THE FOLLOWING ARTICLE APPEARED IN THE

FEBRUARY 2000 ISSUE

THE POISON SLEUTHS

DEATH BY GOLD

-Dr. Anil Aggrawal

"Good morning doctor. Oh, my God, what are you doing today? You have the dead body of an old lady today. She appears to have a gray pigmentation all over her body. What happened to her? Please tell me.”

“Good morning Tarun. The name of this 58 old lady is Rita, and she belongs to a very rich family. She married a relatively young, smart and ambitious doctor about a year back, after the death of her first husband. She was a chronic patient of rheumatoid arthritis - a disease mainly affecting women, in which there is intense pain in the joints- and was constantly taking medications for it. For some days however, she was complaining of vague symptoms, like stomach upsets, sore throat and tongue, a general lassitude and so on. Her own husband -the second one - was a doctor. He was treating her by his own medicines, but when things went out of his hands, he took her to the hospital. The senior doctors at the hospital also couldn't diagnose anything specific, and were treating her along general lines. Today morning her husband reported to the hospital that Rita was dead, and could they please issue a death certificate. That is how the case came to me."

"But you only deal with police cases doctor, and this doesn't seem like a police case to me at all. After all, she was an old lady and was suffering from a disease for which she was taking medications too. The doctors should have issued her a death certificate and that would have been an end of it. Why at all has she been brought to you for a post-mortem examination?"

"Tarun, this lady is worth about 65 crores of Rupees, and her husband Satyanand stands to inherit all that money. Some cousin of Rita has alleged that Rita has not died a natural death as is alleged by Satyanand, but in fact he has killed her by some poison. He has approached the police too, and lodged an FIR to this effect also. That is why her body has come to me. Naturally, like every other time, I have to tell the police, if she died of a natural death, or if some poison was used to finish her off."

"Oh, I see. So what do you think of this case doctor?"

"Tarun, I have taken a detailed history from that cousin of her, from the neighbors and from the doctors at the hospital who treated her. Two or three things have been bothering me quite a lot. Firstly the grayish pigmentation over her body, about which even you commented when you entered this post-mortem room. Secondly that almost all mucus membranes of her body are inflamed. She has an inflammation of her food pipe, wind pipe, her tongue, and even her vagina is inflamed. At her age, I wouldn't expect her vagina to be so inflamed. Moreover she appears to have a strange skin disease. I have examined her skin closely under the microscope and found that she is suffering from a special skin disease known as Lichen planus."

"What does this all point to doctor?"

"Tarun, to me, it seems to be a case of one and only one poison. A very unlikely one for you - one which would undoubtedly baffle you - gold!"

"What? Gold? You must be joking doctor. Never heard of gold being used a poison."

"Death by gold is surely a very very unlikely phenomenon. Nevertheless, it is possible. We must not forget that Rita was suffering from Rheumatoid arthritis, and one of the medications for it is gold. So gold salts were available in her house, and they could jolly well be used to kill her. We must also not forget that her husband was a young and ambitious doctor, and he surely knew that gold salts can be toxic in high doses.'

"Doctor, I feel, we are again on the trails of one of your great poison cases. Can we start the tale of gold from the beginning please? Please tell me about gold in some detail, so I could follow your conversation better."

"First, a few basic facts about gold. Known since antiquity, gold is a soft, malleable, lustrous yellow metal that steadfastly resists corrosion. Its atomic weight is 197 and it is a member of Group 1B in the periodic table of elements. Metallic gold is one of the least active metals chemically. It does not oxidise or burn in air even when heated and it is inert to strong alkalis and virtually all acids, except to selenic acid and to aqua regia, which as you know is a mixture of Concentrated nitric and hydrochloric acid."

"Doctor you were telling me, that Rita was taking gold salts for her ailment. So that means that gold is useful as a medicine too?"

