It has been an interesting and informative run. Some articles have been preserved at the WoodstockCtCafe FB page. If there are any other articles you would like me to preserve let me know. This website will disappear soon. Sayonara. John
It has been an interesting and informative run. Some articles have been preserved at the WoodstockCtCafe FB page. If there are any other articles you would like me to preserve let me know. This website will disappear soon. Sayonara. John
Update from the Courant: “With Putnam Science Academy, which had closed in May, to re-open, the post-grad basketball program will also return next season.
Coach Tom Espinosa, who was to start up a post-grad program at Woostock Academy, will now return to PSA. He confirmed that Mamadou Diarra, who committed to UConn in May, and guard Hamidou Diallo, who is currently being recruited by UConn, will also return.
The Academy played its hand … and then lost.
When I first heard about this I was excited because the varsity basketball team would be interesting to watch. Then I learned that Woodstock Academy actually purchased a graduate program from Putnam Science Academy to claim Diarra and Diallo after investing 100s of thousands of $ on athletic fields. The new football field has produced one win in three years and students suggest that the team is terrible (the scores speak for themselves). They will not play for the varsity. I can just imagine the rational of the Academy Trustees in acquiring this new sports program. I’m sure you can too. Putting that money into legitimate academic programs would have better the way to go, but I don’t think the Trustees have any idea what those programs might be. Also, do you think the secretive Chinese students will open up?
From the Hartford Courant:
“Diarra, a 6-foot-8 power forward who just graduated from Putnam Science Academy, is the Huskies’ first commitment from the Class of 2016. With Putnam Science closing, he will play as a post-grad at Woodstock Academy next season, close enough for the friends he has made in the northeast corner of the state to see him play.
“I don’t know what he’s told you, but UConn has really been his dream school,” said coach Tom Espinosa, who will move from PSA to start the post-grad basketball program at Woodstock.
Diarra, from Queens, N.Y., became a big-time prospect last summer, on the AAU circuit with the New York Jayhawks. As he got back to Putnam in the fall, offers from major programs began to come in. Minnesota, Dayton, Seton Hall and St. John’s were among the schools that showed interest, Espinosa said.
UConn had become very interested in one of Diarra’s teammates, guard Hamidou Diallo, but associate head coach Glen Miller, who works with the program’s big men, spotted Diarra and had coach Kevin Ollie take a look. When Diarra went to the Huskies’ game against Memphis on March 5, he was struck by Ollie’s handling of players. When he returned for a visit in April, and played with some of the current players, Ollie saw enough and made him an offer he would not refuse….
Diallo, a 6-5 shooting guard, will also move to Woodstock Academy next season, for 12th grade. He has reclassified to the Class of 2017, planning to play a post-grad year, but he also has the option of starting college in 2016….”
Before astronomer Hubble’s work in the late 1920s. it was thought that our own galaxy, the Milky Way, was the entire universe. Then Hubble confirmed that our galaxy was only one of billions of galaxies. In the last decade astronomers have discovered planets outside of our solar system, called exoplanets. There have been 4700 planets that have been documented by the phenomenon of ‘star wobble’ caused by the gravitational tug of planets revolving around the star. Based on these recent and limited studies it is estimated that our galaxy’s 200,000 billion stars have billions of planets revolving around them, and that 10% of these have habitable planets, planets that exist in Goldilocks Zones. Such planets are roughly the size of Earth with a rocky surface and close enough to their stars, but not too close, to retain water. More than half of these planets revolve around red dwarfs which are older, dying stars that produce less energy; thus their habitable planets exist in a Goldilocks Zone that is closer to the resident star. We can’t see the red dwarfs in the sky with the naked eye, but they are the majority of stars out there.
Yesterday I got out my slide rule and did some calculations (check my math) to determine the size of our galaxy in numbers that we can relate to (not light years). The average diameter of the Milky Way is 405 quadrillion miles (405 thousand trillion miles; see the diagram of this number).
The space ship, New Horizon, was launched on January 19, 2006. It passed close to Pluto on July 15, 2015. Thus the trip was 9 years, 177 days covering 3 billion miles. Therefore its speed was 866,000 miles/day or 36,084 miles/hr. At this speed it would take 814 billion days or 2.23 billion years to traverse the diameter of the Milky Way.
There is a potentially habitable planet, Kepler 452b, that is 1,400 light-years away or 1.17% of the diameter of the galaxy or 9 billion days away if traveling at the speed of New Horizon. Kepler 452b is a planet a little more than one and a half times as big in radius as Earth that revolves around a Sun-like star in an orbit that takes 385 days, just slightly longer than our own year, putting it firmly in the “Goldilocks” habitable zone where the temperatures are lukewarm and suitable for liquid water on the surface. It’s estimated mass (which has to be confirmed) is about five times that of Earth. The other interesting finding is that this planet has spent six billion years in the habitable zone of its star, longer than Earth. So if some form of life exists there, it has had more time to evolve than life on Earth. It’s quite likely that there are habitable planets closer to our solar system.
a. the Milky Way
b. the width (diameter) of the Milky Way
c. the flight of the New Horizon
Exploits in war should not necessarily be a criterion for running for an elected office. I think this is what Donald Trump was trying to say in his garbled message about John McCain being or not being a hero. Perhaps being successful in business is partly because of his ability to think ‘outside the box.’
My Uncle John was an example of a war hero who was not known publicly or even privately as a war hero. He volunteered for the RAF because the USA was slow to enter WWII. His sole goal was to defeat the Nazis. The book “Tirpitz” describes the sinking of this large battleship near Tromso Norway in 1944 by 18 Lancasters. The following pages mention John or quotes him.
I devoted a major portion of my research years on the protein/gene family of human plastins which my labs at the Pauling Institute (Palo Alto CA), CIMR (San Jose CA), Adeza Biomedical (Sunnyvale CA), and the Palo Alto Medical Foundation in Palo Alto CA cloned and characterized (see article directly below). I discovered this protein in May of 1978 and proposed that it had a role in development of many different kinds of human cancer. Recently there has been a flurry of studies published on the roles of plastins in circulating tumor cells and metastasis. Metastasis is what makes tumors lethal. I am going to update this article as new results are found in the published literature. Here are two papers that were incorporated into Google Scholar in the last seven days.
July 3, 2015
Expression of the PLS3 Gene in Circulating Cells in Patients with Colorectal Cancer
Ryszard Kujawski et al, Medical Univ. of Lodz, Poland
Abstract: Circulating tumor cells (CTC) are cells in circulating blood that have the antigen and gene features of tumor cells of a specific type. Since they can be potentially used in diagnostics and monitoring of treatment of many tumors, they have been attracting attention of researchers worldwide. Plastin-3 (PLS3; T-plastin) is one of such markers of CTC.
The aim of the study was to assess expression of PLS3 in CTC in patients with colorectal cancer, to conduct a statistical analysis and to demonstrate a link between expression of PLS3 and progress of the disease, level of CEA and Ca19-9 markers, gender and age of the patients.
Material and methods. A group of 85 patients of the Department of General and Colorectal Surgery of the Medical University in ?ód? were enrolled in this study. Circulating tumor cells were isolated from whole blood of patients with colorectal cancer and an analysis of PLS3 gene expression in CTC was conducted. The next step was to conduct a statistical analysis and to demonstrate a link between expression of PLS3 in patients’ CTC and progress of the disease, level of CEA and Ca19-9 markers, gender and age of the patients.
Results. PLS3 is a marker which can be potentially used in prediction and monitoring of colorectal cancer. A link between expression of PLS3 in CTC of patients with colorectal cancer and metastasis to lymph nodes has been demonstrated. It may be of key importance how PLS3 could impact the qualification to supplementary cancer treatment in patients with stage II colorectal cancer. A link between expression of PL S3 gene in CTC and gender requires further in-depth studies. It is beyond doubt that PLS3 must be further investigated to determine its role in diagnostics, prediction, treatment and monitoring of treatment of colorectal cancer.
