Maurice Stroun (September 3, 1926 – August 2017) was a Swiss researcher and professor at the University of Geneva in the Department of Plant Biochemistry and Physiology. He is known for first hypothesizing and demonstrating the existence of disease-specific circulating nucleic acids as well as first developing techniques for the detection of tumor-related characteristics of circulating DNA and RNA in plasma and serum, or liquid biopsies as this field is now known.

Early work

In the mid 1960s, Stroun along with colleague, Philip Anker, (also in the Department of Plant Physiology at the University of Geneva) began to study the phenomenon of neoplasms in plants. Building on early grafting studies in plants as well as work by other researchers that demonstrated the transfer of genetic material between bacteria, they hypothesized that a similar phenomenon might occur between bacterial cells and plants.{{Cite web|url=http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=MarkedList&qid=12&SID=4ArgVzHvf1xH6HzTKNA&page=1&doc=1&colName=BCI|title=Web of Science - Starting New Session...|website=apps.webofknowledge.com|access-date=2016-05-05}} Their research in the late 1960s demonstrated that this process did indeed exist {{Cite web|url=http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=MarkedList&qid=19&SID=4ArgVzHvf1xH6HzTKNA&page=1&doc=2&colName=WOS|title=Web of Science - Starting New Session...|website=apps.webofknowledge.com|access-date=2016-05-05}}{{Cite web|url=http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=MarkedList&qid=26&SID=4ArgVzHvf1xH6HzTKNA&page=1&doc=3&colName=WOS|title=Web of Science - Starting New Session...|website=apps.webofknowledge.com|access-date=2016-05-09}}{{Cite web|url=http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=MarkedList&qid=33&SID=4ArgVzHvf1xH6HzTKNA&page=1&doc=4&colName=WOS|title=Web of Science - Starting New Session...|website=apps.webofknowledge.com|access-date=2016-05-09}} and led them to study whether a similar mechanism occurred in higher-order species, where Stroun published further research showing transfer of genetic material from bacteria to frogs. In an article published in Science, November 10, 1972, bacterial RNA was demonstrated in frog brain cells after a bacterial peritoneal infection.{{Cite web|url=http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=MarkedList&qid=40&SID=4ArgVzHvf1xH6HzTKNA&page=1&doc=5&colName=WOS|title=Web of Science - Starting New Session...|website=apps.webofknowledge.com|access-date=2016-05-09}} In the April 1973 issue of the Journal of Bacteriology, Stroun showed transcription of spontaneously released bacterial DNA was found to be incorporated into cellular nuclei of frog auricles.{{Cite web|url=http://apps.webofknowledge.com/full_record.do?product=UA&search_mode=MarkedList&qid=47&SID=4ArgVzHvf1xH6HzTKNA&page=1&doc=6&colName=WOS|title=Web of Science - Starting New Session...|website=apps.webofknowledge.com|access-date=2016-05-09}} In one particular experiment published in the same article, Stroun and his group extracted the auricles of frog hearts and dipped them for several hours in a suspension of bacteria. Afterward, they found a high percentage of RNA-DNA hybridization between bacterial DNA extracted from bacteria of the same species as that used in the experiment and titrated DNA extracted from the auricles which had been dipped in the bacterial suspension. The experiment demonstrated that bacterial DNA had been absorbed by the animal cells. Stroun dubbed this phenomenon has trancession. Professor Straun died in Geneva in 2017.

