Smallpox, Syphilis and Salvation

by Sheryl Persson

  It was a long road for the drug, and Elion helped to fuel the research. Eventually, a group led by Thomas Krenitsky, who had been a colleague of Elion and who now has his own research company, worked through the chemistry to overcome the difficulties that had arisen with synthesis. His invention, known among his colleagues as 506U78, has become the injected cancer drug Arranon. An accumulation of the drug in T-cells inhibits DNA synthesis, stopping rampant cell replication. For some patients Arranon provides another treatment option, and in some cases provides sufficiently long remissions to allow bone marrow transplants to take place.[44] Arranon followed by transplant was the course of treatment for a boy who received the drug when he was four and at the age of ten he was still well and playing Little League baseball.

  ***

  The fight to cure every case of childhood and adult leukaemia continues. Researchers have now turned their attention to stem cells. This is certainly the new frontier in medical science. In August 2006 researchers and their colleagues at the Dana-Farber Cancer Institute and Children’s Hospital in Boston reported on having isolated rare cancer stem cells that cause leukaemia in a mouse model of the human disease.[45] The leukaemia stem cells that were isolated proved to be surprisingly different from normal blood stem cells, a finding that may be good news for developing a drug that selectively targets them.

  The discovery provides answers to the longstanding questions of whether cancer stem cells must be similar to normal stem cells, and what type of cell first becomes abnormal in leukaemia. The research data supports the idea that leukaemia stem cells do not have to originate from normal blood stem cells, an important finding because it indicates that in the future it will be possible to specifically target leukaemia stem cells without killing normal stem cells.

  The researchers at the Dana-Farber Cancer Institute were able to isolate leukaemia stem cells in mice and discovered a gene activity pattern which they called a ‘signature’ of self-renewal.[46] Next they must determine which genes among the several hundred that were particularly active or inactive are the most responsible for the cancer cell’s behaviour. Using the Hitchings–Elion model, these genes might eventually become targets for new types of drugs. So far, researchers have not identified and isolated a pure population of leukaemia stem cells in humans with the disease. But the work which began with Hitchings and Elion continues.

  The Hitchings–Elion partnership was a remarkable one. Gertrude Elion was determined to break down the gender barrier, George Hitchings aided her and medical science was the beneficiary. Professionally Hitchings and Elion were admired by a host of colleagues and students and are remembered for their devotion to science, their cutting edge work and their desire, rooted deep in personal loss, to find a cure for human disease. Devoid of ego, their enthusiasm for their work was contagious and apart from the panoply of weapons they aimed at disease and the drugs that they created through rational drug design, they lit the way for others. Their partnership was even more remarkable because although it took place within a drug corporation laboratory it was not product and reputation driven, but arose from pure altruism and the desire to discover new drugs that gave salvation through science.

  POSTSCRIPT

  In 1998, the company for which both Gertrude Elion and George Hitchings had provided loyal service and inspired research dedicated a new research centre to these two illustrious scientists and humanitarians. The building, which has a cubist-like façade, is called the Elion-Hitchings Building. Although the name of the company is now GlaxoSmithKline, many Hitchings and Elion stories are still told within the walls. The following one about Gertrude Elion may be apocryphal.

  Towards the end of her life, Gertrude Elion pulled into a VIP parking space at GlaxoSmithKline, quite uncharacteristic for a woman who never expected privileges, but which probably had more to do with her age and mobility. She was unknown to the parking-lot guard who suggested as she walked towards the building that there were spaces elsewhere that were not reserved. With poise, the Nobel laureate asked if it would make a difference if her name was on the front of the building. Without hesitation and with great deference, the guard opened the door so that Gertrude Elion could enter her building.

