MALARIA AND DDT

Ancient History

The symptoms of malaria were described in ancient Chinese medical writing, in particular, the Nei Ching edited by Emperor Huang Ti. Hippocrates too noted the principal symptoms. The ancient Indian surgeon Susruta of Banares noted the symptoms of malarial fever and attributed them to insect bites.

The medicinal qualities of the Qinghao plant (Artemisia annua) were discovered in China in 340 AD. Its active ingredient artemisinin was isolated in 1971.

17th Century: Quinine

Long before Europeans came to America, native Indians, including Mayas, Aztecs and Incas, had a well developed understanding of plants, especially those used for medicine. The Badianus Manuscript, written by Martin de la Cruz in 1552, includes more than 200 medicinal plant species. In the early 1600s, during the Conquest of the Inca Empire, the Jesuits learnt from the Incas that the bitter bark of a native tree was given as a beverage for malarial fever.

The tree was named Cinchona after the Countess of Chinchón, wife of Viceroy Luis Jerónimo de Cabrera of Peru. The drug made from its bark is called quinine; its properties are described on the page

http://fennerschool-associated.anu.edu.au/fpt/nwfp/quinine/Quinine.html

A collection of pages on ethnobotany, that is, the study of the relationship and interactions between plants and people, is found at

http://www.accessexcellence.org/RC/Ethnobotany/index.php

The page Medicines there describes several medicinal plants found in Central and South America. For beginners, the page Classification of Plants is also worth reading.

Late 19th and Early 20th Century: Plasmodium, Mosquitoes and DDT

Four early Nobel Prizes in Medicine/Physiology were awarded to scientists who worked on malaria. They are

The setting up of the Nobel Prize Organisation is discussed in the page Chemistry in the Nineteenth Century at this site, which also discusses some early work on organic chemistry. The first page of Paul Müller's Nobel Lecture lists nineteenth century developments in synthetic organic chemistry in more detail.

The first Nobel Prize in Medicine (1901) was awarded to Emil von Behring "for his work on serum therapy, especially its application against diphtheria, by which he has opened a new road in the domain of medical science and thereby placed in the hands of the physician a victorious weapon against illness and deaths".

Camillo Golgi was awarded the Nobel Prize for his discoveries on neurophysiology, but his work on malaria was quoted by Ross. He observed that there were at least two forms of the disease.

Charles Louis Alphonse Laveran was the first to identify malaria parasites. His work, done in November 1880, predates Ronald Ross's, but Ross was awarded the prize first, and his Nobel Prize Lecture, given in expanded form on the web, also covers the work of all his contemporaries.

Ronald Ross (Nobel 1902)
Born: 13 May 1857, Almora, India
Died: 16 Sep 1932, Putney Heath, United Kingdom
Affiliation at the time of award: University College, Liverpool, United Kingdom
Awarded for: Discovery of transmission of malaria by mosquitoes
Image source: University of Liverpool

(A) The discovery of the malaria parasite. In the middle of the nineteenth century, it was discovered by a number of workers that malaria is characterised by the presence in blood of a peculiar granular substance, the malarial pigment or melanin. This observation led to the great discovery of Laveran in 1880, that the melanin is produced in multitudes of amoeboid parasites which live within the blood corpuscles of the patient.

In Section 2 of his Nobel Lecture, Ross states, on this matter:

Taxonomical information on the malaria parasite is given below:

• Genus: Plasmodium
• Higher order taxa: Eukaryota > Alveolata > Apicomplexa > Haemospororida

• Malaria causing species

  Plasmodium vivax	1890	Giovanni Battista Grassi, Raimondo Filetti
  Plasmodium malariae
  Plasmodium falciparium	1897	William W. Welch
  Plasmodium ovale	1922	John William Watson Stephens

• The parasites were first identified by Laveran in 1880.
  A full list of plasmodium species can be found on the TOLWEB PAGE.

The life cycle of the malaria parasite is illustrated in the following image:

Source: http://www.microbiologybytes.com/introduction/Malaria.html

(B) Transmission by mosquitoes. Ross entered the Indian Medical Service in 1881 and commenced on the study of malaria in 1892. In 1894 he obtained a furlough to England and sought the advice of Professor Kanthack, who assured him that Laveran's discovery was no mistake. We quote from Section 5 of his Nobel Lecture.

The theories of King. Laveran, Koch, and Manson are discussed in Section 6. Manson had earlier demonstrated that the disease filaria, which is caused by the filarial worm (wucheria bancrofti), classified in phylum Nemata, is transmitted by mosquito bites. On returning to India, Ross resumed his investigation following Manson's guidance. We quote now from Section 8 of his Nobel lecture:

In Section 10 he relates how he finally found the malaria parasite in the stomachs of mosquitoes.

Taxonomical information on mosquitoes is as follows:

• Genus: Culicidae
• Higher order taxa: Bilateria > Arthropoda > Insecta > Diptera

• Main genera:

  Aedes	Causes dengue
  Anopheles	Causes malaria
  Culex	Causes filaria

• Full list of genera: See http://bugguide.net/node/view/169/bgpage

The development of the main types of mosquito is illustrated next:

Source: Rutgers Center for Vector Biology

(C) Malaria symptoms. These include fever and flu-like illness, shaking chills, headache, muscle aches and tiredness. Nausea, vomiting and diarrhoea may also occur. Malaria may cause anaemia and jaundice because of the loss of red blood cells. Symptoms usually appear between 10 and 15 days after the mosquito bite. If not treated, malaria can become life-threatening by disrupting the blood supply to vital organs. In many parts of the world, the parasites have developed resistance to a number of malaria medicines. (See MALARIA.COM - Malaria Causes and Symptoms.)