An NKX3.1 Binding Site Polymorphism in the L-plastin Promoter Leads to Differential Gene Expression in Human Prostate Cancer
Changhao Chen et al., Sun Yat-Sen Memorial Hospital, Guangzhou, China
Abstract: The L-plastin gene is involved in the invasion and metastasis of prostate cancer. However, the molecular mechanisms underlying L-plastin transcription are unclear. We hypothesize that the occurrence of polymorphic genetic variations in the L-plastin promoter might affect an individual’s susceptibility to prostate cancer. In this study, we identified a single nucleotide polymorphism (SNP) at position -1687 in the L-plastin promoter by genotype sequencing. The SNP-1687 showed different transcriptional activity in the luciferase assay in vitro. The TRANSFAC software was applied to predict the multiple cis-elements, and luciferase assay was used to further identify the L-plastin regulatory region. We performed EMSAs, supershift assays and ChIP-qPCR demonstrated that the transcriptional suppressor NKX3.1 binds to the SNP site of the L-plastin promoter. SNP-1687 (T/T) led to an increase in the affinity of NKX3.1 for L-plastin promoter, resulted in lower levels of L-plastin RNA and protein expression. Furthermore, we collected and sequenced samples from 640 individuals (372 prostate cancer patients and 268 healthy controls) from 2000 to 2013. The results showed that SNP-1687 (T/T) occurred more frequently in the healthy individuals than that in the prostate cancer patients compared to SNP-1687 (C/C). Similarly, SNP-1687 (T/T) genotype occurred more frequently compared to SNP-1687 (C/C) genotype in the patients with low and moderately differentiated tumors. In conclusion, SNP-1687, located in the NKX3.1 binding site within the L-plastin promoter, might reduce the expression of L-plastin and potentially decrease the tumorigenesis and progression of prostate cancer. This SNP could be a potential prognostic factor for prostate cancer. This article is protected by copyright. All rights reserved.
My profession as a Molecular Biologist must seem like an odd pursuit to many. In late 1977 and 1978 my career as an independent researcher started to emerge at Johns Hopkins with my publication of two original research papers in Nature on phenotypic behaviors of cancer cells. These papers made it possible to nail a job at the National Institutes of Health as a Senior Fellow at the Bureau of Biologics with the FDA. It didn’t take me long to capitalize on this freedom and what seemed like unlimited funding to pursue the research that I dreamed up and wanted to do. The following tells what happened next.
There was an article about Linus Pauling in Time magazine in early 1981 about the fact that at the age of 80 he was still seeking a grant from the National Institutes of Health to fund his research on ascorbic acid for treating diseases. This news caught my attention and I looked into the possibility of joining Dr. Pauling’s institute. Toward the end of the summer I was invited to visit the Pauling Institute in Palo Alto, CA to give a seminar on my research at NIH.
In late August, Koloman Laki, an aging scientist at NIH, called me up and invited me over to his lab in NIH Building 10, a short walk across the campus from my lab in NIH Building 37. He was interested in talking to me about my recent discovery of mutations in human non-muscle cytoskeletal actin that was published in Cell in late 1980. This protein is the major architectural protein of all eukaryotic cells and we had shown that it was the most highly conserved protein in evolution of the species from yeast to humans. This fact made these mutations even more interesting.
Koloman was a protege of the Hungarian Nobel Prize winner Albert Szent-Györgyi who, I later learned, was much admired by Dr. Pauling because he had discovered both vitamin C and actin. Koloman described how Szent-Györgyi discovered muscle actin. When I mentioned that I was to visit the Linus Pauling Institute in late September, he told me about Emile Zuckerkandl’s and Dr. Pauling’s work on the ‘biological clock,’ which provided evidence in support of Charles Darwin’s theory on divergence of the species.
Back-tracking several years, the discovery of this actin mutation was made in a mutagenized cell line isolated by Takeo Kakunaga at the National Cancer Institute (NCI) in 1978. During the month that his paper was published, I walked over to NCI from my lab across the street to have a chat with Takeo about using his in vitro transformed Syrian Hamster cells as a model system to identify changes in protein expression that correlated with neoplastic transformation. After describing what I wanted to do, he seemed agreeable but then casually mentioned that he had succeed in transforming human fibroblasts into tumor forming cells. I nearly fell off my chair because human cells had never been transformed in vitro before, a major problem for cancer researchers at that time. I blurted out that we should do the work that I had proposed in his human cell model system, comparing protein expression by the transformed neoplastic cells with their normal precursor cells.
My hypothesis was that this comparison would allow identification of proteins that were turned on or turned off in expression by comparing protein profiles of the most abundant 1,000 proteins expressed in these cells and resolved by high-resolution 2-D gel separation (protein profiling). My plan was to look for charge-altering mutations in proteins that might govern neoplastic transformation and tumorigenesis. A fall-back goal was to define the pattern of qualitative and quantitative changes in protein synthesis to try and get a handle on the mysterious mechanism of human cancer development.
Within two weeks, in May of 1978, I was metabolically labeling the total cellular proteins (with the amino acid S-35 methionine) of the normal fibroblasts and three strains of cell lines derived from the normal culture which were immortalized, only one of which formed subcutaneous tumors in nude mice. After four hours of labeling, I prepared extracts of S-35 methionine labeled proteins from each of the four cultures and loaded 25-microliter aliquots of each sample onto the top of clear noodle-like isoelectric focusing gels (7-inch long urea-polyacrylamide gels with the thickness of spaghetti) which separated the complex mixture of total cellular proteins by their net charge (isoelectric point). These gels were subjected to isoelectric electrofocusing of the proteins overnight. The next morning I harvested the spaghetti-like gels, and incubated them in a detergent that would bind to the proteins to help separate them by their molecular weights in a second dimension. So, these proteins were first denatured and separated by their net charge and then, in a second dimension, separated by their size (mass) on a thin rectangular slab gel.
After about five hours of separation in the second dimension, I was soon to learn that I had separated more than 1,000 denatured protein subunits (polypeptides) by their differing charges and molecular weights. The final step before autoradiography, which revealed the full protein profile, was to fix and stain the gels to get a glimpse of the resolution of these peptide patterns. The staining of these rectangular gels revealed only the most abundant architectural cellular proteins, the most abundant of which were cytoplasmic beta- and gamma-actin, at a ratio of about 2:1 in abundance, respectively. The figure shows what quickly appeared as the gels were de-stained. In the one tumorigenic cell line, instead of seeing a 2:1 ratio of beta- to gamma-actin, a new abundant protein appeared at about one unit more negatively charged (more acidic), and half of the normal beta-actin was lost. The pixilation of these three radioactive “spots” immediately suggested to me that one of the two functional genes (alleles) encoding beta-actin had mutated, possibly due to the replacement of a neutral amino acid with a negatively charged amino acid. This prediction was no mystery to me as I had demonstrated this type of electrophoretic shift in another protein a year earlier at Johns Hopkins.
A number of experiments were done to build the case for the beta-actin mutation, and then I wrote a letter to Klaus Weber at the Max-Planck Institute in Gottingen, Germany, asking for his help in sequencing these actins. His lab was the only one in the world sequencing actins, e.g. the four muscle forms of actins. It only took Klaus two weeks to respond affirmatively, an indication to me that he was eager. I provided him with the actin proteins from this cell line and it took a postdoctoral fellow, Joel Vandekerkhove, and Klaus a little over a year to determine the complete amino acid sequences of the mutant beta-actin and both the wildtype beta- and gamma-actins, to define the mutation that had occurred. We published the result shown above in the top journal Cell in December 1980.
Flash forward to the fall of 1981. In the last week of September, I flew to Oakland, CA and was picked up at the airport by Emile who was President of the Linus Pauling Institute of Science and Medicine. The next morning I stood up in front of Dr. Pauling and the institute staff to tell them about my discovery of a mutant human beta-actin and my speculation on its involvement in neoplastic transformation. The evidence suggested that I had actually discovered at least two mutations in the same gene, each of which caused a progression to a higher malignant state. Dr. Pauling could relate to the way I made this discovery because he was the first to describe a mutation in a gene that caused a disease, in his case a mutation in charge-altered hemoglobin that caused Sickle Cell Anemia.
