On Microbial Antagonism, Antibiotics and Antibiotic Resistance

I am giving a course on Great Scottish Scientists at Strathclyde University and just started my talk on Alexander Fleming - who discovered penicillin in 1928.

The history of infectious diseases is fascinating.  Look closely at how life operates in nature and one can't help but marvel at the complex way different lifeforms interact. The delicate balance among species in nature must not be disturbed; something mankind is doing without regard to consequences. Come to think of it - we humans do a lot of things which can only be called irresponsible - but that is another story.

All life forms in nature operate on the same principle; it is the fight for survival.  Two essentials for survival are nutrients and space and this is what they all compete for.  From humans to microbes - it is the same struggle. Compete to survive!  Sometimes clever associations are formed for mutual benefits - ecosystems operate that way.  You break the chain by removing one species and part of the system collapses.

Historically, humans have suffered various forms of diseases caused by bacteria and viruses (microbes).  At times 50% of the population in Europe died because of rampant infections.  Louis Pasteur confirmed that such infectious diseases are caused by microbes whose sole aim appears to wish to increase their numbers and if humans could help them, then so be it.  Edward Jenner successfully developed vaccinations against smallpox and vaccination has proved to be very effective in controlling some diseases. Joseph Lister made surgery so much safer by using antispetics like phenol and alcohol.

But that is only a limited success.  Harmful bacteria lurk everywhere - from rose bushes to rusted nails.  Even human bodies harbour harmful bacteria which attack when the system is in a weakened state.

Let us not get it wrong - bacteria and viruses do not only attack and harm humans or big life forms.  They are fighting with each other with equal intensity.  Bacteria grow rapidly and need the resources - other microbes which come in their way have to watch out.  The best way to deal with the situation is by chemical means - produce chemicals that are toxic to invading bacteria.  This has been happening throughout the nature.  Plants produce such chemicals to fight microbial attacks, fungii do it, bacteria do it and we humans do it as well.
In 1922, Alexander Fleming discovered Lysozyme in human mucas, tears; in egg white and in all sort of places.  Lysozyme, as the name suggests, is an enzyme that lyses (dissolves) bacteria; but it only effects a few of them.

But what about using the chemicals that microbes produce to fight other microbes.  If we can find the right chemical that kills the infection-causing bacteria then we can use it to control the infection. Bacterial antagonism can really be put to good use.   Of course, the chemical must be tolerated by the human body and not be toxic so as to harm us as well. Gramicidin discovered in 1936 by Rene Dubos was one such chemical - good to kill bacteria but also toxic to humans - so no use to us.
Alexander Fleming discovered penicillin in 1928.  It is produced by the fungus penicillin notatum and the best source was found to be a cantaloupe in Illinois, USA!  Penicillin was found to be effective against gram positive bacteria (these are bacteria that have a particular type of membrane wall structure) and was effective in killing lot of infection causing microbes - pneumonia, meningitis and a whole lot more.  Penicillin is also tolerated by human body very well and this was to become an ideal weapon for fighting infections.
We call this class of chemicals antibiotics.
Streptomycin is another anitbiotic that was discovered by Selman Waksman in 1943 and it was very effective in fighting tuberculosis.

1940s and 50s were really the golden age of antibiotics.  Many more were discovered or synthesized, mainly derivatives of penicillin.  Penicillin alone saved millions of lives.

The thing about life is that there is never a final chapter.  Bacteria don't like getting killed this way and we soon started to see resistant strain of bacteria showing up.  The resistant strain are not affected by the antibiotic any more and we go back to either finding a new antibiotic that is effective in killing the bacteria or have the problem of reverting back to pre-antibiotic age when infections were a real problem.
Bacteria are great in producing resistant strains.  They have survived billions of years because they can quickly and efficiently adapt to changing environments. They multiply fast - so population of resistant bacteria builds up rather quickly. Bacteria mutate frequently and then they have at their disposal clever schemes for defeating the antibiotic attacks.  Bacteria can produce enzymes that breakdown the antibiotic molecules making them ineffective or they can cover the region where antibiotic would bind to the cell.  They also exchange resistant genes with other bacteria in the vicinity and spread the resistant genes very efficiently.

It is thus an ongoing war.  We have to keep inventing/discovering new antibiotics - stronger and stronger ones to fight the resistant strains. Something, we have not done very well for the past 40 years or so.  Drug companies did not see much money in this pursuit and governments also got complacent.  But now the problem of resistant bacteria is such that people are waking up to the reality - Alexander Fleming warned about this in 1945 and we all could see this coming but not much was done in the interim.

Even more complicated situation has arrived in the form that many bacterial strains are resistant to several antibiotics with some now resistant to all known antibiotics.  We soon will come full circle here.

