Before leaving RUTH FADEN we want to make one more point as to goals of TRANSHUMANISTS in this case---that is to corrupt the idea of DOCTORS needing to abide by HIPAA INFORMED CONSENT public policies AND LAWS.
CLINTON NEO-LIBERALS behind AFFORDABLE CARE ACT harp constantly they are making sure global banking medical corporation systems abide by PATIENT RIGHTS---HIPAA----which is privacy and INFORMED CONSENT.
What the MEDICAL ATROCITY doctors of MANHATTAN PROJECT said was this----they could deem at any time the suspension of all HIPPOCRATIC OATH----all DO NO HARM to advance medical products under FALSE PRETENSES.
FADEN AND BEAUCHAMP both have been working to KILL INFORMED CONSENT in medical studies as UNNECESSARY----both are TRANSHUMANISTS and called MEDICAL BIOETHICS.
'A History and Theory of Informed Consent
Ruth R. Faden and Tom L. Beauchamp
In collaboration with Nancy M. P. King
A timely, authoritative discussion of an important clinical topic, this useful book outlines the history, function, nature and requirements of informed consent, focusing on patient autonomy as central to the concept. Primarily a philosophical analysis, the book also covers legal aspects, with chapters on disclosure, comprehension, and competence'.
Below we see today's LAW OF THE LAND IN US------the 99% WE THE PEOPLE are indeed protected by HIPAA----by DO NO HARM HIPPOCRATIC OATH no matter how much those HITLER/MANHATTAN PROJECT BARBER SURGEONS pretend they can SUSPEND all US RULE OF LAW.
These TRANSHUMANISTS are saying BARBER SURGEONS do not need to give INFORMED CONSENT ----they know better.
We claim those 'BARBER SURGEONS' doing those MANHATTAN medical experiments were NOT US MILITARY------
'Hospital officials say they informed Charlton and other living victims of the experiment on behalf of the Atomic Energy Commission in 1974. The Schultzes say they learned about it from a doctor at Strong five years later. Doctors claim Charlton suffered no health problems from the radiation. She died of a heart attack in 1983. But Fred Schultz, now 73, remains bitter. "I was over there fighting the Germans who were conducting these horrific medical experiments," he said. "At the same time my own country was conducting them on my mother."'
What is Informed Consent?
Under the doctrine of informed consent, a doctor must inform a patient as to the risks and benefits of a proposed course of treatment. This information must be provided by the doctor for several reasons:
patients may have a limited understanding of medicine;
patients have the right to know what parts of the anatomy a proposed course of treatment will involve or affect (the right to this knowledge stems from the general right to have autonomy over one’s own body);
patients, if they are not fully informed as to risks and benefits of a proposed course of treatment, may decide to undergo a procedure to which they might not have consented, if they had been informed of the risks involved.
There are consequences to covered entities (healthcare providers) who do not follow the doctrine of informed consent. If a doctor fails to sufficiently disclose risks and benefits of a proposed course of treatment to a patient, and the omission results in some kind of injury to the patient, that results in legal damages, the doctor may have committed an act of negligence, for which he or she can be liable under medical malpractice law.
An example: A patient develops a rare form of cancer, for which there is no conventional therapy. The patient consults with a physician, who advises the patient that an experimental treatment exists. The experimental treatment has been successful in the few cases where it has been tried. Notably, though, the experimental treatment has, in a substantial number of instances, whether successful or not, resulted in undesirable side effects that have significantly impaired the ability of one more major organs to properly function.
Say that the doctor in this hypothetical scenario informs the patient of the experimental treatment. However, the doctor only informs the patient that the treatment exists, and that it has been successful in the few cases where it has been tried. The doctor omits the side effects information. The doctor also gives the patient no information whatsoever about whether, based on the doctor’s knowledge of the particular patient’s medical condition, the treatment poses risks specific to that particular patient.
The patient decides to undergo the treatment. The treatment fails. In addition, a side effect that the doctor failed to warn the patient about develops.
Under this scenario, the doctor may be liable for malpractice, because he or she breached the duty to provide informed consent. That is, the doctor did not provide the patient with enough details to ensure that the patient’s agreeing to the procedure was reasonably well-informed.
If there is a violation of the duty to provide informed consent, the violation results in harm to the patient, and the patient sustains damages (i.e., financial and non-financial losses for which the law requires he or she be compensated), the doctor may have committed medical malpractice.
Over the years, questions have arisen about the scope of the doctrine of informed consent, such as whether doctors must inform patients about each and every potential risk of a procedure; and whether doctors must inform patients about each and every benefit.
State laws – not HIPAA – provide the answers here. Some states impose a “reasonable physician” standard, while others impose a “reasonable patient” standard.
Under the reasonable physician standard, a patient, to successfully sue the doctor, must demonstrate what a reasonable physician would have told the patient under the same circumstances.
