Edward B Lewis 1918-2004, his work, his testimony to the US Congress

http://www.genetics.org/content/168/4/1773.full

Edward B. Lewis, 1918–2004

James F. Crow*, 1 and
Welcome Bender †

+ Author Affiliations

*Genetics Laboratory, University of Wisconsin, Madison, Wisconsin 53706
†Biochemical and Molecular Pharmacology Department, Harvard Medical School, Boston, Massachusetts 02115

1↵E-mail for correspondence: jfcrow@wisc.edu

Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove

EDWARD B. Lewis (Figure 1) started experimenting with Drosophila as a high school student and never stopped. His enthusiasm never waned. Except for 4 years as a meteorologist during World War II, he continued to work with Drosophila until a very short time before his death.

……
Search for Keyword: GO
Advanced Search

Edward B. Lewis, 1918–2004

James F. Crow*, 1 and
Welcome Bender †

+ Author Affiliations

*Genetics Laboratory, University of Wisconsin, Madison, Wisconsin 53706
†Biochemical and Molecular Pharmacology Department, Harvard Medical School, Boston, Massachusetts 02115

1↵E-mail for correspondence: jfcrow@wisc.edu

Next Section

Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F. Crow and William F. Dove
Previous SectionNext Section
A BRIEF BIOGRAPHY (J. F. Crow)

EDWARD B. Lewis (Figure 1) started experimenting with Drosophila as a high school student and never stopped. His enthusiasm never waned. Except for 4 years as a meteorologist during World War II, he continued to work with Drosophila until a very short time before his death.
Figure 1.—
View larger version:

In this page
In a new window

Download as PowerPoint Slide

Figure 1.—

Edward B. Lewis.
Early life:

Ed was born in Wilkes-Barre, Pennsylvania, on May 20, 1918. His father was a jeweler and watchmaker, who learned the trade, but never finished high school. The jewelry store in which he worked was forced to close during the depression of the 1930s and the family had a hard struggle to make ends meet. Nevertheless, the parents never wavered in supporting their two sons. Ed’s brother was 5 years older and was in college when times were the worst. Yet, he managed to get a masters degree in international law and went on to a distinguished career in the foreign service. By the time Ed was in college, his brother was able to provide some financial help, which, along with a job supported by the National Youth Administration, enabled Ed to stay in school.

Ed’s great uncle gave him a flute when he was 10 years old. It was wooden, but his father replaced it with a silver one a few years later. This must surely have represented a considerable sacrifice for the family in those bleak depression years. Ed loved the flute and continued to play at a near-professional level throughout his life. While still in high school, he was a member of the Wilkes-Barre Symphony. He started college at Bucknell on a music scholarship and later played in the University of Minnesota Orchestra. In later years, he found it amusing, and perhaps slightly embarrassing, that A. H. Sturtevant confused the university orchestra with the great Minneapolis Symphony. At Caltech he frequently arranged for lessons with professionals and was an avid performer of chamber music. Along the way he developed a passion for opera and in later life rarely missed a chance to attend a performance. A second interest that started in childhood was animals, especially toads and snakes, which he kept in homemade terraria. This interest also continued throughout his life. Visitors to his home always saw an aquarium, usually with an octopus and several exotic fish and often a terrarium.

Remarkably, two distinguished Drosophila geneticists, Edward B. Lewis and Edward Novitski, attended the same high school in Wilkes-Barre at the same time. Their start with Drosophila began when Lewis noticed an advertisement in the journal Science for Drosophila cultures at one dollar each. He and his friend Novitski used their Biology Club’s meager treasury to order cultures. When the flies came, the two budding scientists immediately began experiments in the high school biology laboratory, thanks to an interested and indulgent biology teacher. After high school Novitski went to Purdue to study with the man who had supplied the original Drosophila cultures, S. A. Rifenburgh. Aided by his music scholarship, Ed Lewis stayed at Bucknell for a year and then moved to the University of Minnesota, chosen because of low out-of-state tuition and no compulsory ROTC. Both Eds were skilled in the art of shortening their college years by passing exams in lieu of courses. Taking advantage of this, Lewis finished at Minnesota in considerably less than the regulation time and Novitski did likewise. Both ended up as fellow graduate students at the California Institute of Technology.
Caltech:

