Stanley Levin, M.D.
Down's Syndrome. Papers and Abstracts for Professionals
Volume 13, No. 1, pp. 1-5, January 1990
Schneider Children's Hospital
Long Island Jewish Medical Center
New Hyde Park, NY 11042
Reprinted with the permission of Mary Coleman, M.D.|
Editor, Down's Syndrome. Papers and Abstracts for Professionals
Parents of Down's syndrome children are doubly unfortunate because, in the absence of any known "cure" for their child's condition, they live continuously in the hope that something will be discovered to help these patients and are therefore prone to be influenced by any suggestion that appears to offer benefit in ameliorating the patient's signs and symptoms, particularly the physical stigmata and diminished intelligence. This is the story of Siccacell therapy.
Over the last 30 years we have become accustomed to reading reports about parents from many parts of the world taking their Down's syndrome (DS) children on a pilgrimage to West Germany for treatment with injections of a "miracle" substance called Siccacell or dried cells from newborn or fetal animals. Stories about successful treatments, or even "cures" for these children have been widely publicized in many countries, mainly in the daily press and in popular magazines, and occasionally in "selected" scientific journals. Under the influence of these publications and "word-of-mouth hearsay", and in the absence of well-informed scientific and medical advice on the subject, stricken and frustrated families often grasp at any "straw" that offers hope of "curing" their DS children. As there is no scientific evidence that the treatment is of any benefit, although there is evidence that it could be dangerous, this short report reviews the painful subject of Siccacell therapy, particularly as it relates to DS.
The father of cell-implant therapy was Paul Niehans who was born in Switzerland in 1882. He started his medical career as a surgeon, and in his private clinic he began to perform "fresh tissue implants" taken mainly from live animals slaughtered specifically for this purpose. Numerous medical, biological and ethical questions were raised about this therapy, and eventually Niehans was expelled or banned from many medical associations. Not-withstanding, by advertising in the daily press he managed to acquire for himself the title of a "miracle doctor" with his claims that it was possible to rejuvenate old people with implants of fresh cells from glands of young animals. When this practice of cell implants developed into a successful "operation", he began implanting animal tissues into muscle, and later injecting cell suspensions for the treatment of various diseases. In 1931 it was reported that Niehans gave an injection of a cell suspension to an allegedly dying woman who suffered from severe convulsions, the result of mistaken removal of her parathyroid glands during a thyroid operation. Assuming that parathyroid glands of humans and of animals have similar properties, Niehans injected the woman with cells taken from animal parathyroid glands. The story goes, that after a single injection, the woman awakened to a new life, saved by the treatment. Following this event, Niehans made cell-therapy a routine procedure, which he advised and used for all kinds of medical problems. He began treating children with DS, went on to treat various genetically inherited diseases as well as acquired diseases, and even went as far as to treat cancer patients.
Niehans died in 1971, and his faithful successor is Dr. F. Schmid, head of a Children's Hospital in Aschaffenberg, West Germany, who today is considered the authority on all aspects of cell-therapy.
Cell-therapy treatment is defined as an injection into the muscle or under the skin of heterologous (derived from a different species) cell suspensions obtained either from an embryo or a young animals. As a rule, organs of sheep embryos in the last stages of inter-uterine development are preferred, or organs from various young animals such as sheep, pigs and cattle.
There are two main forms of cell-therapy:
Today, the majority of cell therapists use dry cells and the company producing Siccacell is located in Frankfurt/Main in West Germany. Surprisingly, a large number of physicians in Europe use cell-therapy regularly and some doctors prepare their own "fresh cells", transferring them directly from live animals to their patients.
Embryonic tissue is used because it protagonists claim certain properties for it, such as; a) specific desirable enzymatic and biochemical activity not found in more mature tissue; b) specific mineral and trace element contact; c) special biological functions; and, d) low antigenicity of fetal cells (?). None of these are based on good and acceptable scientific evidence.
