From Hormone Heresy: Investigation into the theory of hormone replacement goes all the way back to the 1930s with the research of Dr Serge Voronoff. His research involved implanting fresh monkey’s testicles into men’s scrotums, with limited effectiveness. Offshoots of his research led to the grafting of monkey ovaries in women, with rather dire consequences. After several fatalities (to both monkeys and women), the search was redirected to the use of synthetic estrogen. With the advent of World War II, research was put on hold.
400 BCE to First century CE: First skin grafts/flaps for facial reconstruction: In the work Samhita, Indian author Sushruta describes reconstruction of noses and ear lobes using skin grafts from the cheek. (Early research dates Samhita a from about 600 BCE, but modern historians dispute this date, giving a date of 400 BCE to 1st century CE.)
1668: Xenotransplant – First successful bone graft: Dutchman Job van Meeneren documents the use of a bone graft from a dog’s skull to repair a defect in a human cranium.
Meanwhile, other claims say …
1682: Xenotransplant – Another, or the same bone graft but different date?: A bone from a dog is reportedly used to repair the skull of an injured Russian aristocrat (who is later said to have had the bone removed because of threats of exc€ommunication from the church).
1822: First Skin Transplant (autograft): Berger reportedly performs the first skin autograft – but it can only be the first if the procedure described in Sushruta’s Samhita (c. 400 BCE) was theoretical.
1881: First Temporary Skin Transplant (from a cadaver): A surgeon treats a patient, suffering from burns received while leaning against a metal door that was struck by lightning, using skin from a deceased person as a temporary graft.
1901-1903: Discovery of ABO Blood Groups: Viennese physician Karl Landsteiner points out that adverse reactions that occur when humans receive blood from animals may also occur when humans receive blood from other humans. His suggestions receive little attention until 1909, when he classifies the human blood into the A, B, AB, and O groups and shows that catastrophic reactions can occur when a person receives blood from a different group. Compatibility is later found to be not only a requirement for transfusion but for transplantation. In 1930, Landsteiner wins the Nobel Prize in Physiology or Medicine “for his discovery of human blood groups.”
1905: Xenotransplant – First Rabbit Kidney Grafted Into Human: French surgeon Dr. M. Princeteau grafts pieces of a rabbit kidney into a 16-year-old with kidney failure; the patient dies two weeks later.
1906: First Successful Cornea Transplant: Dr. Eduard Zirm, a surgeon working in the Moravian town of Olmutz, performs the first corneal transplant to maintain some degree of transparency. He publishes a paper in the 1906 Archives of Ophthalmology (64:580-591). Few other surgeons match Zirm’s success until after the Second World War, when very fine needles and finer silk become available.
1906: Xenotransplant – First Pig Kidney Grafted into Human: By joining the kidney to the blood vessels of her arm, French surgeon Dr. Mathieu Jaboulay grafts the kidney of a pig to a woman. She lives for one hour.
1908: First Knee-joint Transplant: Dr. Erich Lexer of Germany reports performing the first knee-joint transplant (from a cadaver), but the procedure is unsuccessful.
1909: Xenotransplant – First Non-Human Primate Kidney Grafted onto Human: Dr. Ernst Unger of Germany grafts the kidneys of a macaque onto the thigh of a woman. She dies 32 hours later.
1911: First Vein Transplant: Dr. Yamanouchi performs the first use of homologous vein tissue in arterial reconstruction.
1920: Xenotransplant – First Monkey Testicles Transplanted into Human: At his clinic in France, Dr. Serge Voronoff transplants monkey testicles into a man. By the early 1930s, more than 500 men are reported to have received transplanted testicles.
1923: Xenotransplant – First Lamb Kidney Grafted into Human: Dr. Harold Neuhof grafts the kidney of a lamb into a human patient. The patient dies nine days later.
1944: Research into Rejection: British scientist Peter Medawar discovers that animal embryos exposed to foreign tissues do not reject the tissues and concludes that rejection of a transplant is based on immunologic factors. Meanwhile, Frank Macfarlane Burnet of the University of Melbourne in Australia suggests that the body’s immune cells learn very early on to accept whatever tissues are there as part of the body and only attack and reject material that shows up later. Medawar and Burnet go on to be co-winners of the 1960 Nobel Prize in Physiology or Medicine “for discovery of acquired immunological tolerance.”
