THE FOLLOWING ARTICLE APPEARED IN THE

FEBRUARY 1998 ISSUE

THE POISON SLEUTHS

DEATH BY SMFA

-Dr. Anil Aggrawal

"Good morning doctor. Oh, my God, what are you doing today? You have the dead body of a young woman today. What happened to her? Please tell me."

"Good morning Tarun. The name of this 22 year old female is Kabuli. She had got married to Radhey only a year back. Radhey works in a chemical factory involved in manufacturing various chemicals. Since the marriage day itself, there was a dispute among the couple regarding the insufficient dowry which Kabuli brought from her home. Radhey as well as his parents used to belittle her on every little matter. For about last one week, Radhey suddenly started a soft posture towards Kabuli, as if he had buried all differences with his wife. Last evening he became very sweet to her, and even made a cup of tea for her. She was a bit surprised, but thought that may be Radhey had changed his ways. She took tea, but soon after had vomiting, and seizures. After about 3-4 hours she died. A local doctor was called, who certified the cause of death as heart attack. But the relatives of Kabuli lodged a complaint with the police that Kabuli had actually been poisoned to death by Radhey. Subsequently the police went to Radhey's house and seized the remaining portion of the tea, as well as some other stuff from his almirah. The body of Kabuli was also seized and given to me for post-mortem. Now I have to conduct a post-mortem on the case and tell the police if Kabuli was really poisoned or not."

"Just a minute doc. You said that a local doctor has already certified that the cause of death was heart disease. Then what more do you expect to find?"

"Tarun, the relatives of Kabuli have already lodged a complaint with the police that she has been done to death by Radhey. Kabuli had got married only a year back. Under the Indian law, any death of a married female occurring within 7 years of marriage is termed as dowry death and is taken seriously. Had there been no complaint from Kabuli's relatives side, then everything would have been fine. But since a complaint has already been lodged, the police naturally want to be doubly sure that Kabuli really died of heart disease or not."

"You mean that the local doctor gave a wrong cause of death? Do you?"

"Well, the doctor had not seen Kabuli during life. The doctor could genuinely be mistaken. Sometimes, a doctor may give a cause of death just to avoid harassment to the relatives. If the doctor knows the family personally and is convinced that the death was natural, he would generally oblige the relatives by giving a cause of death, even if he had not seen the patient during life. He does so in order to save unnecessary harassment to the relatives at the hands of the police. Last but not the least, a doctor can actually be bought by unscrupulous relatives, to give a wrong and misleading cause of death."

"Oh, I see. So you are doing the postmortem in order to find out how Kabuli died actually?"

"Exactly. If my findings indicate that Radhey had indeed given poison to Kabuli, he could be prosecuted under section 304B of the Indian Penal Code, which is popularly known as Dowry Death. If the court finds Radhey guilty of murdering his wife, he would get no less than 7 years in jail. This is the punishment prescribed in section 304B of the Indian Penal Code."

"Oh, I see. So what have you found out?"

"Tarun, the most interesting thing is that while Kabuli was drinking tea, she did not complain of any bad odor or taste. This means that the poison, if indeed it was given to her, was tasteless and odorless. The tea also had its normal color, which means that the poison was colorless too. Such poisons, which are colorless, odorless and tasteless are generally very successful homicidal poisons, because the victim can not make out the poison while taking his food. I also took into account that Radhey was working in a chemical factory which was making rodenticides. Rodenticides are very strong poisons and can kill a person within a short time. It was quite possible for Radhey to steal a little quantity of rodenticide from his factory and give it to Kabuli for homicidal purposes. The only rodenticide, which is colorless, odorless and tasteless is a chemical compound known as Sodium Monofluoroacetate which is also known by its acronym SMFA. Its chemical formula is C2H2FNaO2 and it is also known as Compound 1080. Its other names are Sodium fluoroacetic Acid and Sodium fluoroacetate."

"Compound 1080? That's rather a strange name. Why has it been given this mathematical name?"

"That's an interesting question Taurn. But let me tell you about another compound which has been given a mathematical name too. It is arsphenamine, which is known as Compound 606. This has an interesting history too.."