This showing typically requires expert medical testimony. If the expert testimony concludes that a reasonable physician would, under the same circumstances, have told the patient of the side effect that the patient’s doctor did not, the doctor may be liable. If a reasonable physician would not have informed the patient about a side effect (either because, say, the chances of the effect materializing were either miniscule, remote, or wholly hypothetical), then the patient’s doctor who did not inform the patient about the side effect would not be liable.
Other states instead follow what is called the reasonable patient standard. Under this standard, the patient establishes a lack of informed consent when a reasonable person in the position of the patient would have decided against the treatment.
FADEN AND BEAUCHAMP are rewriting thousands of years of MEDICAL MORAL AND ETHICAL practice of DOING NO HARM to justify what modern history has called MEDICAL ATROCITIES. BEAUCHAMP from GEORGETOWN being a FAKE CATHOLIC and FADEN from JOHNS HOPKINS being a FAKE JEWISH PRETENDING they are tied to MORAL ETHICAL PHILOSOPHY in advancing TRANSHUMANISM.
Remember, ALMOST NONE of the research having been down over these few decades has produced anything SOCIAL BENEFIT-----it has produced SICKO AMERICA.
A History and Theory of Informed Consent
Ruth R. Faden; Tom L. Beauchamp
Published by OUP USA, New York (1986)
ISBN 10: 0195036867 ISBN 13: 9780195036862
OUP USA, New York, 1986. Soft cover. Condition: Very Good. 1st Edition. Clearly argued and written in nontechnical language, this book provides a definitive account of informed consent. It begins by presenting the analytic framework for reasoning about informed consent found in moral philosophy and law.
The authors then review and interpret the history of informed consent in clinical medicine, research, and the courts. They argue that respect for autonomy has had a central role in the justification and function of informed consent requirements. Then they present a theory of the nature of informed consent that is based on an appreciation of its historical roots. An important contribution to a topic of current legal and ethical debate, this study is accessible to everyone with a serious interest in biomedical ethics, including physicians, philosophers, policy makers, religious ethicists, lawyers, and psychologists. This timely analysis makes a significant contribution to the debate about the rights of patients and subjects. An authoritative discussion of an important clinical topic, this useful book outlines the history, function, nature and requirements of informed consent, focusing on patient autonomy as central to the concept. Primarily a philosophical analysis, the book also covers legal aspects, with chapters on disclosure, comprehension, and competence.
Those signing the OPINION LETTER to remove RIDER against EMBRYONIC/GENETIC MANIPULATIONS are TRANSHUMANISTS with a lifetime of MOVING FORWARD these global banking 1% goals. Below we see another MEDICAL EXPERIMENT deemed CRIMES AGAINST HUMANITY------while after WW2 doctors involved in these kinds of medical atrocities were EXECUTED AND IMPRISONED-----these cases were called TOUGH DECISIONS in advancing medicine as though it is OK to label these atrocities as 'necessary' using terms like NATIONAL SECURITY. The MANHATTAN PROJECT exposed many US military to research and development exposures of high-grade radiation. That cohort alone would have given many avenues of research.
What we had with these RADIATION INJECTIONS driven by a secret group of medical doctors had nothing to do with NATIONAL SECURITY-----WW2 was over.
'With cancers and radiation sickness on the rise, these scientists knew exactly what they were doing — examining the effects of plutonium isotopes on living beings'.
This case is being made famous TODAY because it is what CLINTON era RADIATION EXPERIMENTS with BODY/BRAIN IMPLANTS was doing in 1990s and these BARBER SURGEONS think they can claim IMMUNITY because of a few PAST MEDICAL ATROCITIES done secretly.
"I was over there fighting the Germans who were conducting these horrific medical experiments," he said. "At the same time my own country was conducting them on my mother."'
FIRST, THIS IS THE CLINTON CONNECTION WITH MANHATTAN PROJECT -----SECOND----UNIVERSITY OF SAN FRAN AND UNIVERSITY OF CHICAGO -----GROUND ZERO FOR THESE MEDICAL ATROCITIES.
The connections of CLINTON----of WARREN as today's Elizabeth Warren----to these MANHATTAN experiments brought to JOHNS HOPKINS as well----show why OUR REVOLUTION for only the global banking 1% ------are FAKE POPULIST-------they are MOVING FORWARD TRANSHUMANISM------ATHEISTS/SATANISTS
Global banking 1% thinks this history of SECRET MILITARY EXPERIMENTATION exempts them from LAWSUITS and CRIMINAL PROSECUTION----when it does the OPPOSITE.
'Stafford Leak “Staff” Warren was a Colonel in the Army Medical Corps and the Chief Medical Officer of the Manhattan Engineer District (MED)'.
These TRANSHUMANISTS are saying BARBER SURGEONS do not need to give INFORMED CONSENT ----they know better.
We claim those 'BARBER SURGEONS' doing those MANHATTAN medical experiments were NOT US MILITARY-----
What was US NATIONAL SECURITY and US military in 1940-50s is the opposite of today---today we have global privatized military corporations tied to OLD WORLD KINGS-----killing our US national sovereignty---not seeing our 99% WE THE PEOPLE as citizens with RIGHTS, FREEDOMS, AND ACCESS TO JUSTICE.
'Milton Stadt, the son of a Rochester subject, told the Advisory Committee the following at a meeting in Santa Fe, New Mexico, on January 30, 1995:
My mother, Jan Stadt, had a number, HP-8. She was injected with plutonium on March 9th, 1946. She was forty-one years old, and I was eleven years old at the time. My mother and father were never told or asked for any kind of consent to have this done to them.
My mother went in [to the hospital] for scleroderma . . . and a duodenal ulcer, and somehow she got pushed over into this lab where these monsters were'.
Revealed: US Government Program Secretly Injected Citizens with Plutonium, Uranium
Published: November 3, 2015
Source: Natural Society
It sounds like a bizarre torture scenario that you’d expect to see blamed on illegal terror organizations, but the individuals behind this crime are actually doctors working for the United States government. Disregarding the health of innocent citizens, the government testers were eager to see how unknowing participants suffered as a result of secret plutonium injection.
It began in 1945, when an employee at the Oak Ridge Nuclear Facility was in a car accident. Ebb Cade survived, but was taken in as a human participant in a disturbing study he did not consent to. It is important to note that this man was a fifty-three-year-old African American, as previous government trials have singled out African Americans and other minorities.
The racist sterilization programs occurred between 1929 to 1974 under an admitted eugenics programs that officials claimed were ‘creating a better society’. Most victims were poor, black women who were ‘deemed unfit to be parents’. Individuals as young as 10 were sterilized simply for not getting along with schoolmates or being promiscuous, and many parents were misled into sterilizing their children.
Ebb Cade was taken and bound to a bed with a broken arm and leg, where doctors interviewed him regarding his current state of health. After determining he was in a state of proper health, doctors secretly injected him with 4.7 micrograms of plutonium on Aptil 10th. It is still unknown who exactly ordered the program within the U.S. government, as they have managed to disassociate themselves with the entire nefarious program. At the time of the injection, scientists were perfectly aware of the negative effects associated with radiation. With cancers and radiation sickness on the rise, these scientists knew exactly what they were doing — examining the effects of plutonium isotopes on living beings.
Prior to the tests on Cade, the scientists injected animals with plutonium and noted the severe adverse effects. In some cases, animals were even fed radioactive waste. In fact, one scientist received a face full of gas and required his stomach to be pumped along with a full face scrub in an attempt to eliminate the threat. The scientists made sure that they were given the full treatment after the exposure. Meanwhile, they were injecting individuals with plutonium.
Scientists took excretions from Cade over the next five days to see how much plutonium retained in his body. They also refused to set his broken bones until April 15th, and cut samples from the bone before doing so to examine the plutonium content in his bone tissue. Fifteen of his teeth were pulled for testing. After all of this, they never informed Cade what they were doing. One nurse said that the tortured Cade escaped in the middle of the night, and he was later found to die in 1953 of heart failure.
HOSTING SERVER NOSY NEIGHBOR as BARBER SURGEON has his NOSY NEIGHBORS following me around pretending I am trying to escape ------as VICTIM OF ILLEGAL RADIATION EXPERIMENTAL STUDIES.
Sadly, Cade was not the last test experiment.
Three human experiments followed, all cancer patients seeking treatment. Instead of treatment, the patients were injected with deadly plutonium in order for government scientists to see the effects.
A man in his sixties with lung cancer, a woman in her fifties with breast cancer, and a “young man” with Hodgkin’s lymphoma were all given the poison. Conveniently, the third patient’s records are not available. He was injected with fifteen times more than any other individual, at 95 micrograms.
MOST OF THESE VICTIM PATIENTS DID NOT HAVE CANCER BUT ORDINARY MEDICAL CONCERNS WHEN THEY WENT TO THE HOSPITAL.
What followed is further widespread testing.
The University of Rochester joined the program, injecting patients with not only plutonium but radioactive isotopes like polonium and uranium. Other institutions like the University of California soon followed suit.
Perhaps most concerning is the fact that this disgusting disregard for human health is not an isolated incident. The Tuskegee syphilis experiment is but one example of secret government human experiments that have run rampant throughout recent history. Taking place between 1932 and 1972, Tuskegee, Alabama, the U.S. Public Health Service knowingly infected poor black men with syphillus in order to test the effects. These men thought that they were receiving free healthcare by the U.S. government.
The list goes on, targeting minorities and the disabled in particular. From forced sterilizations to incognito injections, there is a lengthy history of government testing that shows the blatant disregard for your health by the United States government and elsewhere. With this in mind, is it any wonder why the FDA keeps toxic substances like mercury unregulated among the food supply?
This article is current---2019 written by family OF VICTIMS of MANHATTAN PROJECT medical atrocities. Global banking 1% offer articles and REDACTED TRANSCRIPTS from this period many of which indicate only people terminal were used when in fact most people used were RELATIVELY GOOD HEALTH----broken leg----stomach ulcers----skin disease vectors not fatal.
The LEGAL STANDING of calling PATIENTS----PRODUCTS as is being done with ME----was done back then as well.
Today's SICKO health status for our US 99% WE THE PEOPLE are a result of these 1940-50S era secret medical experiments hitting several hundreds of people----allowed to go MAINSTREAM AS EVIDENCE-BASED MEDICINE.
Again, this is NOT OUR US GOVERNMENT----these structures happened during HITLER/STALIN WW2 to GULAG and soldiers because it is global banking 1% OLD WORLD KINGS----KNIGHTS OF MALTA TRIBE OF JUDAH doing this---
THIS IS NOT ALL-AMERICAN PUBLIC HEALTH.
The lady below is JEWISH as VICTIM of MANHATTAN PROJECT------so, black, white, or brown-----REAL 99% Jewish, Protestant, Muslim, Catholic, HINDI-BUDDHIST get HIT in MOVING FORWARD TELEMEDICINE FOR ALL.
CHADWICK thinks medical ethics are still evolving------CHADWICK is one of the TRANSHUMANIST MOVING FORWARD TOTAL BODY/BRAIN IMPLANT HUMAN INTEGRATION with computers.
'Gary L. Chadwick, Pharm.D., M.P.H. - University of Rochester ...
Gary regularly conducts training sessions and program audits for universities, hospitals and professional societies. Dr. Chadwick is a past President of Applied Research Ethics National Association (ARENA) - the national association for IRBs. Gary was the founding Chair of the Council for Certification of IRB Professionals (CCIP)'.
Manhattan Project: URMC involvement in deadly plutonium injections revisited
Justin Murphy, Rochester Democrat and Chronicle Published
8:10 a.m. ET April 10, 2019 | Updated 4:07 p.m. ET April 10, 2019
Here's a breakdown of the stories right now at
www.democratandchronicle.com. Virginia Butler, Democrat and Chronicle
From 1945-47, doctors at Strong Memorial Hospital secretly injected 11 people with plutonium.
URMC held a discussion of the episode Tuesday, including family survivors.
Part of the focus was on how medical ethics have changed in the last 70 years.
The doctors asked Janet Stadt: Can we move you into a more comfortable room? One where we can offer a better sort of treatment?
And why would she say no?
The 41-year-old hairdresser was at Strong Memorial Hospital with scleroderma, a rare connective tissue condition that at that time, 1946, was often fatal. She had come to Rochester from Belarus, where she was subject to violence as a Jew. The state-of-the-art medical facilities must have seemed magnificent.
Stadt never learned what that better treatment amounted to. All she knew was that after March 9, 1946, she became a very sick woman. She lived an addtional 29 years, undergoing multiple bouts with cancer and frustrating her friends and family who believed her to be a hypochondriac, always complaining about something.
The grave of Harry W. Slack is covered with fall leaves at the Irondequoit Cemetery Friday, November 10, 1995. Slack was one of the Strong Memorial patients secretly injected with plutonium in 1946. (Staff Photo/Shawn Dowd)
The grave of Harry W. Slack is covered with fall leaves at the Irondequoit Cemetery Friday, November 10, 1995. Slack was one of the Strong Memorial patients secretly injected with plutonium in 1946. (Staff Photo/Shawn Dowd) (Photo: Shawn Dowd, Yes-GRN)
It was not until 1992, 17 years after her death, that her family found out she was one of 18 people whom the United States government had secretly injected with plutonium from 1945 to 1947 as part of the Manhattan Project.
None of them ever found out.
"She left (Belarus) to avoid persecution, and she came here and got injected with plutonium," her grandson, Jon Stadt, said Tuesday.
Of the 18 people, 11 were injected at the University of Rochester. The story was a massive scandal when Eileen Welsome, a reporter at the Albuquerque Tribune, published a Pulitzer Prize-winning exposé in 1993.
The families ended up winning a financial settlement from the university. But this Tuesday was the first time UR reopened the painful episode for public examination, hosting a roundtable discussion on the topic with Welsome, Stadt, a bioethicist and the nephew of another experiment subject.
Patients were never informed
In 1945, World War II was still underway and the United States was racing to understand and harness the destructive properties of plutonium, uranium and other elements. The effort was labeled the Manhattan Project, and it resulted in the atomic bombs that fell in Hiroshima and Nagasaki, Japan.
While one army of researchers was trying to figure out how to design plutonium-based weapons, another was studying what the health effects would be. That work was done in labs in Berkeley, California; Los Alamos, New Mexico; Chicago; and Rochester.
Under the supervision of the Department of Defense, a select group of doctors were asked to inject unwitting patients with catastrophic amounts of plutonium, uranium and polonium. None were informed, either in advance or afterward. The intention was to find people with terminal illnesses, though that directive was ultimately not followed.
John Mousso was another unwitting subject. His nephew, Jerry Mousso, later helped organize a survivors' group. In one instance, he said Tuesday, doctors accidentally dropped a vial of uranium on the floor before they could inject it into a woman. It burned a hole in the floor.
The 18 subjects had greatly varying experiences after the plutonium exposure, Welsome said, surviving from 6 days to 29 years afterward. Many suffered from various cancers, mental health problems and other illnesses.
President Bill Clinton formally apologized for the incident in 1995 and the government paid $4.8 million in damages.
CLINTON FAMILY MEDICAL CORPORATION WAS TIED TO THIS MANHATTAN PROJECT CRIMES AGAINST HUMANITY.
Stadt said the money didn't help his family forget the issue. He recalled the first day he received a large box in the mail from the Department of Energy containing recently declassified information about his grandmother that he never possibly could have imagined.
She was labeled HP-8. The acronym, Welsome said, was for "human product."
"It slowly turned me into a very skeptical person with anything to do with government," said Stadt, now the owner of Flour City Pasta.
The illicit injections were only one of several instances of unethical medical testing carried out by the U.S. government in the 20th century; the syphilis experiment in Tuskegee, Alabama is another. The discussion Tuesday was intended in part to encourage current medical providers to think about the ethical implications.
One particularly incriminating factor: while the injections were limited to 1945-47, the research component of the experiment extended for at least 20 more years, including after the project was declassified. Stadt said his grandmother was exhumed and had her bones transferred as late as 1989.
Dr. Gary Chadwick, former director of school's Office for Human Subject Protection, said the concept of informed consent in the 1940s was still very much evolving — as indeed it is today.
"We're still learning about how to treat our fellow human beings when they move from being a patient in a medical setting to a subject in a research setting," he said.
This article tells us there is another SUCCESS with GENE EDITING----THERAPY tied to SICKLE cell. The MEDICAL MEDIA OUTLET is FAKE NEWS FAKE DATA tied to BOSTON MASS HARVARD CHAN PUBLIC HEALTH SCHOOL.
Remember, global banking 1% are DESPERATE to show some success for these few decades of a trillion dollars in Federal research tied to GENETIC THERAPIES. This case of gene therapy with sickle cell is MORE LIKELY the process below called THERAPEUTIC PLASMA EXCHANGE----TPE---which is NOT gene therapy. It involves cryotherapy and BLOOD TRANSFUSIONS.
This young man no doubt had half of his blood removed and treated to be rid of red blood cells as SICKLE CELL---while the blood remaining in his body received red blood cell elimination ---then transfused blood sent back to body is augmented by fresh blood of this man's blood type.
Cytapheresis= cell removal or exchange (requires centrifugal machine)
Conventional Therapeutic Apheresis Modalities
Leukapheresis= white cell apheresis
Erythrocyt-apheresis = red cell exchange(sickle cell, etc.)
11.1: Therapeutic plasma exchange (TPE)
TPE removes large-molecular-weight substances such as harmful antibodies from the plasma. It is usually carried out using an automated blood cell separator to ensure fluid balance and maintain a normal plasma volume. This may require the insertion of a femoral or jugular line to allow adequate blood flow. Typically, 30–40 mL/kg of plasma (1–1.5 plasma volumes) are removed at each procedure and replaced with isotonic 4.5 or 5.0% human albumin solution (some services substitute 25–50% of replacement volume with 0.9% saline). Exchange with fresh frozen plasma (FFP) is reserved for the replacement of ADAMTS13 in thrombotic thrombocytopenic purpura (see below) or to replace clotting factors. A one plasma volume exchange removes about 66% of an intravascular constituent and a two plasma volume exchange approximately 85%. TPE is normally combined with disease modifying treatment, such as immunosuppressive drugs, for the underlying condition.
11.1.1: Indications for therapeutic plasma exchange
TPE should only be carried out in conditions where there is good evidence of its effectiveness. The American Society for Apheresis (ASFA – http://www.apheresis.org) produces regularly updated evidence-based guidelines (last updated in 2010). Table 11.1 shows the 2010 category I ASFA indications for TPE (recommended as first-line therapy). Category II indications (TPE is an established second-line therapy) are shown in Table 11.2. The evidence base is constantly developing and the decision to implement a course of TPE will usually involve discussion with a transfusion medicine specialist or other expert from the team providing the therapy.
Table 11.1 ASFA Category I indications for therapeutic plasma exchange (first-line therapy based on strong research evidence)
The problem with this procedure being experimental ----is that nothing says these SICKLE CELLS taking over RED BLOOD CELLS will not come back----it is not a PERMANENT REMISSION as research knows it.
So, is this REAL SUCCESS in GENE THERAPY?
We are almost sure IT IS NOT. Please stop allowing BARBER SURGEONS and global banking 1% KRACKEN MEDICAL CORPORATIONS sell FAKE DATA FAKE MEDICINE -----with goals of TRANHUMANISM killing our US 99.9% of WE THE PEOPLE.
'New Gene Therapy Shows Promise For Patients With Sickle Cell Disease05:16
March 08, 2019Updated Mar 18, 2019 12:00 AM
A Therapy More Than A Decade In The Making
January-February 2018, Volume 15, Issue 1'
Successes in Gene Therapy: 2017
Jonathan Hoggatt, PhD Assistant Professor, Cancer Center and Center for Transplantation Sciences
Massachusetts General Hospital/Harvard Medical School, Boston, MA Published on: January 09, 2018
September 14, 1990.
Anaheim, California: The Seattle Mariners were playing the California Angels. In the first inning, Ken Griffey Sr. hits a home run to center. Next at bat, his son Ken Griffey Jr. hits a home run to left center, becoming the first father-son duo to hit back-to-back home runs in a major league game.
New York, New York: Madison Square Garden is packed as the Grateful Dead kick off the first of six shows in NYC as part of their tour. The set starts off with Feel Like a Stranger and ends with U.S. Blues.
Bethesda, Maryland: Four-year-old Ashanti DeSilva lies on a bed in the National Institutes of Health’s Clinical Center. Diagnosed with adenosine deaminase severe combined immunodeficiency (ADA-SCID), and no longer responding to PEG-ADA, Ashanti becomes the first patient treated with gene therapy.
Twenty-seven years have since passed, and while Ken Griffey is now retired and Grateful Dead is winding down as Dead and Company, gene therapy is on a remarkable upward trajectory. 2017 is clearly the year when decades of work are finally coming to fruition.
The Ernest Beutler Lecture and Prize was fittingly awarded at the 2017 ASH Annual Meeting to Luigi Naldini and Marina Cavazzana who have been pioneers in driving the field of gene therapy forward. Their lectures eloquently highlighted the long scientific and clinical pursuit that has led to the successes we are seeing today. Patients with ADA-SCID, X-SCID, metachromatic leukodystrophy, Wiskott-Aldrich syndrome, Beta-thalassemia, and other diseases have been treated because of the continued pursuit to advance gene therapies.
The first hematologic gene therapy approval took place in Europe in 2016 with Strimvelis for the treatment of ADA-SCID. In 2017, the first two patients were treated with the commercial product, a remarkable achievement for this year on its own. However, there have now been three gene therapies approved in the United States in 2017. Kymriah, a chimeric antigen receptor T cell (CAR-T) therapy for acute lymphoblastic leukemia; Yescarta, a CAR-T therapy for non-hodgkin’s lymphoma, and Luxturna, an adeno-associated virus (AAV) to correct RPE65 mutations that cause retinal dystrophy.
These clinical approvals pave the way for a wide variety of gene therapies that have made significant steps towards clinical use in the past year. At the 2017 ASH Annual Meeting, clinical data on other AAV products for hemophilia A1,2 and hemophilia B3 were presented. New gene therapy approaches in X-SCID using self-inactivating virus and mild conditioning have shown promising results in generating multi-lineage chimerism.4 Advanced follow-up of patients treated with a lentiviral gene therapy for beta-thalassemia are showing evidence of transfusion independence in 2017,5 and advances in gene-modified cell delivery directly into the bones may increase the efficacy of gene therapy for beta-thalassemia6 and other diseases. As vector development and conditioning regimens continue to improve, gene therapy in sickle cell disease is also beginning to take shape in 2017.7 CAR-T therapies, which use gene therapy techniques to add the chimeric receptor, were so prominent in the 2017 meeting it is impractical to highlight them all here. Hematologists are also leading the way in using gene modified hematopoietic stem cells to treat non-hematologic disorders, such as the phase 2 to 3 data published this past year treating patients with cerebral leukodystrophy.8
As this 2018 edition of The Hematologist hits our readers’ mailboxes, these are the advances I am looking forward to this year. In hematopoietic stem cell therapies, integrating lentiviruses are leading the way, but I expect considerable advances at the pre-clinical or clinical stages of gene editing techniques using CRISPR-cas9 to be headliners at the 2018 meeting. More follow-up, and importantly, larger cohorts of patients across all the diseases discussed above will happen over the next year, and 2018 may be a time when “curative therapy” is attached to more of these strategies. Finally, this year will see a lot of talk about the cost of this new class of medicine – a lot of talk. Clinics providing these new therapies will struggle with costs, patients will have access issues, and ever-increasing ingenuity with reimbursement/payment/money-back guarantees will be constantly in the news. These are important issues, but my hope is that these issues do not distract us from what we are witnessing in our field. Dogged determination in the laboratory and the clinic are leading to incredible results for patients. The first gene therapy approval in the U.S., followed by two more in the same year, seems to be one for the record books, just like father and son back-to-back home runs.
We will leave the discussion of today's MOVING FORWARD mitochondrial genetic therapies filled with FAKE DATA FAKE NEWS bringing billions and billions of research funds and PATIENTS which like PHARMA end in CLASS ACTION LAWSUITS having damaged, killed, been ineffective.
We will return to CLINTON era RAC COMMITTEE tied to the beginning of GENETIC THERAPY studies with this group tasked to oversight and accountability during CLINTON total deregulation of all that is FEDERAL AGENCIES----including medical research. CLINTON FAMILY owned the outsourced corporation tied to MANHATTAN PROJECT and those MEDICAL ATROCITIES----so, BILL AND HILLARY not interested in KNOWING THE TRUTH.
Below we see 2018 what was created in 1995 is being dismantled----no more need to pretend to provide oversight and accountability says LIEBERT----owner of global medical corporation tied to gene editing and FAKE THERAPY products.
HMMMMMMM, YOU SAY THEOLOGIAN AND I SAY FAKE RELIGIOUS LEADERS-----
'The Committee was composed of stakeholders, including basic scientists, physicians, ethicists, theologians, and patients advocates'.
THE CLINE AFFAIR was the earliest OUTING of these genetic therapy research being based on BOGUS DATA------after this
CLINE AFFAIR the FAKE DATA TO BILLION DOLLAR MEDICAL GENE THERAPY PATENTED PRODUCT SOARED.
September 19, 2018
Is the end of the recombinant DNA Advisory Committee
(RAC) a good thing?
by Mary Ann Liebert, Inc
Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans.
Credit: Mary Ann Liebert, Inc., publishers
Recently, the U.S. National Institutes of Health (NIH) and Food and Drug Administration (FDA) called for the eliminating involvement of the Recombinant DNA Advisory Committee (RAC) in human gene therapy experiments, marking the end of an era of federal government oversight. While the RAC played an essential role in helping human gene therapy research evolve to where it is today, James M. Wilson, MD, Ph.D., Editor, Human Gene Therapy Clinical Development, believes this is the right moment for it to exit the stage, as he explains in his Editorial "The RAC Retires After a Job Well Done," Human Gene Therapy Clinical Development.
The RAC initially set guidelines for DNA research, and its role was later expanded to en-compass the review and approval of human gene therapy research. The Committee was composed of stakeholders, including basic scientists, physicians, ethicists, theologians, and patients advocates. "The deliberations often became theatrical and, at times, quite contentious," says Dr. Wilson. Over the years, as the field of human gene therapy ma-tured and became more integrated into the biopharmaceutical industry the potential re-dundancies between the roles of the FDA and the RAC became an increasingly important issue.
"The 2018 proposal...is to completely eliminate the RAC's role in reviewing or monitor-ing human gene therapy studies," says Dr. Wilson. "The new recommendations retain the role of local Institutional Biosafety Committees in the review process, while limiting their evaluation to an assessment of biosafety risks."
Below we see the BIOETHICS of today's TRANSHUMANISTS------we showed these few weeks how absolutely NO scientific method or reliable results even in animals stops MOVING FORWARD EXPERIMENTAL RESEARCH in HUMANS as those FDA AND NIH agencies and this FAKE BARBER SURGEON -----KNOWS.
James M. Wilson, MD, Ph.D., Editor, Human Gene Therapy Clinical Development
This article written in 2001 was well after the 1995 creation of RAC-----and this one study----THE CLINE AFFAIR was a POSTER CHILD for the attitudes and bioethics following RAC.
RAC says of CLINE-------WE DIDN'T SEE THAT COMING!
History| Volume 4, ISSUE 5, P396-397, November 01, 2001
“Cline has done this experiment in the mouse and, as I understand it, it didn't work.
He has made a great conceptual leap from the failure in the model system to trying it in humans.
He is saying, ‘It didn't work in mice, so I'm going to try it in man’” [quoted in].
This was but one of the numerous criticisms voiced when the news media reported that Martin Cline of UCLA had attempted to treat two patients with severe β-thalassemia by transfecting marrow cells with a recombinant human globin gene with a selectable marker. Probably as a result of the furor that arose, not all of the details of the experiment were published. However, relying on his published animal experiments and accounts of the clinical study as they appeared both in the scientific press and in a review written by Cline in 1985 .
I shall try to address the following questions. Did this system work in mice? Was the extensive criticism that was leveled at Cline justified? What impact, if any, did this event have on the subsequent development of human gene therapy?
No wild-eyed renegade, Martin Cline was a highly respected biomedical scientist. Head of the hematology division at UCLA, he had a distinguished and productive career in performing research at the interface of clinical medicine and basic science. He began to work with DNA long before most other clinical investigators. Having initiated one of the early bone marrow transplantation programs at UCLA, his understanding of hematopoietic stem cells and of gene transfer technology qualified him ideally to perform gene transfer studies in humans with genetic diseases of hematopoiesis.
The experiment took place in July, 1980 [
]. Two patients with severe β-thalassemia were the subjects of the study. Marrow cells were transfected with a recombinant genomic β-globin and herpes virus thymidine kinase clone as a selectable marker. About 109 cells were then infused into each patient after a segment of femur had been irradiated with 300 rads [
]. There was no clinical benefit to the patients
1It is difficult to accept the claim that viral sequences were detected in the peripheral blood of the patients for up to 10 weeks after the infusion of 109 marrow cells. A 50-kg patient is estimated [
] to have approximately 1012 nucleated marrow cells. If the transfection efficiency is estimated to be of the order of 1:100,000 (10−5; [
]), 104 of the infused cells would contain the viral DNA, which would be approximately one cell per hundred million marrow cells. No effort to select with methotrexate was made and, even with incorporation of multiple copies of the gene, it is difficult to conceive that Southern blot analysis could detect such a low-abundance gene. Indeed, Cline [
] estimated that, in what he termed an optimistic analysis, an innoculum of 109 marrow cells would contain one pluripotent stem cell.