How do Siccacell products work? Supporters of cell-therapy treatment claim that a diseased organ has to be cured by means of cells from an equivalent healthy one. A diseased kidney is cured with healthy kidney cells. A damaged brain is treated with healthy brain cells, and so on. Niehans suggested three possible ways in which cell-therapy acts:
The effect of cell-therapy on the body is reported to be remarkable. Terms used include: "generally improved intra-cellular metabolism and improved enzymatic control of various organs"; "influence upon all immunological and microbiological processes in the body", and "general beneficial effect on body and soul". In short, cell-therapy is claimed as an excellent treatment for most ailments and diseases. Accordingly, the indications for use of cell-therapy are unlimited and it is recommended therapy in any case of chronic or subacute illness.
It is claimed that following Siccacell injection there is a three-phase process:
Siccacell treatment for DS consists of a series of basic injections of cell suspensions taken from 12 different parts of the fetal brain such as the forebrain, midbrain, thalamus, etc. and mixed in certain proportions. The injections are given every 5-6 months until adulthood.
It is claimed that in DS other organs, besides the brain, are affected because of defective metabolism at the cell surfaces, and that DS is not the result of an abnormal chromosome, but rather that the changed chromosome is one of the accompanying symptoms of the disease and can be repaired. It is therefore recommended that supplemental treatment using suspensions of cells from other organs should also be given.
The aims of cell-therapy in DS are stated to be the following:
The results of cell-therapy in DS have been extensively and repeatedly published by the protagonists of Siccacell therapy as well as by the manufacturer of Siccacell, and are based almost entirely on the subjective reports of practicing physicians without any scientific reasoning or any acceptable physiological explanations. As examples, it was stated that "cell injections into the human body gave astonishing results", or "Siccacell products induce heightened tone of the small bowel and of the sigmoid" or "increase the breathing power of the aorta".
In one report some 200 signs and symptoms found in persons with DS are listed. Siccacell was given to 4000 DS children from 23 different countries and the results were reported as simply "astonishing". A third of all these 200 symptoms disappeared immediately at the very start of the treatment, and an additional third showed marked improvement. This left only one third of the 200 symptoms not responding to the treatment. In other words, it is claimed that as many as 130 symptoms In DS patients respond to this treatment.
Practitioners reporting on the use of cell-therapy claim that the injected Siccacell suspension homes towards the DS patient's brain and once there, improves the outer appearance of the children, induces the skull to grow, and increases the volume of the brain. In addition, an increase in I.Q. is claimed, as well as improved psychomotor ability. It is stated that Siccacell has a beneficial effect on the patient's immunological system, social status and memory and decreases the rate of illness and death among these patients. No scientific evidence is given for these claims.
In an effort to vindicate himself against the criticism and accusations made against him and his methods, Schmid published a pseudo-scientific article in 1981 in which he uses head growth charts in a group of 12 boys and 12 girls with DS to reinforce his claim that there is increased growth of the skull in those who received Siccacell treatment. Like many others, this article is written in a completely unscientific manner. Even if these findings are believed, the question remains as to what happened to the skulls of the 4000 (?) DS children treated by Schmid? Why was there no matched control group? Even if we ignore the failure to demonstrate unequivocally one single successful result achieved with cell-therapy and accept as partial success "the improvement in general well-being of the patient", we are still lacking the comparative proof. However, it must not be forgotten that in addition to the series of Siccacell injections, the patient is expected to radically change the previous life-pattern. Complete rest with avoidance of stress and heat is advised and there is restricted exposure to sunlight and to the use of drugs. Adult patients have to refrain from coffee, tea, and from smoking. In the case of DS children, occupational and speech therapy are stressed, as well as special pedagogic techniques, physiotherapy, and physical exercise. So, if some improvement in the patient's subjective general well-being is observed, it may well stem from instigation of these special treatments which in themselves are important.
