, attributing “higher causes” such as radiation protection, ideology, or concern over fallout from nuclear weapons arms races as the basis for Muller’s “repression” of the Stern-Caspari draft although some of those concerns did not arise until 6 years after Muller’s Nobel Prize. He also makes it seem as if all the other work of other laboratories on radiation genetics and the linearity curve should collapse from this one finding under dispute. It is also disappointing that Calabrese offers no molecular mechanisms like those molecular biologists have offered for the induction of mutations to account for this alleged beneficial effect of low doses of radiation or other agents. He ignores the many variables cited in this account and demands an ideal experiment at low doses without complications despite the numerous variables involved in designing such an experiment. He ignores the attenuated doses studied by Ray-Chaudhury and others and does not explain why they accumulated in Ray-Chaudhury’s work if that total dose was spread at less than chest x-ray exposure each minute.
Elof Axel Carlson
Distinguished Teaching Professor emeritus
Department of Biochemistry and Cell Biology
Stony Brook University
And Visiting Scholar, Institute for Advanced Study
Indiana University (Bloomington).
October 18, 2011
By 1944 the following was known:
1. X-rays induce gene mutations that are indistinguishable from those arising by natural means. Muller noted that in his 1927 X-linked lethal detection stock (ClB) that he also obtained X-linked visible mutations and he mapped them to the same locations as their previously found spontaneous alleles from 1910-1926.
2. X-rays induced a class of mutation not previously described, called “dominant lethals”. It was not known if these were point mutations like the recessive X-linked lethals until 1944 when G. Pontecorvo, using a stock designed by H. J. Muller, detected losses of chromosomes caused by aneucentric chromosomes. These were shown to arise from a single break in a chromosome that led to reunions of replicated chromosome fragments forming a potential acentric chromosome and a potential dicentric chromosome. McClintock had independently found such losses using maize and called this the breakage-fusion-bridge cycle.
3. X-rays induce a large number of chromosome breaks that lead to chromosome rearrangements (worked out for radiation induced chromosome rearrangements in the 1930s). This included inversions and translocations which could be detected genetically and confirmed cytologically.
4. In general the induction of X-linked lethals is linear for doses of 100-6000 R.
5. In general the induction of translocations (as a measure of 2 breaks) was to the 3/2 power instead of the expected square. Muller believed this was associated with the practice of x-raying mature sperm (spermatids or spermatozoa) which tend to have most of the nuceloplasm removed from the nucleus and the chromosomes are pressed close to one another and they are highly coiled and compact. This leads to a single path of radiation producing more than one break. This happens less frequently when immature stages are used where the chromosomes are not compacted and when that is done the incidence of breakage approaches the square of the dose.
6. Attenuated doses (studied by SP Ray-Chaudhury at Edinburgh in 1939 for 400 R given in 30 minutes produced the same percent of x-linked lethals as 400 R given over 28 days). Muller argued that this meant individuals exposed to chest x-rays and practitioners not protecting themselves with shielding were at risk to radiation induced damage at low dose. Because 400 R given over 28 days is like getting a chest x-ray every minute [about 0.01R or 0.0017 R per second] . Most chest x-rays take about 1 second to administer. Thus a low dose of 0.0017R per second over 28 days yields 400 R over 28 days. The effects are cumulative and, as Ray-Chaudhury showed, the percent of induced mutations is the same as that received the acute dose.
Between 1944-1960 the following additional findings were added:
1. The breakage-fusion-bridge cycle was the likely cause of radiation sickness among the survivors of the blast effects of the atomic bombs in Japan. The tissues affected and their symptoms (blistering and reddening of the skin, pinpoint ulceration of the intestinal tract, petechiae or rashes of capillary bleeding inside tissue and in the skin, reduced red blood cell count, reduced white blood count, loss of hair, bleeding from the intestinal tract and vagina were all consistent with those tissues (skin, gut epithelium, capillary endothelial cells, and bone marrow) that had frequent cell cycles replacing tissues exposed to mechanical damage (skin gut and blood vessel lining) or that had high turnover (red and white blood cells). Long term survivors could expect cataracts and increased risk to cancers (usually 7 years for the leukemia to appear and about 25 years for the solid tumors to appear)
2. X-rays cause direct hits to genes causing point mutations and they cause conversion of water to peroxides that act as chemical mutagens and alter nitrogenous bases. Stone, Wyss, and Haas in 1949 showed that bacteria directly exposed to radiation gave only slight more mutations than unexposed bacteria placed on x-rayed food in petri dishes. This showed most of the bacterial mutations from radiation are peroxide induced. This would make a substantial amount of mutations induced by x-rays in humans as similar to effects of exposure to peroxides. Humans have about 70% water in their tissues.
3. Charlotte Auerbach in 1945 published her war-time results (classified as secret until the war ended) on chemical mutagens in fruit flies. She used mustard gas and found most of the mutations induced were fractional or mosaic. It was not until the double helix structure of DNA was worked out in 1953 that this was resolved. Fractional mutations receive one DNA strand with a chemically induced lesion and the complementary strand had the normal complementary base. These two lines of cells are present after fertilization—one leading to mutant expression and one leading to normal expression. In fruit flies the chances of such a mosaic having a gonad with mutant cells present is about 20%. Those progeny show full expression of the mutant.
4. The Watson-Crick double helix model of 1953 led to the study of chemical mutagens on viruses. Three categories were identified by Cricks laboratory and by Benzer’s laboratory in the early 1960s. Transitions were chemical alterations of one purine for another purine or of one pyrimidine for another pyrimidine. Transversions were mutant events in which an altered purine led to altered pyrimidine or the reverse. Frame shift mutations were associated with chemical mutagens that intercalated or inserted a ring shaped molecule, jamming the DNA and during replication leading to losses or gains of one or more pairs of nucleotides. Agents like nitrous acid, hydrogen peroxide, and formaldehyde produce chiefly transitions and transversions. Agents like proflavine or quinacrine (multi-ring compounds) acted as frame-shift agents.
5. In 1952 radioactive fallout was first reported by Japanese fishermen who were exposed to it during the US first H-bomb tests in the Pacific. They had severe radiation sickness.
6. In 1954-1963 there were numerous tests of radioactive fallout from USSR and US atmospheric testing. Barry Commoner studied baby teeth and showed that radioactive elements (especially strontium 90) from these weapons testing was falling on grasslands in the US and entering the milk supply of these children in the United States. The teeth would expose photographic film when these were allowed to rest on it for a day or more.
7. The sequencing of DNA became possible in the 1980s and by the year 2000 it could be extended to whole genomes. Any mutation can be identified (they are sometimes called SNPs or single nucleotide polymorphisms) and this opens up a possible way to look at Japanese atomic bomb survivors or their children to see what SNPs have been induced to control matched populations of nearby Japanese cities not exposed.