Linus Pauling was in the front row and was all smiles. He asked me if I knew who discovered actin. I was prepared to answer that question thanks to Koloman Laki. In the afternoon I met with Emile who offered me a Senior Scientist position at the Institute, which I accepted. At the time it would be me and Dr. Pauling with separate research interests.
So I resigned my secure job-for-life at NIH (I had been promoted to a civil service position from my Fellow position) and moved to Palo Alto to join the struggling Linus Pauling Institute. My technician, Patti Porecca, hired from Bob Gallo’s lab at NIH, would follow me to the Pauling Institute.
Cloning of the Human Beta-Actin Gene
After I arrived at the Pauling Institute, two of my colleagues at NIH and I published a comprehensive study of the changes in protein expression between normal and neoplastic cells in Carcinogenesis using high-resolution computerized microdensitometry to analyze the complex protein patterns (my first paper from the Pauling Institute). This was the first time that such a study had been published, e.g. the comparative profiling of expression of a large number of proteins in neoplastic cells. It was a study of the 1,000 most abundant proteins in normal and neoplastic human cells which revealed potential biomarkers and causative genetic events for human cancer. At the time it was staggering to view these patterns but perfect for my dyslexic brain and mind’s eye. In addition, we had published another paper in Cell that described, for the first time, the progression of a neoplastic human cell to a higher malignant cell following a second mutation in the same beta-actin gene. Early in 1982, Steve Burbeck and Jerry Latter at the Institute set up the same computerized microdensitometry platform I had exploited at NIH.
Jerry Latter gave a stirring talk at Argonne Labs in Chicago demonstrating that computerized microdensitometry of protein profiles could be used to determine the identities of unknown proteins based upon determining their amino acid compositions in situ in protein profiles. This paper was published in Clinical Chemistry in 1984. At the same meeting, Steve Burbeck described a truly innovative invention that could measure beta-particles emitted from radioactive protein profiles to produce a direct image of the protein profile pattern. As a group we had entered an exciting period of discovery and innovation at the Linus Pauling Institute.
Shortly after I arrived in Palo Alto in December 1981, I called Professor Larry Kedes at Stanford and we embarked on a collaboration to clone the human beta-actin gene. His impressive postdoctoral fellow, Peter Gunning, taught me some basic recombinant DNA techniques, and I was off to the races. The difficulty was to identify the functional gene in a sea of actin pseudogenes (sometimes referred to as junk DNA). I used an elegant method of homologous recombination developed in Tom Maniatis’ lab at Harvard that had never been used before to clone a novel gene (In fact, cloning of human genes was just getting started at the time). This was smart because Professor Maniatis would be the chairman of the NIH study section that reviewed my first grant proposal submitted from the Pauling Institute. I did not know it at the time but within a few months after starting this work, I had cloned the functional beta-actin gene a week before Christmas in 1982.
I developed a scheme to identify the correct gene among 300-400 clones of pseudogenes that Patti and I had cloned and the strategy worked. We gave Dr. Sun-Yu Ng the task of sequencing the DNA clone that we were betting on. Rather quickly we determined that we had cloned the functional human beta-actin gene because the DNA sequence that Sun-Yu determined from our candidate clone accurately encoded the amino acid sequence of human beta-actin protein that I had published in Cell in 1980 with Klaus Weber. Quite coincidentally another lab discovered a rat oncogene that was a fusion of part of an actin gene with a tyrosine kinase gene. I sent this information off to the study section that was reviewing my grant in January 1984 as added evidence that the actin gene was in some way relevant to neoplasia.
My colleagues and I at the Pauling Institute and Stanford published our successful isolation of both the mutant and wildtype human beta-actin genes in in October 1984. As shown on the left, we had given Armand Hammer’s name to our cancer research program because of his generosity in helping to fund the Linus Pauling Institute.
In January 1984, I was awarded a grant of about $110,000 a year for two years from the American Cancer Society…what a relief. Later in the spring I received word from Professor Maniatis’ NIH study section that our program would also be funded in June by a grant of about $150,000 a year for 3.5 years from the National Cancer Institute for the same work (this grant was successfully renewed twice for six more years through 1994). I was able to hire Dr. Ching Lin from Iowa State University and Dr. Ng (Sun-Yu) from Kedes’ lab. By 1985 Sun-Yu finished the complete DNA sequencing of the human beta-acid gene and Ching sequenced the copy of the beta-actin gene that had two mutations to formally prove the mutations at the level of the gene. Everything that we had learned about the genetic code and amino acid sequences of proteins made our findings predictable. I had learned from my own research how Darwin’s theory of evolution and natural selection worked.
This was the year I finally successfully transferred in recombinant gene inside a cell in culture. I transferred the mutant human actin gene into a rat fibroblast cell line to show that I had cloned the functional gene which could abundantly express its protein the way the natural endogenous beta-actin gene worked (shown in a protein profile of these actins above).
At this point I had a brief meeting arranged by Emile with Alex Zafferoni, founder and CEO of Alza Corporation (among other successful companies), a block away on Page Mill Road. Zafferoni recommended Bert Roland as a patent attorney. I arranged a meeting with Roland, also a block away, for that afternoon to discuss patenting the human beta-actin gene promoter because of its strong constitutive nature (the engine of the gene that drives its expression and regulation). I told Bert that this was a collaboration with Peter Gunning and Larry Kedes at Stanford. Roland was famous for filing Boyer’s and Cohen’s genetic engineering patent which created Genentech and eventually funded Stanford with hundreds of millions of dollars in royalties.
We published Sun-Yu’s work on the sequence, structure, and chromosomal location (chromosome 7) of the human beta-actin gene in Molecular and Cellular Biology and we published Ching’s work locating three mutations in this gene in the Proceedings of the National Academy of Sciences, sponsored by Linus Pauling. A patent was filed on the beta-actin promoter and over the years it was licensed to about 15 biotech companies by Stanford University. This patent was prosecuted and licensed for the full 17 years (the life of a patent then) but the patent never issued. The Institute’s first royalty check was about $10,000 in 1986, but most of the royalties were earned by Stanford’s patent attorneys.
Peter, Larry and I published a paper in PNAS on the use of the human beta-actin gene promoter for expression of other genes. This vector was distributed to anyone who asked for it – and many did – and to those companies that licensed the invention. At last count this paper had more than 1,000 reference citations.
Our paper popularized the actin promoter as a strong constitutive promoter of foreign gene expression. Soon the rice actin promoter would be used to make Round-up Ready crops by DeKalb Genetics and Monsanto, and giant tilapia fish would be engineered with growth hormone under the control of the fish beta-actin promoter. There were even fluorescent mice running around in Japan created with firefly luciferase expressed by the beta-actin promoter (which I called “the cat’s meow”). Since cytoplasmic actins are the most abundant proteins in most cells you could use the promoter to abundantly express foreign genes in most cells of any animal.
In 1987 we also published the culmination of my research on the mutant beta-actin gene in Molecular and Cellular Biology. When I introduced this gene into non-tumor forming immortalized human fibroblasts they became tumorigenic. The results showed that the more abundant the expression of the mutant beta-actin, the more tumorigenic the non-tumorigenic cells became and the cells that came out of the tumors were enhanced further in the level of mutant beta-actin expression. This was a sensational finding that was the goal of research which began with the discovery of the mutant beta-actin in 1978 at NIH.
The Mutant Beta-Actin Effect was Reproduced and Extended in 2013
John Leavitt in his laboratory at the Linus Pauling Institute of Science and Medicine. Originally published in Science Digest, June 1986.
