POLIOMYELITIS VACCINE - BRODIE VS. SALK
by Fred R. Klenner, M.D. Reidsville, N.C.
It has been said that in science the credit goes to the man who convinces the world, not to the man to whom the idea first occurred. Factually this is not true. Although the Germans made the first practical application of the submarine in World War I, history records that Cornelius van Drebbel invented the first underwater craft which he rowed beneath the surface of the Thames in 1620, and that John P. Holland and Simon Lake produced the first engine-propelled underwater boats in 1898. The same might be said for the Wright brothers in lighter-than-air ships, for Robert Fulton and his steamboat or for a hundred and one other scientific discoveries such as Mendel's law of heredity which lay, unmolested, for 50 years in a small scientific journal on a library shelf in England. Few men who make outstanding contributions to society live to see the fruits of their labours ripen. This 25 to 50 year 'vacuum' exists simply because "the public buys its opinions as it buys its meat, or takes in its milk, on the principle that it is cheaper to do this than to keep a cow. So it is, but the milk is more likely to be watered." All this is applicable to the vaccine for poliomyelitis.
In 1910 Flexner and Lewis [1] gave a 'live virus' vaccine, subcutaneously, to monkeys. The dose was 0.05 cc daily, of a suspension, for 4 days and the series repeated twice with 4 days rest between each set of injections. After the last interval animals received on successive days 0.1 cc, 0.5 cc and 1.0 cc of virus and after one month 5.0 cc. Vaccine 'worked' in experimental animals; was not tried on human subjects. In 1911, Levaditi and Landsteine [2] gave a single subcutaneous inoculation of 0.5 cc of virus suspension previously heated to 50° C for 30 minutes. Vaccine 'did not work'. In a second experiment they employed glycerated virus heated to 50° C for 2 hours. Although this vaccine produced the disease when injected intracerebrally it did not infect when given daily in subcutaneous doses of 2 cc over a period of one month. Vaccine 'did not work'. Kraus, also in 1911(3}, rendered the virus ineffective by treating with 1.5 per cent phenol for 4 days. He injected 5 to 10 cc of the vaccine subcutaneously into experimental monkeys. Vaccine 'worked 100%.' The phenol proved too irritating to the tissues. Also in 1911 Zappert, Wiesner and Leiner [4] injected subcutaneously gradually increasing doses of 'active virus emulsion.' Vaccine 'did not work.' Thompson [5], 1912, inoculated monkeys subcutane ously with sub-infective doses of live virus suspension for 12 days and subsequently at weekly intervals 0.06 cc 0.2 cc, 0.4 cc, 1.0 cc and 2.0 cc. Vaccine 'worked', but animals demonstrated symptoms of excitement, tremor and ataxia during immunization. Thomsen, later, repeated this experiment using a dose schedule one hundredth of the estimated intracerebral infecting dose. This vaccine 'worked 100%' in monkeys without producing symptoms. Abram-son and Gerber [6] in 1918 treated an emulsion of brain and cord of a poliomyelitic monkey for 4 hours with 0.5 per cent formaldehyde. Vaccine 'did not work.' Later they tried to immunize by heat-treating the virus, modifying the method of Levaditi and Land-steine. The emulsion was heated to 55° C for 30 minutes for 2 days, heated to 45° C for 30 minutes on third day and heated to 37° C for 30 minutes on fourth day. Vaccine 'did not work.' Flexner and Amoss [7], 1924, using a so-called immunizing strain of polio virus treated with 0.5 per cent phenol employed the idea of serial passage to reduce virulence. Vaccine 'promising.' McKinley and Larson [8] in 1926 used intra-peritoneally 4 cc of mixture of 5 per cent emulsion of castor oil soap and virus emulsion. Vaccine 'worked 75%.' Aycock and Kagan [9] in 1927 repeated the work of Kraus using phenolized virus treated with 1.0%, 0.75%, 0.50%, and 0.25 per cent phenol. Vaccine 'did not work.' (Kraus in 1911 stated emphatically that only 1.5 per cent phenol to kill the virus would be effective). In a second experiment they injected, sub-cutane-ously, virus from a polio cord dried over caustic potash from one to twenty-six days. Vaccine 'did not work.' In a third experiment they used virus cord exposed to different glycerol-water dilutions (5% to 50% glycerol) for seven months at ice box temperatures. Vaccine 'did not work.' In a fourth experiment virus was put into agar and introduced subcutaneously. Vaccine 'did not work.' In a fifth experiment the live virus was introduced intracutaneously in from 1 cc to 2 cc doses, but distributed to 0.05 cc blebs making 20 to 40 piques each day. Total amount of virus suspension used was from 5 cc to 76 cc given in from 6 to 43 inoculations over a period of 15 days to 5 months. Vaccine 'too variable' in protecting.
Rhodes [10] in 1931 showed that alumina gel C mixed with polio virus in certain proportions using 22.5 grams aluminium per litre at an acid pH of 5.5 resulted in the absorption and inactivation of the virus. Sabin [11] in 1932 confirmed Rhodes observations and showed further that adsorption as well as the inactivation are REVERSIBLE; that is, by changing the pH to the alkaline side with M/15 Na2HP04 it is possible to free the virus in a state in which it is AGAIN capable of producing typical poliomyelitis.