8. Evelyn Witkin discovered there are repair enzymes in cells. These can repair single stranded breaks, double stranded breaks (the most common from x-ray direct hits), thymine dimers (the type formed by exposure to ultraviolet light), and mismatched pairing. When double strand breaks occur and are repaired it is possible for the wrong bases to be inserted in the patched region. These would be expressed as gene or point mutations. There are human genetic disorders with defective repair enzymes. Such disorders (Louis-Barr syndrome, Bloom syndrome) are characterized by frequent cancers and an early death. Bacteria lacking catalase (an enzyme that inactivates hydrogen peroxide) have higher spontaneous mutation frequencies and higher induced radiation mutations.
Concerns about experimental design
Any geneticist doing experiments on dose-response effects has to know this very complex background to designing a low dose experiment and to guard against errors that would obscure what is being tested or the interpretation of the results. Here are some of the difficulties of doing low dose experiments:
1. In fruit flies it is difficult to do experiments that are below 100 R because the scale has to be very large. In general the lower the dose the larger the scale of exposed and control populations are needed. In a fruit fly mutagenesis experiment this is usually done by examining vials of flies that descend from the F2 of P1 exposed flies. If the P1 is a normal male and the F1 is a heterozygous fly containing a marked chromosome and the exposed sperm, each F1 vial set up tests one sperm from the exposed male. If the control rate is about 1 X-linked lethal per 2000 flies examined then the control group of several thousand vials has to differ from the low dose exposed group of several thousand vials being tested. For a control rate of 1 in 2000 the statistical expectation range is 1-12 out of a test using 2000 vials for the control. Thus if a low dose of 50 R is done for an experiment involving 2000 vials for the exposed there may be an incidence of 13. This has a range of 6-18. Since the lower range of the induced overlaps the higher range of the spontaneous range, these are not significant. A tray of vials may contain 100 vials and this mean 20 trays of controls and 20 trays of experimental. A more likely experiment anticipating these low number statistical fluctuations would have to use more vials, say 4000 controls and 4000 vials of the experimental or a total of 80 trays so that the two ranges do not overlap. That’s a lot of work. Before 1957 grant support was mostly private. Sputnik changed that to NSF and NIH money on a large scale. This is one reason why there were so few large scale experiments testing low doses before the Cold War. The USSR did not have atomic weapons until 1952 so the issue of fall out and radiation protection was not as elevated. For this reason it could not have been a fall-out issue that motivated Muller. Whatever Muller’s views were on radiation safety they long predated the World War II use of atomic weapons. He was raising concerns about radiation safety as early as 1928 when he gave a talk on x-ray induced mutations at Waco, Texas and cautioned physicians that they should protect themselves and their patients by using lead shielding. Bentley Glass, who attended that lecture, said physicians walked out in protest.
The issue of hormesis
Hormesis was introduced in 1888 by Hugo Schultz. It asserts that low doses of toxic agents may have beneficial effects by boosting an immune response (or some other beneficial mechanism in plants and organisms lacking an immune system) to the agent. Edward Calabrese is a major supporter of hormesis in a wide range of agents, including carcinogens, mutagens, pharmaceutical agents, and radiations. He has extended hormesis to a study of low dose linear curves for toxic agents and radiations and he has extended hormesis to the presence or absence of threshold doses for radiation. Calabrese is not a geneticist. He received his PhD in 1973 for a study of metabolism in black blow flies from the entomology department at UMass Amherst. The next year in 1974 he received a D.Ed. degree with a dissertation on logo therapy. Logo therapy is the psychiatric system worked out by Viktor Frankl using meaning and purpose to achieve mental health particularly in stressful situations (Frankl survived the Holocaust concentration camps).
Calabrese through a press release accused Muller of being a liar and a bully in getting federal and international agencies to accept the thesis that there is no threshold for the linearity of radiation dose-effect curve (which presently runs from about 100 R to 12,000 R for fruit flies). Muller relied on the work of Ray-Chaudhury for the attenuated doses as a reason to exclude a threshold dose and to uphold the extrapolation of the linearity curve. An attempt by Curt Stern to use 50 R was done with Ernest Caspari and a letter and manuscript draft was sent to Muller shortly before he left for Stockholm to accept his Nobel prize in 1946. Calabrese claims that Muller was upset over the apparent below expected response to the 50 R exposure. This to Calabrese is deceit despite the fact that most scientists do not cite unpublished work and despite the fact that Muller wrote to Stern some of his first impression objections to the interpretation of the results. When the paper was published both Stern and Caspari acknowledged a low probability (about 1%) of the results being consistent with the linearity hypothesis and they discussed what problems were involved in their experimental design.
It is disappointing that Calabrese did not treat this as a dispute in science (they are common). Instead he chose to make a conspiratorial case, attributing “higher causes” such as radiation protection, ideology, or concern over fallout from nuclear weapons arms races as the basis for Muller’s “repression” of the Stern-Caspari draft although some of those concerns did not arise until 6 years after Muller’s Nobel Prize. He also makes it seem as if all the other work of other laboratories on radiation genetics and the linearity curve should collapse from this one finding under dispute. It is also disappointing that Calabrese offers no molecular mechanisms like those molecular biologists have offered for the induction of mutations to account for this alleged beneficial effect of low doses of radiation or other agents. He ignores the many variables cited in this account and demands an ideal experiment at low doses without complications despite the numerous variables involved in designing such an experiment. He ignores the attenuated doses studied by Ray-Chaudhury and others and does not explain why they accumulated in Ray-Chaudhury’s work if that total dose was spread at less than chest x-ray exposure each minute.
Elof Axel Carlson
Distinguished Teaching Professor emeritus
Department of Biochemistry and Cell Biology
Stony Brook University
And Visiting Scholar, Institute for Advanced Study
Indiana University (Bloomington).
October 18, 2011
Monday, October 10, 2011
CONTROVERSIES, REPORTERS, AND SCIENCE
WHEN SHOULD WE INVOKE ULTERIOR MOTIVES IN A SCIENTIFIC CONTROVERSY?