According to publications by cell therapists, hardly any side effects have been noticed and those that occur are negligible, such as slight reddening at the injection site, itchiness, lethargy and a slight increase in body temperature (between 0.5-1.0º C) for one to two days. The manufacturer and Schmid claim that no cases of anaphylactic shock have been observed and explain this on the basis that heterogeneic cells taken from animal embryos are of low antigenicity, do not give rise to antibody production and therefore do not cause severe allergic reactions (?). In the few cases where antibodies have developed, they were reported to have disappeared within four months. Because of this, they recommend injecting Siccacell preparations every 5-6 months (?). They state that if in spite of this, anaphylactic shock occurs, it is probably due to incorrect historical information given by the patient to his doctor (!).
Treatment with Siccacell products requires repeated transplantation of heterologous cells taken from animals. Scientists and immunologists know that the human body will develop early or delayed immunological reactions to these foreign cells in the form of different allergic or immunologic phenomena. All published cell-therapy reports since the 1950's are silent on this point or deny its existence. Despite the enormous advances made over the past 30 years in our knowledge of cell and molecular biology, particularly in the fields of immunology and transplantation, nothing really new has appeared in the hundreds of articles that have been published about cell-therapy during this period. These articles appeared usually in obscure publications or in the form of booklets and catalogues published by the "Company for Cell-Therapy Treatment", and rarely, if ever, in accepted medical journals. We have reviewed dozens of articles and all are characterized by the following:
Despite apparent efforts to conceal vital knowledge about side effects, several sequelae of cell-therapy have been observed. Among these are various serious allergic reactions which may have led to death from anaphylactic shock, immunological reactions leading to gangrene, abscesses at the injection-site, coronary thrombosis, pyelonephritis, encephalities and more. As early as 1958, a report from Vienna noted that repeated injections of homologous or heterologous never tissue into animals leads to immunological reactions which may cause acute encephalitic dermyelinization manifesting itself clinically as neurological disease. They showed that repeated injections of "dry cells" into animals caused the development of antibodies which could cause far-reaching demyelinization. They found that the antigenicity of the cells is not destroyed by lyophilization and it has been clearly shown that antigenicity of nerve tissue remains intact even after formaldehyde fixation, extraction with fatty solvents, boiling, over-heating, treatment with ultraviolet radiation, 24-hour autotysis and lyophitization. In the report, a case of a man who underwent 18 months of cell-therapy and who developed encephalitis and died within 6 weeks of onset symptoms is described. The authors explicitly warned against injection of cells of nerve tissue origin irrespective of the laboratory procedure used to prepare them.
It is worthy of note that the death-rate from infections is high among DS patients partially because of Immune incompetence. It becomes difficult, if not impossible, to establish without controlled epidemiological studies whether Siccacell-treated DS children who developed illnesses and later died, did so from natural causes or as the result of the cell-therapy. This is a crucial point that cries out for proper scientific examination. It would be of great interest to know the number of DS patients that died of infections or from other causes while under Siccacell treatment, but no such evidence is available. It should be emphasized that the exact number of complications and deaths resulting from cell-therapy are not known to any official body. Yet as early as 1955, a short, incomplete survey showed that in 179 sanatoria in Germany, 80 severe complications with 30 ensuing deaths had occurred.
We studied a baby with DS in Israel who was completely healthy till the age of 7 months. The day after receiving Siccacell injections in Germany with cells taken from various organs including the brain, the baby developed severe urticaria over the entire body and face. A week later he had general myoclonic seizures lasting for 8 days. The E.E.G. showed abnormalities with two spike foci. Later when the seizures had stopped under treatment we repeated the E.E.G. and these foci had disappeared. It is logical to assume a relationship between these neurological phenomena and the Siccacell injection, and that the encephalopathy was an immunological reaction to the injected animal antigens. The parents were advised not to repeat the Siccacell injections. To the best of our knowledge, this is the first documented disclosure of an encephalopathic immunological reaction to Siccacell treatment in a child with DS syndrome. These observed side effects are of great concern, but of even greater concern are the so far undisclosed ones.