1945: First Temporary Kidney Transplant: In his 1990 Nobel Lecture, Dr. Joseph E. Murray (one of the surgeons involved in the 1954 first successful live donor kidney transplant), reported on a temporary cadaveric kidney transplant that took place at Peter Bent Brigham Hospital (now Brigham & Women’s Hospital) in Boston: “The very first renal transplant in 1945 at the Brigham deserves special comment. The patient was a young woman in renal failure following obstetrical complications. The purpose of the transplant was to provide temporary renal function until her own kidneys recovered from acute tubular necrosis. … (T)he operation was performed … by Dr. Charles Hufnagel, then a Research Fellow working on vascular grafts, Dr. Ernest Landsteiner, then Chief Resident in Urology, and Dr. David Hume, then Assistant Resident in Surgery. … According to Dr. Robert J. Glaser, who was assistant resident on the medical service at that time, “secretion of urine was minimal, and certainly did not, ‘rescue the woman from her crisis.’ The kidney functioned poorly and only transiently, and the patient continued to have a stormy course, although fortunately, despite our lack of understanding at the time of how best to treat renal shutdown, she ultimately did respond and she left the hospital with normal renal function and in good health.” … Dr. Glaser further reports that her happy state was short-lived because she died a few months later of fulminating hepatitis secondary to pooled plasma infusions which she had received in the course of her treatment.”
1952: First Kidney Transplant: Dr. Hamburger and his team transplant the first human kidney. The kidney is taken from female traffic accident victim and transplanted into her son. The kidney initially functions well, until it is rejected 22 days later.
1954: First Successful Live Donor Kidney Transplant: Drs. Joseph E. Murray, Hartwell Harrison, David Hume, and John Merril perform the first successful kidney transplant at Peter Bent Brigham Hospital (now Brigham & Women’s Hospital>) in Boston. The transplant is from Ronald Herrick into his identical twin Richard. Richard Herrick lives for another eight years. Murray becomes one of the co-winners of the 1990 Nobel Prize in Physiology or Medicine along with E.D. Thomas “for their discoveries concerning organ and cell transplantation in the treatment of human disease.”
1955: First Heart Valve Transplants: Dr. Gordon Murray of Toronto, Ontario, uses the main aortic valve of a male automobile accident victim to perform the world’s first heart valve transplant on a patient with a severely leaking aortic valve. The transplanted valve functioned well for over eight years.
1956: First Bone Marrow Transplant Using Related Donor (see also 1968): Dr. E. Donnall Thomas of Cooperstown, New York, performs the first successful bone marrow transplant that results in long-term survival of the patient. In 1957 he publishes a report of his work, which shows complete remission of leukemia by treating patients with total body irradiation followed by an infusion of marrow from an identical twin. Along with Joseph E. Murray, Thomas is a co-winner of the 1990 Nobel Prize in Physiology or Medicine “for their discoveries concerning organ and cell transplantation in the treatment of human disease.”
1958: Discovery of First HLA Antigen: French physician Jean Dausset describes the first leucocyte antigen, MAC (now known as HLA-A2). The discovery allows for tissue matching beyond blood types. Dausset is one of three co-winners of the 1980 Nobel Prize in Physiology or Medicine “for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions.”
1962: Introduction of Imuran (azathioprine): Research by Gertrude B. Elion and colleague George H. Hitchings (two of the three winners of the 1988 Nobel Prize for Physiology or Medicine “for their discoveries of important principles for drug treatment”) leads to the development of the anti-rejection drug Imuran, which blocks the body’s rejection of foreign tissues.
1962: First Kidney Using Cadaveric Donor: New tissue typing techniques and immune suppression with drugs are used for the first time in a human kidney transplant of a cadaver donor at Peter Bent Brigham Hospital (now Brigham & Women’s Hospital) in Boston.
1963: First Lung Transplant: Dr. James D. Hardy of the University of Mississippi in Jackson, performs the first single human lung transplant, but the patient dies within days.
1964: First Attempted Hand Transplant: A hand is transplanted in Ecuador, but it is rejected within two weeks.