"Sure. Gold, in elemental form, has been employed for centuries to relieve the itching palm. The real interest in gold as a medicine started when in 1890 the great bacteriologist Robert Koch told an international congress in Berlin that gold-cyanide complexes were most effective of all known antiseptics against tuberculosis bacteria, at least when tested in the test tube at high dilution. Unfortunately animals having tuberculosis could not be treated with these complexes. This dampened everybody's interest in gold compounds. In 1924, a Danish veterinarian demonstrated that gold sodium thiosulphate (known as Sanochrysine when sold in the form of a drug) had a beneficial effect in tuberculosis of the cow. Physicians tried the same compound in humans, but no success could be achieved. In those times, arthritis (pain in the joints) was wrongly thought by some to be a tuberculous manifestation. Under this impression Lande in Germany administered aurothioglucose (Solganal, a gold compound prepared by the Schering Corporation), to thirty-nine patients suffering from a variety of complaints. Many of these patients had joint pains due to rheumatic fever, and most of these patients reported relief of joint pain. Lande concluded that a full-fledged trial of the drug in arthritis would be worthwhile. Four years later in 1929, Jacques Forestier in Paris began to use another gold compound, gold-thiopropanol sodium sulphonate (Allochrysine) in rheumatoid arthritis. His observations were favorable, and it were mainly these observations which were largely responsible for the popularity of use of gold compounds in medicine. Therapy with gold compounds now even has a name; it is called chrysotherapy. Gradually the use of gold preparations in arthritic conditions began to spread, but it was not until 1944 that the results of a properly controlled clinical trial were first published by Fraser in Glasgow. He reported that clinical improvement occurred in 82% of 57 rheumatic patients who received intramuscular injections of sodium aurothiomalate (Myochrysin). Sodium aurothiomalate had been investigated in 1939, but only after the Glasgow trial was its value in therapeutics generally accepted. At present Gold is employed mainly in the treatment of rheumatoid arthritis. Its use is usually reserved for those patients with rapidly progressive disease who do not obtain satisfactory relief from therapy with aspirin-like drugs. Gold has however also been used in the treatment of several other diseases, but by and large, its use in other diseases is not very beneficial. Gold has also been used as a prosthetic. Because of its malleability and its anti-corrosive characteristics, gold has been employed as a prosthetic in dentistry and has been used widely as the predominant component of dental alloys containing silver, copper and small amounts of platinum and lead. These alloys can be heat treated to develop strengths as great as 150,000 psi (per square inch). Ophthalmologists have successfully implanted carefully balanced metallic gold weights into eyelids, as a surgical correction for patients who suffer from lagophthalmos. Before proceeding further, I may tell you that lagophthalmos is the technical name for the inability to voluntarily close an eyelid; the name comes from Greek lagos, meaning hare, because many people feel that in this disease, the eyes become rather like those of a hare! Gold has been recently used for delivery of genes inside the cells by genetic engineers. It has been seen that DNA can be absorbed to the surface of minute metallic gold particles and efficiently delivered by a controlled helium pulse to cells of the inferior epidermis. This is a painless maneuver, and results in notably efficient gene expression."

"Oh, I see. It seems, gold is really a useful metal for doctors. Can you tell me which compounds of gold are most commonly used as medications?"

"Sure Tarun. Mainly three compounds of gold are in clinical use. These are aurothioglucose, gold sodium thiomalate and auranofin. Aurothioglucose (SOLGANAL) and Gold sodium thiomalate (MYOCHRYSINE), both contain approximately 50% of gold by weight (For instance, gold sodium thiomalate is C4H3O4Na2SAu. Thus the molecular weight of the molecule comes to 390 of which 197 is gold, making it almost 50% by weight). Solganal is sold as a sterile suspension in a suitable fixed oil. Commercial preparations contain 50 mg/ml. Myochrysine is available as a sterile aqueous solution for injection. The usual dose is 10 mg of either of these compounds in the first week as a test dose, followed by 25 mg in the second and third weeks. Thereafter about 50 mg is administered at weekly intervals until the cumulative dose reaches 1 g (i.e. for about 20 weeks). A favorable response is generally not evident till after a few months. If neither significant toxicity, nor clinical response is visible, the dose is increased, but never more than 100 mg a week. Auranofin is available in India as GOLDAR, and RIDAURA. Both are available as 3 mg tablets, one tablet costing about Rs 12. The oral dose is 6 mg daily (i.e. about 42 mg a week) or one tablet two times a day, for a minimum of 3-6 months. As you can see in the accompanying formulae of these compounds, you will find that all significant medicinal preparations of gold are those in which the atom of gold is attached to an atom of sulphur. Nobody knows how gold salts work as medicines. But two facts are known about gold; one that monovalent gold has a strong affinity for sulphur and two that they have inhibitory effects on various enzymes of the body. This has led theoreticians to speculate that the therapeutic effects of gold salts might derive from inhibition of sulfhydryl systems which are present in the body. I may tell you that sulphydryl enzymes of the body have sulphur as their main component. However, other sulfhydryl inhibitors do not appear to have therapeutic actions in common with gold."

"Doctor, is gold a component of normal human body also?"

"Very little. An average human being has just about 2.45 mg of gold in his body. This however leads us to an interesting fact. Considering that the total population of the earth is about 6 billion at present, it follows, that the total gold contained in all human bodies is about 20 metric tons!"

"Oh, that is really an amazing fact. Doctor, when a patient takes gold salts for his ailment, where does it go? Does it go to joints?"