"Doctor, I am a sucker for interesting scientific histories. Please tell me the history of compound 606, and then of course we can go to the history of compound 1080"

"Alright as you say. Well, you must surely be knowing about the German Scientist Paul Ehrlich (1854-1915). He is often known as the father of antibiotic therapy. In late 1800s and early 1900s - the era during which Ehrlich lived - one of the biggest problems faced by doctors was to create a drug which could kill bacterial cells but NOT human cells. If such a drug could be discovered, it could be given with impunity to humans in order to cure their infections, say syphilis (which as you surely must be knowing is caused by a bacterium known as Treponema pallidum). The drug would then selectively target bacterial cells killing them, while sparing the human cells. Such a drug could be called - as Ehrlich liked calling it during his entire life - a "magic bullet" ; a bullet magical enough to kill bacterial cells while leaving human cells alone. Since human and bacterial cells are so similar in nature biologically, it was difficult to find a chemical which could destroy one type of cell, leaving out the other. But of course there are differences too, and the answer lay in finding those differences and exploiting them.

In the late 1800's, Elrich, was noting with interest that there existed some stains which could stain bacteria but not human cells and vice versa. A cell, as you know, gets stained only when it "takes up" that dye. If bacterial cells and human cells could take up different stains, surely there existed more chemicals which could be differentially absorbed by bacterial and human cells. And surely some could be toxic to them too. Ehrich started from this conjecture and started with one such dye. His aim was of course to find a chemical which could - instead of staining the bacterial cell - KILL it. There was absolutely no luck in the beginning and so he began to chemically alter it little by little, testing each new drug. When he reached 606th compound, he discovered, to his delight, that he had finally synthesized a chemical (it had changed so much by now, that it was no more a stain), which could kill bacteria, especially the bacteria causing syphilis. In the beginning he simply called it Compound 606, because it was the 606th compound synthesized by him. Of course later it became known as arsphenamine and was marketed as Salvarsan."

"That's great. Doctor, you know so many stories. And now, what about the story of Compound 1080? So I take it when Ehrlich reached at 1080th compound, he gave it that name, and that compound was SMFA, right?"

"No, not at all. In fact Ehrlich stopped at 606. To be sure, he did not live much after introducing that compound. Compound 606 was synthesized sometime in 1909 and the first tests on bacteria were announced in the spring of 1910. Ehrlich suffered a stroke in December 1914, and succumbed to a second stroke in August of the following year (1915). No, compound 1080 was not synthesized by him. There was a company, which was synthesizing chemicals for possible pesticide use, and SMFA was the 1080th compound tested by them. You might be interested to know that there is a compound known as Compound 1081 too. It is Fluoroacetamide. This also acts as a rodenticide and insecticide. This was of course the next compound made by the same company."

"Fine. So you concluded that Radhey had given SMFA to Kabuli. Well I haven't heard much about SMFA. Please tell me something about it in detail."

"Tarun, I must tell you that I have not concluded anything yet. I am simply trying to analyze the circumstances, and come to the most logical conclusion. That is what scientific thinking is all about. To tell you more about Sodium Monofluoroacetate, I must tell you that it is a highly toxic rodenticide. It contains fluorine, but its toxicity is not related to its fluoride content, but rather to its interference with the Kreb's cycle..."

"What is Kreb's cycle doctor? This term is rather new to me."

"Tarun before going any further, I must tell you that Kreb's cycle is named after a German-British Biochemist, Sir Hans Adolf Krebs who was born in Germany in 1900. He found out for the first time how lactic acid in the body gets broken down to release energy. Well, to begin from the beginning, glycogen in the liver is first converted to lactic acid, but this step gives only very little energy. Major energy comes from the further breakdown of lactic acid into simpler compounds such as carbon dioxide and water. The exact sequence of breakdown of lactic acid into simpler compounds was first worked out in great detail by Sir Hans Krebs, and hence these steps are known by the name Kreb's cycle. It is also known as tricarboxylic acid cycle. This however is a less fancied name. If any chemical interferes with Kreb's cycle, it would cause death because Kreb's Cycle is the main energy source of the body. Sodium Monofluoroacetate is one such chemical."

"Oh, I see. Since how long do we know about this compound? Looks like it was developed fairly recently."

