Radon and your lungs

Dear Reader,

I suspect that the next post is going to make people hopping mad with me, it is about the idea of using radon-222 as a medical treatment. Now before we go any further I would like to point out that I have no vested interest in the radon industry. Nor do I have a personal grudge against the radon therapy industry.

Now we will begin, I come from a school of thought that holds the view that radon-222 is horrible, this school of thought is the vast collection of people in the radioactivity business who live to hate radium-226 and its daughters. Rather than being a nice playful radioisotope radium-226 is considered to be a nasty so and so. It is an alpha emitter which forms a volatile daughter which also emits an alpha and then attaches its self to dust and smoke particles. In this way it creates a horror of sticky alpha active bits which stick in the lungs and do you a lot of harm.

By comparison plutonium-239 is a much nicer radioisotope to work with, it will not diffuse through gloves or fly through the air with great ease.

Some time ago a student (Hanna) at Chalmers was starting a PhD in radium chemistry, and she had a problem. She needed to work in a glove box. The state regulator were not willing to license the work unless it could be shown that the radon was trapped rather than being dumped up the stack. As an inorganic chemist I got involved, I applied what I know about zeolites and xenon to the problem and I then told the young lady of the joys of silver exchanged zeolite. This then resulted in a paper on radon and silver (Hanna Hedström, Mark Foreman, Christian Ekberg  and Henrik Ramebäck, Radiochimica Acta, 2012, 100(6), 395). We will keep the radon and silver story for another day, back to radon.

I checked the yearly intake limit for radon-222 and for inhalation it is 10 mCi when it is pure, but it is normally encountered with the daughters present. The limit when the daughters are present is 100 μCi (0.1 mCi). For comparison polonium-210 (half life 140 days) has a limit which is lower at 600 nCi per year, I would reason that the longer effective half life of the polonium in a human is likely to be responsible (at least in part) for this difference.

So I went and looked for a short lived noble gas, so I looked at the limit for xenon-133 (5.2 day half life), while there is no ALI for this isotope there is a DAC of 100 nCi (0.1 μCi) per litre. The DAC is a derived air concentration which is the limit for the air which you can breathe for 40 hours a week for one year.

I checked the DAC for radon-222 and it was much lower at 0.00003 μCi per litre (when the daughters are present), which works out as 0.03 nCi per litre or 3 pCi per litre. Now it should be clear to you that the USA’s goverment (NRC) hold the view that radon is very much worse for your health than xenon-133 is.

Even if we use their DAC for radon when the daughters are absent (400 pCi per litre) it is a lot worse than the xenon. We need to ask ourselves why.

Lets start by considering the decay energy, the xenon isotope is a mixed beta / gamma emitter which has an average beta energy of 100 keV. If we ignore skin exposure for a moment and only consider the beta dose to the lungs then 100 nCi (3700 Bq) of xenon-133 in air will deliver 370 MeV of energy into your lungs per second.

The alpha decay energy of the radon is 5489.52 keV, 14.8 Bq (400 pCi) of radon-222 will deliver 81.244896 MeV of energy into your lungs (call that 81.2 MeV) which is less energy. But alpha (α) is a high LET radiation which is considered (on the basis of energy delivered) to be 20 times more harmful to your cells than beta (β) or gamma (γ) radiation. So the effect of the radon on the lungs at the limit will be 4.4 times as harmful as the effect of the beta decay of the xenon.

The biggest problem with the radon is that it forms solid radioactive daughters which emit alpha particles, these daughters can lodge in the lungs where they continue to deliver radiation to the lung tissue. The atoms of radon are likely to come out of you when your breath out (some will diffuse into your blood and then go into the fatty tissues). So as a result you can imagine that radon is considered to be a grave threat to the lungs, it is worst when smoke or dust is present.

