Miodrag (Misha) Radulovacki (
Serbian Cyrillic
The Serbian Cyrillic alphabet ( sr, / , ) is a variation of the Cyrillic script used to write the Serbian language, updated in 1818 by Serbian linguist Vuk Karadžić. It is one of the two alphabets used to write standard modern Serbian, th ...
: Миодраг Радуловачки;
Serbian Latin
Gaj's Latin alphabet ( sh-Latn-Cyrl, Gajeva latinica, separator=" / ", Гајева латиница}, ), also known as ( sh-Cyrl, абецеда, ) or ( sh-Cyrl, гајица, link=no, ), is the form of the Latin script used for writing Serb ...
: Miodrag Radulovački), was a
Serbian American
Serbian Americans ( sr, / ) or American Serbs (), are Americans of Serb ethnic ancestry. As of 2013, there were about 190,000 American citizens who identified as having Serb ancestry. However, the number may be significantly higher, as there w ...
scientist and inventor. He was Professor of
Pharmacology
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
in the
College of Medicine at the University of Illinois at Chicago (UIC), Radulovacki's research accomplishments include: (1) the
Adenosine
Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
Sleep Theory, and (2) pioneering pharmacological studies for the treatment of
sleep apnea
Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...
, together with research collaborator, David W. Carley, (Professor of Medicine at the UIC). Radulovacki and Carley invented several
drug therapies for the treatment of sleep apnea which have been patented by the UIC. The UIC recognized them as the 2010 "Inventors of the Year."
Radulovacki published more than 170 scientific papers.
Radulovacki was also a Foreign Member of the
Serbian Academy of Sciences and Arts
The Serbian Academy of Sciences and Arts ( la, Academia Scientiarum et Artium Serbica, sr-Cyr, Српска академија наука и уметности, САНУ, Srpska akademija nauka i umetnosti, SANU) is a national academy and the ...
.
Early life
Miodrag Radulovacki was born on April 28, 1933, in
Parage, a village in northwestern
Serbia
Serbia (, ; Serbian language, Serbian: , , ), officially the Republic of Serbia (Serbian language, Serbian: , , ), is a landlocked country in Southeast Europe, Southeastern and Central Europe, situated at the crossroads of the Pannonian Bas ...
. Both of his parents were
elementary school
A primary school (in Ireland, the United Kingdom, Australia, Trinidad and Tobago, Jamaica, and South Africa), junior school (in Australia), elementary school or grade school (in North America and the Philippines) is a school for primary ed ...
teachers
A teacher, also called a schoolteacher or formally an educator, is a person who helps students to acquire knowledge, competence, or virtue, via the practice of teaching.
''Informally'' the role of teacher may be taken on by anyone (e.g. wh ...
. At the beginning of
World War II
World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...
, Radulovacki's father was drafted into the
Yugoslav Army
The Yugoslav People's Army (abbreviated as JNA/; Macedonian and sr-Cyrl-Latn, Југословенска народна армија, Jugoslovenska narodna armija; Croatian and bs, Jugoslavenska narodna armija; sl, Jugoslovanska ljudska ar ...
and was later taken prisoner by the invading
Germans
, native_name_lang = de
, region1 =
, pop1 = 72,650,269
, region2 =
, pop2 = 534,000
, region3 =
, pop3 = 157,000
3,322,405
, region4 =
, pop4 = ...
.
In 1943, Radulovacki moved to
Sremski Karlovci
Sremski Karlovci ( sr-cyrl, Сремски Карловци, ; hu, Karlóca; tr, Karlofça) is a town and municipality located in the South Bačka District of the autonomous province of Vojvodina, Serbia. It is situated on the banks of the Danu ...
after his mother accepted a teaching position in the town. Sremski Karlovci (also known as Karlovci), a
baroque
The Baroque (, ; ) is a style of architecture, music, dance, painting, sculpture, poetry, and other arts that flourished in Europe from the early 17th century until the 1750s. In the territories of the Spanish and Portuguese empires including t ...
Serbian town on the banks of the
Danube River
The Danube ( ; ) is a river that was once a long-standing frontier of the Roman Empire and today connects 10 European countries, running through their territories or being a border. Originating in Germany, the Danube flows southeast for , pa ...
, had been home to the Radulovacki family for over 200 years. Radulovacki attended
Karlovci High School or "Gymnasium," which is the oldest high school in Serbia.
Radulovacki called Karlovci Gymnasium the "Serbian
Cambridge
Cambridge ( ) is a university city and the county town in Cambridgeshire, England. It is located on the River Cam approximately north of London. As of the 2021 United Kingdom census, the population of Cambridge was 145,700. Cambridge bec ...
and
Oxford
Oxford () is a city in England. It is the county town and only city of Oxfordshire. In 2020, its population was estimated at 151,584. It is north-west of London, south-east of Birmingham and north-east of Bristol. The city is home to the ...