"Tarun, SMFA was developed during World War II as an alternative to imported natural rodenticides. Because it is so highly toxic, its use is mostly limited to commercial exterminators. It is derived from some plants such as Palicourea (South America), Acacia (Australia), and a few other plants. As I told you earlier, SMFA is a white, odorless, tasteless, water-soluble salt. It looks like flour or baking soda. Unlike thallium about which we talked in one of our earlier meetings (see Science Reporter October 1997, pages 42-46), SMFA can not be absorbed through unbroken skin. However it is readily absorbed through the gastrointestinal and respiratory tracts, mucus membranes and broken skin. It is thus highly toxic when ingested, inhaled in dusts, or absorbed through open wounds."

"Oh, I see. You said that Kabuli had vomiting after taking tea, and also that she had seizures. Are these the symptoms of SMFA poisoning?"

"Well, almost. The toxic effects of SMFA are usually delayed for one to several hours and result from the conversion of the nontoxic fluoroacetate ions to toxic fluorocitric acid, which in turn blocks the Kreb's cycle. I have already told you that this cycle is essential to energy production. I must tell you that this cycle is important in mammalian cells only. Vomiting is commonly seen soon after ingestion. Toxic effects primarily involve the Central Nervous System and the heart. They include nausea and apprehension followed by disturbances of the heart beat, respiratory depression, seizures and coma. Apprehension, auditory hallucinations, and facial paresthesias often precede convulsions. By facial paresthesia, I mean that there are sensory disturbances in the facial area. There may be tingling sensations in the face, or there may be feeling of pins and needles."

"How does death occur in SMFA poisoning doctor?"

"Tarun, death results either from ventricular tachycardia which is a scientific term meaning that the ventricles of the heart start beating too rapidly. You might imagine that this is good for the body, but this is not so. When the ventricles of the heart beat rapidly, they just beat without really pumping any blood. So this in effect is actually a tremendous waste of effort on the heart's part. Death may also occur from the fibrillation of the heart, which is another condition, in which the heart starts beating very rapidly, without pumping adequate amount of blood. It may also occur from respiratory failure which may occur because of pulmonary edema. Pulmonary edema may sound a formidable term to you, but in effect it is nothing but filling up of lungs with water."

"Oh, I see. How much SMFA would actually kill a person?"

"Tarun, SMFA is a dangerous homicidal poison, not only because it is colorless, odorless and tasteless, but also because it kills in very small quantities. In humans, does of 0.5-2 mg/kg of the body weight are highly dangerous. This means that if a man weighing 60 kg ingests about 120 mg (60x2mg), he would be quite serious. Lethal dose is 5 mg/kg. Thus for the same man, the lethal dose should be around 300 mg, which as you can see is really small. Small doses make it that much easier for the poisoner to administer the poison, in his victim's food."

"Oh, I see. Doctor is there any antidote for SMFA, which could have been given to Kabuli to save her life?"

"Unfortunately there is no known antidote for SMFA, which makes it still more dangerous as a homicidal poison."

"So did you find any tell-tale signs of SMFA poisoning in Kabuli's dead body?"

"Tarun, SMFA, does not leave any tell-tale signs in the victim's dead body, which is yet another reason why SMFA is such a good homicidal poison. There are no specific post-mortem findings. However animals who die of SMFA poisoning develop stiffness of limbs rapidly and are found with their extremities in hyperextension. This in plain and simple terms means that the extremities are stretched fully at the joints. I have taken samples of tea taken by Kabuli from her stomach and have run chemical tests on it. And as expected I have found SMFA in it. Not only that, I have also examined chemically the tea remaining in Kabuli's cup, and have found SMFA in that cup too. In Radhey's almirah, the police found a small white packet in which some white salt was present. On chemical analysis, that salt has turned out to be SMFA as well. So there seems little doubt that Radhey had indeed given Kabuli the poison. He had probably stolen some of the rodenticide from his factory, and had mixed it in Kabuli's tea. That was also probably the reason, why he was going so soft towards her for the last one week or so. He wanted to gain, Kabuli's confidence, so she could accept anything from him, without doubting his intentions. Come on, let us tell the police, that Radhey indeed is the killer."

"Oh, how very clever of you doctor. This was a most interesting discussion. Tell me what are you going to tell me the next time?"

"Tarun, next time, I would tell you about a very interesting poison- common salt. You may believe that common salt is not a poison, but interestingly it can be, and has been, used to kill humans!"