I recently spoke with a medical doctor from the Czech republic who runs a radon bath treatment site. He told me that in the Czech Republic that inhalation therapy was banned, he told me that one reason was worker safety. He told me that a patient is immersed in a bath of water (circa 5 kBq per litre) in a air conditioned room. The person is kept very still in the bath, I imagine that by avoiding splashing and stirring of the bath that the rate at which the radon is transferred into the air is reduced.

I also imagine that the Czech treatment room is a damp place which should reduce the number of dust particles per litre of air, this dampness will reduce the likelihood of radioactive dust entering a person’s lungs. I think that a bad environment for radon is always a dry and dusty place, the addition of smoke to radon containing air will always make it even worse. I have horrible visions of a uranium miner having a smoke in the mine while driving a poorly maintained diesel truck in the mine. Both the diesel and the tobacco smoke will increase the harm which the radon will do to his lungs.

A better situation would be the same miner now wearing a dust mask driving a well maintained truck in the mine. While I hold the view that it would be best if the miner gave up smoking totally, if he (or she) abstains from smoking in the mine then it would very good for the worker’s health.

So at least in the Czech Republic some steps have been taken to reduce the amount of lung damage.

Now from what I have read so far it is clear that radon therapy does bring with it a risk. I am sure that the supporters of radon treatment and others will point out that no medical treatment is totally without risk. I agree fully on this point, I have never heard of a medical procedure which is perfectly risk free.

But for a medical procedure to be justified, the benefits must out weigh the risks and costs. I will move onto benefit vs cost later.

Binding to receptors, new drugs and where should drugs come from ?

Well a brother blogger (An alternative medicine doctor) and me have raised some interesting points between us.

In the 1980s and early 1990s the drug companies seemed to think that computational chemistry would be a magic bullet which would give us the next generation of drugs. Sadly it did not work out so well as the drug companies hoped, the thing about computational chemistry is that it is all too easy to favour an answer by your choice of starting instructions (initial coordinates of the atoms). Also the mere binding strength of a drug to a receptor does not give the whole story.

Sadly I have never seen any databases in the public domain for binding strengths of drugs to receptors, but in some papers the binding strengths are listed. I suspect that some drug companies have their own private database of binding constants for some key receptors. One problem I see is that some drugs bind to receptors without turning them on, for example naloxone binds very tightly to the opiate receptors in the human brain but this drug does not turn on these receptors.

I suspect that Christopher will share my view that medicine and the production of medicine should not exist in a vacuum isolated from the rest of society. We need for example to consider the environmental impact of the production of drugs, a good example an early synthesis of ibuprofen produced lots of chemical waste. It used a Friedel-Crafts acylation using aluminium chloride, acetic anhydride and 2-methylpropylbenzene in the first step which will generate lots of aluminium containing waste. The later steps using other reagents also increase the amount of waste produced per kilo of the final drug product. Here is a chemical synthesis scheme for an early ibuprofen synthesis from some of my teaching materials.

An early synthesis of ibuprofen which generates lots of waste, all waste chemicals marked in red.

A later synthesis of the same drug was devised which produces much less waste per kilo of the drug product. This synthesis starts with the same starting materials but instead of using aluminium chloride it uses hydrogen fluoride. While I admit that the HF is a nasty so and so of a chemical (flesh eating horror acid) it is better in industry than the aluminium chloride as the product does not deactivate the catalyst. The key to the synthesis are the two catalytic steps (hydrogenation) and carbonylation using carbon monoxide where no atoms of waste are formed by the reagents when they do their work. This synthesis for the drug is likely to have a smaller impact on the environment.

New synthesis which makes less waste, all waste chemicals marked in blue.

I would like to point out that sometimes a man made pure drug is sometimes better than an poorly defined product from a plant and sometimes the less pure product from the plant is better. Now I will tell you a story about lung cancer and male smoking medical doctors. Some years ago when I was in Aberdeen I went to a lecture given by a man from the Rowett Institute of Nutrition and Health (Now part of Aberdeen University) where he told us some of the latest about vitamins and health. This lecture made me give up vitamin pills and but take up eating more fruit and veg.