  GLOSSARY

  acquired immunity: immunity which is not innate or natural. It is acquired via an infection or through vaccination. It can also be acquired through the transfer of antibodies or lymphocytes from an immune donor.

  actinomycete: a group of fungus-like bacteria, most of which are harmless. Common in soil life, they play a role in the decomposition of organic matter. Selman Waksman discovered that they produce antinomycin, a natural antibiotic.

  antibodies: a type of protein produced as an immune response by specialised B cells in the immune system to foreign substances (antigens) such as chemicals, viruses and bacteria which threaten the body. Each type of antibody is unique and defends the body against one specific type of antigen.

  antigen: a foreign substance (protein, toxin, chemical, virus, bacterium) which when it enters an organism is capable of triggering an immune response.

  antitoxin: an antibody produced by the immune system to counteract a toxin such as a bacterial toxin (exotoxin), an animal toxin (zootoxin) or plant toxin (phytotoxin). The antitoxin neutralises the effect of the toxin. Antitoxins produced within one type of organism can be injected into other organisms, including humans, to kill bacteria and other micro-organisms, as in Blood Serum Therapy. The procedure involves injecting an animal with a safe amount of a specific toxin, for example, diphtheria, allowing the animal to produce the antitoxin needed to neutralise the toxin. Later blood is withdrawn from the animal, the antitoxin is obtained and processed and then injected into a human or another animal to induce passive immunity.

  avirulent: specifically, micro-organisms that are not able to cause disease.

  Chamberland filter: a porcelain filter with small pores used in filtration sterilisation. It was devised by the French bacteriologist Charles-Édouard Chamberland, who was a close associate of Louis Pasteur. His invention facilitated the discovery of microbial exotoxins and filterable viruses.

  DNA sequence information: DNA sequence information is gained through biochemical methods. The DNA sequence is the order of DNA base pairs, nucleotide bases, in a fragment of DNA, a gene, a chromosome of an entire genome. The sequence of DNA comprises the inheritable genetic information for all living organisms.

  exotoxin: a potent toxin (poison) which is a soluble protein formed and excreted by micro-organisms including bacteria, fungi, algae and protozoa. Exotoxins can destroy cells or disrupt normal cellular metabolism in a host. Most exotoxins can be destroyed by heating.

  immunogenicity: the degree to which a substance possesses the ability to create immunity or provoke an immune response within an organism.

  lymphocytes: a class of cells within the immune system that produce antibodies to attack infected and cancerous cells and which are also responsible for the body’s rejection of foreign tissue. This includes B cells which when activated produce antibody and T cells which function in cellular immunity.

  nucleic acid: an essential complex organic acid found in all living cells such as DNA and RNA, consisting of long chains of nucleotide units (composed of phosphoric acid, a carbohydrate and a base derived from purine and pyrimidine) that convey genetic information.

  organic compounds: chemical substances which are organic i.e. their molecules contain carbon. Organic compounds can be found in nature or they can be synthesised in the laboratory.

  pandemic: is an epidemic (a rapidly spreading disease which is more extensive than would normally be expected) which spreads over a vast geographical area or even worldwide and affects a large proportion of the population.

  pathogen: an infectious agent which causes disease to attack its host. A pathogen is usually a biological agent, a micro-organism such as a bacterium, protozoa, virus or fungus.

  pathogenic bacteria: infectious bacteria. Bacteria (singular, bacter
ium) are microscopic, unicellular organisms which are present in the air, in soil, on the skin. While many types cause disease others such as intestinal bacteria which help with the digestion of food, are useful to humans.

  protozoa: a diverse family of single-celled animals most of which can only be seen under a microscope. Protozoa breathe, move and reproduce like multi-celled animals. They live mostly in water or in damp environments. Some can cause disease while others eat harmful bacteria.

  recombinant: in molecular biology refers to genetic recombination, a new combination of genes in a cell or an individual, combinations which are not found in the ‘parent’. These combinations can be genetically engineered in order to change the characteristics of an organism.

  suppurated: discharging pus or festering.

  toxin: poison produced by living organisms or a harmful substance which accumulates in the body. It frequently refers to a protein, highly toxic to other living organisms, that is produced by certain plants, animals and pathogenic bacteria.

  virulent: extremely toxic, specifically in reference to micro-organisms that are markedly pathogenic (disease causing).

  World Health Assembly: the decision-making forum through which the World Health Organization (WHO) is governed by its 193 member states. It meets each year in May in Geneva and is attended by health ministers from all member states. Its executive board is comprised of 34 members who are technically qualified in the field of health. The main tasks of the Assembly are to decide major policy and approve WHO programs and budgets.