As stated above, in 1987, my colleagues at the Pauling Institute in Palo Alto, colleagues at Stanford and I published a paper that clearly demonstrated that expression of a charge-altered mutant human beta-actin (glycine to aspartic acid substitution at amino acid 245; G245D) caused non-tumorigenic, immortalized human fibroblasts to form aggressive tumors in nude mice When these tumor-derived cells were examined, we discovered that they exhibited further elevated expression of the mutant beta-actin and these tumor-derived cells formed tumors even more rapidly – observations that were consistent with the role of this mutation in the tumorigenic phenotype. Furthermore, over-expression of mutant beta-actin was associated with down-regulation of three abundant tropomyosin isoforms in a well-documented transformation-sensitive manner (Leavitt et al, 1986; Leavitt et al, 1987a and Ng et al, 1988). These final papers were the culmination of research conducted at the Linus Pauling Institute from December 1981 to March 1988.
Normally when a scientific observation is never repeated it is usually not worth remembering. In this case, twenty-six years after our 1987 publication, a study was published by Schoenenberger et al. at the Biozentrum in Basel, Switzerland, that reproduced our findings in a different cell system, a rat fibroblast model. Furthermore, these investigators extended our findings by characterizing new aspects of abnormal behavior of the mutant beta-actin and cells that express this aberrant protein, which help to explain of this mutation’s potential role in cancer such as enhancement of tumor cell motility and invasiveness.
In addition to enhancement of tumor growth and alteration of cell shape, the Swiss investigators presented the following findings to clarify and support the oncogenicity of this mutation:
The other surprising finding in my own lab was that cell lines expressing the transfected mutant beta-actin gene did not have higher levels of cytoplasmic actins in them because the two endogenous wildtype beta- and gamma-actin genes were coordinately down-regulated (auto-regulated) so that the relative rates of total actin synthesis remained at the same level compared to S-35 methionine incorporation into 600 surrounding non-actin polypeptides in the protein profile (Leavitt et al, 1987b). This auto-regulation phenomenon was reproduced by Minamide et al. (1997) ten years after we reported it.
Cytoskeletal rearrangement of actin microfilaments, as well as changes in composition of tropomyosin isoforms and other actin-binding proteins, have long been associated with neoplastic transformation. However, before our study, causal mutations in a cytoplasmic actin had apparently not been considered. It is perhaps consistent then that Ning et al. (2014) have recently described genetically inherited polymorphisms in the actin-bundling protein, plastin (also discovered and cloned in my lab at the Pauling Institute), that significantly affect the time of tumor recurrence in colorectal cancer after resection and chemotherapy.
During my tenure at the Pauling Institute, I felt that Dr. Pauling understood and appreciated this work and its relevance to the fundamental nature of cancer development. Progress can be slow, but ultimately true understanding of cancer will emerge from this type of research…and I predict that cytoplasmic actins and actin-binding proteins that regulate actin organization and function in the cytoskeleton will be understood to play a central role in the manifestation of the tumorigenic phenotype.
Pioneering the Field of Proteomics – Discovery of Human Plastins
In the fall of 1985, I went to a small meeting in Heidelberg, Germany, with Steve Burbeck from the Pauling Institute, who had helped me by developing computerized microdensitometry to analyze two-dimensional protein profiles. At this meeting I described our protein profiling work and the discovery of the mutant beta-actins and another interesting protein which I named “plastin.”
Steve Kent, head of the protein sequencing facility in Leroy Hood’s lab at CalTech, heard my talk. We sat across from each other at dinner and he proposed a collaboration to develop methods of sequencing minute amounts of protein leached from spots in high resolution protein profiles. Lee Hood was well known for developing state-of-the-art protein and nucleic acid sequencing methods and machines, and was a founder of Applied Biosystems in Foster City, CA.
After I returned from Heidelberg, Ruedi Aebersold called me from Caltech and we began collaborating on microsequencing of pure nanomolar quantities of unknown proteins of interest eluted out of my protein profiles. In this work we essentially started the field of Proteomics, which was eventually named ten years later by Jim Garrells, a protein profiler at Cold Spring Harbor. Proteomics is the search for and definition of proteins among all of the proteins made by cells that could serve as diagnostic markers and drug targets for diagnosis and treatment of diseases, in our case cancer.
In 1987 we published a landmark paper in PNAS on the microsequencing technique that Ruedi developed. This paper would eventually be cited in references by more than 1,000 other research papers.
I was intrigued by the fact that a major protein of circulating blood cells would be induced during solid tumor cell development because it is well known that solid tumor cells become more anchorage-independent and can circulate like white blood cells to metastasize to other organs. My colleague, David Goldstein, took the lead in examining the expression of this mysterious protein in different cell types of fractionated white blood cells. At the time this protein was assigned only a number (p219/p220) corresponding to its position in two-dimensional protein profiles. We found that this protein was abundantly expressed in all normal white blood cell types that we examined but it was not expressed in normal cells of solid tissues (Goldstein et al, 1985).
When David’s paper was submitted to Cancer Research, the reviews came back positive and the paper was accepted for publication, but one reviewer asked that we give the protein a name. I was thrilled by the thought of naming a protein and its gene which would immortalize our work, so I took on the serious task of coming up with a name that had lasting meaning. My theory was that this cancer marker contributed in some then-unknown way to the plasticity of the cytoplasm in solid tumor cells because of its normal presence in circulating white blood cells. Also, I had seen the great movie, The Graduate, with Dustin Hoffman and recalled that amusing scene depicted in the picture included to the left. So I named the protein “plastin” – the greatest new thing since sliced bread.
I gave a postdoctoral fellow, Mahdu Varma, the task of isolating the cancer-specific leukocyte isoform of plastin (L-plastin) from 140 protein profiles. This protein has now been implicated in metastases in both melanoma and prostate cancer and more recently in breast and colon carcinoma cells. The L-plastin spot was easily recognized and those spots in gels were transferred to nitrocellulose filters, stained, and “snipped out,” effectively removing all the other proteins of the cell. We sent Ruedi a plastic tube containing the 140 “spots” of L-plastin. He had figured out a way to solubilize the protein from the nitrocellulose and was successful in determining the sequence of eight internal oligopeptides of between eight and sixteen amino acids derived by digestion of L-plastin with a proteolytic enzyme.
The peptide amino acid sequences Ruedi determined turned out to be perfectly accurate internal amino acid sequences of plastin when we decoded the sequence of the plastin gene (cDNA) clone from a reverse transcript of the messenger RNA. This was the first time that anyone had done this; this opened up the field of proteomics and has led to the discovery of other diagnostic and drug targets by the same method. A lot of this work was done by Reudi Aebersold because he was flooded by requests for help.
We had chosen L-plastin, normally only expressed in white blood cells (L for lymphocytes), because I had found over the years that this polypeptide was expressed in tumor cells that arose in solid tissues (identified in this electrophoretic image on the left by the two upward arrows), but this protein was absent in the normal cells of tissues in which the tumors arose. After we received the short peptide sequences from Ruedi, we made short DNA antisense probes that would hybridize to DNA sequences encoding these peptides in the human genome in order to fish out the full-length cDNA clones that carried the sequence of the L-plastin gene. Dr. Ching Lin took one of the nucleic acid probes and immediately attempted to screen a tumorigenic fibroblast cDNA library. If we identified any clones that bound this radioactive probe, then we would perform a quick test to determine that we had cloned the L-plastin coding sequence. But science is full of surprises and we found that the first clone Ching isolated detected a gene product that was not in lymphocytes but only in normal human fibroblasts – in other words, it failed the test. This is where Ching’s brilliance took over. He was convinced that this first clone he had isolated was indeed a plastin coding sequence so he used this new clonal DNA as a new radioactive probe against the tumorigenic fibroblast cDNA library. He isolated another clone that passed the test and detected a gene that was expressed in lymphocytes and tumorigenic fibroblasts but not in normal human fibroblasts.
