Discoverer of penicillin Alexander Fleming warned against its overuse and the risk of resistant microorganisms as early as 1945, in his Nobel Prize lecture

"The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.

Here is a hypothetical illustration. Mr. X has a sore throat. He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin. He then infects his wife. Mrs. X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails. Mrs. X dies. Who is primarily responsible for Mrs. X's death? Why Mr. X whose negligent use of penicillin changed the nature of the microbe.

Moral: If you use penicillin, use enough"

Sir Alexander Fleming shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Boris Chain for his discovery of the world's first antibiotic substance benzylpenicillin (Penicillin G) from the mould Penicillium notatum in 1928. He also discovered the enzyme lysozyme in 1923.

Fleming's Nobel Lecture reached from here:Nobel Lecture by Sir Alexander Fleming on December 11, 1945

Yoshinori Ohsumi: Autophagy from begining to end

Yoshinori Ohsumi was influenced by his father, who was a professor of engineering at Kyushu University, He was familiar with academic life while he was growing up. But whereas his father worked in a very industrially oriented field, he was more interested in the natural sciences. In high school, he was interested in chemistry, so he entered the University of Tokyo to learn chemistry. He quickly discovered chemistry wasn't so attractive to him, because the field was already quite established. But he was lucky, he thinks, because the early 1960's was the golden age of molecular biology. He decided he wanted to work on that instead.

There were not very many molecular biology labs in Japan at that time. He joined Dr. Kazutomo Imahori's lab as a graduate student to study protein synthesis in E. coli. Unfortunately, he did not get very good results in his work, and, when he had finished his graduate studies, he discovered it was very difficult to find a good position in Japan. So, on Dr. Imahori's advice, he took a postdoctoral position with Dr. Gerald Edelman at The Rockefeller University in New York.

As a graduate student, he had worked on E. coli., but in Dr. Edelman's lab he switched to working on mammalian cell and developmental biology. He was supposed to establish a system for in vitro fertilization in mice,  but he did not know very much about early embryology and he had only a very small number of eggs to work with. He grew very frustrated. Then, one and a half years later, Mike Jazwinski joined Edelman's lab, and he decided to work with him instead on studying DNA duplication in yeast. That was another huge leap for him, but it was also his first introduction to yeast cells, which he has worked with ever since.

Finally, he was offered a position as a junior professor in Yasuhiro Anraku's lab at the University of Tokyo and was able to return to Japan

For complete interview, read this 2012 interview conducted by Journal of Cell Biology, where Yoshinori Ohsumi explains his progress within the field of autophagy.

Autophagy genes are discovered by Yoshinori Ohsumi for the greatest benefit to mankind

Autophagy has been known for over 50 years but its fundamental importance in physiology and medicine was only recognized after Yoshinori Ohsumi's paradigm-shifting research in the 1990's.

The experiment by 2016 Medicine Laureate Yoshinori Ohsumi demonstrated that autophagy exists in yeast. Ohsumi studied thousands of yeast mutants and identified 15 genes that are essential for autophagy. But even more importantly, he now had a method to identify and characterize key genes involved in this process. This was a major break through and Ohsumi published the results in 1992. First key publication: Takeshige, K., Baba, M., Tsuboi, S., Noda, T, and Ohsumi, Y. (1992). Autophagy in yeast demonstrated with proteinase-defifient mutants and conditoins for its induction. Journal of Cell Biology 119, 301-3011

The term "autophagy" was coined by Christian de Duve in 1963. Our bodies are made up of cells that contain organelles, components with various functions, Albert Claude's research with the newly developed electron microscope and his methods for separating the various parts of pulverized cells using a centrifuge opened up new opportunities for studying cells in detail. In 1995, Christian de Duve discovered previously unknown organelles in the cell, lysosomes. These have important functions in decomposing different types of materials, such as bacteria and parts of cells that have worn out. In 1974 de Duve shared the Nobel Prize in Medicine for discovering the lysosome.

Thanks to Ohsumi and others following in his footsteps, we now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress. After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging.

Disrupted autophagy has been linked to Parkinson's disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. Intense research is now ongoing to develop drugs that can target autophagy in various diseases.

Nobel Prize 2016 in Physiology or Medicine

The 2016 Nobel Prize in Physiology or Medicine is awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy which was announced on 3rd October 2016

This year's Nobel Laureate discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.

The word autophagy originates from the Greek words auto- meaning self and phagein- meaning to eat. Thus, autophagy denotes "self eating." Its a process whereby the eukaryotic cell can recycle part of its own content. This concept emerged during the 1960's, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack like vesicles that were transported to a recycling compartment, called lysosome, for degradation. Unlike other cellular degradation machineries, autophagy removes long lived proteins, large macro molecular complexes and organelles that have become obsolete or damaged. Difficulties in studying the phenomenon meant that little was known until, in a series of brilliant experiments in the early 1990's. Yoshinori Ohsumi used baker's yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells.

Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.

Yoshinori Ohsumi is a professor at the Tokyo Institute of Technology since 2009