news

한어Русский языкEnglishFrançaisIndonesianSanskrit日本語DeutschPortuguêsΕλληνικάespañolItalianoSuomalainenLatina

a miracle anti-cancer drug that once attracted worldwide attention, but in fact has no effective ingredients?

this drug is highly recommended by top medical experts around the world;it has not passed clinical trial review and fda approval, but has been continuously sent to doctors and cancer patients...

when the "anti-cancer" scam was finally revealed, the two doctors were acquitted.

a miracle drug for cancer? no one can replicate the results of the experiment

in the 1950s, there was an anti-cancer drug called krebiozen that was circulated in the united states for more than a decade.

krebiozen was originally discovered by a doctor named durovich, who claimed that the substance was extracted from horse serum inoculated with bovine actinomycetes.

in initial animal experiments, he found that the drug had the potential to treat cancer:within 6 months, 7 of 12 cats and dogs with spontaneous cancer were cured, and the remaining 5 showed "significant improvement." based on its activity in spontaneous tumors in dogs, he determined that the unit dose of the drug was 10 ug.

in 1949, the doctor brought the drug to the university of illinois and introduced it to vice president ivy. in the medical community at the time, ivy was a famous physiologist who had conducted extensive research in cancer physiology and gastroenterology and served as president of the american physiological society.

ivy also appeared as a witness in the nuremberg trials, refuting the nazi doctors' claim that "it was ethical to conduct human experiments", and was therefore hailed as "the conscience of the american scientific community."

durovich's discovery caught ivy's attention. durovich provided 2 grams of krebiozen and persuaded ivy to conduct further research. after conducting animal experiments to determine safety, ivy began to test its efficacy on humans.

ivy (left, andrew conway ivy) and durovic (right, stevan durovic),

image source: science

a year and a half later, ivey held a press conference to announce the "significant clinical improvement" results shown by krebiozen in patient trials:of the 22 cancer patients who participated in the trial, 14 are still alive, and none of the eight patients who died were killed by cancer.

the astonishing research results, coupled with ivy's influence, caused a sensation in the medical community.

meanwhile, durovich founded the krebiozen research foundation, with ivy as chairman. if a doctor voluntarily requested to use the drug on his terminal cancer patients, the foundation would distribute the small amount of krebiozen available as an experimental drug for free.

on the other hand, 10 hospitals and cancer research centers across the country have started experiments to try to replicate ivy's research results.but surprisingly, no researchers other than ivy observed any effect of the drug on cancer.

this raises controversy: can it really be effective in treating human cancer?

regulatory loopholes: drugs continue to reach patients

the drug was first questioned by the american medical association.

in october 1951, jama reported negative data on krebiozen from multiple research institutions. the study reviewed the cases of 100 cancer patients who received treatment and concluded that:the 98 patients did not show "objective improvement," and the "significant effect" reported by ivy was not confirmed, meaning that existing scientific evidence does not support that the drug is effective in treating cancer or any other disease.

in 1952, a clinician conducted a "fishing enforcement". he deliberately wrote to the research foundation, asking for drugs to be used for a patient who had undergone bilateral pneumonectomy. in clinical practice, there were no patients who could survive after complete removal of both lungs. however, no one in the foundation raised any questions, and the drug was delivered to the doctor as usual.

facing the doubts from the medical community, ivy accepted them. but at the same time, ivy insisted that the research on this drug has just begun and further research data is needed. it is too early for the american medical association to make a conclusion at this time.

ivey (third from left) and durovich (second from left) appeared in public with krebiozen

source: references

after distributing the drug for free to doctors for more than three years, durovich submitted a new drug application to the fda in 1954 to begin formal marketing.

the application was ultimately rejected by the fda, but the main reason was not that the drug lacked safety or effectiveness, but that krebiozen was "out of jurisdiction."

according to science, the drug was considered a biological product by the fda, not a hormone. at the time, the agency that actually had jurisdiction over the drug was the u.s. public health service's biological standards division (phs), which had jurisdiction over products such as viruses, serums, and toxins, and had requirements for both "safety and effectiveness."

durovich and ivy disagree with this drug classification, arguing that they have never applied for biological standards.

the uncertainty in jurisdiction has put krebiozen's launch on the market in suspense, but it has not prevented it from continuing to be delivered to doctors and patients as an experimental drug, and gradually changing from free distribution to "donation."

after the marketing application was rejected, the foundation responsible for distributing and evaluating the drug began to seek "donations" from patients who received the drug. according to ivy's records, 1/2 to 1/3 of the approximately 4,200 patients who received krebiozen paid for it.

krebiozen, source: reference

over the course of a few years, the price of this drug treatment increased from free to $9.5 per dose - all of which was not prohibited by the drug-related laws and regulations at the time.

in april 1961, ivy and durovich again submitted an application for new drug approval to the fda, and the following year they publicly announced the efficacy of the drug:

(i) among 4,200 patients, 20% to 70% of patients experienced a reduction in tumor size at different times;

(ii) 33% to 74% of patients experienced pain reduction or elimination at varying periods of time, depending on the type of tumor;

(iii) krebiozen prolonged the activity time of previously bedridden patients in 51% of cases;

(iv) krebiozen extended the lives of 10% of patients by 4 to 12 years, whose doctors had expected them to die in 1 year or less.

this public report has not been confirmed by any other organization, and doubts in the medical community continue to exist.

