Deadly Side Effects New Details Emerge in East German Drug Test Scandal
Nicole Preiss was nine when her mother died in 1986. The woman had been stricken by skin cancer, which was deemed benign at first. But there was something, a strange remark, that little Nicole didn't understand. Why on earth, her stone-faced father and grandparents had asked at the time, did the doctors administer "drugs from the Berlin Westapotheke pharmacy " to her? And why did her condition worsen considerably after that?
Preiss, now 37, is still searching for answers today, still trying to understand what East German doctors did to her mother at a hospital in the city of Erfurt.
She suspects the doctors were testing a new drug from the West on their patient. "My mother's case was even presented in the lecture hall," says Preiss. But the treatment didn't do her any good. "There are too many secrets associated with her death, at the age of only 30," says her daughter, who is now seeking to finally gain access to the files and find answers to the questions of which drugs, which tests and which pharmaceutical companies played a role in her mother's death.
Some 50,000 Participated in Drug Tests
Preiss isn't the only one. Apparently at least 50,000 people in the German Democratic Republic (GDR), or East Germany, served as test subjects for the Western pharmaceutical industry, often unknowingly. Drug manufacturers, especially from West Germany, Switzerland and the United States, engaged GDR hospitals to perform more than 600 clinical drug trials, some with fatal consequences. This emerges from previously unknown documents, to which SPIEGEL has gained access, from the private archives of individual physicians, from the files of the former East German Health Ministry and the Ministry for State Security (Stasi), as well as the country's Institute for Drug Regulatory Affairs.
The East German institutions participating in the arrangement included internationally renowned university hospitals, like Charité Hospital in East Berlin, as well as more than 50 hospitals throughout the country, in such cities as Dresden, Erfurt, Halle, Jena and Rostock.
Virtually every major name in the pharmaceutical industry was involved, including Bayer, Schering, Hoechst, Boehringer, Pfizer, Sandoz and Roche. The companies administered everything produced in their research laboratories: chemotherapy drugs, antidepressants and heart medications, as well as other substances fresh from the laboratory, the effects of which were still largely unknown to scientists.
Human trials are among the darker chapters of the pharmaceutical industry's history. Medical progress has always claimed victims. But medical research becomes particularly dangerous to patients when efforts to benefit mankind are dominated by the quest for quick profits. When this happens, researchers overstep limits that should never be exceeded, jeopardizing the health and lives of people in the interest of improving a company's bottom line.
Today drug manufacturers depend on emerging economies like India, China and Russia when they want to test new drugs quickly and inexpensively. In the 1970s and 80s, though, the ideal testing ground was conveniently nearby: in East Germany.
The mechanism is similar today to the way it was back then. Many patients don't know what their doctors are prescribing to them, regulators in partner countries dispense with thorough testing to secure urgently needed hard currency or modern medical technology, and a critical public hardly exists at all.
The West's Responsibility
The human trials that were conducted in East Germany on behalf of West German firms still haven't been fully investigated, although Germany's current coalition government of the center-right Christian Democratic Union (CDU) and the pro-business Free Democratic Party (FDP) will address the issue on Tuesday. The effort to come to terms with the former East German dictatorship should not consist solely of addressing the issues surrounding the country's notorious secret police, the Stasi, reads a motion for debate in the German parliament, the Bundestag. According to the motion, drug trials in East German hospitals demonstrate that "West German companies also profited," just as they did from forced labor in East German prisons. The lawmakers argue that, for this reason, "society and the scientific community should focus more heavily on" the West's responsibility.
But that is a responsibility that the former business partners have shirked until now. Hospitals are either unwilling to release their records on drug trials involving their patients or they have already destroyed them. This was Nicole Preiss's experience when she wanted to review her deceased mother's medical file, but she isn't the only one.
Pharmaceutical industry leaders are being especially uncooperative. The data from the clinical trials are stored in their archives, and if a number of industry executives have their way, that's where they will stay.