  Notes

  CHAPTER ONE

  [1]Baron, John, 1827, The Life of Edward Jenner, Vol.I, Chapter 4, London, Henry Colburn, cited in Who Named It?

  [2]Strauss, Eugene W. and Strauss, Alex, 2006, Medical Marvels: The 100 greatest advances in medicine, Prometheus Books, New York, p.78.

  [3]Barquet, Nicolau and Domingo, Pere, 1997, Smallpox: The triumph over the most terrible of the ministers of death, Annals of Internal Medicine, Vol.127, Issue 8 (Part 1), pp.635-42.

  [4]Who Named It?, Edward Jenner,

  [5]Macauley, Thomas B., 1800, The History of England from the Accession of James II, Claxton, Remsen and Haffelfinger, Philadelphia, cited in LearnWell.org, Online Continuing Education in Health and Ethics, Nursing Continuing Education Institute, Smallpox Epidemic: Could you deal with it? 2006,

  [6]Saunders, Vicki and Durrheim, David N., 2003, Cuckoos, Cows and a Country Doctor: The pioneering work of a rural health professional in the development of public health, Journal of Rural and Remote Environmental Health 2(2),

  [7]ZKEA Emerging Disease: BiologicalWarfare: Biological-Terrorism, Smallpox History,

  [8]Friedman, Meyer and Friedland, Gerald W., 1998, Medicine’s 10 Greatest Discoveries, New Haven, Connecticut, Yale University Press, p.67.

  [9]The Jenner Museum, Edward Jenner and Smallpox,

  [10] Strauss, Eugene W. and Strauss, Alex, 2006, op. cit., p.104.

  [11] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [12]Tucker, Jonathan B., 2001, Smallpox: From eradicated disease to bioterrorist threat, Center for Nonproliferation Studies, Monterey Institute of International Studies, Washington,

  [13] Strauss, Eugene W. and Strauss, Alex, 2006, op. cit., p.77.

  [14] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [15]Who Named It?, Edward Jenner, loc. cit.

  [16]ABC Radio National, 23 November 1997, Ockham’s Razor transcript 23, ‘Defending Edward Jenner’,

  [17]Who Named It?, Edward Jenner, loc. cit.

  [18] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [19]Parish, H.J., Victory with Vaccines: The story of immunisation, Edinburgh, E & S Livingstone, 1968, cited in Barquet, Nicolau and Domingo Pere, 1997, loc. cit.

  [20] Who Named It?, Edward Jenner, loc. cit.

  [21] Strauss, Eugene W. and Strauss, Alex, 2006, op. cit., p.105.

  [22] Who Named It?, Edward Jenner, loc. cit.

  [23] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [24] History Learning Site, 2000, Edward Jenner,

  [25] Who Named It?, Edward Jenner, loc. cit.

  [26] ibid.

  [27] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [28] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.79.

  [29]Jenner, Edward, An Inquiry Into the Causes and Effects of the Variolae Vaccinae, Or Cow-Pox. 1798, The Harvard Classics: 1909-14, Great Books on Line, bartelby.com,

  [30] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.83.

  [31] Who Named It?, Edward Jenner, loc. cit.

  [32] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.82.

  [33] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [34] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.88.

  [35] Saunders, Vicki and Durrheim, David N., 2003, loc. cit.

  [36] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.89.

  [37] Barquet, Nicolau and Domingo, Pere, 1997, loc. cit.

  [38]National Network for Immunization Information, Vaccine Information: Smallpox,

  [39] Saunders, Vicki and Durrheim, David N., 2003, loc. cit.

  [40]The Jenner Museum, Edward Jenner and Smallpox, loc. cit.

  [41] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.90.

  [42] ibid.

  [43] Saunders, Vicki and Durrheim, David N., 2003, loc. cit.

  [44] Friedman, Meyer and Friedland, Gerald W., 1998, op. cit., p.92.