Ed Lewis arrived at Caltech in the fall of 1939 and began study with Sturtevant. Ed was in Cold Spring Harbor in 1939 (Lewis 2004) and in 1941 attended the Symposium, learning salivary chromosome analysis from B. P. Kaufman. Continuing the hurry-up habit of his college years, he completed his Ph.D. work at Caltech in 3 years, graduating in 1942. By this time the United States was at war and Ed spent one more year at Caltech, learning meteorology and receiving a master’s degree in this subject. He also had a brief excursion into oceanography. In 1943, as he left for military service, he was told by President R. A. Millikan that when the war was over he could return to Caltech as an instructor. He served 4 years as a captain in the U.S. Army Air Corps, most of the time as a weather forecaster in Hawaii and Okinawa. In 1946 he returned from overseas and took up the promised position as instructor at Caltech. His duties included assisting in the laboratory in the introductory genetics course. Later he took over the entire course. He rose rapidly through the ranks, becoming professor in 1956. In 1966 he became Thomas Hunt Morgan Professor of Biology, a position that he held until his retirement in 1988.
Marriage and family life:

In 1946 Ed met Pamela Harrah. George Beadle had recently been brought to Caltech as chairman of the Biology Division and Pam came along as part of his group. She was an active, alert, intelligent, and charming young woman, who shared Ed’s interests in animal life, including arthropods; she wielded a mean insect net. She was also an accomplished artist and enjoyed doing personalized paintings for her friends. These artworks included various objects and symbols that characterized their subject and had a strong surrealist bent. As one of his last acts, Ed arranged for her pictures—many done for well-known geneticists—to be collected and published. Pam also wrote poetry and perceptive character sketches. She had studied genetics at Stanford and soon became a research assistant to Sturtevant and assisted with the Drosophila stocks, of which Ed was curator. Among other things, she discovered the mutant Polycomb, later to play an important role in understanding gene regulation.

In 1946 Pam and Ed were married. Phoebe Sturtevant, wife of A. H. Sturtevant, worked in the Drosophila room at Columbia University. She is said to have told Pam that the way to find a good husband is to work in a Drosophila lab. Pam and Ed were a devoted couple and remained so throughout their life together. They had three sons. One of them, Glenn, died in a mountaineering accident on Christmas Eve 1965. The other two, Hugh and Keith, have gone on to careers of their own. Hugh is a lawyer in Bellingham, Washington, and Keith is a molecular geneticist in Berkeley.

Pam and Ed became even closer after Pam contracted an infection that led to a partial unilateral paralysis, both physical and visual. This made it inconvenient for her to get around, but it did not deter her nor dampen her enthusiasm in the least. She still attended opera performances, went on trips, and frequently entertained students and other friends in their home. Visiting scientists were always welcome.
Personal and scientific life:

Ed’s work schedule was unique. Exercise was an important part of his day and he remained physically fit until his bout with cancer. His movements were quick, mirroring his mind. In the morning was breakfast and exercise. Typically he had lunch at the Athenaeum, with its stimulating assemblage of faculty members from all departments. He then had a nap, returning to the lab in the evening and staying much of the night. There were variations in this pattern, but there was one constant: always he did his major work at night. He usually managed to squeeze in time for flute playing, frequently in his laboratory.

This schedule was sometimes interrupted, especially on weekends, with a trip, often to see an opera. Occasionally during the week he would find someone in the laboratory who was interested in a late night movie, so they would pick up Pam and all see it together. He also enjoyed a local tradition of costume parties. Several times his costumes were judged the most inventive.

Ed worked quietly in the lab and was never one to attract attention. Drosophila research had its ups and downs; during the phage heyday, Ed received little attention. But he never veered from his path. Nevertheless, over the years, he began to attract attention as his pioneering work came to be appreciated. He was also dragged into a public controversy over the carcinogenic effects of low-level radiation. Yet his manner never changed, nor did his work habits. Even the Nobel Prize was taken in stride. He accepted it gladly, but he did not let it go to his head or change his living pattern.
Honors:

Ed was a member of the National Academy of Sciences, American Philosophical Society, American Academy of Arts and Sciences, and the Royal Society of London. He was, successively, secretary, vice-president, and president of the Genetics Society of America. He received essentially all the honors that a geneticist can aspire to. These included the Morgan Medal of the Genetics Society of America, the Wolf Prize, the National Medal of Science, the Lasker Award, and finally in 1995 the Nobel Prize, which he shared with Christine Nüsslein-Volhard and Eric Wieschaus. Although his style was to work a problem thoroughly before publishing and to write sparingly, he nevertheless authored over 50 articles, all solid and several of them classics. Some of the most important are reprinted in Lipshitz (2004a).
Previous SectionNext Section
EARLY WORK WITH DROSOPHILA (J. F. Crow)
Minnesota:

At Minnesota Ed’s mentor was C. P. Oliver, who had been a student of H. J. Muller. Oliver had obtained what was at the time a very surprising result. Heterozygotes between two different lozenge (lz) eye alleles produced a few wild-type progeny and these were always accompanied by a crossover between flanking markers (Oliver 1940). This was one of the first instances in which a single gene appeared to have two components or to actually be two genes. ……

……..Transvection:

Ed’s next discovery he called transvection (Lewis 1954b). He found this while observing two mutants, bx (bithorax) and Ubx (ultrabithorax) in a cis-trans test. As expected, the cis heterozygote, + +/bx Ubx, showed only the dominant effect of Ubx, enlarged halteres. The trans-heterozygote bx +/+ Ubx showed a more extreme mutant phenotype. The surprise came when the two chromosomes were prevented from synapsing closely, because of a strategically located chromosome rearrangement. In this situation the mutant phenotype was even more extreme. Ed interpreted this as the result of gene products moving from one chromosome to another, which would be less effective when the pairing was inhibited.

Ed was able to use this phenomenon to provide a particularly efficient method for detecting chromosome rearrangements. Any chromosome break within ∼500 salivary bands will interfere with pairing enough to show the characteristic transvection phenotype. This means that chromosome rearrangements can be detected in the immediate generation after the break occurs, a great saving of time compared to standard methods that require at least one more generation. Ed applied this to quantifying the effects of different kinds of ionizing radiation in producing chromosome breakage. In particular, neutrons were considerably more effective than X rays or gamma rays (Lewis 1954a). …….

……..From the start, Ed began to induce new mutations. He typically used X rays, and he frequently recovered mutations associated with cytological rearrangements. (Ed was exceptionally skilled at the cytology of salivary polytene chromosomes, and he frequently mapped out rearrangements that included five or more breakpoints.) Ed had no aversion to alkylating agents—he wrote the protocol that virtually all Drosophila workers use for EMS mutagenesis (Lewis and Bacher 1968). However, EMS did not give the number or the variety of BX-C alleles that came with ionizing radiation. In retrospect, the BX-C has relatively little protein-coding sequence, and most single-base changes give no obvious phenotype. This was a lucky accident for the later molecular analysis, since rearrangement mutations were much easier than point mutations to locate on the DNA map. …….

Figure 2.—

The famous four-winged Drosophila.

RADIATION AND CANCER (J. F. Crow)

A lesser known facet of Ed’s life, at least among geneticists, was his influence on radiation carcinogenesis. More than any other person, he was responsible for a shift in public policy on radiation protection from exclusive consideration of genetic effects to greater emphasis on somatic effects, carcinogenesis in particular. It all started when Ed had his customary lunch with a faculty group. Included were physical scientists, who believed that there was a threshold for somatic radiation effects. Ed had been influenced by several statements of Muller arguing that cancer was, at least in part, due to somatic mutations (Muller 1927 and later). Then, Ed thought, it should have the same linear kinetics as germinal mutation.

Ed’s colleagues in the physical sciences were expressing the standard view of the time. The Committee on Biological Effects of Atomic Radiation assumed that there was no threshold for genetic effects, but that there was one for somatic effects, including carcinogenesis (National Academy of Sciences 1956; Crow 1995). Ed decided to look at the data. To him, they suggested linearity at low doses.

Ed was the first to publicly challenge the conventional wisdom. There was considerable interest in this question at Caltech at the time, especially by Beadle, who encouraged Lewis to look into the problem and helped him to obtain data from the Hiroshima and Nagasaki studies. In 1957 Ed published an article in Science in which he suggested, using data from a variety of sources including the Japanese studies, that the effect at low doses might well be linear with no threshold (Lewis 1957). He estimated the average risk for leukemia as 1.0–2.0/million persons/rad/year, a value that has stood up remarkably well. Ed was studiously conservative in not arguing for absence of a threshold, but simply pointing to the evidence.