Thompson and McKinley [12] suggested (1934) that the virus of polio, chemically treated, be it formalin or a fatty acid salt, is still living - though apparently killed. They postulated that since viruses are notoriously intracellular parasites it would seem that the chemical treatment of a virus suspension would first destroy extracellular virus and the intracellular virus would then be released in the body tissues very slowly by destructive action upon the virus-containing cells.
Kolmer [13] (1935) states "that the reduction in virulence of the virus by treatment with sodium ricinolate and phenyl-mercurini-trate is not permanent, since the virus recovered from the cords of monkeys paralysed by intracerebral injections of the vaccine has usually been found apparently as virulent as untreated virus." Brodie [14] (1936] remarked "that formalin treated vacine gives an antibody response ONLY when the formalin acts for the shortest time required to render it non-infective; this suggests the possible presence of an amount of virus too small to infect." Thompson and McKinley (1934) found that when they mixed 0.5 cc of a 16 per cent emulsion polio (Aycock strain) infected monkeycord with the virus of vaccinia that SOLID immunity was produced in monkeys in six weeks. Andrews [15] (1934) working with vaccine virus could prevent infections in monkeys when "serum' was given before the virus, but if given, even 5 minutes after the virus, it was ineffective. The explanation being that in this short interval the virus was already vfixed' to the tissues. Brodie and Goldbloom [16] found, however, that without symptoms of polio, immunity was secured when serum was given at the time of inoculation or within three days preceding or following inoculation of virus. Kolmer (1934) tried a vaccine in which the virus was chloroform-treated according to the Kelser method of preparing antirabies vaccine, but it proved unsafe for human usage. Kolmer and Rule [17] (1934) introduced by stomach tube a living or untreated 2 percent suspension of the virus of poliomyelitic cord in amount of 2 cc for 10 daily consecutive doses, but it failed to "engeder any demonstrable evidence of immunity and similar results were obtained with heated vaccine administered in the same manner." Kolmer [18], then, using the method of McKinley and Larson, demonstrated that a successful vaccine was possible using cords treated with 1 per cent sodium ricinoleate. He incubated the mixture at 37° C for 24 hours, then refrigerated at 4° C to 6° C for 14 days. This 1% solution does not completely kill the virus. Kolmer adopted as inoculation schedule °f 0.5 cc first dose, 1.5 cc second dose and 2 cc third dose, given at 5 day intervals. Given to himself, to experimental monkeys and a poup of children he found that a vaccine prepared in this fashion never produced the slightest evidence of infection in monkeys or humans." Kolmer concluded that three subcutaneous injections at intervals of 5 to 7 days in a dose range from 0.05 cc to 0.1 cc per Kg of body weight to be a safe and effective method for vaccination against acute anterior poliomyelitis. Kolmer reported in 1936 on mass field trials in which 10,725 humans received the attenuated vaccine. He reported no cases of polio from this number who received three injections. (There were 10 cases of polio in this group who received one or two injections, of which five died. Very reminiscent of the present field trials.) Brodie (1934) demonstrated that "live' virus "inactivated' with formalin is antigenic. He also demonstrated that even though phenol produced a safe and effective vaccine it was not as effective as formalized virus and that definite immunity could be developed against the virus of poliomyelitis using virus rendered non-infective by formalin. Brodie [19] cautioned, however, that "polio virus can spread through the central nervous system of an animal in the presence of demonstrable antibody". This was confirmation of what Andrews [20] reported in 1929 that "virus will grow, in tissue culture, in the presence of its own antibody." Teale [21] demonstrated (1935) "the pre-eminence of the state of the tissues in regard to immunity, their capability of dealing effectively with the antigen and the negligible part played by the circulating antibody as such." In November, 1934, Brodie [22] stated that "before giving it to children it was deemed advisable to try the vaccine upon ourself and a group of laboratory volunteers, not that we had any misgivings about the possibilities of infection, but rather to determine whether the vaccine produced any disagreeable local or general reactions." Following this successful trial vaccination in humans, Brodie then gave it to a group of children ranging in ages from 1 to 6 years. Half of the children received one single dose of 5 cc; the other half were given a second shot 11 to 13 days later. (Brodie later suggested that the second shot be given 10 to 20 days after the initial injection). The second injection was divided, giving 1 cc to 2-1/2 cc intracuta-neously and the remainder subcutaneously. The abdominal wall was selected for the site for the injections following the procedure for rabies. Brodie [22] observed that the first injection did not render the "human subject' sensitive to the second dose; that the second dose acted more rapidly than the first and that the second injection gave "considerable additional immunity which lasted at least one year." The intracutaneous route did produce some transient induration, otherwise the vaccination was without reaction. The blood sera of the children receiving a single 5 cc dose neutralized between 100 and 200 infective doses of live virus and those receiving two injections neutralized an additional 200 to 500 infective doses. Brodie elected to settle for germicidally (formalin) inactivated virus because of past experiences by Bedson and others in preparing a successful noninfective chemically treated preparation for such diseases as looping-ill, psittacosis, foot and mouth disease and rabies. Kramer and Green [24] (1945) confirmed Brodie's work by showing that suspensions of polio virus (Armstrong Lansing Strain), inactivated by formalin, retained much of their antigenic property. In 1936, Brodie and Park [25] reported on "field trials' with over 9,000 human subjects conducted in 1935. In so far as was possible each vaccinated individual was matched with a control in the same district and of the same age. Wherever possible playmates were used. There were three cases of polio and one death among those vaccinated. Brodie felt that field trials of at least 50,000 more children should continue to effect a more positive evaluation. (The Park and Brodie vaccine was withdrawn from use on human beings at the request of the directors of the Warm Springs Foundation in Georgia. This group is now known as The National Foundation for Infantile Paralysis, sponsor of the present vaccine. Unfortunately, we have no one today, with authority, who has the courage to stop this 'circus'.) Milzer, Oppenheimer and Lavinson [26] (1945) employed ultraviolet irradiation to inactivate the polio virus which was effected in less than one second exposure. Monkeys receiving three shots developed significant resistance in 2 to 3 weeks. Freund [27] (1951) tried paraffin oil and mycobacteria on the virus to evaluate antibody formation. At present the Germans are reporting on the use of a "live virus' vaccine which according to the report has indicated excellent results. In our own country, Sabin likewise is working with the "live virus' idea. The live virus vaccine would, of course, engender antibody response parallel to the natural infection thus giving enduring immunity.