  [45]Jenner, Edward, 1801, The Origin of the Vaccine Inoculation, London, D.N. Shury, cited in Barquet, Nicolau and Domingo Pere, 1997, loc. cit.

  [46]PBS Online, Science Odyssey: People and Discoveries, World Health Organization declares smallpox eradicated,

  [47]The Jenner Museum, Edward Jenner and Smallpox,loc. cit.

  [48] PBS Online, Science Odyssey: People and Discoveries, loc. cit.

  [49]Tucker, Jonathan B., 2001, Smallpox: From eradicated disease to bioterrorist threat, loc. cit.

  [50].The Jenner Museum, Edward Jenner and Smallpox, loc. cit.

  [51]Retroscreen Virology Ltd, Twenty Five-Years On: Smallpox revisited,

  [52]Organic Consumers Association, 2005, International Campaign to Stop Genetic Engineering of Smallpox Virus Announced,

  [53]Tucker, Jonathan B., 2001, Smallpox: From eradicated disease to bioterrorist threat, loc. cit.

  [54]Organic Consumers Association, 2005, loc. cit.

  [55]Jefferson, Thomas, Letter, 14 May 1806, From Revolution to Reconstruction, 2006, The Letters of Thomas Jefferson: 1743-1826, A Tribute of Gratitude,

  CHAPTER TWO

  [1]Cited in Hawke, Caitlin, 2002, ‘The Cutting Edge: Focus on Anthrax Then and Now’, Pasteur Perspective: The newsletter of the Pasteur Foundation devoted to the world of the Institut Pasteur, No.11, spring, New York, p.1.

  [2]Scientists, Pasteur,

  [3]Coppedge, David, F., 2000, Shining Through Material Darkness: Louis Pasteur, World’s Greatest Creation Scientists fromY1K toY2K,

  [4]De Kruif, Paul, 1927, Microbe Hunters, Harcourt Brace, New York, reprinted San Diego, Harcourt Brace, 1996, p.5.

  [5] Strauss, Eugene W. and Strauss, Alex, 2006, op. cit., p.74.

  [6] Strauss, Eugene W. and Strauss, Alex,
2006, op. cit. p.31.

  [7]Cohn, David V., The Life and Times of Louis Pasteur, 1999, LabExplorer,

  [8] ibid.

  [9] ibid.

  [10]Hellman, Hall, 2001, Great Feuds in Medicine: Ten of the liveliest disputes ever, John Wiley & Sons Inc., New York, p.78.

  [11]Debré, Patrice, (trans: Elborg Forster), 1998, Louis Pasteur, Baltimore, Johns Hopkins Press, p.103.

  [12] Hellman, Hall, 2001, op. cit. p.79.

  [13] Cohn, David V., loc. cit.

  [14]Pasteur, Louis, Lecture at the Sorbonne in 1864, cited in Wilson, John L., Stanford University School of Medicine and the Predecessor Schools: A historical perspective, 1998, Chapter 5, ‘Louis Pasteur (1822-1895)’, Stanford School of Medicine History,

  [15]Scientists, Pasteur, loc. cit.

  [16] Hellman, Hall, 2001, loc cit.

  [17]Coppege, David, F., Shining Through Material Darkness: Louis Pasteur, loc. cit.

  [18] Hellman, Hall, 2001, op. cit., p.85.

  [19] Debré, Patrice, 1998, op. cit., p.142.

  [20]Doctors Independent Network (DIN), Louis Pasteur,

  [21]Pasteur, Louis, Speech to the Academy of Medicine in Paris, cited in Cohn, David V., The Life and Times of Louis Pasteur, 1999, LabExplorer,

  [22]Pasteur, Louis, Germ Theory And Its Applications to Medicine and Surgery: Read before the French Academy of Sciences, 29 April 1878, Internet Modern History Sourcebook, 1998,

  [26]Mollaret, H.H., Contribution to the knowledge of relations between Koch and Pasteur, NTM-Schriftenr. Gesch. Naturwiss, Technik, Med, Leipzig 20 (1983)1, pp.57-65. Translated by Cohn, E.T., Fasciotto-Dunn, B.H., Kuhn, U. and Cohn, D.V., Molleret,