1964: Xenotransplant – First Heart Transplant of Non-Human Primate into Human: Dr. James D. Hardy, of the University of Mississippi in Jackson, uses the heart of a chimp named Bino to transplant into 68-year-old Boyd Rush. The heart is too small to maintain independent circulation and functions for only 90 minutes.
1966: First Pancreas Transplant: Drs. Richard C. Lillehei and William D. Kelly of the University of Minnesota, Minneapolis, transplant a pancreas into a 28-year-old woman; immediately after transplant, her blood sugar level begins to fall, but she dies three months later from pulmonary embolism.
1967: First Successful Heart Transplant: Dr. Christiaan Barnard, at Groote Schur Hospital in Cape Town, South Africa, transplants the heart of an 18-year-old female car accident victim into Louis Washkansky. He dies 18 days later of pneumonia.
1968: Xenotransplant – First Attempted Pig Heart Transplant: Dr. Ross of the National Heart Hospital in London, England, attempts the transplant of a pig heart into a patient, but the heart ceases functioning in minutes.
1968: First Bone Marrow Transplant Using Related Donor For Non-Cancer Treatment: This event is also advertised as the first bone marrow transplant. Specifically, it is the first bone marrow transplant for non-cancer illness, as the 1956 “first” is for a patient with leukemia. Dr. Robert A. Good performs the first non-cancer BMT on a four-month-old boy who has inherited severe combined immunodeficiency syndrome, an illness that has killed 11 male children in his extended family. The marrow donor is his eight-year-old HLA-matched sister.
1969: First Artificial Heart Implant: Dr. Denton A. Cooley implants the first total artificial heart (the Liotta Total Artificial Heart) at the Texas Heart Institute in Houston. The heart is implanted into 47-year-old Haskell Karp and is not intended to be permanent. It is used as a bridge until he can receive a donor heart, which he does 64 hours later.
1969: First Partial Larynx Transplant: A Belgian doctor performs a subtotal transplant of a larynx, but the patient dies without speaking.
1969-1974: Xenotransplant – First Transplants of Non-Human Primate Livers: Dr. Thomas E. Starzl of the University of Colorado in Denver transplants chimpanzee livers into children. The survival rate ranges from one to 14 days.
1973: First Bone Marrow Transplant Using Unrelated Donor: A team at Memorial Sloan-Kettering Cancer Center in New York City performs the first unrelated bone marrow transplant. The five-year-old patient has severe combined immunodeficiency syndrome, and the donor is found in Denmark through the Blood Bank at Rigshospitalet in Copenhagen. The patient receives multiple infusions of marrow and, after the seventh transplant, hematologic function becomes normal.
1974: First Islet Cell Transplant: Dr. David Sutherland of the University of Minnesota in Minneapolis performs the world’s first islet cell transplant. The procedure works for only a short time before the patient’s immune system destroys the new cells.
March 9, 1981: First Successful Heart-Lung Transplant: Dr. Bruce Reitz of Stanford University in California, performs the first successful heart-double lung transplant on 45-year-old Mary D. Golke, who had been diagnosed with primary pulmonary hypertension. Cyclosporine is experimentally used to combat rejection. Golke passed away in May 1986. Golke co-authored a book about her experiences, called I’ll Take Tomorrow.
1982: First Permanent Artificial Heart: Dr. William C. DeVries of the University of Utah in Salt Lake City, implants the Jarvik 7 artificial heart into Barney Clark, a 61-year-old retired dentist. Clark is forced to remain inactive because the heart is kept beating by an external compressor attached to the implant by hoses. Clark lives 112 days.
1983: Cyclosporine Approved for Use: The US FDA approves Cyclosporine, an immunosuppressant drug isolated from a fungus. Cyclosporine revolutionizes organ transplantation because it selectively suppresses the transplant recipient’s immune system, allowing the patient to tolerate the grafted organ but preventing routine infections. Cyclosporine was first shown as an immunosuppressive agent by Swiss physician Jean Borel in 1977.
1983: First Successful Single Lung Transplant: Dr. Joel Cooper of the Toronto Lung Transplant Group, Toronto General Hospital (now part of the University Health Network), performs a single lung transplant on 58-year-old Tom Hall, who suffers from pulmonary fibrosis. Hall lives for more than six years before dying of kidney failure.
1985: Ethics: The Ethics Committee of the Council of the Transplantation Society, an international body, issues guidelines prohibiting the buying and selling of organs and tissues.