Ching (to the left), Madhu, and I, along with Reudi, published the nucleic acid sequences of both clones, the human L- and newly discovered T-plastin proteins, by sequencing of their cDNAs, in Molecular and Cellular Biology in 1988. The discovery of a second isoform of plastin – T-plastin named for tissue plastin as opposed to L-plastin from leukocytes – was a surprise. We now had two genes to characterize at the genomic level. Today, T-plastin is a well-established marker for cutaneous T-cell lymphoma (Sezary Lymphoma, a lethal white blood cell cancer) and L-plastin,which is inappropriately expressed in solid tumor cells (carcinomas, fibrosarcomas, melanomas, etc.). L-plastin and T-plastin are now implicated in many forms of tumor metastasis. It is metastasis that kills us when we develop cancer.
We continued to work on the two plastins and published the full genomic sequences and their chromosomal locations in 1993.
Extension of Our Research on Plastins by Other Labs
The figure below maps the progression of discovery that followed our research on plastins, which began at the Pauling Institute in 1985. The number of our publications by year is shown in red in the graph and research papers published by other labs is shown in the blue bars up through June 2014.
Here are several plastin milestones discovered by other researchers:
These papers were published between the fall of 1985 when we coined the name plastins and June 2014.
These developments are more or less typical of the way science works. Progress in understanding complex phenomena like human cancer is the work of many scientists that builds on the observations of other scientists.
The Linus Pauling Institute was not all work and no play in the 1980s
We worked and played hard at the Institute and Linus Pauling was always there and visible.
We put together a softball team with Jim Fleming, Dan McQueenie, Zelek Herman, myself, and others at the Institute and played departmental teams at Stanford. I think we were called the “Pauling Squeeze.” After these games we would often go dancing at the Class Reunion on El Camino Real near the corner of Page Mill Road.
We were fortunate to have on staff a first rate fundraiser in Richard (Rick) Hicks who arranged wonderful fundraising parties on Nob Hill at the Stanford Court. The most memorable of these parties occurred in late November 1986, when we honored Japanese billionaire, Ryoichi Sasakawa, with the annual Linus Pauling Medal. Another year Carl Sagan and Ann Druyan, who helped Carl put together the Cosmos series, took part. We often saw Dr. Pauling’s sons, Linus Pauling Jr., Peter, and Crellin at these get-togethers and at the Pauling Institute as well.
Here we are at the Stanford Court that night in November 1986 with postdoctoral fellows, Dr. Karin Sturm from Heidelberg, Germany, on the left and Dr. Madhu Varma from Madras, India, on the right. My wife, Becki, is in the middle. I recall that Dr. Pauling enjoyed this night as well.
In 1988, I moved on to become Scientific Director of the California Institute for Medical Research in San Jose and then became Director of Research at Adeza Biomedical in 1991. I spent my final year in 1995 as a Molecular Biologist on contract from the Palo Alto Medical Foundation to the US Air Force Academy in Colorado Springs, where I looked into the mutagenicity of high energy short pulse laser light that was used in the battlefield. I was ready to move on to a new line of work consulting with Biotechnology and Pharmaceutical companies, which lasted for 19 additional years.
We’ve heard a lot of complaints by politicians about these nuclear negotiations on the part of Secretary of State, John Kerry, and the Obama administration. The assumption on the part of these complainers is that the USA will settle for something less than guaranteed scrutiny of Iran nuclear activities. Another assumption by the complainers is that Iran will cheat. But it’s okay for the complainers to complain. They represent a significant part of our society – the ignorant, airhead electorate who simply chime in when Rush Limbaugh and the other extreme right-wingers speak against the negotiations.
I view these protracted negotiations to be extremely valuable exercises which help our leadership to sharpen its understanding of the Iranian leadership and the culture of the country while at the same time maintaining sanctions. This will be the pay-off regardless of whether a deal is struck or not. The longer the negotiations go on, the more that will be learned. It’s a better approach to world stabilization than fighting any war. It’s too bad that the Bush-Cheney administration apparently had no understanding of this process. I don’t know if that administration actually believed that Saddam Hussain was building nuclear capabilities in Iraq, but I do know that if they purported to believe this, the ignorant electorate and their representatives in the US Congress would back this myth. These are the same brainless so-called leaders who today bash the US-Iran nuclear negotiations.
I was against the Iraq War since the war’s inception on March 20, 2003, e.g. “Operation Iraqi Liberation”. First and in retrospect, the cost in innocent Iraqi lives has been estimated at about 115,000, but medical studies have estimated between 400,000 and 600,000 deaths linked to the Iraq War. Furthermore, >4400 US soldiers lost their lives and >32,000 were wounded trying to save us from “Weapons of Mass Destruction” – the Bush-Cheney lie drummed up to justify the War (I’m not using references because this information can be easily found from credible sources). The monetary (direct) cost of this War will ultimately be over $1 trillion before the dust has settled at a cost of over $3 trillion to the US economy. We and our children are being ‘billed’ for this War for generations to come. But more tragically, the Iraq War has led to destabilization of the Middle East. As a result of this war, that leadership has undermined our ability to deal more effectively with the greater emerging military threats from Russia, Iran and Korea, address important national needs, and form international alliances to effectively address other more important global issues in addition to our domestic needs.
In the early 1950s the CIA orchestrated the over-throw of Prime Minister Mohammed Mossadegh, a totalitarian who tried to take over Iran and nationalize Iran’s oil industry (CIA documents on the Internet indicate that orchestration was by my uncle, John H. Leavitt, and his colleague, Kermit Roosevelt). The US supported the Shah who formed favorable alliances with other leaders within the Middle East and resisted the Soviet Union’s influence. The Shah’s prominence in the Middle East definitely suited US and British interests. But in the 1960s and 70s the Shah’s government evolved from benevolent monarchy to an autocracy with the creation of SAVAK, the Shah’s secret police. It’s hard to understand whether SAVAK stimulated Islamic fundamentalism or if SAVAK was a defense against this perceived threat.
The 25 year US-Iranian relationship between the early 50s and the late 70s benefited our country. But our meddling in the Middle East since then ultimately stimulated the emergence of a much greater adversary in the form of Islamic fundamentalism.
Thirty-six years later the US, Britain, and most European countries view Islamic fundamentalism and the Iranian regime as one of our greatest enemies. And, our well-recognized failure in Iraq has only stimulated Islamic fundamentalism, anti-American sentiment, and provided a mechanism for Iran to expand its influence. Soon the southern half of Iraq will be called “Iranq” and the US, as a result of Bush-Cheney leadership, will have caused trillions to be spent in a failed policy that has undermined our country’s ability to deal with our current pressing issues.
From Wolf Guibbory
I received an interesting email from my good friend Cathy.
While reading, I was struck by the stark contrast between the profound sacrifice of our forefathers, juxtaposed against the legacies (or lack of same) of our current crop of lawmakers, who merely receive their salaries and benefits for life, even though they may have been elected to no more than one term. Our representatives or senators like to remind us that they are the guardians of our constitutional rights; that they represent the latest in a long and noble lineage, dating back to those very same forefathers. Remove that association and just how worthy are they of our trust and support?
Most of these people have grown up the sons and daughters of privilege and we all know what our lawmakers reap – but could someone please tell me, exactly what is their badge of sacrifice? I just wonder, how many of them were merchants or farmers? How many came from humble beginnings, have served in the military? How many have gone to war? Who among their children are serving in Iraq and Afghanistan? There are some who might acquit themselves, but not many, most of whom are older, nearing the end of long political careers. While it is we who have elected these people to our nation’s most generous welfare program, nonetheless I am left to ponder – just how many have shown themselves worthy of bearing that mantle worn by our forefathers?
The message which Cathy passed on is greater than mine however, so here is her email (more detail here):
“The 4th of July!!
Have you ever wondered what happened to the 56 men who signed the Declaration of Independence? Their story. . .
Five signers were captured by the British as traitors, and tortured before they died.
Twelve had their homes ransacked and burned.
Two lost their sons serving in the Revolutionary Army; another had two sons captured.
Nine of the 56 fought and died from wounds or hardships of the Revolutionary War.
They signed and they pledged their lives, their fortunes, and their sacred honor.
What kind of men were they?
Twenty-four were lawyers and jurists.
Eleven were merchants.