Edward Calabrese brought a charge against H J Muller [1890-1967] reviving a Cold War claim that exposure to radiation in low doses is either harmless or good for the population exposed to it. A reporter for the Chronicle of Education did an article on it and tried to be balanced in his coverage of the charge by Calabrese that his field of hormesis rules out harmful effects of any low doses of radiations, chemical mutagens, carcinogens, additives, pollutants, and wastes whether in our drinking war, foods, our workplace, or the air we breathe. He claims such noxious exposures stimulate the immune system and give us resistance to these agents or they compensate for the exposure in some unknown way. To me that reeks of self-interest and wishful thinking because the weight of scientific evidence favors, in the peer reviewed published record, harm done to organisms given attenuated doses of radiation. Small exposures to radium by watchmakers in factories during the 1920s resulted in bone cancers to the women who worked in these assembly lines. Physicians and dentists, in the days before there were dosimeters, used to invoke a threshold dose below which radiation did no harm, The test: put your hand under the x-ray machine and if reddening of the skin occurs you have reached the threshold dose. Please don’t try that! There is no dispute by Calabrese and Cold War critics of Muller that high doses of exposure are harmful. How could one deny Hiroshima and Nagasaki or those exposed during accidents to massive doses of radiation? Nor do they deny that it is linear from roughly 100 R to 12,000 R in fruit flies and other systems where such doses could be applied to a set of organisms and sufficient numbers of their progeny be counted for a controlled experiment. But is radiation sickness at high doses the only harm done by exposure to ionizing radiation? What is difficult to do for fruit flies or mice are experiments involving lower doses of 25 R. Why are such experiments difficult? The lower the dose the larger the number of flies or mice you have to involve in an experiment at low doses because those doses may only increase the incidence of mutation by 2 or 3 fold. If the spontaneous rate in a fruit fly experiment is 1 X-linked lethal per two thousand sperm, how many individuals would you use for the treated and controlled? The statistics for small numbers would argue a range of 1-12 per 2000 would be a control rate in any one given experiment. So you would need to examine a much larger number of flies to show more mutations occurred in the low dose and these two results would be non-overlapping. Let us say you did such an experiment and in the controls you sampled 2000 and got 3 mutations and in the exposed (let us say 25 R) you got 12 mutations. You would think, if you didn’t know the statistical issues involved, that 25 R produced those extra mutations. But let us say you repeated the experiment and this time you got 8 controls mutations and 2 at the 25 R range. You would either say radiation did not induce mutations at that dose or you would say radiation is good for you at low doses because you get less mutations by being exposed. Actually in both these experiments you get inclusive results because you haven’t examined a sufficiently large number of vials of flies (each vial represents one exposed or one control sperm). When you have to use tens of thousands of vials you run into a lot of problems because that is as very big experiment. The larger such experiments are, the more variables you introduce and unless the effects are dramatic statistically, it is hard to know how carefully these alternative factors played a role (light, temperature, food batch, being in a tray under other trays or being in the top of several layers of trays in one or two rooms with different conditions. This why attenuated doses are more frequently used to test the presence or absence of threshold effects. The best known was done by Muller’s student in Edinburgh, S P Ray-Chaudhury in 1939. His thesis wasn’t published until 1944 because of the war. Later he went back to India and repeated his technique of attenuated doses once for measuring chromosomes breaks (which he found also to be linear) and once to look again at gene mutations.
In science there is a tradition of challenging the work of one’s peers and repeating the work of one’s peers. Out of this healthy debate emerges more careful experiments and more confidence in the findings found in a first report of something new. For most of tens of thousands of such scientific findings the disputes never leave the professional journals. The issues are strictly scientific. The persons who decide the validity and care of an experiment are other scientists in the field. To get published there is peer review. No one calls in a scientist from another field or a reporter to evaluate the claims of the accuracy of the two experimental groups claiming contradictory findings. Such things happen when the nature of the findings have serious human implications. We have controversy over agents that cause embryo damage (e.g., the thalidomide controversy), over stem cell research (a form of identical twinning from embryonic cells before they have implanted into a uterus), over potential carcinogens (like the butter yellow used to color margarines in the 1940s when the dairy industry forced margarine companies to put a pellet of butter yellow for the purchaser to knead into the white lard-like fat so that customers would not think they are buying real butter). Butter yellow was a liver carcinogen and pulled off the market by our FDA regulatory commission. Frequently in these controversies there are vested interests who favor a view that what they are doing, what they are using, and what they are selling is perfectly safe and that the claims of mutations, cancers, or toxicity are either bad science or politically inspired, or ideological by irrational environmentalists or health nuts. Also in these debates are scientifically not well informed environmentalists, health nuts, and others who without knowledge of the science involved believe everything that is not organic, natural, or familiar should be treated as potentially damaging to the public. It works both ways to our disadvantage because most people involved in the debate are not the scientists involved in the appropriate fields to do so.
I am frustrated when a reporter calls and asks for my “side” of a debate. How do I spend an hour or more trying to show all the variables involved just in the science involved? Should I mention that the accuser of a position I hold is funded by agencies or industries that favor a view that what they do is without harm and no government regulations are needed in an industry which knows best what is harmful and what is harmless? Of course it is irrelevant to the real issue of whether, in this case, low doses are harmful, beneficial, or inactive with respect to the mutation process. But is the scientist on the side of that position a geneticist? No. Should I respect his judgment nevertheless when he has not immersed himself in the field the way Muller did for his entire adult life? Do thousands of hours doing genetics get neutralized by someone doing virtually no genetics and coming in a field of toxicology from a department of entomology for his PhD? Does it matter? Whose job is it to look into this? Is it mine as a geneticist or is it a reporter’s with very little, if any experience in doctorate level genetic experimentation? This forces reporters to look more at motivation, conflict of interest, ideology, scientific method (self-deception, constructed realities, unexamined bias) rather than at the detailed scientific experiments and how they were done and what was inadequate in their experimental design. When science gets politicized by this type of publicized controversy it frustrates everyone involved. I wish I knew a remedy for this. I don’t.
