## Archive for the ‘public health’ Category

### Herbal medicine and its dangers

December 18, 2016

I recently heard a talk by Thomas Efferth of the Institute for Pharmacology of the University of Mainz on herbal medicine. There is a common point of view that substances derived from plants are harmless and good while the chemical drugs of standard medicine are evil. The speaker emphasized that plants have good reasons for not being good to those who eat them. They do not have immune systems of the type we do and they cannot run away and so it is natural that they use poisons to defend themselves. Herbal medicines are effective in some cases but they need to be subject to controls as much as do substances obtained by artificial chemical means. In the talk a number of examples of the dangers of ‘natural’ medicines were presented and I will write about some of them here.

The first example is that of Aristolochia. This a large genus of plants, some of which are poisonous. One of these, Aristolochia clematitis, has been extensively used in herbal medicine. It was used extensively in the west in ancient times and is used in traditional Chinese medicine until today. In the talk the story was told of an incident which happened in Belgium. There was a product sold as a means of losing weight which contained a Chinese plant. It sold so well that the manufacturer’s supplies of the plant were running out. When more was ordered a fateful mistake took place. There are two plants which have the same name in China. The one is that which was originally contained in the weight-loss product. The other is the poisonous Aristolochia fangchi and it was the one which was delivered. This led to more than 100 cases of kidney failure in the people using the product. Another way in which plants can be dangerous is as weeds in crop fields. In the Balkans contamination of grain with Aristolochia clematitis led to a kidney disease called Balkan nephropathy, with 35000 recorded cases. The substance, aristolochic acid, which is responsible for the kidney toxicity is also known to be a strong carcinogen. Interestingly, this substance is not poisonous for everyone and its bad effects depend a lot on the variability in liver enzymes among individuals.

A class of substances used by many plants to protect themselves against insects are the pyrrolizidine alkaloids. These substances are hepatotoxic and carcinogenic. They may move through the food chain being found, for instance, in honey. It has been noted that there may be risks associated to the amount of these substances contained in medicinal herbs used both in the West and in China. It was mentioned in the talk that drinking too much of certain types of herbal tea may be damaging to health. The problem is usually not the plants that are the main components of the teas but other plants which may be harvested with them in small quantities. There is at least one exception to this, namely coltsfoot (Tussilago farfara). In one case the death of an infant due to liver disease is believed to be due to the mother drinking this type of tea during pregnancy. After that the sale of coltsfoot was banned in Germany.

There were some remarks in the talk on heavy metals which I found quite suprising. One concerned ayurvedic medicine which has an aura of being gentle and harmless. In fact in many of these substances certain heavy metals are added delibrately (lead, mercury and arsenic). According to Wikipedia more than 80 cases of lead poisoning due to ayurvedic ‘medicines’ have been recorded. Another remark was that there can be significant concentrations of heavy metals in tobacco smoke. The negative health effects of smoking are sufficiently well known but this aspect was new to me.

Another theme in the talk was interactions between herbal medicines and normal drugs. Apparently it is often the case that patients who use herbal remedies are afraid to mention this to their doctors since they think this may spoil the relationship to their practitioner. Then it can happen that a doctor is suprised by the fact that a drug he prescribes is not working as expected. Little does he know that the patient is secretly taking a ‘natural’ drug in parallel. An example is St. John’s wort which is sometimes taken as a remedy for depression. It may work and it has no direct negative effects but it can be problematic because it reduces the effects of other drugs taken at the same time, e.g. the contraceptive pill. It changes the activity of liver enzymes and causes them to eliminate other drugs from the body faster than would normally happen, thus causing an effective reduction of the dose.

We are surrounded by poisonous plants. I was always sceptical of the positive effects of ‘natural’, plant-derived medicines. Now I have realised how seriously the dangers of these substances should be taken.

### Hepatitis C

May 29, 2016

I once previously wrote something about hepatitis C in this blog which was directed to the mathematical modelling aspects. Here I want to write about the disease itself. This has been stimulated by talks I heard at a meeting of the Mainzer Medizinische Gesellschaft. The speakers were Ralf Bartenschlager from Heidelberg and and Stefan Zeuzem from Frankfurt. The first speaker is a molecular biologist who has made important contributions to the understanding of the structure and life cycle of the virus. For this work he got the 2015 Robert Koch prize together with Charles Rice from the Rockefeller University. The second speaker is a clinician.

