History of Virology

1. LECTURE 2: History of Virology Professor Johnston often said that if you didn't know history, you didn't know anything. You were a leaf that didn't know it was part of a tree.  ~Michael Crichton, Timeline Viro100: Virology 3 Credit hours NUST Centre of Virology & Immunology

2. On the primeval Earth, the surface of the planet is just cooling and beginning to harden into a crust • Rain forms pools containing many organic molecules and the first simple life forms appear. • The first viruses also appear. It is not clear where they have come from: • Independent entities • Cellular origins • Regressive evolution

3. Independent entities maybe these early viruses evolved from the self replicating molecules, believed to have existed in the primitive prebiotic 'RNA world' along a parallel course to cellular organisms. • Cellular origins perhaps they are sub-cellular, functional assemblies of macromolecules which have escaped their origins inside primitive cells. • Regressive evolution maybe these early viruses are degenerate life forms which have lost many functions that other organisms possess and have only retained the genetic information essential to their parasitic way of life.

4. The Year 3700 BC • The first written record of a virus infection consists of a heiroglyph from ancient Egypt, drawn in approximately 3700 BC, • Which depicts a temple priest called Ruma showing typical clinical signs of paralytic poliomyelitis

5. The Year 1193 BC • The Pharaoh Siptah rules Egypt from 1200-1193 BC when he dies suddenly at the age of about 20. • His mummified body lays undisturbed in his tomb in the Valley of the Kings until 1905 when the tomb was excavated. • The mummy shows that his left leg was withered and his foot was rigidly extended like a horse's hoof - classic paralytic poliomyelitis.

6. The Year 1143 BC • Ramesses V's preserved mummy shows that he died of smallpox at about the age of 35 in 1143 BC. • The pustular lesions on the face of the mummy are very similar to those of more recent patients . • However, his head also displays a major wound inflicted either before or shortly after death.

7. The Year 1000 BC • Smallpox was endemic in China by 1000BC. In response, the practice of variolation is developed. • Recognizing that survivors of smallpox outbreaks are protected from subsequent infection,

8. The Year 1796 • In 1796, Edward Jenner vaccinated an 8 year old boy, James Phipps, with material from a cowpox lesion on the hand of a milkmaid, Sarah Nelmes. James, who had never had smallpox , developed a small lesion at the site of vaccination which healed in 2 weeks. • On 1st July 1796, Jenner challenged the boy by deliberately inoculating him with material from a real case of smallpox

9. The Year 1892 • On 12th February, Dmitri Iwanowski, a Russian botanist, presents a paper to the St. Petersburg Academy of Science which shows that extracts from diseased tobacco plants can transmit disease to other plants after passage through ceramic filters fine enough to retain the smallest known bacteria. • This is generally recognized as the beginning of Virology. • Unfortunately, neither Iwanowski nor the scientific community fully realize the significance of these results.

10. Notable Persons and their Contribution to the Science of Virology

11. Walter Reed (1851-1902) • During the Spanish-American War & subsequent building of the Panama Canal, American deaths due to yellow fever were very high. • The disease also appeared to be spreading slowly northward into the continental United States. • Through experimental transmission to mice, in 1900 Walter Reed demonstrated that yellow fever was caused by a virus, spread by mosquitoes.

12. Karl Landsteiner (1868-1943) • Karl Landsteiner (1868-1943) and Erwin Popper proved that poliomyelitis was caused by a virus. • Landsteiner and Popper were the first to prove that viruses could infect humans as well as animals.

13. Francis Peyton Rous (1879-1970) • Francis Peyton Rous (1879-1970) demonstrated that a virus (Rous sarcoma virus) can cause cancer in chickens. (For this work, he was eventually awarded the Nobel Prize, in 1966) • Rous is the first person to show that a virus could cause cancer in animals.

14. Felix d'Herelle (1873-1949) • Following Frederick Twort'swork, Felix d'Herelle independently recognizes viruses which infect bacteria, which he calls bacteriophages(eaters of bacteria). • The discovery of bacteriophages provided an invaluable opportunity to study virus replication.