We were told about a study where vitamin pills had increased the risk of lung cancer in smokers, ex-smokers and asbestos workers one example of this is G.S. Omenn et. al., New England Journal of Medicine, 1996, 334, 1150-1155 where the experiment was stopped early. This was the CARET study. In this study men were given either 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day or a placebo pill. The men on the vitamin pills were suffering more cases of lung cancer than the people taking the dummy pills.

Now I know that you all think that vitamins are good for your health, but this study suggested the total reverse. The man from the Rowette suggested that the reason might be that humans need a series of different isomers of the beta carotene and that by flooding the body with large amounts of one isomer will cause a shortage of the other isomers by overloading the transport process for the beta carotenes with one single compound.

In the end it has been shown that high doses of beta carotene do make smoking more dangerous by a different mechanism but it was an interesting hypothesis (I am not sure if it has been fully tested yet) which made me stop trying to fix a bad diet with vitamin pills. I then tried to eat a better diet with more fresh fruit and veg.

OK the score is now pills 0, plants 1. But after I have irked some of the pill pushers I am about to do likewise with the plant pushers in my next post.

A herb from india

Dear Reader,

Christopher Maloney (“a brother blogger“) has commented recently on a herb from india which is known to contain a substance called Withaferin A which can be isolated from a plant named “winter cherry” or “ashwagandha“. Now this herb is thought to have some useful medical properties, I have looked and in the Cambridge data base an entry for this substance exists.

P. Bandhoria, V.K. Gupta, P. Kumar, N.K. Satti, P. Dutt and K.A. Suri, Anal. Sci. :X-Ray Struct. Anal. Online, 2006, 22, x89 is a paper which reports the strucutre of the compound.

The compound is a steroid which has an epoxide group and a lactone group in it. One paper suggests that the compound is an antiestrogen (E-R. Hahm, J. Lee, Y. Huang and S.V. Singh, Molecular Carcinogenesis, 2011, 50, pages 614 to 624). I have looked at the strucutre of the drug and here it is as a 2D drawing.

Withaferin A

In real life the molecule has a 3D shape, I looked at it using my trusty copy of ORTEP. I have done a few POVray files for you good people to look at. For those of you at home who have copies of POVray I am tempted just to give the code, but for those of you who are not into POVray art here is the the picture.

Spacefilling model of Withaferin

While a spacefilling model is very useful to be able to hold in your hand and view, it has oftein hard to see the wood for the trees. For that reason we tend to use the ball and stick view of a molecule. Here is the ball and stick view of it.

Withaferin ball and stick view

It is interesting to note that back in 1968, A.T. McPhail and G.A. Sim published (J. Chem. Soc. B, page 962) a strcutre of the para-bromobenzoate / acetate ester of withaferin A. I think that the reason that the para-bromobenzoate was used was that it includes a heavy atom which is more easy to find in X-ray crystallography than a carbon, oxygen or hydrogen atom. The idea of the Patterson method is that you solve the crystal strcutre for the very heavy atom only at first and then during the refinement you can locate the carbons, oxygens and hydrogens using electron density maps. What happens is that the crystallographer looks at the difference in the electron densities obtained from the data with the predictions made from the locations of the atoms which have already been found. In this way new (lighter) atoms can be located which improves the quaility of the result.

Before cheap and powerful computers were avaiable to crystallographers the direct methods (which is more computationally intense) was less popular than it is today. Today crystallographers can use both dirrect and Patterson methods, but I know a lot of crystallographers still like to use the Patterson method when they have a heavy atom in a solid.

Well keep tuned, and if you find any interesting herbs then please tell me. I may be able to look them up to see what interesting chemicals they might contain.

Super bacteria as a result of Fukushima ?

Dear Reader,

I am sure that many of you will be aware of Godzilla the movie monster which was a dinosaur which got a dose of radiation and thus turned into the super monster. Also for those readers who were born in the 1980s there is the infinitely more annoying ‘teenage mutant ninja turtles’ who according to one version were pet turtles which encountered some exotic toxin which turned them into super turtles (more like irksome turtles). Here the toxin turned the turtles into super turtles.

Recently I saw a paper which asked the question of would normal bacteria after a dose of Fukushima radiation turn into super germs which would be immune to antibiotic drugs. The good news is that according to Shigeyuki Nakanishi, John E. Moore, Motoo Matsuda, Colin E. Goldsmith, Wilson A. Coulter and Juluri R. Rao in Ecotoxicology and Environmental Safety, 2012, volume 76, pages 169 to 174 it will not happen.

They found that radiation does not turn germs into super germs, I suspect that while the gamma rays may have increased the mutation rate because the microbes were not being subject to attack by antibiotics at the same time the increase in mutation rate did not make the germs evolve.

I suspect that if germs were never exposed to antibiotics that very few germs would be immune to the drugs, the reason is that the immunity to the drug does not give the germ an advantage if the drug is never present.

Also as many organisms evolve an immunity to a drug or a pesticide by changing their biochemistry to make it more “exotic”, the exotic biochemistry might give the organism a disadvantage when the biocide is absent.

For example penicillin stops germs by stopping them making the proteins needed for their cell membranes, if the germs change to have second new enzyme which the penicillin does not deactivate in addition to their normal enzyme then they will have to make a greater effort to grow as they will have to make two enzymes while normal germs only need to make one.

For example I saw an open university film about biology years ago which explained that normal grass can not tolerate copper, but the grass on a mine spoil head is a special grass which can tolerate copper. As a result the grass on the spoil heap is different to the normal grass in a field which is unable to grow on the spoil head.

Because the copper tolerant grass is less able to grow under normal conditions than the ordinary grass the copper tolerant grass is not able to take over the normal land. In the same way I suspect that radiation on its own will not make the germs evolve into antibiotic resistant germs.

I think that the only way to make the radiation turn the germs into antibiotic resistant germs would be to expose a culture of the germs to both radiation and the antibiotic at the same time.

Drugs from a music festival

Dear Reader,

I recently saw a report on ‘the local‘ about a report of drugs appearing in a river as a result of a reggae festival, now when people first read the head line they might expect lurid details of the THC (weed) appearing in the river or some more outlandish drugs. I think it would be hard to observe this drug of abuse appearing in a river for several reasons.

Firstly what ever you think about reggae music and festival goers I suspect that very few people at the music festival have been smoking dope. As a result the amount of THC going into the river is likely to be low.

Secondly THC has a low solubility in water, it is a fat loving (lipophilic) substance which I suspect will bind to the organic matter in the soil. Also I do not think that it will be very mobile in soil.

The drugs which were considered in the study were acidic drugs ibuprofen (legal pain drug), naproxen (legal pain drug), bezafibrate (cholesterol and lipid drug), diclofenac (legal pain drug which kills some birds of prey) and ketoprofen (legal pain drug). Also five basic drugs atenolol (beta blocker), metoprolol (beta blocker), sotalol (beta blocker), acebutolol (beta blocker) and carbamazepine (a mood stabilizer and anticonvulsant).

The acidic drugs are likely to form anions when they enter the soil in urine, in general from the study of nuclear waste it is known that anions tend to be more mobile in soil than cations. As a result the anionic drugs are likely to pass with greater ease through soils. Sadly I have no idea of the soil type at the festival site, in general clay is better at retaining cesium than a peat based soil.

Other than the last drug the basic drugs have lots of frilly bits (oops I mean hydrophilic alkyl groups) which are likely to increase the water solubility of the drugs which will make them more able to enter the river.

Do not do spice !