Edward Calabrese brought a charge against H J Muller [1890-1967] reviving a Cold War claim that exposure to radiation in low doses is either harmless or good for the population exposed to it. A reporter for the Chronicle of Education did an article on it and tried to be balanced in his coverage of the charge by Calabrese that his field of hormesis rules out harmful effects of any low doses of radiations, chemical mutagens, carcinogens, additives, pollutants, and wastes whether in our drinking war, foods, our workplace, or the air we breathe. He claims such noxious exposures stimulate the immune system and give us resistance to these agents or they compensate for the exposure in some unknown way. To me that reeks of self-interest and wishful thinking because the weight of scientific evidence favors, in the peer reviewed published record, harm done to organisms given attenuated doses of radiation. Small exposures to radium by watchmakers in factories during the 1920s resulted in bone cancers to the women who worked in these assembly lines. Physicians and dentists, in the days before there were dosimeters, used to invoke a threshold dose below which radiation did no harm, The test: put your hand under the x-ray machine and if reddening of the skin occurs you have reached the threshold dose. Please don’t try that! There is no dispute by Calabrese and Cold War critics of Muller that high doses of exposure are harmful. How could one deny Hiroshima and Nagasaki or those exposed during accidents to massive doses of radiation? Nor do they deny that it is linear from roughly 100 R to 12,000 R in fruit flies and other systems where such doses could be applied to a set of organisms and sufficient numbers of their progeny be counted for a controlled experiment. But is radiation sickness at high doses the only harm done by exposure to ionizing radiation? What is difficult to do for fruit flies or mice are experiments involving lower doses of 25 R. Why are such experiments difficult? The lower the dose the larger the number of flies or mice you have to involve in an experiment at low doses because those doses may only increase the incidence of mutation by 2 or 3 fold. If the spontaneous rate in a fruit fly experiment is 1 X-linked lethal per two thousand sperm, how many individuals would you use for the treated and controlled? The statistics for small numbers would argue a range of 1-12 per 2000 would be a control rate in any one given experiment. So you would need to examine a much larger number of flies to show more mutations occurred in the low dose and these two results would be non-overlapping. Let us say you did such an experiment and in the controls you sampled 2000 and got 3 mutations and in the exposed (let us say 25 R) you got 12 mutations. You would think, if you didn’t know the statistical issues involved, that 25 R produced those extra mutations. But let us say you repeated the experiment and this time you got 8 controls mutations and 2 at the 25 R range. You would either say radiation did not induce mutations at that dose or you would say radiation is good for you at low doses because you get less mutations by being exposed. Actually in both these experiments you get inclusive results because you haven’t examined a sufficiently large number of vials of flies (each vial represents one exposed or one control sperm). When you have to use tens of thousands of vials you run into a lot of problems because that is as very big experiment. The larger such experiments are, the more variables you introduce and unless the effects are dramatic statistically, it is hard to know how carefully these alternative factors played a role (light, temperature, food batch, being in a tray under other trays or being in the top of several layers of trays in one or two rooms with different conditions. This why attenuated doses are more frequently used to test the presence or absence of threshold effects. The best known was done by Muller’s student in Edinburgh, S P Ray-Chaudhury in 1939. His thesis wasn’t published until 1944 because of the war. Later he went back to India and repeated his technique of attenuated doses once for measuring chromosomes breaks (which he found also to be linear) and once to look again at gene mutations.
In science there is a tradition of challenging the work of one’s peers and repeating the work of one’s peers. Out of this healthy debate emerges more careful experiments and more confidence in the findings found in a first report of something new. For most of tens of thousands of such scientific findings the disputes never leave the professional journals. The issues are strictly scientific. The persons who decide the validity and care of an experiment are other scientists in the field. To get published there is peer review. No one calls in a scientist from another field or a reporter to evaluate the claims of the accuracy of the two experimental groups claiming contradictory findings. Such things happen when the nature of the findings have serious human implications. We have controversy over agents that cause embryo damage (e.g., the thalidomide controversy), over stem cell research (a form of identical twinning from embryonic cells before they have implanted into a uterus), over potential carcinogens (like the butter yellow used to color margarines in the 1940s when the dairy industry forced margarine companies to put a pellet of butter yellow for the purchaser to knead into the white lard-like fat so that customers would not think they are buying real butter). Butter yellow was a liver carcinogen and pulled off the market by our FDA regulatory commission. Frequently in these controversies there are vested interests who favor a view that what they are doing, what they are using, and what they are selling is perfectly safe and that the claims of mutations, cancers, or toxicity are either bad science or politically inspired, or ideological by irrational environmentalists or health nuts. Also in these debates are scientifically not well informed environmentalists, health nuts, and others who without knowledge of the science involved believe everything that is not organic, natural, or familiar should be treated as potentially damaging to the public. It works both ways to our disadvantage because most people involved in the debate are not the scientists involved in the appropriate fields to do so.
I am frustrated when a reporter calls and asks for my “side” of a debate. How do I spend an hour or more trying to show all the variables involved just in the science involved? Should I mention that the accuser of a position I hold is funded by agencies or industries that favor a view that what they do is without harm and no government regulations are needed in an industry which knows best what is harmful and what is harmless? Of course it is irrelevant to the real issue of whether, in this case, low doses are harmful, beneficial, or inactive with respect to the mutation process. But is the scientist on the side of that position a geneticist? No. Should I respect his judgment nevertheless when he has not immersed himself in the field the way Muller did for his entire adult life? Do thousands of hours doing genetics get neutralized by someone doing virtually no genetics and coming in a field of toxicology from a department of entomology for his PhD? Does it matter? Whose job is it to look into this? Is it mine as a geneticist or is it a reporter’s with very little, if any experience in doctorate level genetic experimentation? This forces reporters to look more at motivation, conflict of interest, ideology, scientific method (self-deception, constructed realities, unexamined bias) rather than at the detailed scientific experiments and how they were done and what was inadequate in their experimental design. When science gets politicized by this type of publicized controversy it frustrates everyone involved. I wish I knew a remedy for this. I don’t.
Thursday, October 6, 2011
WHY IS A NOBEL LAUREATE BEING SLANDERED AS A LIAR?
A COLD WAR ARGUMENT REVIVED: JUST A SQUABBLE AMONG SCIENTISTS OR A CONFLICT OF INTEREST AT WORK?
The Chronicle of Higher Education for October 5, 2011 has published a reporter’s analysis of a controversy revived by Edward Calabrese of the University of Massachusetts at Amherst. Calabrese claims that my mentor, H.J. Muller, during his Nobel Prize acceptance speech in 1946 deliberately withheld contradictory information and lied about the effects of low doses of radiation. Muller argued that the work of his laboratory since 1927 and others had shown there was no escape from the conclusion that radiation has no threshold dose and the radiation induced mutations or chromosome breaks are proportional to the dose received. Calabrese claims that just before Muller left he got a working draft of a paper from Curt Stern that showed a dose of 25 Roentgens [25R] did not significantly raise the mutation rate above control levels and this contradicted earlier work of Stern’s that did show such an effect. Muller replied that he could not give attention to the manuscript until he came back. Later he did and Stern published it without claiming a threshold exists or that it contradicted earlier work of his, Muller’s, and others that did show an absence of threshold effects.
According to Calabrese, Muller was motivated by concern of nuclear proliferation and effects of fallout and he convinced his fellow scientists not by science but by ideology to set up radiation protection regulations for the nuclear industry and he scared people into believing low doses of radiation could harm a population. This is false because fallout was first noted in 1952 when our first H bombs were tested in the Pacific. It is false because Muller used many lines of evidence for a cumulative effect of low doses of radiation. S. P. Ray Chaudhury in 1939 showed that a dose of 400 R given in 30 minutes had the same percent of mutations induced as 400 R given over 28 days. Such an attenuated dose is like being exposed to one chest x-ray every 12 minutes for a month. One chest x-ray per 12 minutes is a very low dose [about 0.01R] and yet it accumulates over a month’s exposure.