He was invited to testify before the Joint Congressional Committee on Atomic Energy (JCAE 1957), which he did on June 3, 1957. Again he was cautious. In his words: “The point here, however, is that in the absence of any other information it seems to me—this my personal opinion—that the only prudent course is to assume that a straight-line relationship holds here as well as elsewhere in the higher dose region” (JCAE 1957, p. 959). The next day I testified before the same committee about genetic effects, backed up by a stellar team that included Sturtevant and Muller; both also spoke. Ed and I were invited back by the same committee 2 years later. He did not attend, but sent a statement.

For genetic effects, the linear, nonthreshold assumption aroused little controversy, partly because of the eminence of Sturtevant and Muller, although the estimated numbers were in considerable doubt. The reaction to somatic effects was quite different and Ed quickly found himself embroiled in controversy. His work was challenged by Neil Wald from the Atomic Bomb Casualty Commission in Japan, by Austin Brues of the Argonne Laboratories (Brues 1958), and by no less than Admiral Lewis L. Strauss, chairman of the Atomic Energy Commission (AEC; Lipshitz 2004a, p. 396). Ed’s critics also included Caltech faculty and administrators. The most detailed criticism came from A. W. Kimball, a statistician at the Oak Ridge Laboratory.

Kimball had recently done a statistical study of the Oak Ridge mega-mouse experiments (Kimball 1956). These involved mutations at seven loci, among which the individual rates were different. Kimball asked what the confidence limits would be if these seven loci were used as a basis for inferring the average rate for all loci. For this, he assumed that the underlying rates followed a gamma distribution and this led to confidence limits much larger than would be expected if they were distributed binomially. This analysis met with general approval and was regarded as a major improvement for drawing wider inferences from the data.

Kimball applied similar reasoning to Ed’s data. One minor criticism, which made no difference in the interpretation, was that Ed had stated a 95% confidence limit, which should have been 90%. (Ed had consulted a reference book that had it wrong.) Much more important was Ed’s statistical model. For example, he used a χ2 test to compare two groups of people with different average radiation exposures. Kimball argued that with variable exposure, variation in susceptibility, and other complications, there would be considerable nonbinomial variance, so the assumption underlying the χ2 test was inappropriate. He sent Ed a proposed letter to the journal Science, which Ed sent to me and to Sewall Wright, who had recently become my colleague in Wisconsin.

That summer, 1957, I was in Mishima, Japan, and wrote in longhand supporting Ed’s χ2 calculations: “I have read Kimball’s proposed letter. You are testing whether two samples, 10/23,060 and 26/156,400, can be regarded as drawn from the same population. Whether the individuals in the population have a constant probability of developing leukemia is, I believe, irrelevant.” My view was that we were concerned with the difference between these two populations, not with the larger universe with which Kimball was dealing. I thought we could rely on physical and biological insights to Ed wrote several subsequent papers and letters analyzing other sets of data. One of them (Lewis 1971) suggested that radiation was responsible for increases in leukemia following treatment for hyperthyroidism. This became increasingly important in later years as I-131 exposure to the thyroid was an important consequence of radioactive fallout from nuclear tests. Notably, in all his writings, Ed was not an opponent of the AEC position, but was eager for the truth. This is best illustrated by one of his last analyses. Tamplin and Cochran (1974) had argued that α-emitting particles from plutonium created a “hot-particle” problem. The idea was that a highly localized dose could produce a many times greater effect than if it were evenly distributed. Ed analyzed the data on lung cancers in a group of dogs exposed to plutonium inhalation and found that the rate was no different from what would be predicted from the total dosage if the particles were randomly distributed; there was no evidence for a hot particle effect (Lewis 1976).

For further reading on Ed’s work on radiation, there are three excellent sources: Lipshitz (2004a)(pp. 389ff., 2004b) and Caron (2004). Furthermore, the Lipshitz book has a great deal of information about Ed’s life and work and includes reprints of several of his most important articles, including his Nobel Prize address.

end quote.