"I don't want to see these kinds of investigations here," says Ulrich Vorderwülbecke. He is the director of Research-Based Pharmaceutical Companies (VFA) and has been working as a lobbyist for the last 30 years. "There have been no suspicions so far that something shady was going on," he adds. Vorderwülbecke suggests that an "outside authority," perhaps headed by the German Interior Ministry, should address the issue.
When individual companies are asked today about their former business practices in East Germany, they are suddenly overcome by amnesia. "Well, that was a long time ago," they typically respond. Employees who might be able to provide information on the issue, they say, are no longer employed there, deceased or suffering from dementia. Some companies refuse to talk to journalists altogether.
Recruiting the 'Class Enemy'
In the early 1980s, Fehrbelliner Strasse in Prenzlauer Berg, a neighborhood of East Berlin at the time, was a stronghold of East German opposition. It was home to civil rights activists like Bärbel Bohley, the Catholic congregation of Wolfgang Thierse, who is now the deputy president of the Bundestag, and a rehearsal space used by punk bands like Rosa Extra and Feeling B, a few members of which later formed the metal band Rammstein.
Other residents began noticing unusual activities taking place at Fehrbelliner Strasse 5. "We had no idea what was going on there, but different cars with West German license plates were parked outside every day," recalls Carlo Jordan, a member of the opposition who later became one of the founders of the Green Party in East Berlin.
The civil rights activists had no way of knowing that the East German health ministry had rented an apartment in the dilapidated building in 1983, which was used as a contact point for Western managers. It was officially known as the "Advisory Office for Drugs and Medical Devices" (BBA). According to visitor logs, which read like a who's who of the Western medical industry, there were weeks when up to 40 pharmaceutical industry representatives came to the office.
"Now you too can become one of our customers." Those were the words with which Joachim Petzold, the head of the advisory office, recruited the drug manufacturers, from the West, otherwise known as the class enemy during GDR times, starting in 1983. It was a breakthrough: the institutionalization of a lucrative business relationship.
Up to 800,000 Deutsche Marks Per Study
First lobbyists for the likes of Bayer and Schering had to discreetly negotiate with their East German contacts over patient trials. To that end, marketing people from the West had been regularly traveling to the Leipzig Trade Fair since the 1970s, bringing along gifts for their hosts -- based on the requests, large and small, they had previously received from the heads of East German hospitals. Many of their wishes were fulfilled, not out of charity but for business reasons. The companies donated computers and other equipment, and they also invited East German doctors to attend lavish meetings in the West.
Starting in 1983, the Western companies were able to officially submit their offers to a central office. During their visits to Fehrbelliner Strasse, the pharmaceutical representatives offered the East Germans up to 800,000 deutsche marks per study. Petzold and his comrades at the Health Ministry drummed up the funds for their republic, raising millions for the struggling East German economy. Like a pimp, their government sold its sick citizens and prostituted the country as a laboratory for the West's clinical trials.
The dismal condition of the East German healthcare system was one reason that the Western customers had such an easy job of it. Although East German doctors went to great lengths to improvise as much as possible, citizens faced growing waiting lists for life-saving operations, there was a shortage of effective drugs and necessary treatments were not performed.
Even Ludwig Mecklinger, the then East German health minister, had no illusions. In office from 1971 to 1989, he was known for bluntly stating his position, albeit not openly.
In a 1983 meeting of top East German officials, Mecklinger outlined the extent of the dire problems facing the healthcare system. Mecklinger died in 1994, but according to documents from his archives, he feared "growing frustration within the population and among doctors" in light of the state of healthcare, and noted the East Germany had "fallen almost completely behind" international standards. The country was increasingly behind the curve in all key areas of diagnosis and treatment, Mecklinger wrote, adding that East Germany was inferior to West Germany when it came to mortality rates in almost all age groups in recent years.
Alexander Schalck-Golodkowski, who consistently raised Western capital for the regime in convoluted ways, occasionally managed to come up with injections of funding for hospitals. They were then suddenly showered with gifts of disposable gloves and surgical materials, in the same way people in East Germany could briefly look forward to oranges and bananas during the Christmas season (fruits that were extremely difficult or impossible to get during other times of the year).