DISCUSSION
Many experiments have been conducted during the past 45 years in an
attempt to find a safe, effective vaccine for poliomyelitis. Experience has
proved that recovery from most virus diseases results in permanent immunity.
From these immunized individuals one can find neutralizing or protective
antibodies in their sera. This has led to the FALSE notion that the presence of
neutralizing antibodies in the serum of an individual always indicates immunity.
This is TRUE only when these antibodies are the result of a Natural infection.
As Rivers [28] once put it, "the individual is Known to be immune not because of
the antibodies, but because of recovery from a natural infection as indicated by
the presence of antibodies."
Resistance to infection by individuals vaccinated against, say polio, does not necessarily parallel the number of antibodies present, nor does it indicate that these demonstrated antibodies will neutralize live virus from a natural infection. Vaccinated dogs may possess neutralizing antibodies yet still be susceptible to rabie virus. It has been reported by many investigators that monkeys vaccinated against polio will come down with paralytic infection in spite of the presence of neutralizing antibodies in their sera. Loring [29] in 1947 reported that Brodie had proved in 1934 the presence of neutralizing antibodies in the blood of monkeys and children after immunization with his formalized virus vaccine, but Brodie also further proved that "polio virus can spread through the central nervous system of an animal in the presence of demonstrable antibody." Andrews in 1929 demonstrated "that polio virus will grow, in tissue culture, in the presence of its own antibody." It must be remembered that the virus of poliomyelitis, be it live', 'attenu-ated' or rendered non-infective, acts as though it was a poor antigen. Thus it does not follow that even the 'needle introduction' of live virus into a human will necessarily result in effective immunization against exposure to a nature infection. If a really successful vaccine against polio should be developed, it most assuredly will contain live virus. This, after all, is nature's way of handling the diseases plaguing mankind. Dunkin and Laidlaw have shown that formalized canine distemper virus will produce a fleeting immunity in vaccinated dogs, but in order to get a solid resistance LIVE virus must be employed. This, then, is suggestive of what we might expect for man. The danger in polio, however, rests with the hundreds of strains and in their varying degree in virulence as to strain and as to time and circumstances. An opinion exists with some that the amount of inactive virus is the all important factor; that is, if a sufficient amount were used, a solid immunity would result. McKenzie reported that with small doses of inactivated Rift Valley fever virus he was unable to immunize mice, while with larger doses, 1 cc administered intraperitoneally, he was able to establish a good resistance in the animals to the active agent. Rivers challenged this work. Assuming, he said, that the virus was completely inactivated and that the mice were solidly protected, one must remember that a mouse weighs in the neighbourhood of 20 grams and that 1 cc or 1 gram of the virus emulsion was administered; that is, approximately 1/20 of the body weight. On the basis of these figures a man weighing 150 pounds would require 7-1/2 pounds of vaccine - not a very practical procedure. We have three roads open. We can continue to employ the formalized vaccine developed by Brodie; continue work for the development of a live virus vaccine; give up the idea of a polio vaccine. In a chemically treated virus vaccine we must remember that the possibility always exists that some of the virus units will be completely inactivated while others are only influenced. The evidence points up the fact that when a virus emulsion has been treated with a chemical agent and is still capable of causing disease, even though the incubation period might differ from the natural infection, the virus, if recovered from the unfortunate victim would be found fully virulent. This would suggest that the so-called chemical treatment is equivalent to a dilution. Brodie (1934) in discussing his results with monkeys and children stated, "whether immunity developed from either a 'killed' or 'highly attenuated' antigen can not be definitely stated." As to the use of a live or attenuated virus the end result is just as unpredictable. Investigators in the past have shown that even large amounts of virus in the active state given subcutaneously or intracutaneously frequently fail to produce resistance to infection in monkeys. What is good for the goose is not always good for the gander. A flower from the greenhouse frequently is disappointing once carried home, for it responds differently in its new environment. It seems then that the safest and best thing to do is GIVE UP the idea of a vaccine for poliomyelitis. Dr. Thomas M. Rivers gave this advice in 1936 when he said, "It must be remembered that the vast majority of children vaccinated would never have contracted poliomyelitis even though they had not received the vaccine. For unknown reasons, most children are much more resistant to poliomyelitis than are the remaining few." This small 'remaining few' group is no doubt the ones Salk reported would not and could not make antibodies. Thus it sums itself up so simply: The majority do not need it and the minority can't use it if they get it. It is interesting academically to listen to a prophecy made by Rivers in 1936; to wit: "If I were asked for a prophecy, I would say: If Brodie does not make the time of inactivation of the virus too short, and if he continues to administer the vaccine in the manner now employed, It will be reasonably safe but ineffective, particularly if one expects an appreciable degree of protection to persist for any great length of time." Rivers' prophecy was fulfilled during the 1954 field trials with the 'so-called' Salk vaccine. As revealed in the critical analysis of the Francis report published in the June, 1955 issue of the Tri-State Medical Journal, the vaccine 'was reasonably safe but ineffective." This ineffectiveness of the vaccine was known 'by the proper authorities' long before April 12,1955, and it was this FACT which made imperative the NEW 1955 MODEL. This NEW vaccine is more potent. To accomplish this the time of formalin activity was either shortened or the number of minimal completely paralysing doses of virus was increased. Either procedure would make for a BORDER-LINE vaccine. Your attention is called to the fact that the factual material credited to Dr. Thomas M. Rivers in this paper is the same Dr. Rivers, who on June 23, 1955, before the House Commerce subcommittee said "It would be tragic to halt inoculation." As of 1955 Dr. Thomas M. Rivers is not only DIRECTOR, Rockefeller Institute for Medical Research, but also CHAIRMAN, polio vaccine committee of the National Foundation for Infantile Paralysis. To make an HONEST evaluation of Dr. Rivers' statement before the House Commerce subcommittee, we must fully understand for whom he works. "The Rockefellers own the largest drug manufacturing combine in the world, and use all of their other interest (which is mammoth) to bring pressure to continue and increase the sale of drugs. In addition there are thousands of others controlled through bank loans by Chase National Bank, one of which is the Hearst newspaper empire."[30] Rivers' connection with the National Foundation is self-explanatory. Out of the 20,000 to 30,000 cases of polio reported each year only 8,000 to 10,000 would actually require treatment, using a DRUG as a curative agent. If through intensive newspaper and radio propaganda the necessity of a vaccine could be TATTOOED on the 'minds' of Americans the number of'users' might conceivably run to 100,000,000 annually. This would get roughly, 30,000,000 dollars profit each year. Since 90 per cent of the doctors graduating today think in terms of 'dollars' instead of 'SENSE' there were no misgivings about cooperation from the medical profession. The 'egg' was about to be hatched, but no one thought that it would be a 'MULE'. Tragic to halt the inoculations? Yes! Not for the children, however, but for the Rockefeller Foundation and the National Foundation. Doctors of America, 'cut the strings' and ACT according to your own natural intellect, for some of these children are your own. In 1936 as in 1955 much effort was expended in an attempt to convince the 'world' that the cases of polio following vaccination were 'natural infections' without relation to the injections. The United Press [31] reported May 5, 1955, that three public health experts had found in Idaho that (1) The disease struck in areas where there had been no previous polio cases. (2) Only children who had received the vaccine became ill. (3) The first signs of paralysis occurred in the arm where the children were vaccinated. (4) The paralysis developed first in the upper extremities, although the disease is usually first felt in the legs. In spite of this evidence given by men from his own department, Surgeon General Scheele [32] on May 6, 1955, said, "although 44 vaccinated children have developed polio, this does not mean the Salk vaccine is not safe. They 'probably' had the disease already." In 1936, following cases of polio and deaths from the Kolmer and (later from Brodie) vaccines, the Senior Surgeon of the U.S. Public Health Service, Dr. James P. Leake [33], had enough intelligence and 'guts' to state publicly: "In each instance in which the site of the injection and the site of the first paralysis is known, the latter occurred either in the limb injected, or in the corresponding limb of the opposite side; in other words, the cells of the spinal cord involved were at the same level as the injections. I beg you, Dr. Kolmer, to desist from the human use of your vaccine." In 1955 following polio after vaccination, with cases running towards several hundred and also with deaths, Dr. Van Riper [34] of the National Foundation signs his name to this statement: "It must be emphasized that when poliomyelitis vaccine is given to large numbers of individuals during epidemic periods, a small proportion receiving the vaccine will subsequently experience paralytic disease. This is because the vaccine is not 100 per cent effective; individuals receiving it during the early silent period of an infection may not be protected, but may be subject to a localizing effect of paralysis at the site of injection; and a certain number of cases erroneously reported as poliomyelitis will actually be instances of other diseases with clinical similarities." This is quite a contrast. This v double' talk issued regularly to physicians will be accepted by many, but in some it willv provoke' serious misgivings. Some questions might be: (1) Why, if any risk is present, were the injections started in the Spring of 1955 instead of the Fall of this year? The number of cases reported to-date receiving vaccine is approaching what might have occurred from natural infection, according to known accepted statistics. (2) I am certain that no silent period existed in those cases reported from Idaho, because at that time of year (APRIL) Idaho is still buried in snow. (3) We wonder how many cases erroneously reported as polio were accepted and counted by the National Foundation prior to the present vaccine story. A drowning man will vgrab' at any straw. (4) We wonder what type of vlocal-izing effect' the injections have on bulbar cases?
Entirely too much emphasis has been placed on the presence or absence of antibodies in human sera. Salk in 1953 found 80 per cent of the children tested in the Pittsburgh, Pa., area as being without antibody protection. Salk [35] further pointed out that "poliomyelitis is not a single disease, since it can be caused by any one of three immunologically different viruses." Thus "individuals whose blood is devoid of antibody for any one virus type cannot be regarded as immune to the disease because they have not experienced infection with all three types." Brodie in 1936 reported that under 5 years 85 per cent of children showed no antibody and 75 per cent of the 6-10 year old group, which is 80 per cent. Roughly, then, the antibody factor has remained constant, in spite of the reported yearly increase in the incidence of the disease. As Brodie observed in 1936, "the finding of no antibody makes it difficult to explain why in an epidemic approximately only 1 of 170 children in the age group 1-10 years, showing no antibody, develop the disease. Obviously this 0.6% of 1 per cent represents the group whose constitutional make-up fails to respond to antigen stimulation. Teale answered this in 1935 by demonstrating "the pre-eminence of the state of the tissues in regard to immunity, their capability of dealing effectively with the antigen and the negligible part played by the circulating antibody as such." Salk, in suggesting that no one is immune to polio unless he shows antibody to all three virus types, implies that in travelling from New York to California you can go by train, by plane or by car but that you cannot actually consider yourself being in California unless you travel there by all three routes. The fact that a second attack of polio is recognized as a "medical curiosity,' proves Salk's interpretation to be erroneous. The Vaccine' (antigen) only trips the trigger on the inherent sensitivity possessed by practically all children (99.4%); Kolmer said a "simple natural exposure'did the same thing. Why, then, vaccinate?"
CONCLUSION
A meticulous review of the literature since 1910, dealing with
experimental work pertinent to the development of a vaccine for
poliomyelitis, forces one to conclude from a factual consideration,
that nothing new had been added to the 'picture', so that, in time,
we actually still stand as Brodie left it in 1936. Salk in 1953
reported that his efforts 'carried special blessings,' since the vac
cines of Brodie and Kolmer in the early 1930's "were discontinued*
because the preparations employed were found unsafe for human
use." The experiences to date with the 'so-called Salk vaccine'
would place this product in the same category and it must, there
fore, be discontinued for human use. We are constantly reminded
by politicians, not scientists, that millions have been vaccinated
and only hundreds have developed polio from the injections; what
we are not told is that resistant children are able to stand the
vaccine, while the susceptible children, the ones highly in need of
j protection, cannot resist the 'attenuated active virus' present
in all
of the polio vaccine available, and thus promptly come down with the disease.
Kolmer [36] in 1935 said, "It is likely that resistance to
128
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID
poliomyelitis may be present without demonstrable amounts of this antibody in
the blood, and that tissue resistance may be constituted by body cells
sensitized to virus and capable of rapidly producing antibody upon infection or
vaccination." Rivers, head of the polio vaccine committee for the National
Foundation, reminds us "that the vast majority of children vaccinated would
never have contracted poliomyelitis even though they had not received the
vaccine." The medical profession needs to take inventory; have we been gambling
with the lives of our children for the political and pecuniary gains of a few?
With the 'risk' of acquiring paralytic poliomyelitis running as high as 1 to
100,000[37] and the 'chance' of dying from it as high as 1 to 1,000,000 the
urgency for a protective antigen is not too great. No one can deny that the
'field trials' of 1954 and 1955 were experimental, since parents 'were
compelled' to put their name on the 'dotted line' before their children could
receive these FREE inoculations. Kessel in 1936 [38], reporting on the Brodie
vaccine, said "Minors who took the vaccine were required to have their parents
sign the record" and "volunteers signed a statement recognizing the fact that
the vaccine was in the experimental stage."
Salk in 1953 attempted to discredit the work of Brodie on the premise that his
"studies were conducted before precise knowledge regarding pathogenesis and
immunologic complexity were available." This reasoning might be valid were it
not for the fact that history records the use of sailing boats long before
Archimedes gave to the world the principle of buoyancy. History also records
that it was Brodie and not Morgan, as reported by Salk, who firstN clearly
demonstrated that a formaldehyde-treated suspension of central nervous system
tissue from monkeys induced the formation of appreciable quantities of
antibody.' Brodie in 1934[39] reported that "germicidally inactivated virus for
the production of active immunity has been found successful in many diseases.
This work indicates that definite immunity can be developed against the virus of
poliomyelitis using virus rendered non-infective by formalin." Brodie later
conceded that "whether this immunity developed from either aN killed' orv highly
attenuated' antigen can not be definitely stated." Salk in 1953 intimated that
the original work for selecting the proper strength for the inactivation of the
polio virus was carried out in his laboratory. Brodie [40], May 5,1934, (21
years to the day when the U.S. Public Health investigators released the
information that the cases of polio in Idaho were definitely due to the
so-called Salk vaccine) sent to the Journal of Immunology a paper dealing with
the various concentrations of formalin on mixtures of polio virus. A table of
these experiments by Brodie will
129
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID be found on the following
table.
FormalinCone.M.C.P.Temp.Days ofResults
ofDoses°CContact
cordIntracere-
brally
0.2%10802.0-4.010 Mild attack
0.3%10802.51.5Paralysed
19 days
0.3%10804.53.5No
Paralysis
0.3%10800.5-4.57No
Paralysis
0.3%106001.0-4.010No
Paralysis
0.3%101,6002.0-4.011No
Paralysis
0.3%101,6001.0-4.010No
Paralysis
0.3%101,600 plus1.0-4.010No
Paralysis*
2,800 intraperit-
ioneally and in
10 days 1,600 plus
6,400 intraperiton-
eally.
0.3%101,600 plus1.0-4.010No
Paralysis**
2800 intra-
peritoneally and
in 10 days 1,600
plus 6,400
intraperitoneally
0.4%10802.5-5.51.5Paralysed
7 days
0.5%10802.5-3.51.5No
Paralysis
1.0%103202.5-3.01.5No
Paralysis
1.0%101,6002.0-4.01.5Paralysis
14days
(Incomplete)
(*) and (**) Experiment repeated so as to check spinal fluid which
was negative.(M.C.P.) Minimal Completing Paralysing Dose.
130
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID
Salk reports, 1953, that as "the result of numerous experiments the decision was
made to use 0.4% formalin. Actually 1:4000 formalin is the accepted requirement
for bactericidal effects and one might not be too wrong in believing that this
point was the deciding factor. All investigators are agreed that if the formalin
is allowed to act longer than the time required to destroy infectivity, then
antigenicity will also decline correspondingly until a point is reached where
the virus no longer functions as an antigen. It would appear, from Brodie's
observations, that it would be desirable to increase, reasonably, the strength
of the formalin so as to "cut down' on the time required for inactivation. From
the table of Brodie's experiments we see that 0.4% paralysed the monkeys in 7
days with 36-hour exposure for formalin and virus suspension, where- as with
0.5% the monkeys were not paralysed allowing for the same duration of germicidal
activity. Concentration of virulent virus is a third factor. Brodie found that
with 1.0% formalin a large dose of virus after 36 hours exposure was merely
attenuated and would produce paralysis.
Many other factors were reported by Brodie, but in the reports concerning the
1955 vaccine one is led to believe that these were new observations made by the
1955 author. Kessel, reporting on Brodie's vaccine field trials in 1935 showed
that in one group of 331 vaccinated all remained free of the disease while 6 per
cent of the unvaccinated subsequently developed poliomyelitis. Salk, 1955[41],
writes, "even though the actual determination as to whether or not a
non-infectious vaccine could prevent paralysis in children was yet to be made."
Brodie, 1935, "two animals inoculated with 10 cc amounts of formalized virus
failed to show a demonstrable tissue immunity," but Salk, 1955, continues, "an
interesting observation has been made in other groups of monkeys inoculated on a
single occasion with 10 ml. of vaccine - blood drawn four weeks later revealed a
rather poor response or none at all except Type II. Brodie, 1935, stated, "two
doses when properly spaced gave decidedly better immunity, and small doses of
formalized vaccine was definitely better than large doses." Salk, again 1955,
"this reaffirms, once again, the importance of divided doses for providing
greater effects with less vaccine."
If a vaccine for polio is a 'must', we make these recommendations: (1) Increase
the streiffth of the formalin so as to reduce the 'killing' time. (2) The
vaccine be made up with each type strain in a separate vial. (3) that type III
be injected subcutaneously first, then Type II and finally Type I at 10 day
intervals. (4) That phenyl-mercuric-nitrate 1:80,000 (Kolmer) be used as a
preservative.
I think, though, that Kramer, Schaeffer and Park [42] had the
131
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID
right idea. They concluded one of their papers with this suggestion. "One is
tempted to question the importance of a method of immunization in a disease of
such low incidence as poliomyelitis. The practical application of any such
method must undoubtedly involve the immunization of large numbers of children
who would not get the disease. It might, therefore, be more logical to TREAT the
relatively few who do become ill." This can be done. The employment of ascorbic
acid in amounts of 250 mg per Kg. of body weight, preferably given by needle,
every 6 to 8 hours during the acute systemic phase of the disease will result in
a positive cure in from 48 to 96 hours. D.C.A. in amounts of 1.5 mg to 5 mg
given intramuscularly once each day is a good adjuvant in giving the "adrenals'
support.
These observations, it is hoped, will serve to manoeuvre the intelligence of the
reader to a sound realization of what is happening to the medical profession in
this country. Vaccines can be DILUTED to make them appear safe. As NEWSWEEK [43]
relates, April 25,1955, "The amount of vaccine one monkey can be made to produce
varies with the manufacturer's own method and efficiency. One drugmaker gets
1,700 cc's of vaccine out of every monkey, or enough for a two-shot vaccination
for 850 children. Another manufacturer says he gets 2,500 cc's per monkey." The
newspapers, however, tell us they have only one formula and one procedure.
The results as quoted by just two vaccine makers can be properly interpreted
from Brodie's chart (Conclusion-3). Brodie found that 1.0% formalin would
inactivate virus emulsion equivalent to 320 (2,500 cc's per monkey) minimal
paralysing doses in 36 hours, but if the virus emulsion was increased to 1,600
(1,700 cc's vaccine per monkey) minimal completely paralysing doses it would not
completely inactivate the mixture. No one really knows what is happening to
the immunological complex in those children receiving inoculations and who
remain apparently well. Brodie [44] appreciated the inherent danger of 'vaccine
therapy' by reminding us that "just as doses on the borderline of infectivity of
foot and mouth and looping-ill (a disease in sheep comparable to polio in man)
virus produced infection after prolonged incubation periods and larger
quantities after a shorter incubation period, so inoculation of polio virus
which were infective, but less than the minimal completely paralysing dose, gave
the disease after a prolonged incubation period while very large doses shortened
the incubation period." Actually, thousands of children have developed polio
from the present vaccine since many cases are not reported, either because the
disease is confused with or resembles some other childhood
132
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID
manifestation or the attending physician would not believe polio from the
vaccine was possible. Draper [45] observed that "MOST patients with polio never
develop muscular weakness and that paralysis when it does occur is an accidental
accident precipitated in the latter part or second phase of the course of an
acute systemic infection." In the systemic stage, or first hump, of a well
marked case of polio the clinical picture is that of almost all of the acute
infections of childhood - a flushed, uncomfortable, feverish child; in the
meningeal stage, or second hump, there are added the special signs and symptoms
of meningeal irritability. Of one thing we are certain. The unnecessary addition
of penicillin to the vaccine has unwittingly sensitized hundreds of thousands of
children so that a subsequent injection for some unrelated disease will result
in serious allergic reactions; for others it will bring death. All this results
from haste. Fleming was publishing lengthy reports on penicillin as early as
1927, yet it was 1939 (plus) before the world learned of its potentialities.
Haste makes waste!
During the field trials of 1954 blood samples were taken from ONLY 9,000[46]
children out of 1,829,916 subjects; many of these blood samples came from the
'observed group.' Where is the scientific approach? The 'sampling' of just ONE
apple out of a barrel will never tell you how many 'rotten ones' there are in
the lot. Brodie [47] found a definite relationship between formalized virus
vaccine immunity and the sedimentation rate - that the increase rate of
erythrocytic fall always showed 'during the development of immunity.' If this
simple test can be confirmed it will be of tremendous value, since Brodie
advised giving the second injection "during the rise or height of antibody
response to the first inoculation - not during the lag phase." Let us all
remember as we approach this problem in the future that "any method of
immunization employed in a disease of such low incidence as poliomyelitis MUST
possess the VIRTUE of complete SAFETY, for it is perfectly obvious that an
occasional accident might approach, or indeed exceed, the incidence of the
disease."
REFERENCES
1. Flexner, S. Lewis, P.A. J. A.M.A. Vol. 54 page 1780, 1910.
2. Levaditi, C. Landsteiner, K. Ann. Inst. Pasteur,
Vol. 25,
827 1911.
3. Kraus, R. Review of paper, J. Exp. Med. Vol. 49 960
1919.
4. Zappert, J., Wiesner, R., Leiner, K, Review of
paper, J.
Exp. Med. Vol. 49.
133
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID
5. Thomsen, O., Review of paper, J. Exp. Med. Vol. 49.
6. Abramson, H. L., Gerber, H., J. Immunology, Vol. 3
435
1918.
7. Flexner, S., Amoss, H.L., J. Exp. Med. Vol. 34 625
1924.
8. McKinley, J.C., Larson, W.P., Proc. Soc. Exp. Biol.
& Med.
Vol. 24 297 1926-27.
9. Aycock, W.L., Kagan, J.R., J. Immunology, Vol. 14
851927.
10. Rhodes, C.P., J. Exp. Med. Vol. 53 399 1931.
11. Sabin, A., J. Exp. Med. Vol. 56 1932 307.
12. Thomson, R. I., McKinley, E. B., Proc. Soc. Exp. Biol. &
Med. Vol. 32 1934-35.
13. Kolmer, J.A., Am. J.P. Health, Vol. 26 126 1936.
14. Brodie, M., Am. J.P. Health, Vol. 26 147 1936.
15. Andrews, C, J. Dis. of Child, Vol. 47 1216 1934.
16. Brodie, M., Goldbloom, J. Exp. Med. Vol. 53 883 1931.
17. Kolmer, J.A., Rule, N.M., Journal Immunology, Vol. 26 513
1934.