(D) DDT, abbreviation of Dichloro Diphenyl Trichloroethane, was originally discovered by Austrian student Othmar Zeidler, during the course of his doctoral studies. Its insecticidal properties were investigated by Dr. Paul Müller, an employee of J.R. Geigy, which is now a part of Novartis.

DDT Structural Formula
Molecular formula	C14H9Cl5
Molecular Mass	354.49 gm/mole
Melting point	108.5 °C
Boiling point	260 °C (decomp.)
Chemical name	p,p-dichlorodiphenyltrichloroethane

DDT is produced by the reaction of chloral (CCl₃CHO) with chlorobenzene (C₆H₅Cl) in the presence of sulphuric acid, which acts as a catalyst.

DDT is a colourless crystalline solid with a weak chemical odour. It is nearly insoluble in water, but highly soluble in most organic solvents, fats and oils. According to the wikipedia, the insecticidal action of DDT is due to its effect on neurons. When swallowed by humans, DDT causes headache, dizziness, nausea and vomiting. Information on DDT poisoning may be found at the Hindustan Insecticides Limited Page DDT 75 WP.

The preceding table shows the structure of the isomers of DDT. The prime can be omitted from the second letter without ambiguity; thus p,p'-dichlorodiphenyltrichloroethane can be written as p,p-dichlorodiphenyltrichloroethane. The insecticidal properties of the other isomers are marginal compared to the p,p-type. Next we list the physical properties of the isomers.

(Source: Paul Müller's Nobel Lecture)

In the Lecture, Müller states that he knew, from work done in his firm by Dr. H. Martin and others, that compounds of the general formula

frequently showed oral toxicity to moths. On the matter of industrial production, he states:

Next we come to the history of DDT production:

We see that DDT was discovered before Paul Müller was born. As the text of the original Swiss patent is not available, it is difficult to understand which part of the manufacturing process it applied to, especially in view of the recent order passed against Novartis by the Indian Patent Office. (See www.legalserviceindia.com/articles/no.htm. Novartis was denied the right to a patent on the blood cancer drug Glivec.)

The Patent Report of Bruce and Hagerman states that dichlorodiphenyltrichloroethane, produced by condensing chlorobenzene with chloral, is a waxy solid which is difficult to grind. In their process they produce a friable substance by cooling the product down from a temperature above its setting point (90°C), preferably above 110°C, to a temperature in the range 20-60°C.

(E) Comparison of DDT with older insecticides. Müller lists the properties of an ideal insecticide as follows:

He then lists the properties of known insecticides as follows:

DDT satisfies all the above requirements except no. 2.

Further information on insecticides can be found at alanwood.net/pesticides/class_insecticides.html.

Mid 20th Century Onwards

As far back as 1945, it was realised by the U.S. Department of Agriculture that DDT could cause environmental degradation. However, its use continued while its effects were investigated. an account of this appears in an article by Kenneth S. Davis in American Heritage Magazine, Feb. 1971. DDT was banned in the United States at the end of 1972.

In April 1945,a report by the U.S. Department of Agriculture spoke of DDT as a "two-edged sword," at once the "most promising insecticide ever developed" and the most menacing. A few days before the end of the end of the Second World War, the U.S. Government released DDT for general use. The American Heritage article states:

In January 1958, Olga Huckins wrote a long angry letter to her friend Rachel Carson describing the deadly effect of DDT spraying over her family's private bird sanctuary. She was sickened by the sight of dead and dying fish, crayfish and crabs, staggering as their nervous systems were destroyed.

Working for four years, beginning 1958, Rachel Carson wrote her book Silent Spring, on the effects of chemicals on the environment. In 1963, in response to public concern aroused by the book, President Kennedy's Science Advisory Committee recommended a reduction in DDT use.

Rachel Carson died in mid-April 1964, of cancer. Her biography appears in Time Magazine 29 Mar 1999. Paul Müller died in the following year.

Since DDT is insoluble in water but very soluble in fats, it tends to pass up in the food chain and concentrate in fatty tissues. At every step up the food chain, the relative concentration increases (see table).

Figures from the Lake Michigan area, where DDT was sprayed extensively in the 1960s

Source: http://www.ch.ic.ac.uk/rzepa/mim/environmental/html/ddt_text.htm

DDT in the soil lasts for a very long time. Half of it breaks down in a period which may vary from 2 to 15 years. It may evaporate and enter the air, and some of it may be broken down by the sun or by microorganisms.

DDT is also degraded by some types of fungi, such as the white rot fungus. See for instance the paper by J.A. Bumpus and S.D. Aust in Appl. Environ. Microbiol., Sep 1987 53(9).

DDT in soil usually breaks down to form DDE or DDD.

Effect on humans. DDT, DDD, or DDE enter the body mainly when a person eats contaminated food. Once in the body, DDT can break down to form DDE or DDD which, in turn, break down to other metabolites that leave the body in urine. These compounds are readily stored in fatty tissue, but elsewhere leave the body, mostly in urine, but sometimes also in breast milk.

DDT over a short time affects the nervous system, but over a long period may affect the liver and even cause cancer.

Consequences of discontinuation of DDT spraying. South Africa continued to use DDT after it was banned in the United States. By 1996, malaria deaths there dropped down to below 10,000 annually. It then switched from DDT to another insecticide, with the result that malaria deaths spiked to over 60,000.

As a result of this, the scientific consensus of the present century is in favour of continuation of DDT. See

1. Rachel Carson's birthday bashing - Africa - Salon.com
2. Ethical debate: Doctoring malaria badly: the global campaign to ...

Created on 9 May 2011

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