But his efforts were far from sufficient to rehabilitate the healthcare system. Mecklinger, Schalck-Golodkowski and a small group of experts discussed ways to address the problem. They knew that human trials were required before a drug could be approved, and they also knew that the West German Federal Health Ministry had tightened its requirements for these trials. After the thalidomide (sold under the brand name Contergan in Germany) scandal of the 1960s, the public had become far more critical in the West and was taking a more skeptical view of animal experiments and human trials.
The East German officials agreed that such problems would not arise in the German Democratic Republic (GDR). But they disagreed over how to distribute the hard currency they expected to raise. Schalck-Golodkowski initially wanted to see 60 percent of the proceeds paid to his Berliner Import & Export Gesellschaft (BIEG), whose profits went directly into the coffers of the then East German leader Erich Honecker. Mecklinger preferred to see the money invested in his backward hospitals. After 20 minutes, the meeting ended with Schalck-Golodkowski and Mecklinger agreeing to split the spoils evenly, paving the way for the advisory office in Prenzlauer Berg to begin its work.
No Objections to Using East Germans as Guinea Pigs
A profitable period began for the business partners. Take, for example, Schering. On Oct. 15, 1985, employees of the West Berlin pharmaceutical company, which Bayer acquired in 2006, made a trip to their new testing ground.
Even at the border crossing, executive board member Heinz Hannse and development head Werner-Karl Raff were given preferred treatment. They were greeted in the East by a high-ranking delegation of representatives of the Health Ministry and Charité Hospital, as well as employees of Schalck's BIEG.
The initial negotiations revolved around a series of tests of Rolipram, a psychotropic drug, a contrast agent called Echosan and Iloprost, a drug designed to treat severe circulatory disorders. The East German officials had no objection to allowing their Western partners to use the people of the GDR as guinea pigs.
During a break, one of the Schering executives took aside the Charité representative, Dietmar S. In a private conversation, the two men discussed Schering's desire to have even more drugs tested, including nifedipine, a medication to treat high blood pressure, with which the company hoped to generate substantial profits.
The Schering representative offered Charité a deal worth six million deutsche marks a year, noting that this amounted to a third of the company's entire budget for clinical trials. The GDR, he said, was an attractive business partner for Schering, and the proposed arrangement could spell the beginning of even more lucrative deals. "In our mutually commercial interest," he added, it would be preferable to leave aside the political issues involved.
He also had some good news for Charité, he said, namely that Schering executive board member Hannse had spoken with the then-mayor of West Berlin, Eberhard Diepgen. Hannse, he explained, had discussed with Diepgen "the scope of Schering's business plans with the GDR, so as to possibly set aside potential political reservations of the CDU/FDP Berlin Senate (the official name for the city government), or to secure the necessary political backing."
Conflicts and Moral Qualms
Did the West Berlin Senate provide support for patient trials in the East German dictatorship? "I can no longer recall the exact details," says Diepgen. "If that was the case, we would have treated it as a normal development at the time. We had no reason to review the medical aspects of cases under the jurisdiction of the Federal Health Office."
Stasi reports on conversations among East German doctors highlight the conflicts they faced and the moral qualms they confronted.
According to these reports, Christian Thierfelder, the director of research at Charité, sought to explain the generous offer from the West by saying that, first of all, it offered Schering the opportunity to "bolster its international standing with clinical trial reports from Charité, a reputable institution." Second, Thierfelder argued, Schering was handicapped by the fact that it "could not perform certain tests in West Germany, because of the prevailing public mood there." For this reason, he added, Schering was interested in having trials performed at Charité "that the press in the West has already portrayed as undignified and inhumane."
The company, Thierfelder said, apparently had "general ethical problems when it comes to using human beings as guinea pigs." This was because well-heeled patients in the West were refusing to "submit to such treatments." Thierfelder argued that because Bayer and Hoechst had made similar offers recently at the Leipzig Trade Fair, if the public learned about the trials, the GDR would acquire the dubious reputation of being a "low-cost country" and an "inexpensive proving ground."