".
Radulovacki graduated as
valedictorian
Valedictorian is an academic title for the highest-performing student of a graduating class of an academic institution.
The valedictorian is commonly determined by a numerical formula, generally an academic institution's grade point average (GPA ...
of the Karlovci High School Class of 1951.
Radulovacki gained admission to the
University of Belgrade
The University of Belgrade ( sr, / ) is a public university in Serbia. It is the oldest and largest modern university in Serbia.
Founded in 1808 as the Belgrade Higher School in revolutionary Serbia, by 1838 it merged with the Kragujevac-b ...
School of Medicine
A medical school is a tertiary educational institution, or part of such an institution, that teaches medicine, and awards a professional degree for physicians. Such medical degrees include the Bachelor of Medicine, Bachelor of Surgery (MBBS, M ...
.
Education and scientific career
Radulovacki graduated from the University of Belgrade School of Medicine in 1959.
[Summary biography of Miodrag Radulovacki, Illinois Medicine Fiscal Year 2009 Report - Honor Roll of Donors, page 27 (Prizing Discovery)](_blank)
/ref>
/ref>
/ref> He went on to obtain a PhD in Neurophysiology
Neurophysiology is a branch of physiology and neuroscience that studies nervous system function rather than nervous system architecture. This area aids in the diagnosis and monitoring of neurological diseases. Historically, it has been dominated b ...
. The topic of his PhD thesis was: "Sleep in Split-Brain Cats," partly done at the Brain Research Institute at UCLA.
Radulovacki spent 18 months at the University of California, Los Angeles
The University of California, Los Angeles (UCLA) is a public land-grant research university in Los Angeles, California. UCLA's academic roots were established in 1881 as a teachers college then known as the southern branch of the California St ...
(UCLA) Brain Research Institute where his mentor was Ross Adey. One of the findings of his research at UCLA was that the electroencephalographic
Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocort ...
(EEG) pattern of sleep in cats with split brain to the pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of Va ...
is synchronous in both brain hemispheres
The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...
, indicating the importance of the brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
in sleep regulation.
In 1966, Radulovacki accepted a teaching position with the Physiology
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
Department in the College of Medicine at the University of Khartoum
The University of Khartoum (U of K) ( ar, جامعة الخرطوم) is a public university located in Khartoum, Sudan. It is the largest and oldest university in Sudan. UofK was founded as Gordon Memorial College in 1902 and established in 195 ...
, Sudan
Sudan ( or ; ar, السودان, as-Sūdān, officially the Republic of the Sudan ( ar, جمهورية السودان, link=no, Jumhūriyyat as-Sūdān), is a country in Northeast Africa. It shares borders with the Central African Republic t ...
. There he invented an approach for obtaining cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
using a cannula
A cannula (; Latin meaning 'little reed'; plural or ) is a tube that can be inserted into the body, often for the delivery or removal of fluid or for the gathering of samples. In simple terms, a cannula can surround the inner or outer surfaces ...
to the cisterna magna
The cisterna magna (or cerebellomedullar cistern) is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain. The openings are collectively referred to as the su ...
in the brain of cats. The cannulation method enabled researchers to obtain cerebrospinal fluid during sleep and wakefulness for the analysis of monoamine
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.
All monoamines ar ...
metabolites
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...
. This approach was of interest since Michel Jouvet
Michel Valentin Marcel Jouvet (16 November 1925 – 3 October 2017) was a French neuroscientist and medical researcher.
His works, and those of his team, have brought about the discovery of paradoxical sleep (a term he coined) and to its indi ...
's Monoamine
Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin.
All monoamines ar ...
Theory of Sleep, with serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
as the sleep inducing agent, was dominant at the time. From 1970 to 1984, at the University of Illinois, Radulovacki published a series of papers dealing with the role of monoamines in sleep.
In 1970, Radulovacki was recruited by Klaus Unna to join the Department of Pharmacology in the College of Medicine at the University of Illinois at Chicago as an Assistant Professor. Radulovacki published more than 170 scientific papers during his career at the UIC.
Scientific achievements
Adenosine Sleep Theory
In 1984, Radulovacki postulated the Adenosine Sleep Theory, (JPET, 228: 268-274, 1984). The idea for adenosine's role in sleep occurred to him after reading a paper by Sol Snyder's group (Proc. Natl. Acad. Sci, 78: 3260-64, 1981) about the importance of adenosine receptors in the behavioral actions of methylxanthine
Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, including caffeine, ...
s. In the article, the authors correlated the behavioral excitation produced by theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
in micromolar
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of sol ...
concentrations with the blockade of adenosine receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
.