Dear Reader,

My advice is “do not try to reach heaven or experience a joyous state through the use of drugs, it is likely that you will foul up your life and descend into the depths of hell”.

In the chemical literature I have seen a range of ways people have tried to get high, I would not recommend any of these ways to get ‘high’. All of them have some nasty sting in their tail.

It has come to my attention that a series of indoles which are man made cannabinoids have been sold under names such as “spice”, “Dream” and “K2″. These chemicals do mimic THC in some ways, in common with THC they do have the potential to cause psychosis. I saw one report which cited Lt. Commander Donald Hurst (US Navy) which has messed with some people’s minds in some horrible and weird ways. One of the story reminds me of the disturbances of the mind which are caused by BZ. I have read of how men exposed to BZ have played tennis with imaginary rackets and other odd stuff.

A sailor in the US navy was unable to work out what to do with a sandwich ! These indole drugs are not the harmless highs which some people might tell you they are. In a recent paper Susanna Every-Palmer (Drug and Alcohol Dependence, 2011, 117, 152-157) explained how this drug put a series of people in New Zealand into mental hospitals.

For those of you who do not know BZ is a horrible drug which messes people around a lot. The US miliary considered it as a non lethal chemical agent which would make people unable to fight.

Drug adverts

Dear Reader,

Watch the following film,

http://www.youtube.com/watch?v=eLef9G1PJ7s&feature=feedwll&list=WL

I think that this film shows why Sweden and the UK (and most of the rest of the civilised world) have been very wise to ban marketing of proscription drugs to the general public.

Glue sniffing nightmare

I was innocently going about my work as an academic, I needed some literature references to teach a student about head space GC. (I have to admit I love GC and I dearly love the head space method).

I was somewhat shocked when I saw a paper entitled “A fatality due to inhalation of 1,1-difluoroethane (HFC-152a) with a peculiar device”, it was about some man in his 30s who died after some hardcore “glue sniffing” (more correctly volatile substance abuse). I read the paper and was disgusted, this unnamed man had gassed himself to death while in search of some sort of high.

When I saw the “peculiar device” I was disgusted, it was horrible.

The take home message is do not inhale weird gases to try to get high, it is very horrible. I have read that a common problem is that people under the influence of narcotic gases such as butane tend to hallucinate. They see something which scares then “like Freddy Kruger coming to get them” they then panic. This pushes up their adrenaline level. The combination of the narcotic gas and the adrenaline then causes a cardiac arrest which ends their lives.

So kids (and those with kids) always bear in mind that sniffing glue/gas/aerosols is a very bad idea. Do not do it !

Made, adapted or intended

A cathinone like substance has shown it’s ugly face again, my advice to all people (including the youth of the day) is to avoid mephedrone as if it was the plague.

What I can not understand is why it has not already been banned, UK law on offensive weapons covers “Any article made or adapted for causing injury, or intended to cause injury”. I would say that bath salts such as magnesium sulphate (epsom salt) which are able to simulate a mineral rich hot spring in the comfort of your own house are made / intended for washing your body.

However bath salts containing a psychoactive drug to my mind are clearly not intended for cleaning your body. I think it is a ploy to evade the spirit of the law. I think it is the same level of “wrongness” as the idea of selling scotch whiskey in the school dinner hall as a pencilcase cleaning agent, or how about pints of strong cider as a mouth wash for teenagers sold in the sweet shop !

http://news.yahoo.com/s/ap/20110122/ap_on_re_us/us_dangerous_bath_salts

The Crazy Chemist and his mates

I am currently ‘disgusted from Tonbridge Wells’, yesterday I discovered that the UK government are running an antidrug campaign featuring the “crazy chemist”. (http://www.aldp.ie/uploads/File/The%20Crazy%20Chemist.pdf)

I am a chemist, it has been my job to make molecules for a living. As a result I know something about drugs of abuse, the more I know about ‘drugs of abuse’ the more opposed I have become to recreational use of drugs.