1986: Improving Donor Organ Survival: Researchers Folkert Belzer and James Southard of the University of Wisconsin – Madison develop the UW solution, a synthetic solution that increases storage times from six to 36 hours for organs such as livers and pancreases.
1986: First Successful Double Lung Transplant: Dr. Joel Cooper of the Toronto Lung Transplant Group, Toronto General Hospital (now part of the University Health Network), performs a double lung transplant on Ann Harrison, who suffers from emphysema. Harrison lives until 2001, when she dies of a brain aneurysm.
1988: First Sciatic Nerve Transplant: Drs. Alan R. Hudson and Susan E. Mackinnon, of the University of Toronto, transplant the sciatic nerve of a 16-year-old female, who died from a hemorrhage, into nine-year-old Matthew Beech, who had his sciatic nerve destroyed in a water-skiing accident. Two years after the surgery, Beech could feel pinpricks on the sole of his foot for the first time since the accident, showing that the axons had grown through the graft and down the nerves to the sole of the foot.
1988: First Successful Liver-Bowel Transplant : David Grant of the University Hospital of London Health Sciences Centre in London, Ontario, transplants a liver and six meters (20 feet) of bowel into 41-year-old Doris Wells, who had been unable to eat or drink after having her small bowel removed in 1987. During that time, she was fed intravenously through a device, which she was hooked up to for eight to 12 hours each night.
1988: First Two-In-One Liver Transplant: Two patients at Paul Brousse Hospital in Villejuif, France, receive a liver transplant, when one donated organ is cut in half.
1988: First Human Fetal Cell Transplant: University of Colorado doctors implant fetal cells into a patient’s brain.
A follow-up study of Parkinson’s patients with transplanted fetal cells, which is published in The New England Journal of Medicine on November 26, 1992, indicates promising results. However, in a later study, published by several of the same doctors and appearing in the March 8, 2001 NEJM, finds that the cell transplant benefit occurred in younger patients, not older patients, and that 15% of younger patients suffer irreversible side effects known as disabling dyskinesias.
1989: First Successful Living-Related Liver Transplant: Dr. Christopher Broelsch of the University of Chicago Medical Center transplants a portion of Teri Smith’s liver into her 21-month-old daughter, Alyssa, who suffered from biliary atresia. Both mother and daughter are still healthy today.
1989: First Combination Heart, Liver, and Kidney Transplant: Surgeons at Presbyterian Hospital in Pittsburgh, Pennsylvania, transplant a heart, liver, and kidney into a 26-year-old woman. She survives for four months.
1990: FK506 Available: FK506, or Tacrolimus, under the tradename Prograf, is a derivative of a soil fungus found in Japan. It has immunosuppressive properties very similar to cyclosporine but is 10 to 100 times more potent on a per gram basis.
1990: First Successful Living-Related Lung Transplant: Dr. Vaughn A. Starnes, at Stanford University Medical Center in Palo Alto, California, transplants the lobe of one lung into a 12-year-old girl (the lobe was donated by her mother).
1992: Xenotransplant – First Pig Liver Transplant(s): Doctors at Duke University use pig liver as a “bridge” to keep two women alive while awaiting liver transplants. In one patient, the liver is kept outside the body and hooked to the liver arteries – she survives long enough to receive a human liver. In the other, the pig liver is implanted beside her own liver and she lives for 32 hours.
1992: Xenotransplant – First Bone Marrow (and Kidney) Transplant from Non-Human Primate: University of Pittsburgh researchers transplant baboon bone marrow and a kidney into a patient. The patient dies 26 days later due to infection.
A more famous baboon bone marrow case is the 1995 transplant on Jeff Getty. In July 1995, scientists receive FDA approval to do the transplant on Getty, who has AIDS, in the hopes that the immune cells in the baboon’s marrow would replace those Getty had lost to AIDS (baboon cells are naturally resistant to HIV.) On December 14, 1995, Getty receives two types of cells (immature stem cells and newly discovered facilitator cells) in a procedure performed by Dr. Suzanne Ildstad at San Francisco General Hospital. The cells function only for a brief time. Getty survived almost 11 more years, dying of heart failure on October 9, 2006.