18. Kolmer, J.A., Am. J. Med. Sc. Vol. 188 510 1934.
19. Brodie, M., Am. J. Dis. Child, Vol. 48 57 1934.
20. Andrews, C.H., B. J. Exp. Pathology, Vol. 10 1929.
21. Teale, F.H., J. Immunology, Vol. 28 1935.
22. Brodie, M., Proc. Soc. Exp. Biol. & Med. Bol. 32 300
1934.
23. Brodie, M., J. Immunology, Vol. 27 1934.
24. Kramer, S.D., Green, H.A., J. Immunology, Vol. 50 275
1945.
25. Brodie, M., Park, W.H., Am. J.P. Health Vol. 26 119 1936.
26. Milzer, A., Oppenheimer, F., Levinson, S.O., J. Imm.,
Vol. 50 1945.
27. Freund, J., Review Am. J. Clin. Path. Vol. 21 645 1951.
28. Rivers, T.M., Am. J. P. Health, Vol. 26 136 1936.
29. Loring, H.S., Schwerdt, C.E., Lawrence, N., Anderson,
J.C., Science, Vol. 106 104 1947.
30. Bealle, M.A., The Drug Story, Health Research, Mokelumne
Hill, Calif.
31. Reidsville Review, may 5, 1955.
32. Reidsville Review, May 6, 1955.
134
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID
33. Leake, J.P., Discussion of Polio Papers, Am. J.P. H. Vol.
26,
148 1936.
34. Van Riper, H.E., Report to Physicians-Polio Vaccine, June
22, 1955.
35. Salk, J.E., J. A.M.A., Vol. 151, 1081 No. 13, 1953.
36. Kolmer, J.A., Rule, Anna., J. Immunology, Vol. 29, 175,
1935.
37. Sabin, A.B., Immunity & Vaccine, Mod. Med. May 15,1955.
38. Kessel, J.F., Dis. of Polio Papers Am. J.P.H., Vol. 26,
145,
1936.
39. Brodie, M., Science New Series, Vol. 79, Jan.-June, 1934.
40. Brodie, M., J. Immunology, Vol. 28, 1, 1935.
41. Salk, J.A., Am. J.P., II, Vol. 45, No. 2, Feb., 1955.
42. Kramer, S.D., Schaeffer, M., Park, W. II., J. Imm. Vol.
27,
199,1934.
43. Newsweek, April 25, 1955 (Magazine).
44. Brodie, M., J. Immunology, Vol. 25, 71, 1933.
45. Draper, G., J. A.M.A., Vol. 68, April 21, 1917.
46. Time Magazine, April 25, 1955.
47. Brodie, M., J. Immunology, Vol. 32, 1934.
135
SIGNIFICANCE OF HIGH DAILY INTAKE OF ASCORBIC ACID (Reprinted from The Tri-State
Medical Journal, July 1955).
APPENDIX
(Information available after this paper was sent for publication)
(1) Melnick (1955), studying 70 strains of polio virus
represent
ing one single type as shown by neutralization tests, found
that when tested against standardized sera of each immuno-
logic type by complement fixation roughly half of the strains
demonstrated dual antigenicity while others showed triple
antigenicity. Predominant antigenic activity indicated well-
defined overlapping between Type I and Type II and between
Type II and Type III. This could explain the epidemiologic
finding that with Type II antibody present in the sera,
immunity to Type I and/or Type III exists. (Melnick, J.L.,
Proc. Soc. Exp. Biol. and Med. 89, 131 (May) 1955).
(2) British health authorities cancelled the use of the
so-called
Salk polio vaccine as too dangerous. Said Dr. Graham Selby
Wilson, director, Public Health Laboratory Service, "I do not
see how any vaccine prepared by Salk's method can be
guaranteed to be safe." (Time magazine, July 25, 1955).
136
CHAPTER SIX
THE ROLE OF VITAMIN C IN EXERCISE
Three Published Papers: 'Joggers Beware' (Archie Kalokerinos and Glen Dettman)
'To Run or Not to Run' (Arthur Mowle)
A Report on Australian League Footballers
Supplemented with Vitamin C
Glen Dettman
and Izrael Zimmerman, M.B.B.S., F.R.A.C.G.P.
These papers indicate the necessity for sufficient vitamin C to be available for
those engaged in athletics and vigorous exercising, (e.g.. marching troops).
It is known that sailors pushing the capstan around during the days of Captain
Cook would often drop dead on the spot! Their vitamin C supplied would become
depleted, cellular function would cease and life could no longer be sustained.
We refer to these as SUDDEN ADULT DEATHS (SADS). A similar pathway occurs in
SIDS.
Any cause of stress, a minor illness such as a cold, antibiotics, cough mixtures
containing sedatives and antihistamines, an immunisation, indeed anything that
may cause an increased utilization of vitamin C, can put that subject at risk.
During the 'double blind trial' of the Australian League Football Team, Dr.
Zimmerman decided to stop the trial midway through, as he could see the
difference between the supplemented and the non-supplemented (i.e.., those on
the placebo), stating that it was unconscionable to continue the trial. His
clinical perceptions were 'spot on'.
Note the report of Dr. Mowle in 'To Run or Not to Run' which supports these
previously reported clinical facts.
137