In the highly developed societies with good hygiene and clean environment, people do not normally suffer many minor infections.  This also means that they do not develop immunities the same way as societies in the past, who were exposed to many more microbes as routine, did. We also live in much more crowded cities and we travel more. All this can spread infections quickly and efficiently.  When an infection strikes, we shall be less well prepared and the death rates will be correspondingly higher.

The prognosis is not good.

Scottish Nobel Prize Winners (updated January 2022)

Scotland is a small country but its contributions in sciences and other fields have been disproportionately large.  This is evidenced by the number of Nobel Prizes awarded to people of Scottish origin or who have done their main work while in Scotland. In the following, I have collected brief biographies of the Scottish Nobel Laureates.   

ScienceforAll is a programme to promote science awareness in the community through talks on a variety of science related topics.  I started the programme in 2006 at the time of my retirement from Glasgow University. I continue to be associated with GU as an honorary fellow.  Further information about the past activity of the programme is available at

http://ektalks.blogspot.com

ektalks@yahoo.co.uk

About Nobel Prizes

Alfred Nobel (1833 - 1896), a Swedish industrialist, amassed a fortune during his lifetime.  He earned  most of his wealth from his 355 inventions, of which dynamite  is the most famous.   An article in a French newspaper published an obituary of Alfred Nobel (instead of his brother's)  which disconcerted Nobel and made him apprehensive about how he would be remembered. Nobel bequeathed 94% of his total assets, US$186 million to establish the five Nobel Prizes.

Nobel's will specified that his fortune be used to create a series of prizes for those who confer the "greatest benefit to mankind“ in physics, chemistry, peace, physiology or medicine and literature. Since 1901, Nobel Prizes have been awarded annually in the above five disciplines. 

Economic Sciences was added in 1968. 

 

Nobel stated that the Nobel Prizes in Physics should be given "to the person who shall have made the most important 'discovery' or 'invention' within the field of physics.”

2016 Nobel Laureates in Chemistry:
Sir Fraser Stoddart was born in 1942 in Edinburgh and currently works in Northwestern University in Illinois.  He shared the Nobel with Professor Jean-Pierre Sauvage (University of Strasbourg) and Professor Bernard Feringa (University of Groningen).
The Nobel was awarded for their work of creating microscopic controllable machines that are more than 1000 times smaller than the width of a human hair.  Yet, they operate much-like large scale machinery with rings spinning round axles, components moving back and forth along tracks, platforms that rise and fall.
2016 Nobel Laureates in Physics:
David Thouless was born in 1934 in Bearsden. He is an emeritus professor at the University of Washington.
Michael Kosterlitz was born in 1942 in Aberdeen. He is currently affiliated to Brown University.  Both David and Michael won "this year's Nobel for their theoretical work that discovered a set of totally unexpected regularities in the behaviour of matter, which can be described in terms of an established mathematical concept - namely, that of topology."This has paved the way for designing new materials with novel properties and there is great hope that this will be important for many future technologies."

Sir James W Black Uddingston, Lanarkshire (1924 – 2010)

Scottish doctor and pharmacologist.  He spent his career both as researcher and as an academic at several universities. Black established the physiology department at the University of Glasgow, where he became interested in the effects of adrenaline on the human heart. He went to work for ICI Pharmaceuticals in 1958 and, while there, developed propranolol, a beta blocker used for the treatment of heart disease. Black was also responsible for the development of cimetidine, an H2 receptor antagonist, a drug used in a similar manner to treat stomach ulcers. He was awarded the Nobel Prize for Medicine in 1988 for work leading to the development of propranolol and cimetidine.

Sir John Boyd Orr  1st Baron Boyd-Orr;  Kilmaurs, Kilmarnock (1880 - 1971)

a Scottish teacher, doctor, biologist and politician; studied at University of Glasgow. Received the 1949 Nobel Peace Prize for his scientific research into nutrition and his work as the first Director-General of the United Nations Food and Agriculture Organization (FAO). He was the co-founder and the first President (1960–1971) of the World Academy of Art and Science (WAAS)

Sir Alexander Fleming Darvel, East Ayrshire (1881 – 1955)

Discoverer of Penicillin  Nobel Prize 1945
Full Biography available here

Arthur Henderson   Glasgow (1863 - 1935)

A British iron moulder and Labour politician. He was the first Labour cabinet minister, the 1934 Nobel Peace Prize Laureate and served three terms as the Leader of the Labour Party. He was popular among his colleagues, who called him "Uncle Arthur" in acknowledgement of his integrity, devotion to the cause and imperturbability. He was a transition figure whose policies were closer to the Liberal Party for the trades unions rejected his emphasis on arbitration and conciliation and thwarted his goal of unifying the Labour Party and the trades unions.

