Arvid Carlsson MD (1923 to Present) and Still Going Strong at 94!

Editor’s note: Short background

 

Kathleen Montagu (died 28 March 1966) was the first researcher to identify dopamine in human brains. Working in Hans Weil-Malherbe’s laboratory at the Runwell Hospital outside London, the presence of dopamine was identified by paper chromatography in the brain of several species, including a human brain. Her research was published in August 1957, followed and confirmed by Hans Weil-Malherbe in November 1957.

 

Nobel Prize-rewarded Arvid Carlsson to be the first researcher to identify that dopamine is a neurotransmitter. His research was published in November 1957, along with colleagues Margit Linsqvist and Tor Magnusson.

 

Arvid Carlsson (born 25 January 1923) is a Swedish neuropharmacologist who is best known for his work with the neurotransmitter dopamine and its effects in Parkinson’s disease. For his work on dopamine, Carlsson was awarded the Nobel Prize in Physiology or Medicine in 2000, along with American co-recipients Eric Kandel at Columbia University and Paul Greengard at Rockefeller. Carlsson was born in Uppsala, Sweden, son of Gottfrid Carlsson, historian and later professor of history at the Lund University, where he began his medical education in 1941. In 1944 he was participating in the task of examining prisoners of Nazi concentration camps, whom Folke Bernadotte, a member of the royal Swedish family, had managed to bring to Sweden. Although Sweden was neutral during World War II, Carlsson’s education was interrupted by several years of service in the Swedish Armed Forces. In 1951, he received his M.L. degree and his M.D. He then became a professor at the University of Lund. In 1959 he became a professor at the University of Gothenburg.

 

In 1957 Kathleen Montagu succeeded in demonstrating the presence of dopamine in the human brain; later that same year Carlsson also demonstrated that dopamine was a neurotransmitter in the brain and not just a precursor for norepinephrine. Carlsson went on to developed a method for measuring the amount of dopamine in brain tissues. He found that dopamine levels in the basal ganglia, a brain area important for movement, were particularly high. He then showed that giving animals the drug reserpine caused a decrease in dopamine levels and a loss of movement control. These effects were similar to the symptoms of Parkinson’s disease. By administering to these animals L-Dopa, which is the precursor of dopamine, he could alleviate the symptoms. These findings led other doctors to try using L-Dopa on patients with Parkinson’s disease, and found it to alleviate some of the symptoms in the early stages of the disease. L-Dopa is still the basis for most commonly used means of treating Parkinson’s disease.

 

While working at Astra AB, Carlsson and his colleagues were able to derive the first marketed selective serotonin reuptake inhibitor, zimelidine, from brompheniramine. Zimelidine preceded both Fluoxetine (Prozac) and Fluvoxamine as the first SSRI, but was later withdrawn from the market due to rare cases of Guillain-Barre syndrome.

 

Still an active researcher and speaker at over 90 years of age, Carlsson, together with his daughter Maria, is working on OSU6162, a dopamine stabilizer alleviating symptoms of post-stroke fatigue.

 

Stephen L. Hauser MD (1949 to Present)

Photo credit: UCSF Medical Center, https://commons.wikimedia.org/w/index.php?curid=15734615

 

Stephen L. Hauser is the Robert A. Fishman Distinguished Professor and Chair of the Department of Neurology at the University of California, San Francisco (UCSF), where his work has focused on immune mechanisms and multiple sclerosis (MS). Hauser is a principal investigator of a large multinational effort to identify genetic effects on MS, and part of the team that identified that humoral immune mechanisms are important in the pathogenesis of MS lesions, leading to the development of B-cell based therapies for MS. He has contributed to the establishment of nationwide and international genetics consortia that have identified more than 50 gene variants that contribute to MS risk.

 

Using comparative genomics between African-American and Caucasian MS populations, Hauser’s group was able to identify HLA-DRB1 as the primary MS signal in the MHC, and also fine map other secondary loci in this region.

 

In 2007, as a senior organizer of the International Multiple Sclerosis Genetics Consortium (IMSGC), Dr. Hauser helped identify the first two non-HLA genes involved in MS susceptibility, IL-2R (CD25) and IL-7R (CD127). In 2010, his laboratory published the complete genome sequences and the epigenome of identical twins discordant for MS. By mid-2011 more than fifty MS associated risk alleles were identified, and by now nearly the entire array of common variants associated with MS susceptibility have now been mapped. Hauser also has focused on the role of the B cell and immunoglobulin in the pathogenesis of the disease. He developed and characterized an MS disease model that replicated the core feature of vesicular demyelination previously observed in MS, and demonstrated that this pathology resulted from the synergistic effects of autoreactive T-cells and pathogenic autoantibodies.

 

In 1999, Hauser published work identifying specific myelin reactivity of these autoantibodies deposited in areas of myelin damage in MS brains. Hauser translated this finding into a new potential therapy for MS. He led a large-scale clinical trial with rituximab, a chimeric monoclonal antibody that depletes CD20+ B cells, and demonstrated robust efficacy in relapsing remitting MS. A second trial in primary progressive MS reported in 2009 that rituximab may similarly be effective in patients with primary progressive MS who also have evidence of ongoing inflammatory CNS disease. More recently, a third clinical trial with a fully humanized anti-CD20 monoclonal antibody, ocrelizumab, replicated the results of the rituximab trial in relapsing remitting MS. With the MS Bioscreen project, Hauser has pioneered precision medicine for complex diseases like MS, creating an “actionable digital growth-chart for complex traits”

 

Hauser is a graduate of MIT (Phi Beta Kappa) and Harvard Medical School (Magna Cum Laude). In 2010 Hauser was appointed to the Presidential Commission for the Study of Bioethical Issues. He is a co-editor of the textbook Harrison’s Principles of Internal Medicine and past editor-in-chief of the Annals of Neurology. Hauser trained in internal medicine at the New York Hospital-Cornell Medical Center, in neurology at the Massachusetts General Hospital (MGH), and in immunology at Harvard Medical School and the Institute Pasteur in Paris, France, and was a faculty member at Harvard Medical School before moving to UCSF. Hauser received the 2013 Charcot Award from the Multiple Sclerosis International Federation, the Jacob Javits Neuroscience Investigator Award, and the John Dystel Prize for Multiple Sclerosis Research. In 2011 he delivered the Robert Wartenberg Lecture at the American Academy of Neurology, an honor given for excellence in clinically relevant research. Hauser is also the chair of the Committee on Gulf War and Health Outcomes for the Institute of Medicine and a Fellow of the American Academy of Arts and Sciences and the Association of American Physicians.
In addition to the research of Dr. Hauser, there is a long history of studying MS called by some: the Viking Gene.

 

Detail of Robert Carswell’s drawing of MS lesions in the brain stem and spinal cord (1838). Credit: Wikipedia

 

Robert Carswell (1793-1857), a British professor of pathology, and Jean Cruveilhier (1791-1873), a French professor of pathologic anatomy, described and illustrated many of the disease’s clinical details, but did not identify it as a separate disease. Specifically, Carswell described the injuries he found as “a remarkable lesion of the spinal cord accompanied with atrophy”. Under the microscope, Swiss pathologist Georg Eduard Rindfleisch (1836-1908) noted in 1863 that the inflammation-associated lesions were distributed around blood vessels. The French neurologist Jean-Martin Charcot (1825-1893) was the first person to recognize multiple sclerosis as a distinct disease in 1868. Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The first attempt to establish a set of diagnostic criteria was also due to Charcot in 1868. He published what now is known as the “Charcot Triad”, consisting in nystagmus, intention tremor, and telegraphic speech (scanning speech) Charcot also observed cognition changes, describing his patients as having a “marked enfeeblement of the memory” and “conceptions that formed slowly”. Diagnosis was based on Charcot triad and clinical observation until Schumacher made the first attempt to standardize criteria in 1965 by introducing some fundamental requirements: Dissemination of the lesions in time (DIT) and space (DIS), and that “signs and symptoms cannot be explained better by another disease process”. Both requirements were later inherited by Poser criteria and McDonald criteria, whose 2010 version is currently in use. During the 20th century, theories about the cause and pathogenesis were developed and effective treatments began to appear in the 1990s.
Historical cases