a scholar pointed out in jama that according to the data published by the foundation, about 79.5% of doctors only used krebiozen to treat one patient:if this medicine is effective, it will definitely bedoctors use it over and over. why do so many doctors only use it once?」

in order to respond to the doubts of the medical community and to obtain more financial support and further research, the foundation invited the national cancer institute of the united states to review the drug and fund subsequent clinical trials after confirming the effectiveness of the drug.

truth and deception

all of this was pushed to the forefront of public opinion by all parties in 1962.

in august 1962, the national cancer institute of the united states formed a 24-member cancer expert committee to review krebiozen. the foundation was asked to provide drug samples to the fda and the national cancer institute of the united states.

the expert group reviewed krebiozen. source: fda

when the expert group was stalled due to insufficient data in case records, the fda sent the expert group the treatment records of 508 patients in the foundation's files that it investigated.

in these treatment records, the expert team found something strange:for example, four years after a bladder cancer patient who used krebiozen died, ivy's follow-up records for the patient showed that "cystoscopy results were normal and the patient recovered well"...

the data on 22 patients that ivy initially announced at a press conference were also wrong. in fact, 10 of the patients who received treatment had died, and all of them died of cancer.

along with the treatment records, the fda's chemical experts also provided an analysis of the drug's ingredients: krebiozen is actually creatine, which exists naturally in the muscles of humans and animals.the analysis directly overturned the previous theoretical basis - durovich said that the drug was a hormone that inhibited the proliferation of cancer cells.

what's even more ironic is that mass production of this drug is much easier than durovich imagined.

previously, durovich had been using benzene to extract krebiozen. as an amino acid derivative, creatine is extremely difficult to dissolve in benzene, but if pure water is used as a solvent, he can actually obtain hundreds of times more drugs from each horse than before.this may also explain why when the fda later tested more drug samples, it found that some of them did not even contain creatine, but only the solvent mineral oil.

creatine, source: references

in october of the following year, the national cancer institute publicly announced that the drug was completely ineffective and the government would not fund any trials of it.

in the national cancer institute report, the panel stated:based on the reviewed data and the objective criteria used to assess antitumor response, we unanimously conclude that krebiozen is ineffective as an antitumor agent.although a very small number of patients experienced varying degrees of tumor regression during treatment, the effectiveness of most of them is questionable."

separately, the director of the national cancer institute said there was no reason to conduct any more clinical trials because the drug's theory had been invalidated and it had not shown "sustained strong anti-cancer activity" in experimental animals.

image source: science

after being sued by the government, the two doctors were acquitted

without any government funding, the drug also faced accusations of being sold illegally: in the same year that the review began, the fda changed its regulations on new drugs.

after the thalidomide incident, the fda passed the kefauver-harris drug amendments, which cover new drug effectiveness, production control, and notification of approval or withdrawal of approval to ensure drug effectiveness and higher drug safety.

this is the first time that drug manufacturers must prove to the fda that their products are effective before they can be sold.

subsequently, krebiozen was banned from circulation in various states, and the us government also launched an indictment against durovich and ivy, charging them with conspiracy, mislabeling drugs, and making false statements to the government. if convicted, the two will face hundreds of thousands of dollars in fines and life imprisonment.

but after a nine-month criminal trial, durovich and ivy were acquitted.

according to science, the only surviving records of the trial show a split among the jury involved in the conviction:the witness stand and the gallery were filled with supporters of the drug, including patients who were still using it. on the other hand, ivy's previous reputation also influenced the jury's judgment - before the krebiozen incident, he was hailed as "the conscience of the american scientific community."

after being acquitted, durovich, who brought the drug to the united states, was accused of tax evasion and fled the united states. the fda director angrily rebuked:krebiozen is a cruel scam, and every day someone with a treatable cancer relies on it, they are one day closer to death.」

acknowledgements: this article was professionally reviewed by zhou yebin, a genetics doctor and pharmaceutical r&d scientist

【note】

reviewed by zhou yebin, phd in genetics and pharmaceutical r&d scientistopinion:

the krebiozen incident happened a long time ago, but the issues it reflected, such as how to determine the effectiveness of a drug, what kind of verification procedures the drug needs to go through before it is delivered to patients, and how regulatory authorities should manage it, are all directions that the medical and pharmaceutical fields have been constantly thinking about, exploring, and improving over the past half century.

some situations in the krebiozen incident are unlikely to happen again due to the significant improvement in supervision. for example, the fda has more complete supervision of clinical trials, and it is unlikely that krebiozen, which has not been verified since preclinical animal experiments, has been used by a large number of patients and tried to market it with unverified test data, will happen.

on the other hand, star scientists/doctors like krebiozen who use their personal influence to promote drugs that lack necessary evidence have not completely disappeared.with the rise of social networks, this is even more likely to happen than in krebiozen's time, and it is also more likely to pose a wider threat.

we may never know why ivy, who was once the conscience of the scientific community and stood in the nuremberg tribunal to refute the nazi doctors, chose to play such an ignominious role in the krebiozen incident. perhaps even the best scientists have blind spots in their understanding, or perhaps greed for money and fame can break anyone's moral bottom line.

all we can do is to summarize and remember the lessons of past catastrophic events such as krebiozen and thalidomide, insist on giving priority to scientific evidence, and be more vigilant and less blindly follow any authoritative personal opinions.