1995: Xenotransplant – Fetal Pig Cell Brain Cell Transplants: Dr. James Schumacher, a research fellow at McLean Hospital in Belmont, Massachusetts, a Harvard-affiliated facility, performs the first transplant of fetal pig brain cells into 57-year-old Tony Johnson, a Parkinson’s patient. After the surgery, Johnson’s movements become smoother and his speech is clearer.
1995: CellCept Approved for Use: CellCept (mycophenolate) receives FDA approval for the prevention of organ rejection in the case of kidney transplants. It goes on to receive approval for use in heart transplants (February 1998) and liver transplants (July 2000).
1995: Transplantation of All Abdominal Organs: In order to transplant a new kidney, pancreas, stomach, liver, large and small bowel, and one iliac artery, doctors at the University of Miami in Florida remove all abdominal organs from a patient with Gardner’s syndrome.
1997: Zenapax Approved for Use: The US FDA recommends the approval of Zenapax (daclizumab) for preventing acute organ rejection in patients receiving renal transplants.
1998: First Total Larynx Transplant: Dr. Marshall Strome leads a team of Cleveland Clinic doctors in performing a total larynx transplant on 40-year-old Timothy Heidler, whose larynx was destroyed 20 years before in a motorcycle accident. Three days after the surgery, Heidler is able to speak for the first time since the accident.
1998: First (Semi) Successful Hand Transplant: Dr. Jean-Michel Dubernard performs a hand transplant on New Zealander Clint Hallam in Lyon, France. After reportedly not following correct anti-rejection treatment or physical therapy, the hand is amputated at the patient’s request on February 2, 2001.
1998: First Combined Liver and Bone Marrow Transplant: Surgeons at King’s College Hospital in London, England, perform the first combined liver and bone marrow transplant procedure on 18-year-old Hugo Hennessy, who is suffering from CD40 Ligand Deficiency, which kills 75% of sufferers by age 20.
1998: First Unrelated Stem Cell Transplant: Doctors at the AFLAC Cancer Center of Egleston Children’s Hospital at Emory University in Atlanta perform an unrelated donor cord blood stem transplant on Keone Penn, a 12-year-old with sickle cell anemia. In June 2003, Penn provides testimony about the procedure, which cured his sickle cell disease, before the Senate Commerce, Science and Transportation Subcommittee on Science, Technology and Space.
1999: New Procedure to Enable Kidney Transplant: Researchers from the University of Maryland Medical Center in Baltimore announce the development of a new procedure called High PRA Rescue (high panel reactive antibody rescue). High PRA can be developed after a pregnancy, a previous blood transfusion, or an earlier kidney transplant. The blood of individuals with High PRA (about 20% of people on the kidney transplant list) has high levels of rejection antibodies, putting sufferers at a greater risk of rejection than cell-mediated rejection. As the antibodies will react with a large portion of the population, the condition significantly increases their waiting time for a kidney.
The High PRA Rescue procedure involves plasmapheresis, in which patients are connected to a machine that removes their blood, separates the serum containing the antibodies, returns the red and white cells and platelets, and replaces the serum with a protein solution. Patients are also treated with three anti-rejection drugs.
1999: Rapamune Approved for Use: The US FDA recommends the approval of Rapamune (Sirolimus) to prevent organ rejection in adult renal transplant patients.
1999: The Edmonton Protocol: Drs. James Shapiro and Jonathan Lakey of the University of Alberta in Edmonton perform an islet cell transplant on patients who do not require other organ transplants (e.g., kidney) but who have had severe problems with diabetes (type I). The new treatment method involves injecting islet cells from donor pancreases into a patient’s portal vein in a non-surgical procedure in combination with steroid-free anti-rejection drugs: Sirolimus (Rapamune), Tacrolimus (FK506 Prograf), and Daclizimab (Zenapax). The cells migrate to the pancreas, where they produce insulin. The Edmonton group initially works with seven patients, all of whom become insulin independent after the procedure (The New England Journal of Medicine, July 27, 2000).
In September 2000, centers in the United States, Germany, Italy, and Switzerland begin participating in the Immune Tolerance Network multi-center trial of the Edmonton Protocol. For more information, see: Clinical Islet Transplant Program.