Radulovacki reasoned that if the blocking of adenosine receptors produces excitation, then perhaps stimulation of the same receptors could induce sleep. He knew that experiments by John Phillis and his group (Can. J. Physiol. Pharmacol. 57:1289-1312, 1979), which utilized an iontophoretic application of adenosine in the brain, had demonstrated adenosine's depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the ...
effect on the responses of neuron
A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...
s in several brain regions and that the general neurophysiological
Neurophysiology is a branch of physiology and neuroscience that studies nervous system function rather than nervous system architecture. This area aids in the diagnosis and monitoring of neurological diseases. Historically, it has been dominated b ...
effects of adenosine were shown to be inhibitory. In addition, the preliminary experiments in dogs by Haulica ''et al.'' (J. Neurochem. 21:,1019–20, 1973) and the administration of adenosine into the brains of rats, cats and fowl suggested that adenosine was able to produce behavioral
Behavior (American English) or behaviour (British English) is the range of actions and mannerisms made by individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as well ...
sleep
Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...
. The explanation of adenosine's hypnotic
Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
effect was through its interaction with serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
, widely believed to be a sleep inducing agent. However, since there was no suggestion how this adenosine-serotonin link was achieved, experiments highlighting the potential role of adenosine in sleep had largely been forgotten.
Research collaboration with David W. Carley
In 1993, Radulovacki started a collaboration with David W. Carley, a Professor of Medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
, Bioengineering
Biological engineering or
bioengineering is the application of principles of biology and the tools of engineering to create usable, tangible, economically-viable products. Biological engineering employs knowledge and expertise from a number o ...
and Pharmacology at the UIC. Their research efforts focused on developing pharmacological approaches for the treatment of sleep apnea
Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...
. Since there were no medicines to alleviate this condition, Radulovacki and Carley set out to develop a drug treatment. Their initial work focussed on an experimental
An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previously untried. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a ...
model
A model is an informative representation of an object, person or system. The term originally denoted the plans of a building in late 16th-century English, and derived via French and Italian ultimately from Latin ''modulus'', a measure.
Models c ...
of sleep apnea in rats, initially testing the effects of adenosine compounds. Eventually, they obtained positive results using serotonin and other compounds. As a result, the UIC patent
A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...
ed their discoveries, obtaining numerous US and international patents.
Patents for sleep and sleep-related disorders include:
# "Hypnotic Composition and Method of Inducing Sleep"; Inventor: Miodrag Radulovacki, US Patent 4537907, August 27, 1985. (This patent was issued to UIC before Radulovacki started his collaboration with Carley in 1993).
# "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,331,536 B1, December 18, 2001.
# "Neuropharmacological Treatments of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,555,564 B1, April 29, 2003.
# "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,727,242 B2, April 27, 2004.
# "Neuropharmacological Treatment of Sleep-Related Breathing Disorders"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 6,974,814 B2, December 13, 2005.
# "Pharmacological Treatment for Sleep Apnea"; Inventors: Miodrag Radulovacki and David W. Carley, US Patent 7,160,898 B2, January 9, 2007.
# "Method for Treating Sleep Apnea"; Inventors: David W. Carley and Miodrag Radulovacki, US Patent 7,705,039 B2, April 27, 2010.
# "Methods for treating sleep disorders by cholecystokinin (CCK) receptor B antagonists": Inventors: David W. Carley and Miodrag Radulovacki, US Patent 8,053,413 B2, Nov. 8, 2011.
# "Pharmacological treatments for sleep disorders (apnoe) with prostanoid receptor antagonists", Inventors: David W. Carley and Miodrag Radulovacki, US Patent 8,076,315, Dec. 13, 2011.
Inventor of the Year 2010
Radulovacki was named the 2010 Inventor of the Year at the University of Illinois, alongside Carley. Radulovacki and Carley were honored by the University of Illinois for producing a dozen potential treatments for sleep apnea, many of which are now under consideration for commercial development. Their results have culminated in an IllinoisVentures-supported start-up company, Pier Pharmaceuticals, that focuses on the treatment of obstructive sleep apnea.
Membership in the Serbian Academy of Sciences and Arts
In October 2003, the Serbian Academy of Sciences and Arts in Belgrade elected Radulovacki as one of its Foreign Members for his significant scientific research contributions in the fields of Neuropharmacology, sleep disorders and sleep-related breathing disorders.