Calabrese claims low doses are either harmless to an exposed population or that they are beneficial to the individual because he believes low doses of radiation; chemical mutagens, carcinogens, and toxins are actually beneficial. He calls this hormesis but he does not provide a molecular basis for it in contrast to the way geneticists use molecular biology in detail to describe mutagenesis, gene replication, protein synthesis, and the formation of biochemical pathways. He believes low doses of such chemical and physical agents stimulate the immune system and make one resistant. He deplores nuclear regulation and similar regulation on the chemical industry, the food industry, and the pharmaceutical industry. He feels billions of dollars have been wasted for regulations that are not needed. During the Cold War, on different grounds, a generation or two earlier, critics of Muller claimed “a little bit of radiation is good for you” or that without that small dose of radiation how would humans be able to evolve to a higher level of abilities and health? These are fake arguments. Most geneticists would refute them. Calabrese first contacted me in April 2011 and I sent him arguments and references that he ignored for his two articles which appeared in public health journals.
It is also bothersome that a substantial part of Calabrese’s research support comes from chemical companies and the nuclear industry. He lists the Nuclear Regulatory Commission and the Florida Power and Light Company, and Electric Power Research Institute by name but most of his support he describes as supported by “multiple sponsors.” There are people who claim that the money given them does not influence their views or objectivity. Every congressional representative and Senator who has received lobbying money from those industries will tell you that. But is it true? Why do we demand judges to recuse themselves when they try cases in which they have a relationship, personal or through business?
My worry is that this slander of Muller’s reputation as a liar is appearing when the Tea Party and its industry-friendly Republican or Libertarian allies are making an effort to get rid of regulations that allegedly impede business and cost jobs. It is a self-serving argument that appeals to those with a financial interest in these industries. It also tries to convince workers that this elimination of safety regulations is in their interest. I believe, to the contrary, that workers in these industries and most of the public are being betrayed by these industries for almost all the gains unions won and legislation won since the 1930s. I hope those of you reading this blog will help refute that campaign.
The Chronicle of Higher Education for October 5, 2011 has published a reporter’s analysis of a controversy revived by Edward Calabrese of the University of Massachusetts at Amherst. Calabrese claims that my mentor, H.J. Muller, during his Nobel Prize acceptance speech in 1946 deliberately withheld contradictory information and lied about the effects of low doses of radiation. Muller argued that the work of his laboratory since 1927 and others had shown there was no escape from the conclusion that radiation has no threshold dose and the radiation induced mutations or chromosome breaks are proportional to the dose received. Calabrese claims that just before Muller left he got a working draft of a paper from Curt Stern that showed a dose of 25 Roentgens [25R] did not significantly raise the mutation rate above control levels and this contradicted earlier work of Stern’s that did show such an effect. Muller replied that he could not give attention to the manuscript until he came back. Later he did and Stern published it without claiming a threshold exists or that it contradicted earlier work of his, Muller’s, and others that did show an absence of threshold effects.
According to Calabrese, Muller was motivated by concern of nuclear proliferation and effects of fallout and he convinced his fellow scientists not by science but by ideology to set up radiation protection regulations for the nuclear industry and he scared people into believing low doses of radiation could harm a population. This is false because fallout was first noted in 1952 when our first H bombs were tested in the Pacific. It is false because Muller used many lines of evidence for a cumulative effect of low doses of radiation. S. P. Ray Chaudhury in 1939 showed that a dose of 400 R given in 30 minutes had the same percent of mutations induced as 400 R given over 28 days. Such an attenuated dose is like being exposed to one chest x-ray every 12 minutes for a month. One chest x-ray per 12 minutes is a very low dose [about 0.01R] and yet it accumulates over a month’s exposure.
Calabrese claims low doses are either harmless to an exposed population or that they are beneficial to the individual because he believes low doses of radiation; chemical mutagens, carcinogens, and toxins are actually beneficial. He calls this hormesis but he does not provide a molecular basis for it in contrast to the way geneticists use molecular biology in detail to describe mutagenesis, gene replication, protein synthesis, and the formation of biochemical pathways. He believes low doses of such chemical and physical agents stimulate the immune system and make one resistant. He deplores nuclear regulation and similar regulation on the chemical industry, the food industry, and the pharmaceutical industry. He feels billions of dollars have been wasted for regulations that are not needed. During the Cold War, on different grounds, a generation or two earlier, critics of Muller claimed “a little bit of radiation is good for you” or that without that small dose of radiation how would humans be able to evolve to a higher level of abilities and health? These are fake arguments. Most geneticists would refute them. Calabrese first contacted me in April 2011 and I sent him arguments and references that he ignored for his two articles which appeared in public health journals.
It is also bothersome that a substantial part of Calabrese’s research support comes from chemical companies and the nuclear industry. He lists the Nuclear Regulatory Commission and the Florida Power and Light Company, and Electric Power Research Institute by name but most of his support he describes as supported by “multiple sponsors.” There are people who claim that the money given them does not influence their views or objectivity. Every congressional representative and Senator who has received lobbying money from those industries will tell you that. But is it true? Why do we demand judges to recuse themselves when they try cases in which they have a relationship, personal or through business?
My worry is that this slander of Muller’s reputation as a liar is appearing when the Tea Party and its industry-friendly Republican or Libertarian allies are making an effort to get rid of regulations that allegedly impede business and cost jobs. It is a self-serving argument that appeals to those with a financial interest in these industries. It also tries to convince workers that this elimination of safety regulations is in their interest. I believe, to the contrary, that workers in these industries and most of the public are being betrayed by these industries for almost all the gains unions won and legislation won since the 1930s. I hope those of you reading this blog will help refute that campaign.
Friday, September 2, 2011
FAKE ADS September 2, 2011
It is disappointing that there are people who are unscrupulous and use the names of others to promote their products and services or to endorse their reputations. I just changed my password to my email account after being hacked. I wish it to be known that I do not endorse products (e.g., pharmaceuticals), services (e.g., airline bookings), or job opportunities and work at home for pay schemes. Unfortunately, I just finished a scholarly book on the history of sex determination and it will be going into production early next year. As a result of Googling documents I needed for this study, I have been flooded with invitations to hire sexual escorts, get blow jobs, or find sexual pen pals on the web,. At age 80 I desire none of these services. I will leave this Blog for the indefinite future so that if you happen to see me endorsing one of those out of character ads, you will know it is a fake.
Wednesday, August 31, 2011
Blog August 31 My books
ELOF AXEL CARLSON
Books Published
1. The Gene: A Critical History Saunders 1966
I showed how the idea of hereditary units evolved from mid-19th century to the early 1960s. In each chapter I showed how a new idea or interpretation contended with one or more rival views of the same data. I explored what made one side win out and why some concepts are revived a generation or more after they were in contention. The entire book was based on my reflections on published articles of those in contention.