15. Wendell Stanley (1887-1955) • Wendell Stanley (1887-1955) crystallizes tobacco mosaic virus (TMV) and shows that it remains infectious (Nobel Prize, 1946). • Stanley successfully isolated TMV in pure crystalline state, he concluded that it must be protein or special class of enzyme. • Stanley's work is the first step towards describing the molecular structure of any virus and helps to further illuminate the nature of viruses.

16. Max Theiler (1899-1972) • Max Theiler was the first to propagate yellow fever virusin chick embryos and successfully produced an attenuated vaccine. Theiler's vaccine was so safe and effective that it is still in use today! • This work saved millions of lives and set the model for the production of many subsequent vaccines. For this work, Theiler was awarded the Nobel Prize in 1951.

17. The Year 1939 Emory Ellis (1906-) and Max Delbrück (1906-1981) • Established the concept of the "one step virus growth cycle" essential to the understanding of virus replication. • This work laid the basis for the understanding of virus replication and life cycle • They demonstrated virus particles do not "grow" but are instead assembled from preformed components.

18. The Year 1941 • George Hirst demonstrated that influenza virusagglutinates red blood cells. • This was the first rapid, quantitative method of measuring eukaryotic viruses.

19. The Year 1945 • Salvador Luria (1912-1991) and Alfred Hershey (1908-1997) demonstrated that bacteriophagesmutate. (Nobel Prize, 1969) • This work proves that similar genetic mechanisms operate in viruses as in cellular organisms and lays the basis for the understanding of antigenic variation in viruses. Salvador Luria (1912-1991) Alfred Hershey (1908-1997)

20. The Year 1949 Thomas Weller (1915–) Frederick Robbins (1916–) John Enders (1897-1985) John Enders, Thomas Weller (1915–) and Frederick Robbins (1916–) were able to grow poliovirus in vitro using human tissue culture. (Nobel Prize, 1954) This development led to the isolation of many new viruses in tissue culture.

21. The Year 1950 • André Lwoff (1902-1994) Louis Siminovitch and NielsKjeldgaard discovered lysogenic bacteriophages in Bacillus megaterium irradiated with ultra-violet light and coined the term prophage. (Nobel Prize, 1965). • Also in 1950, the World Health Organization proposed a programme to eradicate smallpox from the Americas. This was acheived in 8 years.

22. The Year 1952 Renato Dulbecco showed that animal viruses can form plaques in a similar way to bacteriophages. (Nobel Prize, 1975) Alfred Hershey (1908-1997) and Martha Chase demonstrated that DNA was the genetic material of a bacteriophage.

23. The Year 1957 Alick Isaacs and Jean Lindemann discovered interferon. Although the initial hopes for interferons as broad spectrum antiviral agents equivalent to antibiotics have faded, interferons were the first cytokines to be studied in detail.

24. The Year 1963 Baruch Blumberg discovers hepatitis B virus (HBV). (Nobel Prize, 1976) Blumberg went on to develop the first vaccine against the HBV, considered by some to be the first vaccine against cancer because of the strong association of hepatitis B with liver cancer.

25. The Year 1970 Howard Temin (1934-1994) and David Baltimore independently discovered reverse transcriptase in retroviruses. (Nobel Prize, 1975). The discovery of reverse transcription established a pathway for genetic information flow from RNA to DNA, refuting the so-call "central dogma" of molecular biology.

26. Year 1973 Peter Doherty and Rolf Zinkernagl demonstrate the basis of antigenic recognition by the cellular immune system. (Nobel Prize, 1996) The demonstration that lymphocytes recognize both virus antigens and major histocompatibility antigens in order to kill virus-infected cells established the specificity of the cellular immune system.

27. Year 1983 Luc Montaigner and Robert Gallo announced the discovery of human immunodeficiency virus (HIV), the causative agent of AIDS. In only two years since the start of the AIDS epidemic the agent responsible has been identified.

28. Year 2001 The complete nucleotide sequence of the human genomeis published. About 11% of the human genome is composed of retrovirus-like retrotransposons: "transposable elements in which transposition involves a process of reverse transcription with an RNA intermediate similar to that of a retrovirus".

29. History is a kind of introduction to more interesting people than we can possibly meet in our restricted lives; let us not neglect the opportunity.  ~Dexter Perkins Thank You!