Replies

Auschwitz

Experimental Auschwitz
Auschwitz applied most of its energies to killing people, but its openness to virtually any form of human manipulation inevitably resulted in a wide variety of additional experiments. Eduard Wirths, as chief doctor, was the Auschwitz sponsor and facilitator of most of these experiments, particularly those in which there was interest from Berlin at a higher level. An example here is the continuous experimental activity of SS Captain Dr. Helmuth Vetter, a key figure in pharmacological “trials” in Auschwitz and elsewhere. He was employed for many years with Bayer Group WII of the I. G. Farben Industry, Inc., Leverkusen, and, at Auschwitz, retained his connections. He ran medical trials for Bayer in Auschwitz and Mauthausen (and possibly in other camps) on several therapeutic agents, including sulfa medications and other preparations whose content is not exactly known.*
Vetter commuted between Auschwitz and Mauthausen in order to supervise the study of the effects of “ruthenol” and “3582” on many different serious medical conditions (typhus, typhoid, paratyphoid diseases, diarrhea, tuberculosis, erysipelas, and scarlet fever among others); but of the 150 to 250 patients he gave these medications to on the contagious disease ward in Auschwitz, about 50 were suffering from typhus. The impression of prisoner doctors was that these agents were of no therapeutic use, and some patients seemed to die quickly after receiving them. Vetter was reluctant to accept these negative findings, always insisting that better results had been obtained in other camps.⁵⁰
Vetter drew other SS doctors into his research, including Eduard Wirths. The latter became not only what one observer called Vetter’s “official deputy” in Auschwitz but later actively pursued typhus trials himself, in which four Jewish inmates, artificially infected with typhus because there were no active cases available, were killed. These were apparently an extension of Vetter’s work. Vetter represents the Nazi research functionary, in whom ordinary medical vanities became lethal. He found in Auschwitz a testing area where he need not be restrained either by compunctions about harming — or killing — research subjects, or by rigorous judgments about therapeutic effects.
__________
* Among these preparations were ones numbered 3582 (a nitroacridine preparation), V1012, and ruthenol (a combination of preparation 3582 and arsenic acid).

London

Drug trial disaster baffles experts, but report clears firm
By Jenny Booth and agencies
An interim report from Britain's medicines watchdog today said there was no obvious explanation for what went wrong during a catastrophic drug trial which left six volunteers near death.
Six healthy young men suffered organ failure and violent, life-threatening side-effects after being injected with the anti-inflammatory drug TGN1412 during a clinical trial in north-west London on March 13.
One volunteer injected with a placebo instead of the real drug described how he watched his fellow volunteers at Northwick Park Hospital screaming and vomiting and passing out within minutes of the injections.
The men, who were paid £2,000 to take part in the trial, were taken from the small private research unit to the intensive care department of the adjoining NHS hospital, and placed on life support.
The drug was developed by TeGenero, a small German research company, as a possible treatment for rheumatoid arthritis, leukaemia and multiple sclerosis.
After laboratory analyses and tests on animals, TGN1412 was cleared for its first trials on humans, which were carried out by Parexel, a medical research company. The human volunteers were given doses 500 times lower than those given to monkeys.
Today the Medicines and Healthcare Products Regulatory Agency said that its investigation into the incident had found no evidence that there was any problem with the way the drug was manufactured or administered.
"There’s no simple explanation of what happened," said Professor Kent Woods, the chief executive of the MHRA, which regulates 350 Phase 1 clinical trials -- the first testing on humans -- in the UK every year.
In a statement, Professor Woods added that the drug did not appear to have been contaminated "or to have contained anything other than the correct ingredients".
"Neither have we found anything in the way the trial was run which contributed to the adverse reactions experienced by the volunteers – it was run according to the agreed protocol, and the correct dose of the product was given to the patients."
The MHRA said that its findings were not conclusive and there was more investigation still to be done. "There are still further tests planned and until these are complete we cannot be firm about our conclusions. However, if these findings were to be confirmed, it would indicate that this product showed a pharmacological effect in man which was not seen in pre-clinical tests in animals at much higher doses.
"The Secretary of State for Health has therefore agreed to establish a group of leading international experts in the field to examine the issue further. The group will need to review the evidence from the TGN1412 case and consider what necessary changes to clinical trials may be required."
Sam Lister, Health Correspondent for The Times, said the inability of the MHRA to identify an obvious mistake in the conduct of the trial only increased the doubts surrounding the testing of radical new drugs.
"The findings of the interim report cast further uncertainty over the entire field of biological agents with novel modes of action, such as TGN1412," he said.
"While the discovery of human error, contamination or a diversion from the agreed trial protocol would have allowed the investigation to focus on a specific problem, the actual pharmacological cause of the disastrous adverse reactions in humans still remains unknown."
TeGenero welcomed the report. "We are grateful to the MHRA for their conduct of this investigation," the company said in a statement. "The preliminary findings of the investigation underline that we observed the highest standards in developing this drug and that these symptoms were both unexpected and unforeseeable."
But Martyn Day, a solicitor representing four of the volunteers, said the MHRA's interim findings left a series of questions unanswered and claimed that his clients were unaware that they would be testing such an innovative drug.
"If it had been explained that it was so new, then there’s not the slightest chance that one of them would have gone through with the test. For £2,000? Not the slightest chance," he said.
Mr Day also questioned why the men were injected with the drug in quick succession. Mr Day said nurses gave the volunteers their doses of TGN1412 within ten minutes of each other, rather than testing one man and waiting to see if any vigorous side-effects took hold.
The Academy of Medical Sciences appeared to support his contention today, issuing a paper called Testing Antibody Therapies, which highlighted what it called "usual practices" for administering drugs in Phase 1 trials.
"It would be usual practice to administer a single dose in a single patient, who would then be observed for an appropriate period of time," the paper said.
Today a fifth victim of the drugs trial was allowed to go home. Only one of the six volunteers now remains in Northwick Park Hospital and he is no longer in intensive care.
Dr Ganesh Suntharalingam, clinical director of intensive care at the hospital, said: "I am pleased to say that all six patients transferred to us from the Parexel unit have now been discharged from critical care, and five have now gone home.
"One patient continues to receive treatment in hospital and is making steady progress. All the patients will remain under close follow-up by other specialists as they continue their recovery."