In regard to Lewis’ position on internal emitters: Pecher and Aebersold 1939-1941 (published 1941) found that a small amount of Strontium 89 as an internal emitter equated to a large dose of external whole body radiation. In regard to the Beagle plutonium injection and inhalation studies, cancers in the animals occurred at sites adjacent to the internalised plutonium.

Neither the Lewis position nor the Tamplin position actually contradicts the Aebersold/Pecher calculations and observations. The GE data confirms that the main hazard from an internal emitter is confined to tissue the emitter is embedded in. It is difficult to envision a whole body insult from an internal emitter when the evidence suggests that the actual insult produced by the internal emitter is only manifested by disease production confined to the locale occupied by the internal emitter.

Lewis in his testimony to Congress also focussed upon the threat posed by Iodine 131 to the thyroid.

In addition to LET insult, the chemical effect and the oxygen effect as produced by the interaction of radiation with the cell present as factors leading to harms.

The idea that substances such as Sr89 present low dose rates to adjacent cells is a ludicrous view in my opinion.

Pecher and Aebersold’s findings are based on human data in the context medicine in the pre war setting where patients gave consent for experiment treatment. The only controversy in these findings being the reasons behind the loss of this work to medicine over decades. To emerge by independent rediscovery in 1973 (Firusian et al, Germany.)

Whereas the work of Pecher and Aebersold remained classified secret until the the 1970s. Medicine was kept in ignorance whle the military and fallout research arms of the AEC coninued to use the data on a daily basis within the setting of weapons research.

If the Pecher treatment as described in 1941 had been approved for general use in 1950, the medical data sheet on the nature of what is a major fission fallout product would have been in the public domain from that time. And this knowledge would have undercut the AEC’s assurances of safety relating to nuclear fallout. Secrecy for political purposes.

The uncovering of this suppression in recent years casts into doubt to a very great degree the motives of nuclear authorities as they conduct their buisness in the modern world.

Regardless of Lewis’ views relating to the burden of internal emitters, and in seeming contradiction to it, he presented to Congress the view that I131 in fallout presented grave risks to people via insult to the thyroid. Even if the dose and dose rate could be assigned to the whole body, Lewis obviously admits that the effects of internal emitters in thyroid tissue present insult to that tissue. Full stop.

The AEC’s position regarding Sr89 in fallout during the hearings was deceptive. In answer to Lewis and others they failed to admit that which they were retaining as secrets, denying to the expert witness with contrary views, denying it to Congress, denying it to the field of medicine and denying it to the people of the United States and the world.

Having spent a number of years researching the specific Sr89 suppression both on my own and in collaboration with members of the Pecher family both in Belgium and the United States, I conclude that even today the purposes and motives behind this suppression are clear. There is no safe dose. Sr90 is not the only strontium component in nuclear fallout. There are at least 5 strontium fission isotopes. In terms of energy deposition into biological material, the dose rate presented by Sr90 is one of the lowest of all the Sr fission radionuclides. I have attempted to study the political history of only one fission product. There are hundreds.

The Agency for Toxic Substances and Disease Registry (ATDSR) gives the data sheets for strontium. The pdf “Chemical and Physical Information 4. Chemical and Physical Information” gives the Chemical Identity, Physical, chemical and radiological properties and the fission isotope list for strontium. The GE datasheet for Sr89 confirms Pecher findings. And thus contrasts most strongly with nuclear authority assertions regarding to strontium in fallout.

The ATSDR data which gives the Strontium fission isotope table can be downloaded at:
http://www.atsdr.cdc.gov/toxprofiles/tp159-c4.pdf

Sr89 is an immediate hazard. When this fact was presented to the Congressional Hearings of the 1950s, it was heavily disputed by the AEC.

There is without doubt an internal emitter problem. It is not a low dose rate problem.

Simply applying the truncated and thus ill informed public statements issued by current and past nuclear authorities to the plight of nuclear victims is insufficient, for those authorities have historically hidden the very existence of significant internal emitters. They have used national security laws in a manner which breaches the standards of civilised and ethical behaviour. The early Sr89 work fell in a date range which excluded it from the investigations of the ACHRE committee. That committe investigated the period from 1942. Pecher died in August 1941. The findings of the ACHRE however most definately apply to the suppression of the strontium data from 1945 onward.

Paul Langley.


%d bloggers like this: