Georg Ivanovas From Autism to Humanism - systems theory in medicine
The real challenge in regard to methodology and epistemology lies in the ‘viral flora’.
The difference to the bacterial flora is that the viral flora crosses individual boundaries. It oversteps the boarder from me to other and the border from one generation to the next. Viruses are more involved in human recursive processes than bacteria and by that they have more long term effects. They might become part of the human genome with positive and negative effects (Zimmer 2008). Knowledge on the viral flora is quite new and there is no adequate concept until now. The current findings give only an outline on how adaptation and learning involve virus’ functions.
In the first place it is important to know that viruses might persist, despite sufficient T cell immunity. This is known for the human erythrovirus (Norja et al 2006), for the syncytial virus (RSV) (Schwarze et al 2004) and the metapneumovirus (HMPV), discovered 2001 (van den Hoogen et al 2004). The last two often provoke bronchiolytis in small children and their persistence has been associated with asthmatic disease, as is the case with a growing numbers of viruses (Infectious Diseases Society of America 2007). In order to improve the health of the patients strategies to eliminate the viruses have been discussed. But this approach might be a fallacy. Either the persistence of these viruses is an expression of an inadequate immune response, or it is the (evolutionary) aim that they persist. In the first case, the immune response should be improved. In the second case, the persistence of the virus might have benefits for the host. Under both circumstances nothing is won by the eradication of the virus.
The persistence of an infectious agent able to change the whole adaptation (Grenfell et al 2004) might be helpful as it leads to a steady immune response that exerts an immune pressure onto other viruses persisting in the human, called ‘cross-protective immunity’ (Holmes 2007), which might be another explanation for the hygiene hypothesis.
The simultaneous infection with the GB virus, a close relative of the hepatitis C virus, leads to a survival benefit in AIDS (Pomerantz/Nunnari 2004; Williams et al 2004a; Xiang et al 2004). Also measles have a protective effect in AIDS (Moss et al 2002). On the opposite the cytomegalovirus is associated with a poor prognosis (Deayton et al 2004).
It is known that the infection with measles also has a protective effect for asthma (Benn et al 2004). Asthma is also improved through the infection with hepatitis A in certain genetically susceptible persons (McIntire et al 2004). The AAV2, a harmless virus present in many humans, is known to kill cancer cells and humans carriers tend not to develop cervical cancer associated to the human papilloma virus (HPV) (Meyers2005). Also the latency of the Herpes virus is associated with a better protection against bacterial infections (Barton et al 2007).
That is, viruses harmful under certain conditions are helpful under other conditions. This is very much the same with what is seen with Helicobacter and its relation to gastritis, oesophagitis and cardia cancer.
What happens now if such an ecological flora is altered through vaccination? Will it do more harm than good (Ruby et al 2004)? It is very difficult to raise this issue, as no other subject is so emotionally and irrationally discussed as vaccination. Nevertheless, it is crucial to understand the issue in the context of complexity.
Varicella is a harmless disease in early years. The mortality is about 0,41 per million inhabitants. In later years the complications of the disease rise, and, when the virus persists, this might lead to herpes zoster. Through vaccination mortality could be reduced to 0,14 per million (Nguyen et al 2005). Also the occurrence of Herpes zoster in the adult declined (Oxman et al 2005). Therefore varicella is included into the normal vaccination program in many countries. But in general the health problem caused by the varicella virus is quite small as its mortality is extremely low. Concerning herpes zoster it could be demonstrated in line with the hygiene hypothesis that elder people having regularly contact with young children have quite a smaller probability to develop the disease (Thomas et al 2002).
What will happen when varicella is eliminated from the viral spectrum? Will health improve or not? We have no idea what role varicella plays in our viral flora (the adaptation hypothesis) and we have no idea what people who suffer now on herpes zoster will suffer when the varicella virus is no longer present (the inadequate immune response-theory).
If the aim is to avoid complications or infections in grown ups the exposition to the virus could be promoted, as well. This is nothing else than the probiotic concept in the field of viruses. In my youth this was propagated by mothers. Whenever a child had measles or varicella, all children of the neighbourhood were collected to play with the infected child. Proposing a measles party today provokes rather fierce reactions. Measles became a feared disease. It is difficult to say whether the complications found in spontaneous outbreaks of measles really justify these fears. In any case the reaction of the medical world, the media and the readers of newspapers is enormous (Arenz et al 2003, Papania/Strebel 2005, Steinhauer 2008 and readers comments).
In order to judge the complications of a viral disease it is not sufficient to take only the immediate impact of the disease into account. Also short and long term consequences for health in general have to be observed. .Furthermore, there is also a social aspect which might be important in long term considerations.
When the Incas first came in contact with the European varicella virus and with measles this had a disastrous effect for their population. The same was true for the Red Indians. The events in North and South American can be compared with the Spanish flu 1918/1919. Confronted with a totally new virus, an avian type of influenza, millions died. This first contact lead to an overreaction of the immune system which provoked most deaths (Kobasa et al 2004, Kash et al 2006). The same seems to be true for the Avian flu virus H5N1 (Jong et al 2006). May be an overreaction is the typical pattern when a population is exposed to a new germ for the first time.
These disastrous reaction cannot be attributed only to the lack of antibodies. If a community has lived with a germ for a longer time, also the individual which never had contact with it before and has no specific antibodies is, in a way, protected and the reaction is smoother. This has been observed with measles in America or with syphilis (as an example of a bacterial disease) in Europe.
Three mechanisms might play a role. First, an epigenetic transmission (chap. 4.3) might provide some specific information about the germ. Second, a population might develop a cross-immunity through an ecological context (gut flora, persisting viruses). Third, the virus might change after several transmissions from human to human. There are indications for all three possibilities and these possibilities might even work hand in hand.
The question remains, whether it is useful to vaccinate against of large variety of viruses with an unknown long term effect, as there are no ideas about how this changes the human adaptation in general and to other viruses in special. Will other viruses become more potent? And what happens in times of war or famine when vaccination programs are no longer available? There was never a long period of time in human history with such stable conditions that exhaustive vaccination programs would have been possible. The reoccurrence of a disease in a situation when the community has ‘forgotten’ how to react adequately, might lead to such a disastrous effect as varicella and measles had in 15th and 16th century in America. Such effects are already feared in some African countries where polio has been eradicated through vaccination campaigns of the WHO. The reoccurrence of the virus finds now a susceptible population who never had a contact with the virus (it has been formerly eradicated) nor is it sufficiently vaccinated due to social factors (MacKenzie 2006).
Another question is, whether it is useful to vaccinate against a variety of viruses that on one side produce some harm, on the other side protect against some chronic disease? Already there are some propositions to vaccinations with living germs in order to stimulate the human immune system as the lack of infections facilitates the emergence of allergic disease (Asuitran et al 2004). In its final consequence such an idea aims to reinvent the viral flora. .
The nonlinear nature of the immune reaction to virus infections shall be highlighted with the following experiment: The Coxsackie virus is structurally similar to the polio virus although it provokes a totally different disease. Coxsackie is responsible mainly for catarrh like symptoms and rarely has severe complications. The discrepancy between the morphological similarity and the different clinical picture was explained by different receptors at which they dock. But when mice were genetically altered such that there were no more ‘polio receptors’ anymore, the animals developed the typical picture of polio when the Coxsackie virus was injected (Dufresne/Gromeier 2004). This finding reminds the receptor theory explaining the relation between helminths and atopic disease.
The fear is now that if the polio virus is totally eradicated and no more vaccination is performed, then may be the Coxsackie viruses will lead to a polio like diseases. Although such a conclusion is too speculative, it shall hint to problems that might arise when the viral flora is changed actively in a process which has been called ‚conscious purpose’ (chap. 6.1). In reflecting and discussing such problems there is no lack of data, but a lack of epistemological tools. This shall be demonstrated with the following example.
A survey found that the vaccination of children in Guinea Bissau lead to an increased overall mortality (Kirstenssen 2000), whereas another study showed that the vaccination with DPT and BCG in Burkina Faso lead to a decrease in overall mortality (Vaugelade et al 2004). The discussion of these results remained mainly on the level of the validity of the data (Hall 2004). By that the question of long term effects for the health of people in general and for the overall mortality in special could be avoided.
Without a sound epistemology it is impossible to tackle such questions as the specific-unspecific issue spoils everything. One contribution to the discussion even spoke of “non-specific "non-effects" of vaccination” (Fine 2004). However, the long term effects of a vaccination for the health in general have to be considered carefully in order to come to sound results (Shann 2004). That they are currently called unspecific is only due to the used theory. A more adequate theory makes it perfectly easy to model the underlying processes and to judge short and long term effects. We have proposed the concept of learning (Ivanovas et al 2007) which will be discussed later (chap. 4.3).