Hepatitis C is transmitted by blood to blood contact. According to Zeuzem the main cause of the spread of this disease in developed countries is intravenous drug use. Before there was a test for the disease it was also spread via blood transfusions. (At one time the risk of infection with hepatitis due to a blood transfusion was 30%. This was mainly hepatitis B and by the time of discovery of hepatitis C, when the risk from hepatitis B had essentially been eliminated, it had dropped to 5%.) He also mentioned that there is a very high rate of infection in certain parts of Egypt due to the use of unsterilized needles in the treatment of other diseases. Someone asked how the disease could have survived before there were injections. He did not give a definitive answer but he did mention that while heterosexual contacts generally carry little risk of infection with this virus homosexual contacts between men do carry a significant risk. The disease typically becomes chronic and has few if any symptoms for many years. It does have dramatic long-term effects, namely cirrhosis and cancer of the liver. He showed statistics illustrating how public health policies have influenced the spread of the disease in different countries. The development in France has been much more favourable (with less cases) than in Germany, apparently due to a publicity campaign as a result of political motives with no direct relevance to the disease. The development in the UK has been much less favourable than it has even in Germany due an almost complete lack of publicity on the theme for a long time. The estimated number of people infected in Germany is 500000. The global number is estimated as 170 million.

There has been a dramatic improvement in the treatment of hepatitis C in the past couple of years and this was the central theme of the talks. A few years ago the situation was as follows. Drugs (a combination of ribavirin and interferon $\alpha$) could be used to eliminate the virus in a significant percentage of patients, particularly for some of the sub-types of the virus. The treatment lasted about a year and was accompanied by side effects that were so severe that there was a serious risk of patients breaking it off. Now the treatment only lasts a few weeks, it cures at least 95% of the patients and in many situations 99% of them. The side effects of the new treatments are moderate. There is just one problem remaining: the drugs for the best available treatment are sold for extremely high prices. The order of magnitude is 100000 euros for a treatment. Zeuzem explained various aspects of the dynamics which has led to these prices and the circumstances under which they might be reduced in the future. In general this gave a rather depressing picture of the politics of health care relating to the approval and prescription of new drugs.

Let me get back to the scientific aspects of the theme, as explained by Bartenschlager. A obvious question to ask is: if hepatitis C can essentially be cured why does HIV remain essentially incurable despite the huge amount of effort and money spent on trying to find a treatment? The simple answer seems to be that HIV can hide while HCV cannot. Both these viruses have an RNA genome. Since the copying of RNA is relatively imprecise they both have a high mutation rate. This leads to a high potential for the development of drug resistance. This problem has nevertheless been overcome for HCV. Virus particles are continually being destroyed by the immune system and for the population to survive new virus particles must be produced in huge numbers. This is done by the liver cells. This heavy burden kills the liver cells after a while but the liver is capable of regenerating, i.e, replacing these cells. The liver has an impressive capability to survive this attack but every system has its limits and eventually, after twenty or thirty years, the long-term effects already mentioned develop. An essential difference between HIV and HCV is that the RNA of HCV can be directly read by ribosomes to produce viral proteins. By contrast, the RNA of HIV is used as a template to produce DNA by the enzyme reverse transcriptase and this DNA is integrated into the DNA of the cell. This integrated DNA (known as the provirus) may remain inactive, not leading to production of protein. As long as this is the case the virus is invisible to the immune system. This is one way the virus can hide. Moreover the cell can divide producing new cells also containing the provirus. There is also another problem. The main target of HIV are the T-helper cells. However the virus can also infect other cells such as macrophages or dendritic cells and the behaviour of the virus in these other cells is different from that in T-helper cells. It is natural that a treatment should be optimized for what happens in the typical host cell and this may be much less effective in the other cell types. This means that the other cells may serve as a reservoir for the virus in situations where the population is under heavy pressure from the immune system or drug treatment. This is a second sense in which the virus can hide.

Some of the recent drugs used to treat HCV are based on ideas developed for the treatment of HIV. For instance a drug of this kind may inhibit certain of the enzymes required for the reproduction of the virus. There is one highly effective drug in the case of HCV which works in a different way. The hepatitis C virus produces one protein which has no enzymatic activity and it is at first sight hard to see what use this could be for the virus. What it in fact does is to act as a kind of docking station which organizes proteins belonging to the cell into a factory for virus production.