Nine were farmers and large plantation owners; men of means, well educated.
But they signed the Declaration of Independence knowing full well that the penalty would be death if they were captured.
Carter Braxton of Virginia, a wealthy planter and trader, saw his ships swept from the seas by the British Navy. He sold his home and properties to pay his debts, and died in rags.
Thomas McKeam was so hounded by the British that he was forced to move his family almost constantly. He served in the Congress without pay, and his family was kept in hiding. His possessions were taken from him, and poverty was his reward.
Vandals or soldiers looted the properties of Dillery, Hall, Clymer, Walton , Gwinnett, Heyward, Ruttledge, and Middleton.
At the battle of Yorktown, Thomas Nelson, Jr., noted that the British General Cornwallis had taken over the Nelson home for his headquarters. He quietly urged General George Washington to open fire. The home was destroyed, and Nelson died bankrupt.
Francis Lewis had his home and properties destroyed. The enemy jailed his wife, and she died within a few months.
John Hart was driven from his wife’s bedside as she was dying. Their 13 children fled for their lives. His fields and his gristmill were laid to waste. For more than a year he lived in forests and caves, returning home to find his wife dead and his children vanished.
So, take a few minutes while enjoying your 4th of July holiday and silently thank these patriots. It’s not much to ask for the price they paid.
Remember: freedom is never free!
Patriotism is NOT a sin, and the Fourth of July means more than beer, picnics, and baseball games. True “reflection” is a part of this country’s greatness.”
First, there are people who worship what Satan represents in the Abrahamic religions. Bible thumpers have been preaching this for centuries, primarily to drum up business. Well, it turns out they were right, except that the real followers of Satan aren’t the ones we have been warned about. They are instead people who know that to convert the maximum number of souls into fellow travelers, they must pretend to be Christians. The other religions won’t do because they don’t harbor as many hypocrites as Christianity so it would be much harder for a worshiper of Satan to pass as say a Jew or a Buddhist or a Muslim or even an Atheist. By the way, I won’t use the term Satanist because that word describes a believer in a religious code that does NOT generally subscribe to the beliefs of true worshipers of Satan. So for convenience, I’ll call these people Christophobes, or just Phobics for short.
Since they disguise themselves as Christians, how do we tell Phobics from true Christians? Actually, that is a lot easier than you might think.
First, Jesus was a logical, pragmatic individual. Credited with infinite intelligence and wisdom, He taught that humans could acquire the Grace of God (and pretty much everything else) through selfless, charitable and loving actions. These teachings seemed contrary to how the real world worked when He was alive and seem even more so today. Still, He was right. Whether the Son of God or not, He had a lock on the best way to achieve success in every aspect of life, both here and in the hereafter.
Secondly, Phobics aren’t the brightest light bulbs in the Universe. They can be wily, manipulative, devious, even sometimes possess superior brains. Nevertheless their essential souls are immature so they rarely recognize when their actions are self-defeating.
Combine these two facts and you have your blueprint. Look at people (remember – they are supposed to be Christians) and see if they only SAY they follow the teachings of Jesus or if they actually DO follow His teachings. Because they aren’t too imaginative, most of them are quite incapable of disguising their transgressions against Him.
Now, about Karma. In the 1960s, gays didn’t give a rat’s patootie about the word “Marriage.” “Civil union” was fine. They wanted to have insurance, file tax returns, get hired and fired, live where they wanted and could afford, adopt, and a host of other things governed by the law, just like straight people. Enter the Phobics.
Mean-spirited and stupid, Phobics lobbied their representatives and wrote and passed laws to harass, intimidate and deny homosexuals their rights under the Constitution. They went out of their way to classify a civil union as not a marriage, inferior to “real” marriage, and not deserving of the same protections as marriage. BTW, Phobics still don’t realize that the Constitution starts with, “We the People,” and that means ALL the People. The Phobics thought they could get away with violating the Constitutional rights of homosexuals, whom they regarded as inferior, and in fact they made a pretty good run at it. But here’s the gotcha.
Over the years, homosexuals came to realize that Phobics had embedded the word marriage into so many laws in so many places that even if they ever DID get “civil union” recognized as equal to “marriage” UNDER THE LAW, they would still have to fight for centuries to obtain equal rights across the United States. So, they did the only logical (Christian?) thing. They switched to fighting for the word marriage to include homosexual unions. And now they’ve succeeded.
Yup! Karma’s a bitch.
BTW, here’s a heads up about the next battle of the Phobics: health care. I just hope it takes less than 60 years for We the People to figure out that health care providers and insurance companies are too interested in making money to “promote the general Welfare.”
I watched the documentary “The Plow That Broke the Plains” that was produced by the Federal government in 1937 on UTube and read the books “The Worst Hard Time” by Timothy Egan and “The Great Crash 1929″ by Galbraith. My interest was to understand the hardships of the Great Depression to learn about the impact of our recent Great Recession. The Recession was difficult for many but nothing like the Depression era of the 1930s when both grandparents of my family lost almost everything that they owned and had to start over.
When I returned to Colorado Springs where I was doing contract work at the Air Force Academy in the spring of 1995 after attending one of daughter Christina’s plays in Odessa TX, I decided to drive north of Amarillo on Route 287 through the Oklahoma panhandle to get back to Colorado. It turned out to be a rather scary drive. If my car had broken down, I would have been at the epicenter of the Dust Bowl of the 1930s, e.g. “No Man’s Land”. Who knows what would have happened to me, if I sought help on that desolate road. If you see that part of Oklahoma between Boise City and the Colorado border on this route, you will see the devastation of the dusters that destroyed hundreds of millions of acres of prairie grasslands in the 1930s leaving sand moguls in the depression era Dust Bowl that spanned from southwestern Nebraska, down western Kansas, down eastern Colorado, the Oklahoma panhandle in the western part of the state, eastern New Mexico, and then down into Northern Texas.
One of the features of the demise of the Earth in the movie Interstellar was its depiction of this dust bowl scenario and the deadly silicosis (pulmonary fibrosis) that also killed many inhabitants of the Dust Bowl in the 1930s. As Timothy Egan said this was “The Worst Hard Time” and place during the great depression era. In New York City after the stock market crashed you didn’t die unless you jumped out of a building window. In the Dust Bowl you died young and early if you just lived there. In those times the nature of pulmonary fibrosis (also called silicosis) was unknown. Today it is known that pulmonary fibrosis is more deadly than cancer with a life expectancy of 3-5 years upon diagnosis. The cellular mechanism of this disease is just becoming understood. I was fortunate to understand the importance of the launch in October 2014 of Esbriet for treatment of idiopathic pulmonary fibrosis, and my Intermune stock rose from $15 a share to $75 a share when Roche bought Intermune.
Most of the Dust Bowl farmers and their families who lost their livelihoods and lives in the 1930s were innocent in causation of the Dust Bowl but the Roosevelt Administration was able to determine the cause. It wasn’t the weather.
From the late 1800s into the 1920s, the Federal government promoted homesteading and over-farming of a land, the grassland prairie that wasn’t meant to be tilled. A study by Hugh Bennett, an appointee of Roosevelt, determined that the cause of the Dust Bowl was not the weather because there was no significant change in the pattern of dry and wet spells. This was a land without rivers for the most part. The watering of the prairie was due to the Ogallola Aquifer, a lake 700 feet below the surface of the prairie. There were no nearby mountain ranges or Colorado rivers on this side of the continental divide to feed enough water to this area.