But such qualms were apparently overcome. Representatives of both sides met once again two weeks later, this time at Schering, where they signed a framework agreement, to be followed by several agreements on individual testing series.
Fatalities and Snail-Paced Investigations
In addition to Charité, many other East German hospitals began testing drugs on their patients. The trials resulted in several fatalities, which the participating hospitals were slow to investigate. Some studies had to be discontinued because of serious side effects that had suddenly occurred.
"I experienced it myself," says Hubert Bruchmüller, 59, from the eastern German state of Saxony-Anhalt. A former electrician, he was diagnosed with myocarditis when he was 35. "I might be the only survivor of clinical trials that were performed at the Lostau Chest Clinic in 1989," he says.
His family doctor had referred him to the hospital near the eastern city of Magdeburg, he says, "because, as he said, they had a new drug there for me." The word "test" wasn't mentioned, he adds. His doctor, he says, told him that he should take advantage of the opportunity, and that if he did he would have access to the drug in the future. "I wasn't suspicious at all, and I went there full of hope. Nothing was explained to me, and I didn't have to sign anything, either."
Bruchmüller was given shiny yellow capsules from a small container labeled: "Cardiac agent, patient No. 030," by Sandoz. The pharmaceutical company is part of Novartis today. When his roommate, who received the same treatment and was listed as "patient No. 029," collapsed and, according to the medical record, died of "acute cardiac failure," the test of Sandoz's antihypertensive drug Spirapril was abruptly terminated.
Apparently the case of Patient No. 29, as well as that of another fatality, was not investigated. The only reference to it is a brief comment in the files of the Zentraler Gutachterausschuss für den Arzneimittelverkehr, a board that evaluated adverse drug reactions for the Health Ministry in East Berlin. The minutes of a meeting that took place on March 6, 1990, shortly before the demise of the GDR, included the following remark: "Prof. Dr. Assmann is to be reminded of her duty to provide a statement on the two fatalities in Lostau."
Bruchmüller, who still has his Sandoz pill container with a few pills left in it, paid another visit to Lostau last winter. He was permitted to take a brief look at his medical file, but he has since been waiting for months for the copies he requested.
The doctors involved in the study in 1989 are now far away, working at private hospitals somewhere in Germany. "And besides, who is in a position to fight the powerful pharmaceutical companies?" Bruchmüller asks, sounding resigned.
Other drug trials also resulted in fatalities. In 1988 Hoechst, now part of the Sanofi Group, tested the drug Trental, a treatment for poor blood circulation, in East Germany.
Hoechst had the drug tested against a placebo. The subjects were not told whether they were taking the real drug or the placebo. Two patients died. Although the trial was eventually terminated, the East German clinical investigators took their time doing so. At a meeting on Feb. 17, 1989, they decided to establish a task force to address problems with the trial, and they also requested a complete list of infusion volumes before taking further action.
Problems were also encountered with Ramipril, a drug developed by Hoechst to treat high blood pressure. In the Ramipril trial, half of the patients were also placed in the placebo group, which meant that they were exposed to the risk of stroke or heart attack. The doctors treating the patients were also kept in the dark over which patients received the drug or the placebo.
The East Germans involved in the business end of the deal were ecstatic. The trial would generate 500,000 deutsche marks in revenue, and it had "produced the best result to date in this field!"
But a senior physician at Charité at the time voiced concerns, saying: "The company wants to demonstrate efficacy and sell the drug." The Hoechst trial, he told a senior Stasi officer, could "lead to acute hazards to health and even death. And the doctor doesn't even know what's happening, which prevents him from responding, that is, if that's even possible anymore and the patient hasn't died yet."
When the doctor took his case to Petzold at the advisory office on Fehrbelliner Strasse, who had prepared the agreement with Hoechst, he was unsuccessful. The disappointed physician reported "that others signed the agreement, over the heads of Charité, focusing primarily on the money," which was "unacceptable."
Drugs Administered to Babies
Boehringer Mannheim, now owned by the Roche Group, even conducted experiments in East Germany that it would have hard a hard time explaining to West Germans. The company tested erythropoietin (commonly known as EPO), a substance that has been abused as a performance-enhancing drug, on "premature babies," according to 1989 reports.
Thirty preemies weighing between 750 and 1,500 grams (1.6 to 3.2 lbs.) were given the hormone to stimulate the production of red blood cells at Charité. The study protocol called for administration of the synthetically produced agent at three-day intervals. The tiny subjects were between four and 25 days old. Today the manufacturer is either unable or unwilling to explain how the drug was administered to the babies.
Meanwhile, Bayer was testing nimodipine, a drug used to improve cerebral blood flow, at the Central Clinic for Psychiatry and Neurology in East Berlin. Some of the subjects were alcoholics in acute delirium who, as a result of their condition, could not be questioned to obtain their consent. According to hospital records, the drug reduced their blood pressure and caused perspiration and trembling.
The Role of Doctors
Ulrich Moebius, a doctor who went from being a pharmaceutical manager to a critic of the industry after the Contergan affair, characterizes these tests as a crime. "They could have killed people," he says. Bayer rejects the accusations, saying that East German physicians were the ones who proposed the tests.
Severely depressed East German citizens were also used in drug trials. Instead of treating patients in acute phases with drugs with demonstrated efficacy in treating their disease, Charité doctors used them to test two antidepressants known for their severe side effects, levoprotyline and Ludiomil. The trial was done of behalf of Swiss firm Ciba-Geigy, which is now part of Novartis. Moebius, the co-founder of arznei-telegramm, a German medical journal critical of the pharmaceutical industry, classifies levoprotyline as one of the so-called dirty drugs. The East German tests would not have been possible in Western countries he says.
But the East German clinical investigators running the trial almost never detected problems with the patient trials, either because they could not or would not recognize them. In response to the sudden cardiac death of a patient who had participated in a trial involving Roche's drug carvedilol in 1989, they merely concluded that the patient's death was to be "classified as an event possible within the context of his illness." What exactly happened was never determined.
Could the physicians involved at GDR hospitals have recognized the dangers of the drug trials? Should they have opposed the Socialist Unity Party (SED) officials' deals with the Western pharmaceutical industry, and should they done more to protect the interests of their patients?
Harald Mau developed the pediatric surgery department at Charité, which he headed until 1983. He later become director of pediatric surgery and eventually was named dean of the hospital. Few people are as familiar with Berlin's largest hospital.
The dictatorial system left research directors and medical directors with no alternatives, he says. "One mistake, or one objection, and they would no longer have enjoyed the benefits resulting from the pharmaceutical testing," says Mau, who retired four years ago. Some gave and others took, he explains, and those who didn't participate with sufficient enthusiasm faced the wrath of their colleagues, because their lack of cooperation translated into the loss of benefits for their respective departments.
'It Brings In Hard Currency, So We'll Do It!'
"If we were lucky, the proceeds went directly to the department, and instruments could be purchased. If things didn't go well, the clinic kept the money or it was spent at the Charité level," says Mau. In the context of the competitive socialist system, the hospital administration would announce, at the end of each year, the amount of deutsche marks each department had earned. This meant that doctors who conducted the studies for Western companies were constantly under pressure to acquire hard currency in competition with one another. Mau remembers a sentence often uttered by senior physicians at Charité at the time: "It brings in hard currency, so we'll do it!"
Mau himself conducted clinical trials with antibiotics in his pediatric ward. "Everyone knew that when a new narcotic or a new sedative was coming, we would try it out, all in the context of 'testing,'" says Mau. Hospital staff documented the drugs' effects on patients for the Western pharmaceutical companies. The study protocols clearly defined how often they were to take various readings, including blood pressure and lipid and cholesterol levels.
Everything was done in a strictly hierarchical manner, and providing doctors with insights into the system frowned upon. The medical director at Charité passed on the orders to conduct trials to the clinic directors, who in turn notified the department heads. The drugs were always supplied through the hospital pharmacy, where they were treated like gold. The doctors were told: "We have received a Western drug, and you now have the opportunity to use it." But they were also expected to carefully document everything, which they were told was Charité's contribution in return for receiving the drugs.