2. Genes, Radiation and Society: The Life and Work of H. J. Muller Cornell 1981
Muller was my mentor and I used interviews of his colleagues and students as well as the many tens of thousands of letters in the IU Lilly Library archives to construct his life and relate it to his scientific work and his applications of science to society. I found his social views on science (positive genetics by choice and radiation protection) consistent but his basic science shiftged with each new institution he joined. Muller was intense, committed, idealistic, and often wrong in his trust in the leadership of movements he admired. He had contradictory features to his personality and generated foes as often as generated admirers. His ability to bounce back from his set-backs, many self-imposed, I found remarkable.
3. Human Genetics (text) Heath 1984
I used this as a text for my Biology 101-102 course at Stony Brook University. My non-majors course did not fit the prevailing market’s idea of a biology for non-majors text. I felt it was better to work with most of what I taught than to teach a course for lower division undergraduates with no text book at all. In this book I covered the cell, the gene, developmental biology (the life cycle), evolution, and molecular biology. I considered these five concepts the foundation for understanding biology. I related problems of society to these five concepts and felt I had provided the science a person needs to know to be an informed citizen.
4. The Unfit: A History of a Bad Idea Cold Spring Harbor Laboratory Press, 2001
This is a history of the roots of eugenics, before eugenics had its name in 1883. People have designated other people as unfit to reside among their peers or even unfit to live since biblical history was recorded. It shifted from transgressions against God as the cause of their being unfit to a scientific basis in the 1700s when masturbation became the first alleged cause of unfit people described as degenerates. Degeneracy theory had a strong appeal in the nineteenth century as the industrial revolution created urbanization and the problems of dealing with paupers, psychotics, the mentally retarded, vagrants, orphans, the physically handicapped, the aged, and the criminal. After Weismann’s work on the germplasm as unaltered by environmental conditions, the isolation of degenerates occupied social workers and physicians, leading to the asylum movement, marriage law restrictions, and compulsory sterilization of the unfit. I show how the two wings of the eugenics movement revolved in the 20th century and why state-mandated eugenics died.
5. Mendel’s Legacy: The Origin of Classical Genetics Cold Spring Harbor Laboratory Press 2004
Classical genetics was assembled from breeding analysis, cell biology, reproductive biology, evolution, population genetics, and biochemistry. Molecular genetics begins in the 1950s with the recognition of nucleic acids as the chemical basis for gene structure and function. I show how these components developed, most of them initially in Europe and by 1902-1920 mostly in the United States with the theory of the gene and the chromosome theory of heredity. I argue that the American PhD starting at Johns Hopkins University in 1876 created the interdisciplinary approach that brought about these unions of disciplines. I also argue that incrementalism and new technologies are characteristic of biological revolutions and not paradigm shifts.
6. Times of Triumph, Times of Doubt, Science and the Battle for Public Trust Cold Spring Harbor Laboratory Press, 2006
Scientists are often idealistic and have good intentions when applying their knowledge to society. Why then are there bad outcomes that sometimes arise from these applications. I discuss these concerns for thalidomide, radiation usage, DES or diethylstilbestrol in medicine, DDT and other pesticides, Agent Orange and other herbicides, eugenics, and other instances of known failures. There are also fears of science that are unjustified and that have not led to harm such recombinant DNA technology and genetically modified foods. I argue that where regulation is either self-imposed or regulated by the state, there is a more careful monitoring of the transition of laboratory findings to commercial or health usage.
7. Neither Gods nor Beasts: How Science Is Changing Who We Think We Are. Cold Spring Harbor Laboratory Press, 2008
Many philosophers and scientists accept a universal human nature for our species. I argue that this is disputable. But what is not disputable is the way we transform our understanding of ourselves and society through new knowledge, especially scientific findings. I show how this came about first through human anatomy and physiology, leading to a shared understanding of the mammalian body that made it likely an evolutionary origin would be found to explain those resemblances. I show that when the microscope was added to the tools for studying our bodies, we became aware of our cellular composition. This led in turn to the recognition of cells associated with reproduction. This led to the recognition of chromosomes involved in the fertilization process and the genes in those chromosomes as the basis for life itself. With the introduction of biochemical processes and their genetic control in the 1940s humans began to see themselves differently. It led to concepts of molecular disease, of the kinship we can explore through our DNA sequences, and the deep understanding of fundamental processes in metabolism. None of these could have been predicted by theory alone. As we begin to isolated our neuronal functions, synaptic associations, and genetic functioning in regions of our brains that understanding will be more surprising and informative to our sense of who we are.
8. Mutation: The History of an Idea From Darwin to Genomics. Cold Spring Harbor Laboratory Press, 2011
This work covers the evolution of scientific language and how it changes each generation in response to new findings and new technologies. I begin with Darwinian fluctuations, the idea of “bud sports,” atavisms, and the amateur breeder’s vocabulary of the mid 1800s. I show how Bateson introduced a new set of terms (homeotic and meristic variations) and conflicts broke out over continuous and discontinuous traits as the driving mechanism of evolution. I show how Mendelism, the chromosome theory of heredity, and the work of Morgan and his students shifted the vocabulary of classical genetics. The molecular era had a similar transforming effect on genetics, with base replacements, transitions, transversions, and frame shift events associated with point mutations. As tools revealed DNA sequences and as gene structure proved more complex than bacterial models, the vocabulary for introns, exons, splicing, and other features of genetic transcription and translation multiplied. Popular views of mutations also changed with somewhat different meanings associated with the new terminology.
Other books (edited):
9. Modern Biology Braziller 1967
I use a selection of articles or excerpts from books that first introduced ideas of the cell, the gene, the life cycle, evolution, and molecular biology. I intended it for classes where undergraduate students could learn about how science works through reading of original published research articles.
10. Man’s Future Birthright: Essays on science and Humanity by H. J. Muller [edited by Elof Carlson] SUNY Press 1973
Muller’s social essays include his views on eugenics, radiation safety, reading science fiction, extraterrestrial life, freedom, peace, the evolution of values, and his views of what the world will be like in 100 years.
11. The Modern Concept of Nature: Essays on theoretical biology by H. J, Muller [edited by Elof Carlson] SUNY Press 1973
I chose essays on mutation, inducing mutations with radiation, chromosome breakage as a tool, how physics can solve genetic problems, genetics in relation to evolution, and the gene as the basis of life,
12. Gene Theory Dickenson Publishing Company 1967
The articles I included were on gene continuity and discontinuity, pseudoallelism, genetic fine structure, the structure of DNA, on genetic colinearity, on the molecular basis of mutation, on the operon model of regulation, and three different views of the gene.