The prairie had been the homeland of the Native American who hunted buffalo. Then cattle barons moved in and the buffalo and Native Americans were moved out breaking a federal treaty. In 1890, 10 million acres of prairie in the Dust Bowl were used to grow wheat. This number grew to 200 million acres by the 1920s after the price of wheat sky-rocketed due to the demand for wheat in Europe. This drove the homesteading process for normal citizens and immigrants, and greed on the part of speculators as the government promotions suggested, you could get rich quickly by becoming a wheat farmer. But after the Great War ended, the foreign demand for wheat declined and disappeared and piles of wheat were left rotting in train yards. Much like the investors on Wall Street in the late 1920s who borrowed to reinvest and recover their losses, the wheat farmers planted more wheat and tried to make a profit with two crops. In the process the sod busters destroyed the prairie grasslands and the wind which had always been there swept away the soil, sending it east. In deed, in the 1930s dark clouds of dust invaded east coast cities and ships off the east coast. Hugh Bennett was giving his pitch on the need to reclaim the prairie to a Congressional committee when a duster rolled through Washington DC. Taking advantage of the timeliness of the storm, Hugh invited the congressmen to the window to see for themselves.
Sequence of events that led to the Dust Bowl (click to enlarge thumbnail):
1. Cattle barons moved into the prairie originally ceded to Native Americans and the buffalo;
2. Homesteading for the purpose of growing wheat was promoted by the federal government;
3. Wheat crops replaced the cattle covering 200,000,000 acres;
4. The repeated tilling busted and destroyed the native sod based grasslands;
5. The country without rivers became barren and the natural trade winds started pick up the fertile soil;
6. Impassible dunes started to form around all structures;
7. Dusters rolled, one after another, including this one on Black Sunday which reached the east coast; and
8. Invading every crevasse, peoples’ houses and lungs filled with dust.
When the Wye Oak sprouted between 1542 and 1555 (based on tree ring analysis) it escaped trampling and logging by Native Americans when early European settlers were absent. By 1607 when James Town was founded a little further south in what became southern Virginia, the tree was probably too large to be disturbed.
First 52 Years of the Maryland Wye Oak:
This is not about schools or politics. It’s about a special oak tree growing next to the Pink House – the one that doesn’t discard its dead leaves in the fall like most other trees in the forests of Woodstock.
In June of 2002 a tree growing in Wye Mills Maryland (Maryland Eastern Shore) was lost to hurricane winds. This tree was determined to be more than 460 years old, a stately tree that was old when settlers colonized North America. Before its demise, this tree was purchased by the state of Maryland in 1939 and declared “Maryland’s State Tree” e.g. “The Wye Oak”. The base of the tree was 31 feet 8 inches in circumference, the tree was 96 feet tall, and the crown spread 119 feet covering nearly a third of an acre.
Needless to say, the sudden loss of this tree upset everyone in this small town and many others in Maryland who knew of this tree and its history.
These acorns were given to my father and mother who planted them in a small pot. One sprout emerged which was allowed to grow for about two years. In 1994 the seedling was transplanted near the Pink House. This ’Woodstock Wye Oak’ is now 16 years old and on this early March day is looking robust with its full head of brown fall leaves. The second picture is of this same tree today (June 22, 2015), 7 years later. Now this tree is 23 years old.
Hopefully Woodstock’s Wye Oak will still be standing in Woodstock in the year 2400. Unfortunately this plaque is not there anymore.
On Friday morning, June 5th, I logged into my accounts at the Bank of America (BofA) as I do routinely in the early morning. An hour or two later I had reason to go back and check one of my accounts. During the time that had elapsed a charge of $670 plus a $20 international transaction fee were added to my Visa card pending. I went to the website of the company where the purchase was made and found an online men’s clothing store, TM Lewin, in Britain. I immediately called Becki in New Hampshire and confirmed that she did not make this purchase. In fact we have never purchased anything from this store. Frightened by this, I immediately called BofA and was transferred to their fraud unit. After I explained that we did not make this purchase, the person I was speaking to said, ‘It is fraud’, and explained that if the charges post to my account, they will be removed. In the meantime, BofA cancelled my card and promised to send a new one. By Tuesday the charges had posted. I called BofA again and the charges were removed by the next day with the caveat that I would be responsible for these charges if the BofA ultimately concluded that the purchases were mine.
After all of this a package came from TM Lewin presumably containing the goods that had been purchased with my Visa card. I was uncertain what to do. Then after a few days Becki opened the package and found the packing slip shown below.
According to this slip, four pairs of expensive men’s pants were purchased by a “Penny Leavitt” at 16315 Wild Oak Lane in Conroe Texas 77302 USA. Penny had used our surname to make the purchase.
Becki searched this address at 411.com and found four persons living at that address with the surname “Dunn” including “Mrs. Penny Dunn (first thumbnail below; click to expand). I can’t prove that this is the person who actually made this purchase because it could possibly be someone else in this family or a neighbor or acquaintance. But the fact that someone named “Penny” lives at that address is too much of a circumstance to ignore. The second thumbnail locates Conroe TX just north of Houston, and the third thumbnail shows the house at 16315 Wild Oak Lane.
I called the fraud unit at BofA back and told them that we had now received a package with an order slip and gave them the name and address of Mrs. Penny. I said that I did not know how TM Lewin found our address, the billing address of my credit card. I assume that the vendor had access to the billing address through BofA and that TM Lewin decided to mail the purchase to the billing address (possibly out of suspicion), rather than the mailing address given by Mrs Penny.
I then emailed “customer.services” at TM Lewin and then gave them this same information, stating emphatically that I did not make this purchase and that I insist on returning the goods.
Here is the response from TM Lewin that came almost immediately:
“I am sorry to hear that you have been a victim of credit card fraud on this occasion. Here at TM Lewin we take fraud very seriously and as a result, all of our orders go through stringent security checks to in an attempt to prevent cases like this from occurring. Inevitably however a small number do manage to slip through the net and it would appear that this is what has happened on this occasion.
You may send the goods back to the address attached.
We really appreciate your help on this matter and would like to thank you for the time you will be taking to return the order back to us. If you require any further assistance, please do not hesitate to contact me back.
After this frightening experience I checked my credit score finding that shown in the fourth thumbnail. So far, so good.
BofA said that the Police Department in Conroe TX will be notified. I doubt that anything will be done about this unless other frauds have been perpetrated at this address.
This is a flashback to September 30, 2010 when we were five years old. Since then we have slowed but the pendulum is now starting to swing back and we will start speaking up more often.
The Cafe is 5 years old tomorrow, October 1st 2010. We are still very active in spite of Facebook and the competing newspaper blogs which also have, for the most part, diminished in readership. In the 5 years of our existence we have posted 1776 articles and 16,398 comments. [As of June 17, 2015 the Cafe has posted 2,711 articles and >23,000 comments]
Gone are Connecticut’s most active CT political blog CTLocalPolitics, the Pomfret blogs, FreeNorwich (one article per month), BlogNetNews which rated blogs (and rated the Cafe #1 and #2 in the state on multiple occasions), the UnTruth website (nothing since January) and others.
Our early article “In Woodstockistan” angered Woodstock Academy Trustee, Ernie Wetzel, and the then elected officials of the town of Woodstock. We were anonymous then which heightened the mystery.
Rachel Dolezal has stated that she identifies herself as a black person. I accept this. I am always impressed with people who strive to become someone they perceive to be better than what others may allow them to be. Even though her genes suggest that she is white, her genes don’t differentiate her from the next person in terms of the person they become, and their contributions to society and betterment of the human race. A lot of us do this. We identify ourselves as Republicans, Democrats, Independents, Libertarians, Christians, Muslims, Catholics, Jews, so on and et cetera. Our genes don’t change when we commit to this transition.
In 1983 I hired David G. as a laboratory technician in Palo Alto. I learned that David was transgender only when I contacted his reference from medical school. Initially he didn’t recognize ‘David’ but quickly realized that I was inquiring about one of his students who he knew as “Denise”. I had already had a favorable impression of David and David’s reference was very supportive. I remember thinking that David had something to prove so I hired him and was never disappointed.
Denise and David had the very same genetic make-up yet the person who David became worked much better for him in life. I think the same will be true for Rachel.
Point/Counterpoint on Rachel’s position:
Lynne: Wanting to identify as black, I can understand.
John:We will have to see how this shakes out. I can understand her parents hurt but we will have to see how that shakes out as well.
Lynne: Well, the whole issue with the parents/family seems to run disturbingly deep.