Immunological dangers: Based on our current knowledge, repeated injections in humans of heterologous cells could trigger very strong immunological reactions with stimulation of lymphocyte proliferation. Prolonged stimulation of this kind could lay the foundation for the development of autoimmune or even malignant processes in the future. In other words the treatment of a child with injections of animal cells could lead to autoimmune or malignant disease manifesting itself a number of years after the Siccacell treatment was given. This aspect has not been studied.
Over the years, many delegations of physicians and scientists visited Nlehan's clinic in order to investigate for themselves the true facts about cell-therapy. In general, they categorically declared that they found it to be based on pseudo-scientific foundations and reported that not a single case of successful cell-therapy treatment could be objectively proved. "Successful treatments" cited at conferences of cell-therapy practitioners were proved later to be incorrect and even basically untrue. Of major importance was the fact that we could find only three controlled research experiments which were carried out by physicians and scientists who were independent of Dr. Schmid and his colleagues and in which Siccacell products were administered in double-blind studies to DS patients. There was no difference in the results between the group of patients receiving Siccacell compared to those receiving placebos. To be exact, in one study a negative influence was demonstrated in those patients receiving Siccacell, in that a larger number of treated children had lower I.Q. at the end of the study than those treated with placebo, but this finding was not statistically significant.
Following a stormy debate on Siccacell treatment in West Germany's State Office for Youth, Family and Health several years ago, a State Commission was appointed to investigate the subject thoroughly and to publish its conclusions. At the same time the German Academy of Pediatrics established their own investigative commission which consisted of outstanding physicians and scientists including specialists and professors in pediatrics, endocrinology, genetics and pediatric neurology. Their conclusions and findings of the German State Commission mission received wide publicity and were published in 1975 in several articles in the major West German Pediatric Journal. These articles exposed in a very clear manner the true nature of Siccacell therapy and the character of its protagonists. The committee expressed its surprise at the lack of any scientific proof regarding its usefulness, and remarked on the absence of results based on well-controlled, prospective and extensive studies. The finding of the commissions were unanimous on all subjects under discussions.
Two independent university commissions consisting of renowned pediatric neurologists were established in Switzerland (Bern and Zurich) to study these cell-therapy claims. The conclusions of these commissions are similar to those of their West German colleagues, and state clearly that the therapy is of no practical use and may be dangerous. The U.S. government, through the F.D.A., does not permit clinical experiments with Siccacell in patients, or even its transport across state lines, because the data forwarded by the protagonists did not sufficiently convince them of either its efficacy or its safety.
In 1979 and 1982 two commissions were established in Israel at the request of the Ministry of Health to investigate the subject of Siccacell. After long deliberations and intensive literature research (upon which the present article is based), the commissions came to the conclusion that the product is of no value whatsoever in the treatment of DS children. Moreover, they found that the injection of heterologous cells into human beings constitutes a distinct danger, Norway has banned importation of Siccacell because of side effects that have occurred. More recently, the German Drug Administration has withdrawn the license for Siccacell and all other fetal cell preparations, and these substances are no longer on the market.
The claims of cell therapists are based on far-fetched, unacceptable theories as well as personal experiences which have not been scientifically proved. It has been stated that "as far as it was possible to follow-up treated patients, it appeared that Siccacell therapy may have a suggestive psychological value as a placebo. It is well known from the use of placebos that it is possible in certain cases to achieve improvement (even if only temporary) by instilling hope in the patient. But promise to improve or heal cancer patients or DS patients with Siccacell therapy without offering any proof, borders on an untruth and becomes fraud when large sums of money are involved." In general, cell-therapy appears to be based upon mystic theories far removed from reality. This form of therapy gives false hopes to parents of DS patients as the promises can never be realized. It gives parents the wrong impression concerning the true nature of their child's condition, and leads to waste of time and money which could far better be spent in educating and training the child in accepted child-development clinics.