Books in preparation:
1. Sex Determination: A History [in production, Indiana University Press, estimated date of issue, September 2012]
I cover views of sex determination in antiquity based on anatomy, temperature, activity, and celestial events. I introduce Aristotle’s, Plato’s, and Galen’s views of sex determination and their influences in medieval thinking on sex determination. I cover the discovery of the egg, the discovery of sperm, the proof that a union of one egg and one sperm results in a new life cycle, the working out of male and female reproductive organs, the discovery of sex hormones, the chromosomal basis of sex determination, comparative sex determination across the phyla, and the genetic and molecular basis for sex determination. I show the imperfections of the sex determining process and the formation of chimeras, mosaics, hermaphrodites, and pseudohermaphrodites. I distinguish the sex determination phenomena from gender differentiation and socializing and show how this has led to conflicts of religion, society, the law, and the public perception of sex. I attempt to relate the top down (gender studies) approach with the bottom up ( biological) approaches.
2. Agent Orange: How a plant growth hormone became an agent of war [sixth draft completed]
The idea of physical or chemical influences on plant growth begin with Darwin’s experiments on plant responses to light and gravity. In the early twentieth century plant diffusible substances were identified as controlling the bending of stems by differential cell multiplication. The hormone involved was called auxin. By the 1930s synthetic auxins were being tested as plant regulators to produce seedless varieties and to stimulate rapid growth from cuttings and isolated plant tissue. During World War II the synthetic auxins 24D and 245T were identified as agents that could kill broad-leafed plants. The research was shifted to secret studies at Fort Dietrich in the US and independently by British investigators to see if these agents could be used to destroy crops of the enemy. The war ended before they could be used. They were revived by the British in the Malay insurgency and adopted by the Vietnamese through consultation with US military and defense research agencies (especially DARPA). The escalating use of a mixture of these two agents, called Agent Orange, resulted in substantial ecological changes in the sprayed areas but the military value is disputed by the military itself. Health effects have been reported since the first synthesis of chlorinated herbicides in the factories that make them, among civilians exposed to them, and among workers spraying them. Of particular concern after the war ended was the effect on Us and other veterans as well as on the Vietnamese population. I show that a clear cut answer is not possible and that there is presently no way to assess the actual damage done to health or heredity of these veterans. The issue is essentially a political one and not a scientific one.
3. Faust: My First 50 Years [a novel, second draft completed]
4. A More Perfect Union [a novel, first draft completed]
5. Bits and Pieces: A Memoir of my Youth [first draft completed]
6. Memoirs of Florence Dawald Miller [completed, privately printed, Bloomington Indiana July 2011]
7. Dialogs with my Dead Father [first draft completed]
8. Human and medical genetics: a history [eight chapters done of projected 24]
9. Life Lines [100 essays from my newspaper column, first draft completed]
10. My Heroes [7 of 17 chapters completed]
11. The Pleasures of Living: How to enjoy life without relying on the supernatural [First draft completed]
12. The Good Teacher [first draft completed]
13. The Biology of Human Sexuality [text, first draft completed]
14. The last Evolutionist [novel, first draft completed]
15. The Science Maven [novel, first draft completed]
16. Genes, Sex, and Evolution: A discussion [novel written as Platonic dialogs, first draft completed]
If you are an editor, publisher, or literary agent and wish more details on my unpublished books and works in progress, please contact me at ecarlson31@gmail.com
Books Published
1. The Gene: A Critical History Saunders 1966
I showed how the idea of hereditary units evolved from mid-19th century to the early 1960s. In each chapter I showed how a new idea or interpretation contended with one or more rival views of the same data. I explored what made one side win out and why some concepts are revived a generation or more after they were in contention. The entire book was based on my reflections on published articles of those in contention.
2. Genes, Radiation and Society: The Life and Work of H. J. Muller Cornell 1981
Muller was my mentor and I used interviews of his colleagues and students as well as the many tens of thousands of letters in the IU Lilly Library archives to construct his life and relate it to his scientific work and his applications of science to society. I found his social views on science (positive genetics by choice and radiation protection) consistent but his basic science shiftged with each new institution he joined. Muller was intense, committed, idealistic, and often wrong in his trust in the leadership of movements he admired. He had contradictory features to his personality and generated foes as often as generated admirers. His ability to bounce back from his set-backs, many self-imposed, I found remarkable.
3. Human Genetics (text) Heath 1984
I used this as a text for my Biology 101-102 course at Stony Brook University. My non-majors course did not fit the prevailing market’s idea of a biology for non-majors text. I felt it was better to work with most of what I taught than to teach a course for lower division undergraduates with no text book at all. In this book I covered the cell, the gene, developmental biology (the life cycle), evolution, and molecular biology. I considered these five concepts the foundation for understanding biology. I related problems of society to these five concepts and felt I had provided the science a person needs to know to be an informed citizen.
4. The Unfit: A History of a Bad Idea Cold Spring Harbor Laboratory Press, 2001
This is a history of the roots of eugenics, before eugenics had its name in 1883. People have designated other people as unfit to reside among their peers or even unfit to live since biblical history was recorded. It shifted from transgressions against God as the cause of their being unfit to a scientific basis in the 1700s when masturbation became the first alleged cause of unfit people described as degenerates. Degeneracy theory had a strong appeal in the nineteenth century as the industrial revolution created urbanization and the problems of dealing with paupers, psychotics, the mentally retarded, vagrants, orphans, the physically handicapped, the aged, and the criminal. After Weismann’s work on the germplasm as unaltered by environmental conditions, the isolation of degenerates occupied social workers and physicians, leading to the asylum movement, marriage law restrictions, and compulsory sterilization of the unfit. I show how the two wings of the eugenics movement revolved in the 20th century and why state-mandated eugenics died.
5. Mendel’s Legacy: The Origin of Classical Genetics Cold Spring Harbor Laboratory Press 2004
Classical genetics was assembled from breeding analysis, cell biology, reproductive biology, evolution, population genetics, and biochemistry. Molecular genetics begins in the 1950s with the recognition of nucleic acids as the chemical basis for gene structure and function. I show how these components developed, most of them initially in Europe and by 1902-1920 mostly in the United States with the theory of the gene and the chromosome theory of heredity. I argue that the American PhD starting at Johns Hopkins University in 1876 created the interdisciplinary approach that brought about these unions of disciplines. I also argue that incrementalism and new technologies are characteristic of biological revolutions and not paradigm shifts.
6. Times of Triumph, Times of Doubt, Science and the Battle for Public Trust Cold Spring Harbor Laboratory Press, 2006
Scientists are often idealistic and have good intentions when applying their knowledge to society. Why then are there bad outcomes that sometimes arise from these applications. I discuss these concerns for thalidomide, radiation usage, DES or diethylstilbestrol in medicine, DDT and other pesticides, Agent Orange and other herbicides, eugenics, and other instances of known failures. There are also fears of science that are unjustified and that have not led to harm such recombinant DNA technology and genetically modified foods. I argue that where regulation is either self-imposed or regulated by the state, there is a more careful monitoring of the transition of laboratory findings to commercial or health usage.