Richard Henderson (1945 - ...) was born in Edinburgh.  Awarded 2017 Nobel Prize in Chemistry for electron microscopy of biological molecules.  Shared the prize with Joachim Frank and Jacques Dubochet.

Sir Peter W Higgs   Newcastle upon Tyne  (1929 -   )

British theoretical physicist, 2013 Nobel Prize laureate and emeritus professor at the University of Edinburgh where he has stayed since 1954. He is best known for his 1960s proposal of broken symmetry in electroweak theory, explaining the origin of mass of elementary particles in general and of the W and Z bosons in particular. This so-called Higgs mechanism, predicts the existence of a new particle, the Higgs boson (which was often described as "the most sought-after particle in modern physics". CERN announced on 4 July 2012 that they had experimentally established the existence of a Higgs-like boson, but further work is needed to analyse its properties and see if it has the properties expected from the Standard Model Higgs boson. On 14 March 2013, the newly discovered particle was tentatively confirmed to be + parity and zero spin

John J R MacLeod   Clunie, Dunkeld  (1876 - 1935)

Scottish biochemist & physiologist. Studied at University of Aberdeen.  Chief interest in carbohydrate metabolism.

He is noted for his role in the discovery and isolation of insulin during his tenure as a lecturer at the University of Toronto, for which he and Frederick Banting received the 1923 Nobel Prize in Physiology or Medicine

David McMillan (1968 - ...) was born in Bellshill, Scotalnd.  

David was awarded the 2021 Nobel Prize for Chemistry for the development of asymmetric organocatalysis and shared it with Benjamin List.

Sir James Alexander Mirrlees   Kirkcudbrightshire  (1936 - 2018)

Scottish economist and winner of the 1996 Nobel Memorial Prize in Economic Sciences. Mirrlees was educated at the University of Edinburgh (Mathematics and Natural Philosophy in 1957) & Cambridge (Mathematical Tripos) and PhD in 1964 with thesis title Optimum planning for a dynamic economy). Mirrlees and Vickrey shared the 1996 Nobel Prize for Economics "for their fundamental contributions to the economic theory of incentives under asymmetric information“. His students have included eminent academics and policy makers. 

Sir William Ramsay   Glasgow (1852 - 1916)

Scottish chemist who discovered the noble gases and received the Nobel Prize in Chemistry in 1904 "in recognition of his services in the discovery of the inert gaseous elements in air" (along with his collaborator, Lord Rayleigh, who received the Nobel Prize in Physics that same year for their discovery of argon). After the two men identified argon, Ramsay investigated other atmospheric gases. His work in isolating argon, helium, neon, krypton and xenon led to the development of a new section of the periodic table.  Named the gas, which is inert, with the Greek word for "lazy", "argon"

In the following years, he discovered neon, krypton, and xenon.  He also isolated helium which had been observed in the spectrum of the sun but had not been found on earth. In 1910 he also made and characterized radon.

Ronald Ross  Almora, India (1857 - 1932)  (Not sure about) 

Indian-born British medical doctor who received the 1902 Nobel Prize for Physiology or Medicine for his work on malaria. His discovery of the malarial parasite in the gastrointestinal tract of mosquito led to the realisation that malaria was transmitted by mosquitoes, and laid the foundation for combating the disease. He worked in the Indian Medical Service for 25 years. It was during his service that he made the groundbreaking medical discovery. In 1926 he became Director-in-Chief of the Ross Institute and Hospital for Tropical Diseases, which was established in honour of his works. 

Sir Alexander R Todd  (1907 - 1997) Baron Todd of Trumpington, Glasgow 

British biochemist whose research on the structure and synthesis of nucleotides, nucleosides, and nucleotide coenzymes gained him the 1957 Nobel Prize for Chemistry.

BSc from Glasgow University in 1928. In 1955, he elucidated the structure of vitamin B12, later working on the structure and synthesis of vitamin B1 and vitamin E, the anthocyanins (the pigments of flowers and fruits) from insects (aphids, beetles) and studied alkaloids found in hashish and marijuana. He served as chairman of the Government of the United Kingdom's advisory committee on scientific policy from 1952 to 1964. 

Charles T R Wilson   Glencorse, Midlothian;  (1869 - 1959)

Scottish physicist and meteorologist who received the 1927 Nobel Prize in Physics for his invention of the cloud chamber.  In 1893 he began to study clouds and their properties. He worked for some time at the observatory on Ben Nevis, where he made observations of cloud formation. He then tried to reproduce this effect on a smaller scale in the laboratory in Cambridge, expanding humid air within a sealed container. He later experimented with the creation of cloud trails in his chamber caused by ions and radiation. For the invention of the cloud chamber he received the Nobel Prize in 1927.