Yugoslav Student Summer Program
In 1990, Radulovacki initiated the Yugoslav Student Summer Program at the University of Illinois
The University of Illinois Urbana-Champaign (U of I, Illinois, University of Illinois, or UIUC) is a public land-grant research university in Illinois in the twin cities of Champaign and Urbana. It is the flagship institution of the Univer ...
at Chicago (UIC) and the University of Illinois at Champaign-Urbana (UIUC) after the creation of International Linkage Agreements between the UIC and the Universities of Belgrade and Novi Sad
Novi Sad ( sr-Cyrl, Нови Сад, ; hu, Újvidék, ; german: Neusatz; see below for other names) is the second largest city in Serbia and the capital of the autonomous province of Vojvodina. It is located in the southern portion of the Pan ...
in Yugoslavia. The Yugoslav Student Summer Program lasted for 12 years and had 304 participants.
Philanthropy
In 2005, Radulovacki established the Miodrag Radulovacki Family Prize for Excellence in Basic Sciences at the University of Illinois College of Medicine at Chicago. The purpose of the prize, given annually, is to honor a fourth year Medical student who displays a high degree of intellectual integrity and who has demonstrated strong academic achievement. The prize consists of a plaque and a check for $1,000.
Radulovacki made numerous contributions to his home town of Sremski Karlovci
Sremski Karlovci ( sr-cyrl, Сремски Карловци, ; hu, Karlóca; tr, Karlofça) is a town and municipality located in the South Bačka District of the autonomous province of Vojvodina, Serbia. It is situated on the banks of the Danu ...
.
*In 2007, Radulovacki restored the symbol of Sremski Karlovci, a baroque fountain called the Four Lions Fountain, located in the central square of the city.
*In 2009, Radulovacki restored the baroque façades of the Ecological Center in Karlovci which occupies a historic building in the center of the town.
*In 2010, Radulovacki restored the monument of Serbian poet, Branko Radičević
Aleksije "Branko" Radičević ( sr-Cyrl, Алексије Бранко Радичевић, ; 28 March 1824 – 1 July 1853) was a Serbian poet who wrote in the period of Romanticism.
Biography
Branko Radičević was born in Slavonski Brod on 1 ...
(Radichevich), at Stražilovo (Strazhilovo) which is located on a mountain-top surrounded by forests in the Fruška Gora
Fruška gora ( sr-Cyrl, Фрушка гора; hu, Tarcal-hegység) is a mountain in Syrmia, administratively part of Serbia with a part of its western side extending into eastern Croatia. The area under Serbian administration forms the country ...
(Frushka Gora) National Park
A national park is a nature park, natural park in use for conservation (ethic), conservation purposes, created and protected by national governments. Often it is a reserve of natural, semi-natural, or developed land that a sovereign state dec ...
near Karlovci.
*In 2011, Radulovacki financed the construction of a self-sustaining ecological building with solar panels
A solar cell panel, solar electric panel, photo-voltaic (PV) module, PV panel or solar panel is an assembly of photovoltaic solar cells mounted in a (usually rectangular) frame, and a neatly organised collection of PV panels is called a phot ...
and geothermal heat pump
A ground source heat pump (also geothermal heat pump) is a heating/cooling system for buildings that uses a type of heat pump to transfer heat to or from the ground, taking advantage of the relative constancy of temperatures of the earth through ...
s in the courtyard of the Karlovci Ecological Center. In recognition of Radulovacki's philanthropy, the ecological center was renamed the Ecological Center Radulovački.
Personal life
Radulovacki lived in Chicago
(''City in a Garden''); I Will
, image_map =
, map_caption = Interactive Map of Chicago
, coordinates =
, coordinates_footnotes =
, subdivision_type = Country
, subdivision_name ...
. He was a cross-country skier. He participated in several Birkebeiner-Kortelopet cross-country ski marathons in Cable-Hayward, Wisconsin
Wisconsin () is a state in the upper Midwestern United States. Wisconsin is the 25th-largest state by total area and the 20th-most populous. It is bordered by Minnesota to the west, Iowa to the southwest, Illinois to the south, Lake M ...
. Radulovacki died on May 27, 2014 in Belgrade, Serbia, while on two-week trip to promote his philanthropic projects. He is survived by two sons and four grandchildren.
Selected publications
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Related publications
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References
{{DEFAULTSORT:Radulovacki, Miodrag
1931 births
2014 deaths
Scientists from Chicago
People from Sremski Karlovci
American inventors
Yugoslav emigrants to the United States
University of Belgrade Faculty of Medicine alumni
Neuropharmacology
Serbian inventors
Serbian scientists
American people of Serbian descent
Members of the Serbian Academy of Sciences and Arts
University of Khartoum faculty
Yugoslav expatriates in Sudan