2000: First Womb Transplant: Dr. Wafa Fageeh at King Fahad Hospital and Research Centre in Jeddah, Saudi Arabia, transplants the uterus of a 46-year-old into a 26-year-old woman. The uterus produces two menstrual periods before it fails after three months and has to be removed.
2003: First Jawbone Transplant: Surgeons at Rome’s Istituto Regina Elena transplant a mandible from the body of a 39-year-old man into an 80-year-old man who has advanced cancer of the mouth.
2003: First Tongue Transplant: A team of Austrian doctors at Vienna’s General Hospital performs a 14-hour tongue transplant on a 42-year-old man suffering from a malignant tumor affecting his tongue and jaw.
2004: First Ankle Transplant: In August, a team of Italian surgeons led by Dr. Sandro Giannini, transplanted the ankle of a 17-year-old boy (who had died in a car accident) into Silvano Bordon, a 48-year-old rally driver, who had lost mobility of his foot in an accident in 1991.
2005: First Living Donor Islet Transplant: On January 19, a team of surgeons at the Kyoto University Hospital in Japan, under the supervision of Dr. James Shapiro (see 1999: The Edmonton Protocol), took islet cells from the pancreas of a 56-year-old woman and transplanted them into the liver of her 27-year-old diabetic daughter. The transplanted cells began producing insulin within minutes.
2005: First Partial Face Transplant: On November 27, maxillofacial surgeon Dr. Bernard Devauchelle and a team of surgeons performed the world’s first partial face transplant at a hospital in Amiens, in northern France. They grafted a nose, lips, and chin onto a 38-year-old woman, Isabelle Dinoire, who had been disfigured by a dog bite received in May 2005.
2006: First Penis Transplant: Dr. Weilie Hu and surgeons at Guangzhou General Hospital in China performed a penis transplant on a 44-year-old man whose penis had been damaged in a traumatic accident. The donor was a 22-year-old man. Ten days after the surgery, the man had been able to urinate normally. However, the penis was removed two weeks later due to “a severe psychological problem of the recipient and his wife.” There had been no signs of rejection.
2008: First Double Arm Transplant: Between July 25 and 26, doctors at Germany’s Munich University Clinic spent 15 hours grafting a pair of arms onto Karl Merk, a 54-year-old farmer who had lost his arms just below the shoulder in the accident six years ago. By the time of a follow-up news item in October 2008, there had been no signs of rejection, and he could perform simple tasks, like opening doors and turning on light switches.
ESTROGEN, PROGESTERONE AND HORMONE REPLACEMENT THERAPIES
History, Health Risks, Where Progestin Fits In, Hormones Mean Big Money,
Natural Progesterone – The Safe Alternative, References
Estrogen Replacement Therapy (ERT) and Hormone Replacement Therapy (HRT) have traditionally been used by menopausal women to combat the adverse symptoms associated with the process. Most women experience menopause sometime around age 50.
According to Sherrill Sellman, author of Hormone Heresy, investigative hormone replacement dates back to the 1930s with the research of Dr. Serge Voronoff. His research involved implanting fresh monkey’s testicles into mens scrotums, with limited effectiveness. This led to the grafting of monkey ovaries in women, with dire consequences.
Sellman notes that hormone replacement really didn’t get rolling until the 1960s. In 1966 a New York gynecologist, Dr. Robert Wilson, wrote a best-seller called Feminine Forever, extolling the virtues of estrogen replacement. His book sold over 100,000 copies in the first year.
According to Wilson, estrogen replacement was a kind of long-sought-after youth pill that would save poor, fading women from the horrors of age. He popularized the erroneous belief that menopause is an estrogen deficiency disease.
According to Dr. John Lee, in his book, What Your Doctor May Not Tell You about Menopause, Ayerst, the first maker of a conjugated estrogen (Premarin) encouraged Wilson in his publicity for estrogen replacement therapy. The Wilson Foundation was set up for the sole purpose of promoting the use of estrogen drugs. The pharmaceutical industry generously contributed over US$1.3 million to this effort.
Estrogen replacement therapy took off. However, there really was not any solid research behind the idea.. According to Dr. Lee, the approval of estrogen as a prescription drug was based on a “dubious study with a relatively small number of women in Puerto Rico who took birth control pills.” In this study. 20 percent of the women complained of side effects, but, according to Lee, they were dismissed as neurotic.
Estrogen replacement therapy moved on………..
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