7. Neither Gods nor Beasts: How Science Is Changing Who We Think We Are. Cold Spring Harbor Laboratory Press, 2008
Many philosophers and scientists accept a universal human nature for our species. I argue that this is disputable. But what is not disputable is the way we transform our understanding of ourselves and society through new knowledge, especially scientific findings. I show how this came about first through human anatomy and physiology, leading to a shared understanding of the mammalian body that made it likely an evolutionary origin would be found to explain those resemblances. I show that when the microscope was added to the tools for studying our bodies, we became aware of our cellular composition. This led in turn to the recognition of cells associated with reproduction. This led to the recognition of chromosomes involved in the fertilization process and the genes in those chromosomes as the basis for life itself. With the introduction of biochemical processes and their genetic control in the 1940s humans began to see themselves differently. It led to concepts of molecular disease, of the kinship we can explore through our DNA sequences, and the deep understanding of fundamental processes in metabolism. None of these could have been predicted by theory alone. As we begin to isolated our neuronal functions, synaptic associations, and genetic functioning in regions of our brains that understanding will be more surprising and informative to our sense of who we are.
8. Mutation: The History of an Idea From Darwin to Genomics. Cold Spring Harbor Laboratory Press, 2011
This work covers the evolution of scientific language and how it changes each generation in response to new findings and new technologies. I begin with Darwinian fluctuations, the idea of “bud sports,” atavisms, and the amateur breeder’s vocabulary of the mid 1800s. I show how Bateson introduced a new set of terms (homeotic and meristic variations) and conflicts broke out over continuous and discontinuous traits as the driving mechanism of evolution. I show how Mendelism, the chromosome theory of heredity, and the work of Morgan and his students shifted the vocabulary of classical genetics. The molecular era had a similar transforming effect on genetics, with base replacements, transitions, transversions, and frame shift events associated with point mutations. As tools revealed DNA sequences and as gene structure proved more complex than bacterial models, the vocabulary for introns, exons, splicing, and other features of genetic transcription and translation multiplied. Popular views of mutations also changed with somewhat different meanings associated with the new terminology.
Other books (edited):
9. Modern Biology Braziller 1967
I use a selection of articles or excerpts from books that first introduced ideas of the cell, the gene, the life cycle, evolution, and molecular biology. I intended it for classes where undergraduate students could learn about how science works through reading of original published research articles.
10. Man’s Future Birthright: Essays on science and Humanity by H. J. Muller [edited by Elof Carlson] SUNY Press 1973
Muller’s social essays include his views on eugenics, radiation safety, reading science fiction, extraterrestrial life, freedom, peace, the evolution of values, and his views of what the world will be like in 100 years.
11. The Modern Concept of Nature: Essays on theoretical biology by H. J, Muller [edited by Elof Carlson] SUNY Press 1973
I chose essays on mutation, inducing mutations with radiation, chromosome breakage as a tool, how physics can solve genetic problems, genetics in relation to evolution, and the gene as the basis of life,
12. Gene Theory Dickenson Publishing Company 1967
The articles I included were on gene continuity and discontinuity, pseudoallelism, genetic fine structure, the structure of DNA, on genetic colinearity, on the molecular basis of mutation, on the operon model of regulation, and three different views of the gene.
Books in preparation:
1. Sex Determination: A History [in production, Indiana University Press, estimated date of issue, September 2012]
I cover views of sex determination in antiquity based on anatomy, temperature, activity, and celestial events. I introduce Aristotle’s, Plato’s, and Galen’s views of sex determination and their influences in medieval thinking on sex determination. I cover the discovery of the egg, the discovery of sperm, the proof that a union of one egg and one sperm results in a new life cycle, the working out of male and female reproductive organs, the discovery of sex hormones, the chromosomal basis of sex determination, comparative sex determination across the phyla, and the genetic and molecular basis for sex determination. I show the imperfections of the sex determining process and the formation of chimeras, mosaics, hermaphrodites, and pseudohermaphrodites. I distinguish the sex determination phenomena from gender differentiation and socializing and show how this has led to conflicts of religion, society, the law, and the public perception of sex. I attempt to relate the top down (gender studies) approach with the bottom up ( biological) approaches.
2. Agent Orange: How a plant growth hormone became an agent of war [sixth draft completed]
The idea of physical or chemical influences on plant growth begin with Darwin’s experiments on plant responses to light and gravity. In the early twentieth century plant diffusible substances were identified as controlling the bending of stems by differential cell multiplication. The hormone involved was called auxin. By the 1930s synthetic auxins were being tested as plant regulators to produce seedless varieties and to stimulate rapid growth from cuttings and isolated plant tissue. During World War II the synthetic auxins 24D and 245T were identified as agents that could kill broad-leafed plants. The research was shifted to secret studies at Fort Dietrich in the US and independently by British investigators to see if these agents could be used to destroy crops of the enemy. The war ended before they could be used. They were revived by the British in the Malay insurgency and adopted by the Vietnamese through consultation with US military and defense research agencies (especially DARPA). The escalating use of a mixture of these two agents, called Agent Orange, resulted in substantial ecological changes in the sprayed areas but the military value is disputed by the military itself. Health effects have been reported since the first synthesis of chlorinated herbicides in the factories that make them, among civilians exposed to them, and among workers spraying them. Of particular concern after the war ended was the effect on Us and other veterans as well as on the Vietnamese population. I show that a clear cut answer is not possible and that there is presently no way to assess the actual damage done to health or heredity of these veterans. The issue is essentially a political one and not a scientific one.
3. Faust: My First 50 Years [a novel, second draft completed]
4. A More Perfect Union [a novel, first draft completed]
5. Bits and Pieces: A Memoir of my Youth [first draft completed]
6. Memoirs of Florence Dawald Miller [completed, privately printed, Bloomington Indiana July 2011]
7. Dialogs with my Dead Father [first draft completed]
8. Human and medical genetics: a history [eight chapters done of projected 24]
9. Life Lines [100 essays from my newspaper column, first draft completed]
10. My Heroes [7 of 17 chapters completed]
11. The Pleasures of Living: How to enjoy life without relying on the supernatural [First draft completed]
12. The Good Teacher [first draft completed]
13. The Biology of Human Sexuality [text, first draft completed]
14. The last Evolutionist [novel, first draft completed]
15. The Science Maven [novel, first draft completed]
16. Genes, Sex, and Evolution: A discussion [novel written as Platonic dialogs, first draft completed]
If you are an editor, publisher, or literary agent and wish more details on my unpublished books and works in progress, please contact me at ecarlson31@gmail.com
Monday, August 8, 2011
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.
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