The surgeons, neurologists and pediatricians working in the wards were given pills, as if out of thin air, without being told the circumstances under which they had made it across the Berlin Wall. "No one knew what agreements had been signed, and with whom," says Mau.
All of this was kept from patients, who were inadequately informed about the risks and side effects of the drugs being tested on them. A written informed consent was viewed as unnecessary.
Issues related to informed consent were handled by the SED medical officials, in direct coordination with the drug makers. In the case of Hoechst, for example, the company expressly declared in 1989 that it agreed with "information about the drugs remaining with the investigator and not being given to the patient."
This statement appears in the minutes of a meeting between Hoechst managers and an East German representative in Frankfurt on March 6, 1989. "The patient's consent is documented by the signatures of the treating physician and one witness," the document also reads. A comparable approach would have been inconceivable in West Germany. The company did not respond specifically to questions about the case.
Extremely Awkward Insights for Drug Makers
Such insights into their past are extremely awkward for the drug makers, which, following a wave of mergers, have mutated into giant global corporations. They don't coincide with the preferred self-image of an industry that pledges to uphold exemplary ethical standards. "In every clinical trial, the safety of participants is more important than anything else," writes the VFA in a statement. "We are responsible not only to ourselves, but to the entire world," Bayer HealthCare avers in its Global Guidelines.
The companies are especially confident when it comes to one issue: The human trials in East Germany were also done strictly according to protocol. Pfizer, the world's largest pharmaceutical company, which acquired Mack Illertissen, a company that had ordered many clinical trials on the other side of the Berlin Wall, insists that it is "not aware of any information on these issues."
Bayer also believes that everything was done by the book, says a spokesman. "At Bayer, all clinical trials were conducted and still are conducted in accordance with uniform global standards." Officials at Boehringer Ingelheim claim to be aware of only three studies conducted in the former East Germany, even though records indicate that there were at least twice as many.
Even the German government has done little to clear up this particularly dirty chapter of inter-German relations. But this is especially relevant, because the drugs tested in the GDR were later approved by the West German Federal Health Office, which was part of the Health Ministry. "Everyone at the Federal Health Office knew that Western companies were conducting clinical trials in East Germany," says Peter Schönhöfer, who headed the Office's department for post-approval drug safety until 1982. "No one ever asked why or how."
And yet there were high-level political talks on inter-German cooperation in medicine. For instance, records show that when West German Health Minister Rita Süssmuth (CDU) met with her East German counterpart, Mecklinger, she stated in a private conversation that West Germany had a special interest in "cooperation in scientific research."
Klaus Jürgen Henning, who in the 1980s was the spokesman for the Federal Health Office, which reported to Süssmuth, says today that when it came to drug licensing, West German officials had no concerns about studies done at East German hospitals, and that they were treated as the equivalent of West German studies. A spokesperson for Süssmuth says that she "was too unfamiliar with the issue" and that she could provide no "detailed information about trials in the GDR."
Time of the Essence for Researching Trials
The recent debate over the use of forced prison labor in East Germany shows that avoiding and ignoring the mistakes of the past isn't the only approach. In March, the Union of Associations for Victims of Communist Tyranny launched a research project on the issue in March. The effort is funded by furniture retailer IKEA, which had some of its products, including the Billy line of bookshelves, manufactured in East German prisons.
Germany isn't nearly as far along when it comes to addressing the pharmaceutical trials. Volker Hess, a medical historian, is finally interviewing contemporary witnesses at Charité and wants to see the archives completely declassified, so that researchers can identify the perpetrators and the victims. A two- to three-year research project would be needed, says Hess, although, as he notes, the VFA hasn't been willing to provide any funding for the effort yet.
Time is of the essence, because of the risk of important evidence of the human trials being lost. As part of regular housecleaning, Charité is in the process of destroying its files from 1983. In an old warehouse in Berlin's Tempelhof district, forklifts are currently transporting boxes of records to be destroyed.