The majority of chemists I know are opposed to the production and use of recreational drugs. I am not able to name any person that I know who has a chemistry degree who is ‘pro drugs’.

All professions have their bad apples, but very few chemists turn out to be seriously morally bad ones. If the home office want to educate people about the perils of designer drugs then I would suggest that they consider the following case and scrap the ‘crazy chemist’.

There was a US college chemistry student who was a grade A1 bad boy chemist. His story is one which is also educational, he figured out a way to get very high on home-made super version of pethidine. He then made an error while cooking a batch and then gave himself Parkinson’s disease in his twenties with his home made brew! He then got treated for this condition and then went and promptly took a cocaine overdose and died. What a horrible waste of a life !

(http://www.scq.ubc.ca/the-shaking-palsy-a-review-of-parkinsons-disease/) (Also see DAVIS GC, WILLIAMS AC, MARKEY SP, EBERT MH, CAINE ED, REICHERT CM, and KOPIN IJ, “Chronic Parkinsonism Secondary to Intravenous-Injection of Meperidine Analogs”, Psychiatry Research, 1979, volume 1, pages 249-254)

To be frank with you the idea of being stuck (fully awake) in the psychiatric ward unable to move with the mis diagnosis of catatonic schizophrenia which does not respond to any form of treatment is perfectly horrible. I think it is far worse than most of the horror tales which are used in antidrug lessons for children ! I might one day tell you about MPTP but not today, back to the matter at hand !

I feel that this ‘crazy chemist’ is a slur on my profession, rather than calling for an instant ban on the ‘crazy chemist’ I would like to suggest that the home office should first consider adding some new characters to their public education campaigns.

1. The naughty milkman who adds water to the milk to make extra money

Down at the dairy watch him add 10% water to the milk.

See how he fails to wash his hands after taking a trip to the loo.

See his friend who cooks up toxic baby milk

Watch him supply milk to the wake for the baby who died of toxic baby milk

2. The crocked policeman.

Watch him make up evidence to harm the innocent.

Look at him tampering with evidence.

Hear him telling lies in court.

Look at him beating some poor passer by

3. The naughty motor mercanic

Hear him lieing to the car owner

Watch him issue a MOT certificate for a car which he knows is unsafe

and worst of all….. wait for it….

here it comes…

4. The waste of space, greedy, lazy, corrupt and stupid politician.

Watch him make sound bite statements about subjects he knows nothing about just so he can make himself look good in the media.

Hear him lie to the public and the house of commons.

Pay attention to him voting for unjust laws.

See how he claims for silly expenses like champagne for filling his bathtub.

See how he wastes time being lazy.

See him take bribes and see how he drags other people’s good names into the mud !

Also the term crazy is wrong, there are people out there (chemists included) who suffer from mental handicaps and mental illness. The term crazy can be offensive to these people, I feel that it is deeply wrong to mock a person because of their illness or to use a medical term as an insult for a person.

Always bear in mind what the bible says on this matter (Leviticus 19:14 King James Version)

“Thou shalt not curse the deaf, nor put a stumblingblock before the blind”

Or in modern english

“I am the LORD your God, and I command you not to make fun of the deaf or to cause a blind person to stumble.”

My understanding of this that it is a command for us not to mock a person because of a medical condition which they had no control over. The blind normally do not have any choice regarding their vision, and many “crazy” people never had a choice of “do you want to get a sickness of the mind”. While parts of the UK government are trying to do the noble work integrate people with mental health problems into the community, another part is using stereotypes of an evil mad scientist. I think that it is another reason to retire the “crazy chemist”.

PS. Most of the time when chemists get involved in drug abuse it is helping society deal with the problem of drug abuse. Chemists create and operate many of the tools which help keep drugs off the streets. Such as the field test for cocaine. You will all have seen the liquid go blue in the films, this is an example of chemistry in action (This test is based on the coordination chemistry of cobalt(II)).