Photographic study of locomotion of an MS female patient with walking difficulties created in 1887 by Muybridge. Photo credit: Wikipedia
There are several historical accounts of people who probably had MS and lived before or shortly after the disease was described by Charcot. A young woman called Halldora who lived in Iceland around 1200 suddenly lost her vision and mobility but, after praying to the saints, recovered them seven days after. Saint Lidwina of Schiedam (1380-1433), a Dutch nun, may be one of the first clearly identifiable people with MS. From the age of 16 until her death at 53, she had intermittent pain, weakness of the legs, and vision loss – symptoms typical of MS. Both cases have led to the proposal of a “Viking gene” hypothesis for the dissemination of the disease. Augustus Frederick d’Este (1794-1848), son of Prince Augustus Frederick, Duke of Sussex and Lady Augusta Murray and the grandson of George III of the United Kingdom, almost certainly had MS. D’Este left a detailed diary describing his 22 years living with the disease. His diary began in 1822 and ended in 1846, although it remained unknown until 1948. His symptoms began at age 28 with a sudden transient visual loss (amaurosis fugax) after the funeral of a friend. During his disease, he developed weakness of the legs, clumsiness of the hands, numbness, dizziness, bladder disturbances, and erectile dysfunction. In 1844, he began to use a wheelchair. Despite his illness, he kept an optimistic view of life. Another early account of MS was kept by the British diarist W. N. P. Barbellion, nom-de-plume of Bruce Frederick Cummings (1889-1919), who maintained a detailed log of his diagnosis and struggle. His diary was published in 1919 as The Journal of a Disappointed Man.

Gerontology

The hand of an older man. Source: Wikipedia Commons

 

Gerontology, from the Greek, geron, “old man” and -logia, “study of”; coined by Ilya Ilyich Mechnikov (in 1903) is the study of the social, cultural, psychological, cognitive, and biological aspects of aging. It is distinguished from geriatrics, which is the branch of medicine that specializes in the treatment of existing disease in older adults. Gerontologists include researchers and practitioners in the fields of biology, nursing, medicine, criminology, dentistry, social work, physical and occupational therapy, psychology, psychiatry, sociology, economics, political science, architecture, geography, pharmacy, public health, housing, and anthropology.

 

Gerontology encompasses the following:

 

  1. studying physical, mental, and social changes in people as they age
  2. investigating the biological aging process itself including aging’s causes, effects and mechanisms (biogerontology)
  3. investigating the social and psycho-social impacts of aging (sociogerontology)
  4. investigating the psychological effects on aging (psychogerontology)
  5. investigating the interface of biological aging with aging-related diseases (geroscience)
  6. investigating the effects of an ageing population on society (demography)
  7. exploring the relationship between the aging and their environment (environmental gerontology)
  8. applying this knowledge to policies and programs, including the macroscopic (for example, government planning) and microscopic (for example, running a nursing home) perspectives.

 

The multidisciplinary nature of gerontology means that there are a number of sub-fields, as well as associated fields such as physiology, anthropology, social work, public health, psychology and sociology that overlap with gerontology. One of the world’s oldest drugs which was first mentioned by Hippocrates in the 5th Century BCE could help restore memory in Alzheimer’s patients, scientists hope. Salsalate, which comes from the same family as aspirin, was typically used to treat inflammatory conditions like rheumatoid arthritis. But a new study suggests that it can prevent the build-up of toxic proteins in the brain and even reverse damage already done, unblocking pathways and restoring memory.

 

In the medieval world, several physicians wrote on issues related to Gerontology. Avicenna’s The Canon of Medicine (1025) offered instruction for the care of the aged, including diet and remedies for problems including constipation. He also wrote on the aches and conditions of the elderly. His scholarly work covers sleep disorders, forgetfulness, how to strengthen memory, and causes of mortality. Ishaq ibn Hunayn (died 910) wrote works on the treatments for forgetfulness (U.S. National Library of Medicine, 1994).

 

While the number of aged humans, and life expectancy, tended to increase in every century since the 14th, society tended to consider caring for an elderly relative as a family issue. It was not until the coming of the Industrial Revolution that ideas shifted in favor of a societal care-system. Some early pioneers, such as Michel Eugene Chevreul, who himself lived to be 102, believed that aging itself should be a science to be studied. Elie Metchnikoff coined the term “gerontology” c. 1903. However, it was not until the 1940s that pioneers like James Birren began organizing gerontology into its own field. Recognizing that there were experts in many fields all dealing with the older population, it became apparent that a group like the Gerontological Society of America (founded in 1945) was needed. Two decades later, James Birren was appointed as the founding director of the first academic research center devoted exclusively to the study of aging, the Ethel Percy Andrus Gerontology Center. The Baltimore Longitudinal Studies of Aging began in 1958 in order to study physiological changes in healthy middle-aged and older men living in the community by testing them every two years on numerous physiological parameters. In 1967, the University of South Florida and the University of North Texas (formerly North Texas State University) received Older Americans Act training grants from the U.S. Administration on Aging to launch the nation’s first degree programs in gerontology, at the master’s level. In 1975, the University of Southern California’s Leonard Davis School of Gerontology, became the country’s first school of gerontology within a university and, later, offered the first PhD in Gerontology degree. Gerontological Education has flourished in the United States since 1967 and degrees at all academic levels are now offered by a number of colleges and universities. One of the pioneering gerontologists, Robert Neil Butler, pushed for care and respect of the elderly. Several university-based centers on aging have been founded such as the Duke University Center on Aging, the University of Georgia Institute of Gerontology, the Center of Aging at the University of Chicago, and the Stanford Center on Longevity. Currently, PhD programs in gerontology are available at Miami University, the University of Kansas, University of Kentucky, University of Maryland Baltimore, University of Massachusetts Boston,[19] and the University of Southern California.

 

The world is forecast to undergo rapid population aging in the next several decades. In 1900, there were 3.1 million people aged 65 years and older living in the United States. However, this population continued to grow throughout the 20th century and reached 31.2, 35, and 40.3 million people in 1990, 2000, and 2010, respectively. Notably, in the United States and across the world, the “baby boomer” generation began to turn 65 in 2011. Recently, the population aged 65 years and older has grown at a faster rate than the total population in the United States. The total population increased by 9.7%, from 281.4 million to 308.7 million, between 2000 and 2010. However, the population aged 65 years and older increased by 15.1% during the same period. It has been estimated that 25% of the population in the United States and Canada will be aged 65 years and older by 2025. Moreover, by 2050, it is predicted that, for the first time in United States history, the number of individuals aged 60 years and older will be greater than the number of children aged 0 to 14 years. Those aged 85 years and older (oldest-old) are projected to increase from 5.3 million to 21 million by 2050. Adults aged 85–89 years constituted the greatest segment of the oldest-old in 1990, 2000, and 2010. However, the largest percentage point increase among the oldest-old occurred in the 90- to 94-year-old age group, which increased from 25.0% in 1990 to 26.4% in 2010. With the rapid growth of the aging population, social work education and training specialized in older adults and practitioners interested in working with older adults are increasingly in demand.

 

Genetic theories of aging propose that aging is programmed within each individual’s genes. According to this theory, genes dictate cellular longevity. Programmed cell death, or apoptosis, is determined by a “biological clock” via genetic information in the nucleus of the cell. Genes responsible for apoptosis provide an explanation for cell death, but are less applicable to death of an entire organism. An increase in cellular apoptosis may correlate to aging, but is not a ‘cause of death’. Environmental factors and genetic mutations can influence gene expression and accelerate aging. More recently epigenetics have been explored as a contributing factor. The epigenetic clock, which objectively measures the biological age of cells and tissues, may become useful for testing different biological aging theories. General imbalance theories of aging suggest that body systems, such as the endocrine, nervous, and immune systems, gradually decline and ultimately fail to function. The rate of failure varies system by system. Accumulation theories of aging suggest that aging is bodily decline that results from an accumulation of elements. Elements can be foreign and introduced to the body from the environment. Other elements can be the natural result of cell metabolism. An example of an accumulation theory is the Free Radical Theory of Aging. According to this theory, byproducts of regular cell metabolism called free radicals interact with cellular components such as the cell membrane and DNA and cause irreversible damage.

The idea that free radicals are toxic agents was first proposed by Rebeca Gerschman and colleagues. In 1956, Denham Harman proposed the free-radical theory of aging and even demonstrated that free radical reactions contribute to the degradation of biological systems. Oxidative damage of many types accumulate with age, such as oxidative stress that oxygen-free radicals, because the free radical theory of aging argues that aging results from the damage generated by reactive oxygen species (ROS). ROS are small, highly reactive, oxygen-containing molecules that can damage a complex of cellular components such as fat, proteins, or from DNA, they are naturally generated in small amounts during the body’s metabolic reactions. These conditions become more common as we age, including diseases related to aging, such as dementia, cancer and heart disease.

DNA damage has been one of the many causes in diseases related to aging. The stability of the genome is defined by the cells machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. One hypothesis proposed by Gioacchino Failla in 1958 is that damage accumulation to the DNA causes aging. The hypothesis was developed soon by physicist Leo Szilard. This theory has changed over the years as new research has discovered new types of DNA damage and mutations, and several theories of aging argue that DNA damage with or without mutations causes aging.

 

To demonstrate how far the interest in longevity goes, Google has a separate division called Calico to study this aspect of aging.


What is Alphabet? Alphabet is mostly a collection of companies. The largest of which, of course, is Google. This newer Google is a bit slimmed down, with the companies that are pretty far afield of our main internet products contained in Alphabet instead. What do we mean by far afield? Good examples are our health efforts: Life Sciences (that works on the glucose-sensing contact lens), and Calico focused on longevity. Fundamentally, we believe this allows us more management scale, as we can run things independently that aren’t very related. What could be better? No wonder we are excited to get to work with everyone in the Alphabet family. Don’t worry, we’re still getting used to the name too!

 

Kfar Shaul Mental Health Center in Jerusalem

Psychiatric hospital Kfar Shaul In Jerusalem – Source: Wikipedia, Public Domain, Creative Commons

 

Kfar Shaul Mental Health Center, established in 1951, is an Israeli public psychiatric hospital located between Givat Shaul and Har Nof, Jerusalem. It is affiliated with the Hadassah Medical Center and the Hebrew University of Jerusalem. The hospital is Jerusalem’s designated psychiatric hospital for tourists who display mental health disturbances, and is widely known for its research on Jerusalem Syndrome.

 

The Givat Shaul mental health center opened in 1951, utilizing the houses and school building of Deir Yassin, which had been left untouched. It was originally a therapeutic community of 300 patients who spent most of the day working outdoors. It was called the Kfar Shaul Government Work Village for Mental Patients. In its early years, the majority of the patients were Holocaust survivors.

 

The hospital is equipped with Snoezelen rooms, a Dutch therapy technique which uses controlled stimulation of the five senses to benefit the mentally and physically disabled. The hospital is known in particular for its association with Jerusalem Syndrome, a condition in which the sufferer is gripped by religious delusions. The hospital sees some 50 patients a year who are diagnosed with the condition Israel psychologist Gregory Katz has said many of the patients are Pentecostals from rural parts of the United States and Scandinavia. The syndrome was first diagnosed in 1993 by Yair Bar-El, a former director of the hospital. In 2000, archaeologists unearthed the remains of a winepress dated to the Byzantine or Roman era on the grounds of the hospital.

 

The Shaare Zedek Medical Center, which means: “Gates of Justice,” is a major hospital in JerusalemIsrael established in 1902. Source: Wikipedia, Public Domain, Creative Commons

 

Original, 1902 Shaare Zedek hospital building on Jaffa Road, now headquarters of the Israel Broadcasting Authority. Source: Wikipedia, Creative Commons

 

 

Shaare Zedek was the first large hospital to be located in the Western portion of Jerusalem and is today the city’s fastest growing hospital and the only major medical facility in the city’s center. After the Ottoman Turks gave permission in the 1890s, and with funding from European donors, the hospital was built on Jaffa Road, two miles (3 km) outside the Old City. Its opening ceremony took place on January 27, 1902. Dr. Moshe Wallach was the director from then until 1947. Schwester Selma lived in the hospital and cared for abandoned children. The building in Bayit Vegan was inaugurated in 1980. In December 2012, Shaare Zedek assumed operational control over Bikur Cholim Hospital and merged many of its activities. The hospital treats over 600,000 patients per year in more than 30 inpatient departments and over 70 outpatient units and maintains a very active academic service as a leading research and teaching institution. Shaare Zedek is classified as a public/private hospital, serving as a non-profit institution and dependent on donor support for capital development, while committed to offering advanced medical care for the wider Jerusalem-area community.

Stephan Wolfram (1959 to Present)

Stephen Wolfram at home. Source: Wikipedia

 

Target Health Inc. is an eCRO, that creates software for clinical trials and is interested in how Big Data is sorted through, especially for application to medical research, and clinical trials.

 

Wolfram Alpha (also: WolframAlpha and Wolfram|Alpha) is a computational knowledge engine or answer engine developed by Wolfram Research, which was founded by Stephen Wolfram. Stephen Wolfram is a brilliant computer scientist/physicist who thinks about the world and its issues, in a very Big way. Wolfram Research is an online service that answers factual queries directly by computing the answer from externally sourced “curated data“, rather than providing a list of documents or web pages that might contain the answer as a search engine might. Wolfram Alpha, which was released on May 18, 2009, is based on Wolfram’s earlier flagship product Wolfram Mathematica, a computational platform or toolkit that encompasses computer algebra, symbolic and numerical computation, visualization, and statistics capabilities. Additional data is gathered from both academic and commercial websites such as the CIA’s The World Factbook, the United States Geological Survey, a Cornell University Library publication called All About Birds, Chambers Biographical Dictionary, Dow Jones, the Catalogue of Life, CrunchBase, Best Buy,the FAA and optionally a user’s Facebook account.

 

Stephen Wolfram (born 29 August 1959) is a British-American computer scientist, physicist, and businessman. He is known for his work in computer science, mathematics, and in theoretical physics. He is the author of the book A New Kind of Science. In 2012 he was named an inaugural fellow of the American Mathematical Society. His recent work has been on knowledge-based programming, expanding and refining the programming language of Mathematica into what is now called the Wolfram Language. His book An Elementary Introduction to the Wolfram Language appeared in 2015 and Idea Makers appeared in 2016.

 

Stephen Wolfram was born in London in 1959 to Hugo and Sybil Wolfram. Wolfram’s father, Hugo Wolfram (1925-2015), a textile manufacturer born in Bochum, Germany, served as managing director of the Lurex Company, makers of the fabric Lurex, and was the author of three novels. He emigrated to England in 1933. When World War II broke out, young Hugo left school at 15 and subsequently found it hard to get a job since he was regarded as an “enemy alien.“ As an adult, he took correspondence courses in philosophy and psychology. Wolfram’s mother, Sybil Wolfram (1931-1993) was a Fellow and Tutor in philosophy at Lady Margaret Hall at University of Oxford from 1964 to 1993. She published two books, Philosophical Logic: An Introduction (1989) and In-laws and Outlaws: Kinship and Marriage in England (1987). She was the daughter of criminologist and psychoanalyst Kate Friedlander (1902-1949), an expert on the subject of juvenile delinquency, and the physician Walter Misch (1889-1943) who, together, wrote Die vegetative Genese der neurotischen Angst und ihre medikament?se Beseitigung. After the Reichstag fire in 1933, she emigrated from Berlin, Germany to England with her parents and Jewish psychoanalyst, Paula Heimann (1899-1982).

 

As a young child, Wolfram initially struggled in school and had difficulties learning arithmetic. At the age of 12, he wrote a dictionary on physics. By 13 or 14, he had written three books on particle physics. They were not published. Wolfram was a wunderkind. By age 15, he began research in applied quantum field theory and particle physics and published scientific papers. Topics included matter creation and annihilation, the fundamental interactions, elementary particles and their currents, hadronic and leptonic physics, and the parton model, published in professional peer-reviewed scientific journals including Nuclear Physics B, Australian Journal of Physics, Nuovo Cimento, and Physical Review D. Working independently, Wolfram published a widely cited paper on heavy quark production at age 18 and nine other papers. He continued to do research and to publish on particle physics into his early twenties. Wolfram’s work with Geoffrey C. Fox on the theory of the strong interaction is still used in experimental particle physics.

 

He was educated at Eton College, but left prematurely in 1976. He entered St. John’s College, Oxford at age 17 but found lectures “awful“, and left in 1978 without graduating to attend the California Institute of Technology, the following year, where he received a PhD in particle physics on November 19, 1979 at age 20. Wolfram’s thesis committee was composed of Richard Feynman, Peter Goldreich, Frank J. Sciulli and Steven Frautschi, and chaired by Richard D. Field. A 1981 letter from Feynman to Gerald Freund giving reference for Wolfram for the MacArthur grant appears in Feynman’s collective letters, Perfectly Reasonable Deviations from the Beaten Track. Following his PhD, Wolfram joined the faculty at Caltech and became the youngest recipient of the MacArthur Fellowships in 1981, at age 21. In 1983, Wolfram left for the School of Natural Sciences of the Institute for Advanced Study in Princeton, where he conducted research into cellular automata, mainly with computer simulations. He produced a series of papers systematically investigating the class of elementary cellular automata, conceiving the Wolfram code, a naming system for one-dimensional cellular automata, and a classification scheme for the complexity of their behavior. He conjectured that the Rule 110 cellular automaton might be Turing complete.

 

A 1985 letter, from Feynman to Wolfram, also appears in Feynman’s letters. In it, in response to Wolfram writing to him that he was thinking about creating some kind of institute where he might study complex systems, Feynman tells Wolfram, “You do not understand ordinary people,“ and advises him “find a way to do your research with as little contact with non-technical people as possible.“ In the mid-1980s, Wolfram worked on simulations of physical processes (such as turbulent fluid flow) with cellular automata on the Connection Machine alongside Richard Feynman and helped initiate the field of complex systems, founding the first institute devoted to this subject, The Center for Complex Systems Research (CCSR) at the University of Illinois at Urbana-Champaign and the journal Complex Systems in 1987. Wolfram led the development of the computer algebra system SMP (Symbolic Manipulation Program) in the Caltech physics department during 1979-1981. A dispute with the administration over the intellectual property rights regarding SMP – patents, copyright, and faculty involvement in commercial ventures – eventually caused him to resign from Caltech. SMP was further developed and marketed commercially by Inference Corp. of Los Angeles during 1983-1988. In 1986 Wolfram left the Institute for Advanced Study for the University of Illinois at Urbana-Champaign where he founded their Center for Complex Systems Research and started to develop the computer algebra system Mathematica, which was first released in 1988, when he left academia. From 1992 to 2002, Wolfram worked on his controversial book A New Kind of Science,which presents an empirical study of very simple computational systems. Additionally, it argues that for fundamental reasons these types of systems, rather than traditional mathematics, are needed to model and understand complexity in nature. Wolfram’s conclusion is that the universe is digital in its nature, and runs on fundamental laws which can be described as simple programs. He predicts that a realization of this within the scientific communities will have a major and revolutionary influence on physics, chemistry and biology and the majority of the scientific areas in general, which is the reason for the book’s title. Since the release of the book in 2002, Wolfram has split his time between developing Mathematica and encouraging people to get involved with the subject matter of A New Kind of Science by giving talks, holding conferences, and starting a summer school devoted to the topic.

 

In March 2009, Wolfram announced Wolfram|Alpha, an answer engine. Wolfram|Alpha later launched in May 2009, and a paid-for version with extra features launched on February 2012. The engine is based on natural language processing and a large library of algorithms, and answers queries using the approach described in A New Kind of Science. The application programming interface allows other applications to extend and enhance Alpha. Wolfram believes that as Wolfram Alpha comes into common use, “It will raise the level of scientific things that the average person can do.“ Wolfram|Alpha is one of the answer engines behind Microsoft’s Bing and Apple’s Siri answering factual questions. In June 2014, Wolfram officially announced the Wolfram Language as a new general multi-paradigm programming language. The documentation for the language was pre-released in October 2013 to coincide with the bundling of Mathematica and the Wolfram Language on every Raspberry Pi computer. While the Wolfram Language has existed for over 25 years as the primary programming language used in Mathematica, it was not officially named until 2014. Wolfram’s son, Christopher Wolfram, appeared on the program of SXSW giving a live-coding demonstration using Wolfram Language and has blogged about Wolfram Language for Wolfram Research. On 8 December 2015, Wolfram published the book “An Elementary Introduction to the Wolfram Language“ to introduce people with no knowledge of programming to the Wolfram Language and the kind of computational thinking it allows. Both Stephen Wolfram and Christopher Wolfram were involved in helping create the alien language for the film Arrival, for which they used the Wolfram Language. The significance that data has on the products Stephen creates transfers into his own life. He has an extensive log of personal analytics, including emails received and sent, key strokes made, meetings and events attended, phone calls, even physical movement dating back to the 1980s. He has stated “[personal analytics] can give us a whole new dimension to experiencing our lives“.

Sources: Wikipedia; Edge.org

 

Click here to read a short piece by Stephan Wolfram, written beautifully with great clarity, about his vision of artificial intelligence and how humans should deal with it, through a shared language, through personal analytics and more. To know more about shared language, all humans should read, the recently published: An Elementary Introduction to the Wolfram Language. If you saw the Academy Award nominee, Arrival, you would have heard a version of this shared language, which a human linguist, is finally able to understand.

 

Beauty is truth, truth beauty, – that is all

Ye know on earth, and all ye need to know.’

John Keats

 

TED talk by Stephan Wolfram Computing a Theory of Everything

 

History of Cupping as a Medical Device

Cupping set, London, England, 1860-1875 Cupping was a method of bloodletting, a practice once carried out to treat a wide range of diseases and medical conditions. Warm glass cups were placed on the skin to draw blood believed to be harmful to health to the surface of the skin. In wet cupping, the blood was released from the body using a lancet or scarificator (a set of spring-operated lancets). The set was made by S Maw & Son, a surgical instrument maker based in London. Medical Photographic Library.

 

Woman receiving fire cupping at a roadside business in Haikou, Hainan, China. Source: Wikipedia Commons

 

 

According to traditional Chinese medicine (TCM), cupping is a method of creating a vacuum on the patient’s skin to dispel stagnation (stagnant blood and lymph), thereby improving qi flow, in order to treat respiratory diseases such as the common cold, pneumonia and bronchitis. Cupping also is used on back, neck, shoulder and other musculoskeletal conditions. Its advocates claim it has other applications as well. Cupping is not advised, in TCM, over skin ulcers or to the abdominal or sacral regions of pregnant women. For over 3,000 years, the practice has been typically performed unsupervised, by individuals without any medical background. Iranian traditional medicine uses wet-cupping practices, with the belief that cupping with scarification may eliminate scar tissue, and cupping without scarification would cleanse the body through the organs. Individuals with a profound interest in the practice are typically very religious and seek “purification.“

 

There is reason to believe the practice dates from as early as 3000 BCE. The Ebers Papyrus, written c. 1550 BCE and one of the oldest medical textbooks in the Western world, describes the Egyptians’ use of cupping, while mentioning similar practices employed by Saharan peoples. In ancient Greece, Hippocrates (c. 400 BCE) used cupping for internal disease and structural problems. The method was highly recommended by Muhammad. and hence well-practiced by Muslim scientists who elaborated and developed the method further. This method in its multiple forms, spread into medicine throughout Asian and European civilizations. In China, the earliest use of cupping that is recorded is from the famous Taoist alchemist and herbalist, Ge Hong (281-341 CE.). Cupping was also mentioned in Maimonides’ book on health and was used within the Eastern European Jewish community. There is a description of cupping in George Orwell’s essay “How the Poor Die“, where he was surprised to find it practiced in a Paris hospital.

 

Cupping has gained publicity in modern times due to its use by American sport celebrities including National Football League player DeMarcus Ware and Olympians Alexander Naddour, Natalie Coughlin, and Michael Phelps. Brad McKay,MD, wrote that Team USA was doing a great disservice to their fans who might “follow their lead“, calling cupping an “ancient (but useless) traditional therapy. Practicing surgeon David Gorski claims, it’s all risk for no benefit. It has no place in modern medicine. Critics of alternative medicine such as Harriet Hall, Mark Crislip, Simon Singh and Edzard Ernst have characterized cupping as pseudoscience nonsense, a celebrity fad, and gibberish. They’ve stated that there is no evidence that cupping works any better than a placebo. Pharmacologist David Colquhoun writes that cupping is laughable and utterly implausible. Sources: Wikipedia; WebMD

 

A Glimpse into the Disease and Trauma of Andy Warhol’s Life

Andy Warhol (1928-1987) in 1975. Source: Mondadori Publishers, gettyimages.co.uk, Public Domain, Wikimedia Commons

 

Retired Seattle surgeon and medical historian, John A. Ryan Jr. with his wife, Jody

Source: http://www.virginiamasonfoundation.org/john-ryan

 

Though Andy Warhol’s death has been associated with routine gallbladder surgery over the past three decades, one medical expert is saying that the legendary pop artist’s death shouldn’t be considered such a shock. “This was major, major surgery – not routine – in a very sick person,“ medical historian and retired surgeon Dr. John Ryan told The New York Times in a recent phone interview. Ryan, is the meritus chief of surgery at Virginia Mason Hospital in Seattle, Washington, and has been spending the past four years since his retirement studying Warhol’s medical history. Warhol’s family had a history of gallbladder issues, and Warhol himself had been very ill for at least a month before his death. However, his fear of hospitals combined with his hefty workload made him put his health on the back-burner.

 

In terms of Warhol’s early health: in third grade, he had Sydenham’s chorea (also known as St. Vitus’ Dance), the nervous system disease that causes involuntary movements of the extremities, which is believed to be a complication of scarlet fever which causes skin pigmentation blotchiness. Often bedridden as a child, he became an outcast at school and bonded with his mother. At times when he was confined to bed, he drew, listened to the radio and collected pictures of movie stars around his bed. Warhol later described this period as very important in the development of his personality, skill-set and preferences. After graduating from high school, his intentions were to study art education at the University of Pittsburgh in the hope of becoming an art teacher, but his plans changed and he enrolled in the Carnegie Institute of Technology in Pittsburgh, where he studied commercial art.

 

Warhol went in for a seemingly simple gallbladder operation in 1987 but ended up dying just 12 hours later – shocking the nation. But now, Dr. Ryan says we should have seen the icon’s death coming. According to Dr. Ryan, who presented his findings, last week at the annual meeting of the Pacific Coast Surgical Association, Warhol’s death should not have come as such a surprise. Looking at the pop artist’s medical history, Dr Ryan discovered that Warhol had almost 15 years of gallbladder trouble and a family history of it as well. Warhol’s father had his gallbladder removed in 1928, the same year his son was born. Warhol had been sick for at least a month before his death, although he had attempted to hide it. His fear of hospitals was another factor in his lack of receiving any serious treatment. The revered artist had a fear of hospitals which had delayed his ability to receive serious treatment. Further medical records research showed Dr Ryan that Warhol was dehydrated and gaunt from having barely eaten in the previous month. Additionally, Warhol had been taking speed daily for years. And he was still feeling the effects of a brush with death in 1968 after he was shot by Valerie Solanas, a radical feminist writer. At that time, he had been declared dead in the emergency room and had nine damaged organs – Warhol’s surgeon gave even odds on the artist lasting the night. His recovery left him with a lifetime of trouble with eating and swallowing, as well as a split in his abdominal muscles that gave him a large hernia. After he survived the gunshot wounds, for the rest of his life, Warhol had to wear a special truss or corset to hold his innards together.

 

So in 1987, on top of the gallbladder removal, and repair to his stomach wall, according to reports, the operation seemed to go well, and Warhol was in his room making calls that evening. A private nurse who went to check on him at 4am said he still seemed fine. But about two hours later, Warhol was found blue and unresponsive, and resuscitation efforts failed. An autopsy concluded that �ventricular fibrillation’ was the cause of death, meaning that Warhol’s heart had quivered and stopped. Stewart Redmond Walsh, a professor of vascular surgery at the National University of Ireland, Galway, has researched sudden death after surgery, and says it’s more common than we think. He explained that when a sick body goes through the trauma of a major surgery, the entire body feels the stress, not just the organ being operated on, which can be fatal. When Dr Ryan entered the data from Warhol’s case into the new Surgical Risk Calculator of the American College of Surgeons, it put such a patient’s chance of dying at 4.2 percent.

 

Andy Warhol suffered from many health problems throughout his life

 

Gallbladder

Andy Warhol’s family suffered from a history of gallbladder illness. In 1928, his father Orenja, had his gallbladder removed. And less than 12 hours after a routine gallbladder removal, Warhol passed away from complications.

 

Chorea 

At the age of eight, Warhol came down with a rare disease known as chorea, or St. Vitus’ dance, characterized by involuntary movement, disturbed gait, grimacing, and hypotonia, or abnormally low muscle tone. Originally, Warhol was diagnosed with rheumatic fever. At the time, before antibiotics, approximately 10 percent of cases of rheumatic fever worsened and became chorea. Warhol stayed in bed for about ten weeks. When he finally returned to school, he had a relapse of the illness on the first day and returned to bed.

 

Skin

Blotchy skin is a common symptom of chorea. By the time Warhol became famous, in the early 1960s, the blotches had gone away, but they marked his face in adolescence and early adulthood, and he had bad skin his entire life. He wrote: �I had another skin problem, too – I lost all my pigment when I was eight years old. Another name people used to call me was “Spot“.

 

Drug Use

Warhol also had a huge drug problem. His New York City studio, the Factory was the hip hangout for amphetamine (speed) users. In particular, Warhol was addicted to Obetrol, marketed today as Adderall, a fairly common drug used to treat ADHD. He took a daily dose throughout his life.

 

Shooting

In June 1968, he was shot at close range by Valerie Solanas, a radical feminist writer. For the rest of his life he wore a corset that held his bowels together where his ruined abdominal muscles could no longer.

 

Hypochondria 

He also worried about �catching’ cancer, his fluctuating weight, colds that he was convinced presaged pneumonia, about brain tumors and strokes, blood pressure and blackouts. In the last years of his life, Warhol worried most about AIDS, and carefully avoided those (even close friends or ex-lovers) whom he knew to be suffering from the �magic disease’.

Sources: NY Times, Wikipedia, DailyMail.uk.com;

 

A Short History of MRIs

MRI Scanner Mark One. The first MRI scanner to be built and used, in Aberdeen Royal Infirmary in Scotland. Source: Andy Gaskell – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=54271471

 

U.S. President George W. Bush with the six 2003 American Nobel laureates in the Oval Office. From left to right, Dr. Roderick MacKinnon, New York City (chemistry); Dr. Anthony Leggett, Urbana, Illinois (physics); Dr. Robert Engle, New York City (economics); Dr. Alexei Abrikosov, Argonne, Illinois (physics); Dr. Peter Agre, Baltimore, Maryland (chemistry); and Dr. Paul Lauterbur, Urbana, Illinois (physiology/medicine). Source: This work is in the public domain in the United States because it is a work prepared by an officer or employee of the United States Government as part of that person’s official duties under the terms of Title 17, Chapter 1, Section 105 of the US Code; Wikipedia Commons

 

Magnetic resonance imaging was invented by Paul C. Lauterbur in September 1971; he published the theory behind it in March 1973. The factors leading to image contrast (differences in tissue relaxation time values) had been described nearly 20 years earlier by Erik Odeblad (physician and scientist) and Gunnar Lindstrom. In 1950, spin echoes were first detected by American, Erwin Hahn and in 1952, Herman Carr produced a one-dimensional NMR spectrum as reported in his Harvard PhD thesis. In the Soviet Union, Vladislav Ivanov filed (in 1960) a document with the USSR State Committee for Inventions and Discovery at Leningrad for a Magnetic Resonance Imaging device, although this was not approved until the 1970s. By 1959, Jay Singer had studied blood flow by NMR relaxation time measurements of blood in living humans. Such measurements were not introduced into common medical practice until the mid-1980s, although a patent for a whole-body NMR machine to measure blood flow in the human body was already filed by Alexander Ganssen in early 1967. In the 1960s and 1970s the results of a very large amount of work on relaxation, diffusion, and chemical exchange of water in cells and tissues of all sorts appeared in the scientific literature. In 1967, Ligon reported the measurement of NMR relaxation of water in the arms of living human subjects. In 1968, Jackson and Langham published the first NMR signals from a living animal.

 

Raymond Damadian’s “Apparatus and method for detecting cancer in tissue“ Source: This patent drawing by Raymond Damadian, belongs to a US govt Patent number 3789832 filed 17 March 1972, issued Feb 5, 1974. Image is from the US Patent and Trademark Office.

 

 

In a March 1971 paper in the journal Science, Raymond Damadian, an Armenian-American physician and professor at the Downstate Medical Center State University of New York (SUNY), reported that tumors and normal tissue can be distinguished in vivo by nuclear magnetic resonance (“NMR“). He suggested that these differences could be used to diagnose cancer, though later research would find that these differences, while real, are too variable for diagnostic purposes. Damadian’s initial methods were flawed for practical use, relying on a point-by-point scan of the entire body and using relaxation rates, which turned out not to be an effective indicator of cancerous tissue. While researching the analytical properties of magnetic resonance, Damadian created a hypothetical magnetic resonance cancer-detecting machine in 1972. He filed the first patent for such a machine, U.S. Patent 3,789,832 on March 17, 1972, which was later issued to him on February 5, 1974. Zenuemon Abe and his colleagues applied the patent for targeted NMR scanner, U.S. Patent 3,932,805 on 1973. They published this technique in 1974. Damadian claims to have invented the MRI. The US National Science Foundation notes “The patent included the idea of using NMR to ‘scan’ the human body to locate cancerous tissue.“ However, it did not describe a method for generating pictures from such a scan or precisely how such a scan might be done.

 

Meanwhile, Paul Lauterbur at Stony Brook University expanded on Carr’s technique and developed a way to generate the first MRI images, in 2D and 3D, using gradients. In 1973, Lauterbur published the first nuclear magnetic resonance image and the first cross-sectional image of a living mouse in January 1974. In the late 1970s, Peter Mansfield, a physicist and professor at the University of Nottingham, England, developed the echo-planar imaging (EPI) technique that would lead to scans taking seconds rather than hours and produce clearer images than Lauterbur had. Damadian, along with Larry Minkoff and Michael Goldsmith, obtained an image of a tumor in the thorax of a mouse in 1976. They also performed the first MRI body scan of a human being on July 3, 1977, studies they published in 1977. In 1979, Richard S. Likes filed a patent on k-space U.S. Patent 4,307,343. During the 1970s a team led by John Mallard built the first full-body MRI scanner at the University of Aberdeen. On August 28,1980 they used this machine to obtain the first clinically useful image of a patient’s internal tissues using MRI, which identified a primary tumor in the patient’s chest, an abnormal liver, and secondary cancer in his bones. This machine was later used at St Bartholomew’s Hospital, in London, from 1983 to 1993. Mallard and his team are credited for technological advances that led to the widespread introduction of MRI.

 

In 1975, the University of California, San Francisco Radiology Department founded the Radiologic Imaging Laboratory (RIL). With the support of Pfizer, Diasonics, and later Toshiba America MRI, the lab developed new imaging technology and installed systems in the US and worldwide. In 1981 RIL researchers, including Leon Kaufman and Lawrence Crooks, published Nuclear Magnetic Resonance Imaging in Medicine. In the 1980s the book was considered the definitive introductory textbook to the subject. In 1980 Paul Bottomley joined the GE Research Center in Schenectady, NY. His team ordered the highest field-strength magnet then available – a 1.5 T system – and built the first high-field device, overcoming problems of coil design, RF penetration and signal-to-noise ratio to build the first whole-body MRI/MRS scanner. The results translated into the highly successful 1.5 T MRI product-line, with over 20,000 systems in use today. In 1982, Bottomley performed the first localized MRS in the human heart and brain. After starting a collaboration on heart applications with Robert Weiss at Johns Hopkins, Bottomley returned to the university in 1994 as Russell Morgan Professor and director of the MR Research Division. Although MRI is most commonly performed at 1.5 T, higher fields such as 3 T are gaining more popularity because of their increased sensitivity and resolution. In research laboratories, human studies have been performed at up to 9.4 T and animal studies have been performed at up to 21.1 T.

 

Reflecting the fundamental importance and applicability of MRI in medicine, Paul Lauterbur of the University of Illinois at Urbana-Champaign and Sir Peter Mansfield of the University of Nottingham were awarded the 2003 Nobel Prize in Physiology or Medicine for their “discoveries concerning magnetic resonance imaging“. The Nobel citation acknowledged Lauterbur’s insight of using magnetic field gradients to determine spatial localization, a discovery that allowed rapid acquisition of 2D images. Mansfield was credited with introducing the mathematical formalism and developing techniques for efficient gradient utilization and fast imaging. The actual research that won the prize was done almost 30 years before while Paul Lauterbur was a professor in the Department of Chemistry at Stony Brook University in New York.

Rebecca Davis Lee Crumpler MD, First African American Female Physician

Rebecca Crumpler plaque. Source: Kate Kelly, americacomesalive.com

 

Cover of A Book of Medical Discourses by Rebecca Lee Crumpler

Source: nih.gov; Wikipedia; The National Library of Medicine believes this item to be in the public domain 

 

Rebecca Davis Lee Crumpler, nee Davis, (February 8, 1831 – March 9, 1895) was the first African-American woman to become a physician in the United States. She married Arthur Crumpler who had served with the Union Army during the American Civil War. Her publication of A Book of Medical Discourses in 1883 was one of the first written by an African American about medicine. Rebecca Davis was born in 1831 in Christiana, Delaware to Matilda Webber and Absolum Davis. She was raised in Pennsylvania by an aunt who cared for infirm neighbors. Crumpler later attended the elite West Newton English and Classical School in Massachusetts where she was a special student in mathematics. Crumpler moved to Charlestown, Massachusetts where she married Wyatt Lee, a Virginia native on April 19, 1852. During the next eight years, she was employed as a nurse until she was accepted into the New England Female Medical College in 1860. It was rare for women or black men to be admitted to medical schools during this time, and during the antebellum years, medical care for poor blacks was almost non-existent.

 

When the Civil War began, Crumpler was forced to quit her school. She went back to college in 1863, but her financial aid was no longer available. To complete her schooling, she won a tuition award from the Wade Scholarship Fund, which was established by the Ohio abolitionist, Benjamin Wade. When she graduated in 1864, Rebecca Lee was the first African-American woman in the United States to earn a Doctor of Medicine degree, and the only African-American woman to graduate from New England Female Medical College. The school closed in 1873, without graduating another black woman, when it merged with Boston University. Crumpler describes the progression of experiences that led her to study and practice medicine in her A Book of Medical Discourses (1883):

 

“It may be well to state here that, having been reared by a kind aunt in Pennsylvania, whose usefulness with the sick was continually sought, I early conceived a liking for, and sought every opportunity to relieve the sufferings of others. Later in life I devoted my time, when best I could, to nursing as a business, serving under different doctors for a period of eight years (from 1852 to 1860); most of the time at my adopted home in Charlestown, Middlesex County, Massachusetts. From these doctors I received letters commending me to the faculty of the New England Female Medical College, whence, four years afterward, I received the degree of Doctress of Medicine.“

 

Crumpler first practiced medicine in Boston, primarily for poor women and children. During this time she “sought training in the ‘British Dominion.’ In St. John, New Brunswick, on May 24, 1865, Rebecca married Arthur Crumpler, a former fugitive slave from Virginia who had served with the Union Army at Fort Monroe, Virginia. After the American Civil War ended in 1865, she moved to Richmond, Virginia, believing it to be

 

“a proper field for real missionary work, and one that would present ample opportunities to become acquainted with the diseases of women and children. During my stay there nearly every hour was improved in that sphere of labor. The last quarter of the year 1866, I was enabled to have access each day to a very large number of the indigent, and others of different classes, in a population of over 30,000 colored.“

 

Crumpler worked for the Freedmen’s Bureau to provide medical care to freed slaves; She was subject to “intense racism“: “men doctors snubbed her, druggist balked at filling her prescriptions, and some people wisecracked that the M.D. behind her name stood for nothing more than ‘Mule Driver.“  By the time she moved back to Boston her neighborhood in Joy Street, Beacon Hill was a predominantly African-American community. She

 

“entered into the work with renewed vigor, practicing outside, and receiving children in the house for treatment; regardless, in a measure, of remuneration.“

 

Rebecca and Arthur were active members of the Twelfth Baptist Church where Arthur was a trustee, and in mid-December, 1870, their daughter, Lizzie Sinclair Crumpler, was born at their 20 Garden Street home. When Massachusetts Senator Charles Sumner died in 1874, Rebecca was in Delaware. At a service in his honor,

 

“Rebecca Crumpler, MD read a beautiful original poem on the death of Sumner wherein she touchingly alluded to his love for the gifted Emerson.“

 

By 1880 Rebecca and Arthur had moved to Hyde Park, Boston. There was no great demand for her service in the community. She was no longer practicing medicine by 1883, when she published A Book of Medical Discourses from the notes she kept over the course of her medical career. It was dedicated to nurses and mothers, and focused on the medical care of women and children. Although “no photos or other images“ of Rebecca Crumpler survive a Boston Globe article described her this way.

 

“She is a very pleasant and intellectual woman and an indefatigable church worker. Dr. Crumpler is 59 or 60 years of age, tall and straight, with light brown skin and gray hair.“

 

A drawing of Arthur Crumpler, however, has survived. It appears in the feature article about him previously cited. Rebecca Crumpler died on March 9, 1895 and is buried at the Fairview Cemetery near her residence in Hyde Park. She was survived by her husband, Arthur, who died in Boston in 1910. The Rebecca Lee Society, one of the first medical societies for African-American women, was named in her honor. Her home on Joy Street is a stop on the Boston Women’s Heritage Trail.

 

Arthur Crumpler, Husband of Dr. Rebecca Lee Crumpler

 

Sketch of Arthur Crumpler, Boston Daily Globe from 1898

Source: Kate Kelly, americacomesalive.com
Arthur Crumpler escaped slavery and overcame the fact that slaves were prevented from learning to read or write; he attended night school when he was in his sixties. The article in The Boston Daily Globe in 1898 about him as a good student was a well-deserved bonus but he had already lived a full and productive life. Crumpler was born a slave in Southampton County, Virginia. He belonged to Robert Adams who owned the estate where his mother worked. Arthur’s father, Samuel, a slave on a neighboring plantation, was owned by a white man named Benjamin Crumpler. While Arthur belonged to his mother’s master, he took his name from the surname his father must have used.  When Arthur was nine, his master died unexpectedly. Because Robert Adams had several sons, his estate (including the slaves) needed to be sold to apportion the wealth among his children. Arthur had liked living on the Adams estate, so he came up with an idea that he thought might get the attention of Robert Adams’s oldest son, John. Arthur approached John and said, “John, I can wrestle you down!“ as he told a Boston reporter many years later. John didn’t believe that a nine-year-old slave boy could take him down, but Arthur was strong and tough. Before long the young white master had had enough. Arthur’s gamble paid off as he had hoped – he earned John’s admiration. All of the other slaves were sold, but John kept Arthur for himself. John Adams took Arthur with him to Smithfield, Virginia, for a year. Then Adams decided it would be more profitable to lease Arthur to other men. He made a deal with a slave trader to take Arthur for four years. It is not clear what work this entailed, but at the end of the four years, Arthur was returned to John Adams. By this time, John had married, and his in-laws needed help. John gave them Arthur. While working for John Adams’s in-laws, Arthur worked at harvesting and processing apples. Arthur described to a reporter from The Boston Daily Globe an improvement he made to an apple-paring machine used on the plantation. John Adams stopped by to check on things one day. He observed what Crumpler could do with the mechanism he had fashioned. He removed Arthur from the in-laws’s apple farm and told Arthur he would give him his pick of a new trade. Arthur could choose carpentry, shoemaking, blacksmithing, or brick-laying. While no one quite knows what transpired here, Adams may have realized how capable Arthur was and wanted to put him in a job where Adams could make money from his work. But there is also the possibility that John Adams saw a way to profit from Arthur’s improvements on the device. By rewarding him with other options, it might keep him from telling others about his invention. There is no patent for an apple-parer that would match Arthur’s or John Adams’s dates or location, but it is still possible that Adams found a way to sell or benefit from Arthur’s accomplishment. Blacksmithing was Arthur’s choice of the new trade he wanted to learn so Adams arranged for him to apprentice to the local blacksmith. Arthur earned $250 per year plus clothing (it would have been usual for the master to take the money). Arthur learned blacksmithing, but soon seemed restless. Adams set him up in his own shop to try to keep him from running away as other slaves were doing.

 

When the Civil War began with the attack at Fort Sumter in 1861, the slaves in the Smithfield area saw their opportunity to escape. Crumpler and many others ran from their masters. They made their way to the Norfolk Navy Yard where they took refuge on the The U.S.S. Cumberland. The gunboat soon went on to Fort Monroe where many of the former slaves disembarked. Crumpler got a job at Fort Monroe to shoe horses, and he proved to be of great value to the Union in that capacity. Later he worked for Union General McClellan on the Virginia peninsula. By July 1862, Crumpler was ready to leave Fort Monroe and go to Boston where he knew other slaves had settled. He was supposed to collect $160 from the Union Army for his services. The quartermaster had to inform him that they couldn’t begin to pay him that much. Why didn’t he settle for $40? Crumpler was eager to move on, so he agreed. The Army wanted him to sign an agreement to accept $40 as compensation. “They took hold of my hand and held it while I made an �X’ to something.“ t was then that Arthur made a promise to himself:

 

“I made up my mind I would never make an X again beside my name written by someone else, and I have kept my word. I have learned to write.“

 

When Arthur Crumpler arrived in Boston, he was taken in by Nathaniel Topliff Allen who ran a school in Cambridge. Crumpler slept in the barn, and did chores to earn his keep. It is around this time that he must have met his future wife, Rebecca Davis Lee Crumpler. (Rebecca had been previously married to a fellow named Wyatt Lee. Lee passed away in 1863.) Rebecca had been a student at Allen’s School, and Nathaniel Allen may have introduced the two. At any rate, Rebecca and Arthur were married in St. John, New Brunswick, on May 24, 1865. In 1870, Rebecca gave birth to their only child, Lizzie Sinclair Crumpler. Rebecca set up a medical practice in Boston (she was the first African American female doctor), and Arthur may have switched from being a blacksmith to being a porter at this time. His work involved taking care of stores in Boston – an occupation that he pursued for many years. Both Arthur and Rebecca were devout and involved church members. Rebecca recognized Arthur’s interest in learning, and she encouraged him to sign up for night classes early in their marriage. But he became frustrated. To ease his discomfort, Rebecca offered to read and write for him – and she did so until her death in 1894. From an article in The Boston Daily Globe on April 3, 1898, we learn how Arthur Crumpler learned to manage on his own. “When she [Rebecca] passed away, I found that I should have to depend upon myself if I wanted to learn anything. I could not read the newspapers during the last war, but if we have a war now, I shall be able to read all about it myself. I can do my own signing, and I am not making any more crosses.“ The reporter writes that Arthur had spent the previous three years attending Franklin Evening School, a school that attracted a diverse immigrant student body as most people worked during the day and then took classes at night. “I find considerable pleasure in reading my Bible and papers and books. I sit down and practice my writing lessons, and write my own letters, and then I sit down and add up, subtract, multiply, and divide my figures all by myself. There is nothing to excuse any colored man or woman in the city of Boston from learning how to do these things,“ said Arthur to the reporter. The headline for the article was “Boston’s Oldest Pupil.“ (The article states that he was age 74 but in working through his personal details, it is more likely that he was 64 as he was probably born in 1834 or 1835.) The headline also could have been “Boston’s Happiest Pupil.“

 

Only once did Crumpler return to Virginia. He attended a reunion of the Grand Army of the Republic in Washington. He returned to Virginia afterward, looking for a sister. On the last day he had before returning to Boston, he heard news of her: she married and moved to Tarboro, North Carolina, and had several children. Before 1898 (when the article was published), Arthur re-connected with one family member. One of his sister’s children came north and located Arthur. In 1898, Crumpler was living in a one-room apartment on Piedmont Street. The apartment was filled with books and one well-displayed Bible. These must have given Arthur enormous pleasure. When Arhur Crumpler died in 1910, he left all his possessions to his niece Maggie King of 50 Hickory St. Orange, New Jersey. (Perhaps this was the child of his sister whom he met later in life.) As his executor, Arthur Crumpler named the reverend of the church he attended, the Calvary Baptist Church in Boston.

William Bradley Coley MD – Pioneer of Immunotherapy

William Bradley Coley (center)

 

William Bradley Coley (1862 – 1936) was an American bone surgeon and cancer researcher and the pioneer of cancer immunotherapy. He developed a treatment based on provoking an immune response to bacteria. In 1968 a protein related to his work was identified and called tumor necrosis factor-alpha.

 

William Coley was born to a very old Connecticut family, on January 12, 1862 in Westfield, to Horace Bradley Coley and Clarina B. Wakeman. He went to college at Yale and graduated from Harvard Medical School in 1888. He then joined the staff of the New York Hospital as an intern on the surgical service, following which he began his career as a bone surgeon at New York Cancer Hospital (which later became part of the Memorial Sloan-Kettering Cancer Center). Coley became more interested in cancer treatment when one of his early patients, Elizabeth Dashiell, died from bone cancer. While going through hospital records, Coley found a sarcoma case study of one patient named Fred Stein, whose tumor disappeared following a high fever from erysipelas infection, now known as Streptococcus pyogenes. This sparked Coley’s interest and drove him to find what few examples of similar cancer treatment had been previously recorded. He discovered that other medical pioneers including Robert Koch, Louis Pasteur, and Emil von Behring, had recorded observations of erysipelas infection coinciding with cancer regression.

 

From 1925 to 1933, Coley served as Surgeon-in-Chief of the Hospital for Special Surgery in New York City, where he developed the theory that post-surgical infections had helped patients to recover better from their cancer by provoking an immune response. In 1891 he began to experiment by deliberately causing this phenomenon, injecting streptococcus bacteria directly into people being treated; later because this had the adverse effect of causing infection, he switched to using dead bacteria. Coley published the results of his work as a case series, making it difficult to interpret them with confidence. According to the American Cancer Society, “More research would be needed to determine what benefit, if any, this therapy might have for people with cancer“. Cancer Research UK say that “available scientific evidence does not currently support claims that Coley’s toxins can treat or prevent cancer“. People with cancer who take Coley’s toxins alongside conventional cancer treatments, or who use it as a substitute for those treatments, risk seriously harming their health. By 1901, the development of x-rays as a cancer treatment showed great promise. In particular, the therapy resulted in immediate tumor destruction and pain relief. Although Coley claimed successful treatment of hundreds of patients, the absence of proven benefit or reproducibility led to broader emphasis on surgery and on the newly developing field of radiation therapy. This decision was borne out by the eventual successful treatment of millions of people worldwide with radiation therapy. Coley arranged for a wealthy friend to provide funds to purchase two x-ray machines for his use. However, after several years of experience, Coley came to the conclusion that the effect of that primitive x-ray therapy in the untrained hands of experimenters was localized, temporary and not curative. The scientific majority disagreed, most notably his contemporary James Ewing. His contemporary critics cited the dangerous and unpredictable effects, predominantly the fever caused by the bacteria, that the vaccine had upon individuals weakened by cancer. Furthermore, the vaccine had to be made to a patient’s exact needs, making it more labor-intensive, time-consuming and expensive.

 

In 2009, Coley’s theory that immune systems in humans functioned in a cycle was demonstrated by a research team led by Associate Professor Brendon Coventry, which could have significant ramifications for cancer treatment. In 2005, drug makers including Pfizer and Sanofi-Aventis had a renewed interest in modern versions of Coley’s Toxins. Pfizer has acquired the Coley Pharmaceutical Group, set up in 1997. The historical results of Coley vaccine therapy are difficult to compare with modern results. Coley’s studies were not well controlled and factors such as length of treatment and fever level were not adequately documented. Many of his patients had also received radiation and sometimes surgery. According to the analyses of Coley Nauts and Starnes, treatment success correlated with length of therapy and the fevers induced by the toxins. Coley’s daughter, Helen Coley Nauts, established the nonprofit Cancer Research Institute in 1953 to study her father’s work. The organization has since become a leader in funding research in immunology and tumor immunology at universities and hospitals worldwide.

 

Today immunotherapy (plus personalized medicine) is cutting-edge cancer treatment. But more than 100 years ago, it was extremely difficult to get other physicians to agree with William Coley MD. Here is a more detailed account of the cases contributing to Dr. Coley’s ideas:

 

In the late summer of 1890 young Coley was getting ready to examine a new patient at his practice in New York City. What he didn’t know was that the young woman waiting to see him would change his life and the future of cancer research. Her name was Elizabeth Dashiell, also known as Bessie. Bessie was 17 and showed up complaining of a problem with her hand. It seemed like a minor injury, just a small bump where she’d hurt it, but it wasn’t getting better, and she was in a lot of pain. She’d seen other doctors but nobody could diagnose the problem. At first Coley thought Bessie must have an infection. But when he took a biopsy, it turned out to be a malignant, very advanced cancer called a sarcoma. In those days there wasn’t very much anyone could do for Bessie. This was before radiation and chemotherapy, so Coley did the only thing he could – he amputated Bessie’s right arm just below the elbow in an attempt to stop the disease from spreading. Sadly, it didn’t work, and within a month, according to David Levine, the cancer had spread “to her lungs, to her liver and all over her body.“ Bessie’s final days were wrenching and painful. Coley was with her when she died on Jan. 23, 1891. Bessie’s death made a huge impression on the young surgeon. “It really shocked him,“ says Stephen Hall, who wrote about Coley in his book A Commotion in the Blood: Life, Death and the Immune System. Bessie’s death also spurred Coley into action. There wasn’t a lot known about cancer at the time, so Coley started digging through dozens upon dozens of old records at New York Hospital. He was looking for something that would help him understand this cruel and aggressive disease. As a student, Coley had read Charles Darwin, and one of the lessons he took away from Darwin, Hall says, was to always pay attention when there’s a biological exception to the rule. “To ask yourself: Why this has happened?“ Coley discovered one of these biological exceptions. It was the case of a German immigrant named Fred Stein. Stein had been a patient in New York Hospital eight years earlier. He had a tumor on his neck that doctors tried to remove several times. Unfortunately for Stein, the tumor kept coming back and doctors expected him to die from the disease. Then Stein contracted a serious infection of the skin caused by the strep bacteria. “It looked like Stein’s days were numbered,“ Levine says. But Stein didn’t die. In fact, his tumor disappeared, and he was discharged. Coley wondered if all these years later, Stein could still be alive. So in the winter of 1891, William Coley the surgeon became William Coley the detective. He headed for the tenements of the Lower East Side of Manhattan where the German immigrant community lived. He knocked on door after door asking for a man named Fred Stein who had a distinctive scar across his neck. After several weeks of searching, Coley found him alive and cancer-free. So why did Stein’s cancer go away and stay away after he got a bacterial infection? Coley speculated that the strep infection had reversed the cancer. and wondered what would happen if he tried to reproduce the effect by deliberately injecting cancer patients with bacteria. He decided to test his idea on people who were the most seriously ill. His first subject was an Italian immigrant named Zola who, just like Bessie Dashiell, was suffering from sarcoma. Zola had tumors riddling his throat. He was so sick he could barely eat or speak or even breathe. For months Coley would try to make Zola sick from infection by creating little cuts and rubbing the strep bacteria into them, Hall says. There would be “a slight response but not too much.“ Then Coley got his hands on a much stronger strain of the bacteria. This time, Zola became violently ill with an infection that could easily have killed him. But within 24 hours, Zola’s orange-sized tumor began to liquefy and disintegrate. “This was a phenomenon that occurred rarely, but when you saw it you were utterly astonished,“ Hall says. Zola completely recovered. Coley knew he was on to something. He kept experimenting and refining his use of bacteria. Eventually, he named the treatment Coley’s toxins.

 

It was an exciting time. Coley was having tremendous success and his efforts were celebrated in America and abroad. But Bradley Coley Jr., William Coley’s grandson, says the American medical establishment at the time was skeptical. Nobody knew how Coley’s toxins worked, or why they worked sometimes and not others. Not even Coley could explain it. That’s largely because the immune system was still a mystery and would remain so for decades to come. When radiation therapy came along in the early 1900s, interest in Coley’s toxins was completely overshadowed by this new therapy. When his grandfather died, Bradley Coley says, “All interest in [Coley’s toxins] stopped.“ And quite possibly, that’s where Coley’s legacy would have ended except for this: After Coley’s death in 1936, his daughter, Helen Coley Nauts, started looking through her father’s papers while doing research for his biography. She found about 1,000 files of patients her father had treated with Coley’s toxins. She spent years carefully analyzing these cases and could see that he had extraordinary rates of success in regressing some cancerous tumors. She couldn’t get anyone interested in studying her father’s work, so she decided to do it herself. With a small grant, in 1953 Helen Coley Nauts started the Cancer Research Institute, dedicated to understanding the immune system and its relationship to cancer. In the more than 60 years since, researchers have expanded their understanding of the immune system dramatically and today, that understanding is paying off. Treatments that harness the power of the immune system are now available for a range of cancers such as stomach, lung, leukemia, melanoma and kidney. Jedd Wolchok, chief of the melanoma and immunotherapeutics service at Memorial Sloan Kettering Cancer Center, says any treatment currently in use that exploits the power of the immune system to fight cancer has to “tip its hat“ to the work William Coley began more than 100 years ago. William Coley’s intuitions were correct: Stimulating the immune system may be effective in treating cancer. He was a model of the clinician-scientist, treating patients and using his practice to initiate research and build theories. But he was a man before his time, and he met with severe criticism. Despite this criticism, however, Coley stuck with his ideas, and today we are recognizing their potential value.

Sources: NIH.gov; The University of Iowa; npr.org; Wikipedia

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