"Tarun, gold does go to the affected joints where its concentration is about ten times that in muscle, bone or fat. When one takes 50 mg of gold, about half of it disappears from the body in about 7 days. Technically doctors like to put this fact by saying that the half-life of gold is about 7 days for a 50-mg dose. You must however not confuse this half life with that used in radioactivity. But when a patient goes on taking successive doses, the half life lengthens, and values of weeks and months may be observed after prolonged therapy. After a cumulative dose of 1 g of gold, about 60% of the amount administered is retained in the body. In normal adults, minute amounts of gold can be detected in the hair, nails and skin. Using Neutron Activation Analysis (NAA), values ranging from 0-1.1 micrograms per gram of dry tissue weight, with a mean of 0.35 micrograms per gram (i.e. 0.35 ppm) have been reported. Following a course of gold therapy for 12 months, an increase of about 2-5 fold in these values occurs. After termination of treatment, urinary excretion of gold can be detected for as long as a year, even though concentrations in blood fall to the normal trace amounts in about 40 to 80 days. Substantial quantities of gold have been found in the liver and skin of patients many years after the cessation of therapy. Large amounts of gold salts, or their metabolic by products are commonly contained within phagolysosomes called aurosomes. The excretion of gold is 60 to 90% renal and 10 to 40% fecal, the latter mostly by biliary secretion.

"Doctor, now I feel, I know enough about gold compounds used as medications. Now tell me what are their adverse effects, and how can they be used as poisons."

"Tarun, with gold therapy, skin and mucus membranes are affected most, and occur in about 15% of all patients. Skin reactions may vary from simple redness to severe inflammation. The minimum cumulative dose of gold salts that has been associated with skin reactions is 250 mg. Dermatitis is so common that, out of all reported adverse reactions to gold therapy, almost 66% constitute diverse forms of dermatitis. Lesions of mucus membranes include stomatitis, pharyngitis, tracheitis, gastritis, colitis, glossitis and vaginitis, as we have seen in Rita's case. As with silver, a gray-to-blue pigmentation (Chrysiasis) may occur in skin and mucus membranes, especially in areas exposed to light. This pigmentation is due to the excessive collection of aurosomes in the skin cells. We have seen this too in her case. In 5-8% of patients, the kidneys may be affected to some extent. Kidneys may begin to pass proteins and even blood in about 1-3% of cases. Gold may also cause severe blood disorders, inflammation of the brain and peripheral neuritis, and of the liver. The usual fatal dose of gold is 50-500 mg/kg of the body weight. This means that for a person weighing 50 kg, which was Rita's weight, a dose of gold, as little as 2500 mg is sufficient to kill. We have seen that the Commercial preparations of Aurothioglucose (SOLGANAL) contain 50 mg/ml. This means that an injection of about 50 ml of this drug was sufficient to kill her. Before proceeding further, I must tell you the contraindications of gold therapy. Contraindications of a therapy means those conditions, in which that particular therapy should not be performed, otherwise it could prove dangerous. Gold therapy is contraindicated in patients with kidney, liver and blood diseases. Patients who have recently received radiation (as those suffering from cancers) should also not receive gold. Gold is also poorly tolerated by aged individuals, and should thus be given to them with care. I have examined Rita's body, and have found that she was suffering from kidney ailments. Thus gold should not have been administered to her in the first place. Obviously this fact was known to Satyanand. She was an old patient too, in which case too, gold should not have been given to her. Now I think I know what happened. Satyanand was administering gold to her unsuspecting wife for quite some time, under the pretext that he was giving her medicines. Rita had no reason of suspecting him. Even if she had consulted some other doctor, he would have told her that he was giving her the right drug. That was precisely his plan. He knew that nobody would suspect him of administering her a poison, as gold is commonly used as a drug in rheumatoid arthritis, which was exactly what Rita was suffering from. But he was administering gold to her in very high quantities. Rita did get some symptoms of gold poisoning, and to show to everyone, that he was really concerned about her, he took her to various hospitals fully convinced that the doctors wouldn't be able to diagnose gold poisoning in her case, because it is so rare. And he was right! Then yesterday night, or probably early in the morning today, he gave her a heavy dose of gold by injection - may be about 40-50 ml-, thus giving a final blow to her. I have examined her liver, spleen and lymph nodes chemically and have found heavy doses of gold in those organs. Satyanand would have tough time explaining how such large doses of gold reached her organs. I also examined Rita's hip area where Satyanand gave her the last injection, and the muscle beneath is loaded with gold. This also is a point against him. Satyanand had probably used gold in the belief that nobody would ever be able to catch him, as this is a poison, so rarely used. But the typical hue of Rita's body, and her other body findings gave him away. Come, let us tell the police that Rita did not die a natural death. It was Satyanand, who administered her gold to kill her."

"Unbelievable! This was a most interesting discussion doctor. Tell me what are you going to tell me the next time?"

"Tarun, next time, I would tell you about a very interesting poison - Radon."