, and they were not harmed, but it developed that Cline had not received permission from UCLA's institutional review board. Although permission had been obtained from the institutions in Jerusalem and Naples where the studies had been performed, it seems that the protocol was modified after permission had been obtained.
Had this approach been validated with animal studies?
Indeed, Cline had published two papers in major journals, one in Nature in which mouse marrow cells had been transfected with dihydrofolate reductase (DHFR) and one in Science in which the herpes simplex thymidine kinase gene had been used to induce methotrexate resistance. The studies were elegantly designed. Marrow cells from a mouse strain with a marker chromosome (T6T6) were transfected and mixed with sham-transfected cells from the wild-type strain. The ratio of injected cells was compared with the ratio as determined by karyotype studies of the irradiated, reconstituted mouse. All appropriate controls were done. But in neither case was the recombinant construct that was used in the clinical trials studied. The investigations of DHFR are not particularly relevant to the subsequent human studies, because this selectable gene was not used. However, the effect of DHFR was modest at best: with methotrexate treatment of the animals, a selective effect was seen in five independent experiments involving 19 mice, and in two experiments no effect was seen. In the case of the herpes simplex thymidine kinase, the data were even more sparse. Results are reported in only two animals in which the percentage of cells with the T6T6 karyotype were 74% and 84%, respectively, when an absence of any effect would have given a 40% value. Two years later additional data were published on 93 mice that received a mixture of herpes virus thymidine kinase transformed and mock transformed marrow. Perhaps these data were available to the investigators at the time of the clinical trial, but the results were not impressive. Only “33 percent of animals demonstrated at least transient predominance of the karyotype of the transformed marrow population; however, with all tk vectors, karyotype predominance was stable for more than two months in only 13 percent of animals” [
]. As we are not told what percentage of the mice showed at least transient predominance of the mock transformed cells, and there must have been some such animals, it is not clear that any effect, even the transient one, was actually demonstrated in this larger group.
It is evident, then, that clearly positive results were not obtained in mice. However, success in animal studies should not be made a prerequisite to all human clinical investigations; negative animal studies do not preclude success. They merely make success much less likely. Nonetheless, the success or failure of investigations in animal models must have a role in making a risk/benefit assessment. Even had the murine data shown that there was considerable selection in favor of the transformed cells the chances for success of the human studies would have been vanishingly small. It would be less than fair, however, to suggest that as knowledgeable and insightful an investigator as Cline was unaware of this fact. Indeed, Cline states that “the patients were told that the likelihood of it working was very small.” It is obvious that his intent was to test the technology [
]. To perform such investigations is a standard practice in the testing of drugs. The principal purpose of “phase 1” studies is to establish a tolerated dose. If a therapeutic effect is achieved, well and good, but therapeutic success is not a primary goal. Of course the risk/benefit ratio must be taken into account, and this becomes increasingly difficult as both the risk and the potential benefit approach zero. It must be remembered that in the time during which these studies were performed there was anxiety bordering on hysteria concerning the risks of recombinant DNA.
Fostered in part by the molecular biology community itself, this unreasonable fear was nonetheless a fact of life, and probably contributed, at least in part, to the harsh reaction to Cline's studies. In actuality the 300 rads of ionizing irradiation delivered to these patients probably constituted more of a risk, especially because they were clearly not terminally ill, as suggested by one of the news reports [
]. Nearly five years after the experiment they were stated to be in essentially unchanged condition [
Perhaps more important was the fact that Cline had violated the rules that had been established. Although he thought that consent of the institutions where the work was to be done was sufficient, this was not the case, and Cline himself later acknowledged that he had “exercised poor judgment in failing to halt the study and seek appropriate approval” [
Review of the entire episode leads to the conclusion that the clinical studies undertaken by Cline and his colleagues in 1980 were premature. The vehemence of the reaction may well have been conditioned, at least in part, by personal considerations. This event may actually have had a somewhat favorable effect on the development of gene therapy. First, it put clinical investigators on notice that it was necessary to adhere scrupulously to the rules that had been established. Second, because no harm came to the patients, the studies may have helped to abate the unreasoned fear of the consequences of administering recombinant DNA molecules. Yet beyond its effect on the development of gene therapy, the episode is a tragic one because it interrupted the efforts of a highly talented, productive scientist who was in too much of a hurry to see patients benefit from the marvels of modern molecular biology.
HURRY TO SEE THE BENEFIT TO PATIENTS OR HURRY TO BENEFIT FROM PRODUCT PATENTS?