The hepatitis C virus is a valuable example which illustrates the relations between various aspects of medical progress: improvement in scientific understanding, exploitation of that information for drug design, political problems encountered in getting an effective drug to the patients who need it. Despite the negative features which have been mentioned it is the subject of a remarkable success story.

### Symposium in Mainz on controversies in biomedicine

October 26, 2014

Last Friday I attended a symposium on controversies in biomedicine at the Academy of Science and Literature in Mainz. There were a number of talks and a round table discussion at the end. The event itself was not the scene of much controversy. It seems that most of the people attending had a positive attitude to biomedical research. At least there was not much sign of the contrary in the questions after the talks. I thought that an event like this might have attracted more participants with a critical view of the subject but that does not seem to have been the case. The one vein of controversial discussion was between some journalists who had been invited for the round table (from Bavarian TV, Süddeutsche Zeitung and Frankfurter Allgemeine Zeitung) and the majority of the participants who were presumably scientific researchers in one form or another. The journalists expressed the opinion that scientists did not take part actively enough in public debates and the scientists suggested that journalists often sensationalized scientific subjects of public interest.

The first talk, by Christof von Kalle was about gene therapy. This taught me a number of things concerning this subject which I did not previously know much about. One example he discussed was that of X-linked SCID (severe combined immunodeficiency). The first choice of therapy for this fatal condition is a bone marrow transplant but this is dependent on the availability of a suitable donor. In other cases gene therapy was tried. It often cured the SCID but a high proportion of patients later got leukemia. A promoter in the inserted DNA had not only activated the gene it was supposed to but an oncogene as well. My one criticism of the talk is that the speaker packed in much too much information, sometimes flashing slides for just a couple of seconds. The next talk was by Bernhard Fleckenstein on pathogenic viruses. His main theme was biosecurity and biosafety. The first has to do with preventing voluntary misuse (such as bioterrorism) and the second with preventing accidents. I learned that this is still the subject of lively discussion. One amazing story is that there was an attempt to stop a paper written in Holland being published in the US by claiming that it was an export and that therefore an authority in Holland responsible for exports of goods had the right to forbid it. There is no doubt that experimental work on influenza viruses which are both highly virulent and highly infectious could be dangerous. However in my opinion it makes no sense to ban such research or to try to keep the results secret. This is because I think that somebody will do the research anyway, despite bans, and any important results will leak out. I think that the danger is minimized if the research is legal and open rather than illegal and secret. The next talk, by Martin Lohse, was on the necessity of animal experiments. One aspect which came out clearly was the tension between the legislation limiting research on animals and that requiring a certain amount of such research in the form of testing before a new drug can be approved.

Over lunch I had some stimulating conversations with other participants. The first talk after lunch was by Jörg Michaelis on the benefit or otherwise of screening, in particular for cancer. He recounted his own experience in organizing a large study on the use of screening of small children for neuroblastoma, with negative results. He then surveyed what is known about the value of various other types of screening. In particular he stated that screening for skin cancer, as paid for by the German public health service is not justified by any scientific evidence. Nobody in the audience contradicted this. The last talk of the day, by Uwe Sonnewald was about green genetic engineering. Among other things he presented statistics on the huge difference in the level of the use of these techniques in the Americas and in Europe, particularly Germany. If the bar representing Germany had not been a different colour it would have been invisible. The meeting ended with the round table. I just want to mention one point which arose there. In a recent post I mentioned the negative attitude to science and technology, particular in the area of biomedicine, which I notice in Germany. (This was one motivation for me to attend the event I am writing about here, with the idea of collecting arguments in support of science.) Of course this was a recurrent theme in the symposium in one form or another, particularly during the round table. An idea which appeared repeatedly, implicitly or explicitly, during the day was that the troubled relationship of the Germans to this subject could have to do with thinking of the abuses carried out by certain German doctors during the time that the Nazis were in power. This is maybe an obvious point but in the discussion someone (I think it was Christof Niehrs) introduced another idea, one which was new to me. He asked if it was possible that this troubled relationship perhaps goes back much further, namely to the period of romanticism when there was a reaction in Germany against the rationalism of the Enlightenment. I found this symposium very informative and it provided me with a lot of material which I can use in the future in discussions on this type of subject.