A further aspect, normally forgotten in the usual discourse was raised by Bleuler. Two years after the Spanish flu he called the handling of the epidemic as embarrassing for the medical science. In his opinion the occasion was missed to understand what kind of natural treatment (in modern terms: non specific treatments) would have be best to prevent such disastrous complications in the case of a future epidemic (Bleuler: 54-56). A main concern of him was to promote a sufficient robustness which might help to withstand the negative effects of a flu.
This is a typical change of the context, a clash between first (chap. 6.8) and second order (chap. 6.9) strategies. First order strategies are mostly promoted today: development of antiviral drugs and vaccination (Pearson 2004d, White et al. 2009). But in a new pandemic with an avian virus neither the vaccination will be possible in time (MacKenzie 2005), nor the drugs will be sufficiently available (Abbott 2005), and/or both might not work.
The currently spreading flu (H1N1) is a good example (summer 2009). Neuraminidase inhibitors might help a little or not (Kawai et al 2009) and a vaccination is not available. When available, it might be too late for a major effect on the spreading of the disease. That is, the treatment of the flu is ‘symptomatic’. This means
a) bacterial superinfections are treated with antibiotics,
b) anti-pyretics are given to relieve the symptoms.
Whereas the first strategy is meaningful, there is a lack of scientific evidence in the case of anit-pyretics. Moreover, there is some evidence that anti-pyretic therapy does more harm than good (chap. 6.8). If we add further that hospital treatment is rather problematic because of nosocomal infections and/or medical errors (chap. 3.6) and that a research showed that 6 of every 100 patients dying in a hospital die due to adverse drug reaction, mainly due to anti-inflammatory drugs and anti-pyretics (Universida de Granada 2008), Bleuler’s valuation of the flu is as apt as a hundred years ago.
Non-specific treatments are still no issue in the medical discourse. Searching pubmed for the key words ‘H1N1’ and ‘recommendations’ (31.7.09) leads to articles about vaccination and drugs. The search for ‘H1N1’ and ‘diet’ leads only to one older article recommending energy restriction on the basis of animal testing (Ritz et al 2008). That is all. Some physicians might have a certain knowledge about a proper dietetic treatment in the case of a viral infection. But this is not the normal case.
Of course, there are many ways to improve the immune-reaction in the case of an infection. Many of them might be far more effective than neuraminidase inhibitors. Water applications as proposed by Preßnitz or Kneipp (chap. 5.4.c) are empirically known to be very helpful. But such knowledge is neglected. Related research is scarce and only published in third degree papers a result of the publication bias (chap. 2.1). Under the aspect of robustness or resilience the handling of the current viral pandemic is not optimal, for sure, as too few factors (vaccination and antiviral drugs) are taken into account. The argumentation is comparable in many other diseases. However, it is more prominent in viral diseases as the possibilities of a specific treatment are rather limited.
Viral infections play a central role and are the greatest force in driving evolution (Weatherall 2003; Bradbury 2004). This does not necessarily require many generations. Genetic change is rather quick (University of Utah 2007) and not random (Pennisi 1998). For example, genes and viruses are able to exchange material recursively (Ruby et al 2004). Old viruses might become part of the genome and participate in the immune defence. This happened to the so-called endogenous retrovirus (RNA based). These viruses normally behave indifferent or are helpful, sometimes even essential (Dunlap et al 2006), for example, during pregnancy (Society for General Microbiology 2008). But under certain conditions, e.g., through an infection with a wild virus or through severe mental stress they become harmful. Then these viral genes start to produce molecules that are considered as foreign by the immune system, which might eventually lead to an autoimmune disease (Furlow 2000).
That is, certain persons will benefit from a viral infection, others will be harmed, and even this might change according to environmental conditions. The viral flora is therefore deeply interwoven into all processes of the human physiology and reproduction. The understanding of the viral flora will probably help to understand better the development of chronic diseases.
Naturally, the viral flora interacts with the bacterial flora and probably with helminths. But also prions play a role in the adaptation and the development of the immune system (Bradbury 2004; Pearson 2004). Until now we have not the slightest idea how all these mechanisms interfere. Furthermore, the whole is embedded in epigenetics (chap. 4.3), influences epigenetics and even might be the driving force for epigenetics (Goldenfeld/Woese 2007).
Such changes might persist across a number of generations. All this needs more complex epistemological tools than the concept of a specific therapy of a specific disease.