John: I know of someone close to my family who claimed that a long time friend of her parents was actually her father, not her real father. This was the doctor who delivered her at birth. I know this person to be a paranoid schizophrenic, not severe but nevertheless not sane. Fifty years after her birth she went so far as to contact the man and this man became very disturbed and contacted the real parents asking them to bar her from ever contacting him again. Rachel does not seem insane but we will see.
Lynne: There is something very odd going on, certainly. The tweets aren’t “speculation”, though, in many cases.
Like the one that says “Rachel Dolezal saying she pretended to be black for her own survival is an insult to the black lives that really are at risk.” or “She said she went from transracial to biracial to African-American. Honey, my blackness is NOT an experiment.” The issue here is that she is appropriating someone else’s identity, and those someone elses do not have a choice about their identity — being able to put that identity on and take it off at will is very much a position of privilege. And there is little wonder that the people who don’t have that privilege, and are disadvantaged by it on a largely permanent basis, can be resentful.
And let’s be quite honest, here, white people are NOT in a position to tell them they shouldn’t be. That’s just wrong on all sorts of levels.
And that isn’t speculation about motives or anything, that is a legitimate reaction on the part of people who have that identity whether they want to or not.
John: Don’t you think, Lynne, she has created a unique identity, rather than having appropriated someone else’s?
Bill: Thank you for bringing this up. Race vs. culture is a tough one. Perhaps her kids summed it up best when they said “she’s of the human race and identifies with Black culture.” While we may never know the answers to some of the troubling questions (nor is it really any of our business), perhaps all we really need to know is what her record shows and what her public statements say. On both accounts, she seems credible and sincere. Her record for doing good and fighting for social justice is admirable. Her Facebook statements and her interview with Matt Lauer this morning show an intelligent woman with sincere motivations. Anything else is just speculative.
Lynne: Bill, you are getting unduly defensive here.
But you are also not really entitled to tell people in a minority that their reactions to someone using their minority are not legitimate — or logical. YOU are not really in a position to say to someone that something which you don’t think is an insult, is not an insult even if they think it is, and this is especially a problem if you happen to be in a majority position (a position of privilege) dictating to someone in a minority position (a position of disadvantage).
Bill: Being in the minority doesn’t mean we shouldn’t expect a logical argument from them. To lower that standard simply because they are a minority is insulting- not only to them, but to us as well. And let’s face it, 17 tweets doesn’t represent the entire minority. I can probably find 17 tweets that are supportive of Dolezal. Again, I wouldn’t expect universal acceptance of Dolezal’s actions. Certainly there are a lot of questions, but until we know the answers, most of the criticism seems to be either speculative or, in my opinion, hateful. Just go on her face book page and read some of the comments. It will turn your stomach. So yes, I may be a bit defensive but its on her behalf not mine- and for the sake of logic and human compassion.
Lynne: Bill, this is about not devaluing other people’s experience. You can say “I don’t agree with those reactions” perfectly legitimately. What you CANNOT do is say “those reactions aren’t true.” Yes they are. They are true and perfectly legitimate reactions. That doesn’t mean you have to agree. It does mean you don’t get to call them “false” or tell people that they aren’t allowed to feel insulted because -you- deem it illogical. Do you see the distinction? And the criticism, such as it is in those tweets, is in many cases not speculative at all. She did claim to be black, and the physical reality is that she is not black by any measurable metric. She did tell a story about her upbringing which is false. Those are things we really need to accept as fact.
Feeling upset at that is not “speculative”, and while statements can certainly be hateful, and I genuinely hope she doesn’t get hit with too much of that, feeling upset about her doing it isn’t, in itself, hateful.
She has put herself in a tough place right now.
Diane Olivia: No one will ever know her motivation–however, why do we care? My ancestry is mixed Scandinavian mostly but who knows? Maybe a long time ago… And, why do we care?
Lynne: Racial identity. No. She has appropriated a racial identity, and moreover, a false racial _story_ that she has told people.
John: I wonder how many of us have a black person in our ancestry. Didn’t some white women who married black men try to quell prejudice by appropriating some black characteristics?
Lynne: Understand: when transsex people identify as the opposite sex to what they were born, the majority I’ve met or read essays by don’t say “I was born [a]“, they say “I was born [b] but never felt [b]; I want to be [a] because I feel that I am [a] and should always have been [a]” — but then, they take steps to become [a] and wish to be fully identified as [a], and I can actually totally get that.
And I also get that similar options don’t exist for “race” or skin colour.
But if they did, and she said “I was born [b] but never felt [b]; I want to be [a] because I feel that I am [a] and should always have been [a]“, wrt to “race” or skin colour or whatever, and then took steps to become that [a], I could actually be on board with it.
What I cannot be on board with, is the falsehood of claiming that her entire experience growing up was [a]. Because it wasn’t.
If someone transitions from male to female, then their experience is female once they transition, or at least start to transition. Before that, then the world reacts to them as if they were male (whether they want it to or not). It’s truthful to say there are problems in this, and these aren’t problems they can avoid. It isn’t truthful to say that these are exactly the same problems faced by someone who is born female and who has the world react to them as if they were female from day dot.
Each individual has the set of problems they don’t have a choice about facing. Pretending that someone has always faced someone else’s problems, though, when they haven’t, is what makes up appropriation.
I’m not positive I’m expressing this perfectly, but do you follow?
Lying about her family, however, is deeply problematic.
Lynne: FWIW, somewhere in my ancestry I have Native American. I have no idea what tribe; he was a rapist and didn’t stick around to introduce himself properly. But I would never in a million years think of id’ing myself as “Native American”, because ancestry or not, my actual skin tone is Celtic phosphorescent fishbelly white, and I grew up in a white-bread, middle-class, suburban white family, and like it or lump it, that’s what shaped the reactions of the people around me for my childhood.
I don’t get to say I have the same experience as someone growing up on a Rez.
Jim: I think you are obfuscating, John. As a scientist you know that there are absolutes, uncertainties, and certainly things that are simply not true. Things that can be measured are easily characterized as true, untrue or uncertain. Things that are subjective are more difficult. You and I believe that Ellie is a beautiful child, but a Martian, or even a Nigerian, might not. What one believes and “feels” is subjective.
One’s genes, those things that determine race, are not subjective; they can be analyzed. And so they fall into the category of absolutes. From what I have read, the genes of this women are indisputable those of the white race. (I recognize that due to millions of years of evolution even “white” is not absolute, but I suspect that as far as race is concerned, she is white, not black.)
If one identifies with that which he believes blacks believe in, this does not make him black. She should have said something like “I feel as if I were black”, or “I identify with black ideas”, etc. Saying that she is a black person is untrue, and detracts from important contributions she has, or would have made.
John: I don’t know how it detracts if there has been no malice or profit-making. I just wonder if she has a black person in her ancestry. How many of us do? After all we have some Neanderthal DNA in us even though so much time has passed since Neanderthals disappeared.
Peter: I’m afraid to say Rachel Dolezal has much bigger issues then we know. There are many more statements that she has made that can be understood as very strange. Example, that she was raised in a Tee Pee. I think she may be a very nice person but the truth to me always over rides everything else. It’s the only starting point we can trust. I think Brian Williams is probably a very nice person but because of his exaggeration on his news reporting I would rather hear from others in the state of the union. Sorry Brian and Rachael. The truth can be very painful at times but for me it is one of the most beautiful parts of life, and may be misunderstood.
Jane: So what was Michael Jackson all about? He clearly identified as being white and a female. He went out of his way to have “white” children.
John: We have close to 40 comments here from intelligent people who in some ways represent a jury, Wolf. This thread is similar to the types of exchanges we had at my website, the Cafe, between 2005 and 2012 when people started to migrate to FB. The different opinions like yours help to crystallize my understanding of this issue. I remain amazed though by the emotion and in some cases the vitriol that people have for and against Rachel. I am epithetic toward her. The fact is, we humans are all related and the world might be a better place if more of us considered that. I had that discussion with a Nigerian woman in my early years of blogging around 2004.