Extension to humans and cancer

Building on their work and taking notice of the work of Henry G. Kunkel, whose group made the association of higher levels of circulating DNA and lupus,{{Cite journal|title=Deoxyribonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus.| pmc=292857 | pmid=4959277 | doi=10.1172/JCI105479| volume=45| issue=11 | year=1966| journal=J. Clin. Invest.| pages=1732–40 | last1 = Tan | first1 = EM | last2 = Schur | first2 = PH | last3 = Carr | first3 = RI | last4 = Kunkel | first4 = HG}}{{Cite journal|title=The Occurrence of Single-Stranded DNA in the Serum of Patients with Systemic Lupus Erythematosus and Other Diseases|journal=The Journal of Clinical Investigation |pmc=302243 | pmid=4629907|doi=10.1172/JCI107165|volume=52|issue=1|year=1973|pages=198–204 | last1 = Koffler | first1 = D | last2 = Agnello | first2 = V | last3 = Winchester | first3 = R | last4 = Kunkel | first4 = HG|url=https://www.ncbi.nlm.nih.gov/}} Stroun started studying whether circulating DNA could be associated with malignancies such as cancers in humans.{{Cite web|url=http://cancerres.aacrjournals.org/content/35/9/2375.full.pdf|title=2375.full.pdf|website=cancerres.aacrjournals.org|access-date=2016-05-09}} In a 1977 issue of International Review of Cytology, Volume 51, Anker and Stroun wrote that when foreign DNA is transcribed into a cell of a different organism, "this general biological event is related to the uptake by cells of spontaneously released bacterial DNA, thus suggesting the existence of circulating DNA. In view of the malignant transformations obtained with DNA, the oncogenic (cancer-causing) role of circulating DNA is postulated."1977 issue of International Review of Cytology, Volume 51, Anker and Stroun.

In the late 1970s, building on the discovery of circulating DNA in human blood by Mandel and Metais,Mandel P, Métais P: Les acides nucléiques du plasma sanguin chez l'Homme. CR Acad Sci Paris 142: 241–243, 1948. Leon and his collaborators developed a radioimmunoassay for measuring nanogram quantities of nucleic acids in serum. This technique enabled them to observe that cancer patients tended to possess a greater quantity of circulating DNA in serum (on average) than their healthy counterparts.{{cite journal|title=Radioimmunoassay for nanogram quantities of DNA|doi=10.1016/0022-1759(75)90106-4|pmid=1206227|volume=9|issue=2|pages=157–164|journal=Journal of Immunological Methods|date=December 1975|last1=Leon|first1=S.A.|last2=Green|first2=A.|last3=Yaros|first3=M.J.|last4=Shapiro|first4=B.}}{{Cite journal|url=http://cancerres.aacrjournals.org/content/37/3/646.long|title=Free DNA in the Serum of Cancer Patients and the Effect of Therapy|issue=3|pages=646–650|journal=Cancer Research|volume=37|access-date=2016-05-09|date=March 1977|last1=Yaros|first1=M. J.|last2=Sklaroff|first2=D. M.|last3=Shapiro|first3=B.|last4=Leon|first4=S. A.|pmid=837366}}{{cite journal|title=Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease|journal=Cancer|doi=10.1002/1097-0142(19830601)51:11<2116::AID-CNCR2820511127>3.0.CO;2-S|volume=51|issue=11|pages=2116–2120|year = 1983|last1 = Shapiro|first1 = Bernard|last2=Chakrabarty|first2=Milankumar|last3=Cohn|first3=Edwin M.|last4=Leon|first4=Shalom A.|pmid=6188527|s2cid=21520710 |doi-access=free}} This led Stroun to explore if other methods could be developed to not only detect the overall abundance of nucleic acids in patients with disease (and specifically cancer) but to also detect the disease-specific components of such circulating nucleic acids themselves. Unlike bacterial transformations in plants and animal cells involving clear transfer of separately identifiable nucleic acids, it was not clear how malignancy in cancer arose, although there were many competing theories. Stroun’s postulate that neoplastic malignancy was associated with the presence of tumor specific nucleic acids, led to extensive research by his group of circulating nucleic acids in cancer patients in the late 1980s.{{Cite journal|title=Isolation and characterization of DNA from the plasma of cancer patients.|pmid=3653190 | volume=23|issue=6 |year=1987|pages=707–12 | last1 = Stroun | first1 = M | last2 = Anker | first2 = P | last3 = Lyautey | first3 = J | last4 = Lederrey | first4 = C | last5 = Maurice | first5 = PA | journal=Eur J Cancer Clin Oncol|doi=10.1016/0277-5379(87)90266-5 }}{{Cite journal|title=Neoplastic characteristics of the DNA found in the plasma of cancer patients.|pmid=2779946 | volume=46|issue=5 |year=1989|pages=318–22 | last1 = Stroun | first1 = M | last2 = Anker | first2 = P | last3 = Maurice | first3 = P | last4 = Lyautey | first4 = J | last5 = Lederrey | first5 = C | last6 = Beljanski | first6 = M | journal=Oncology | doi=10.1159/000226740}}

Detection of circulating tumor nucleic acids in human cancer patients

In the late 1980s and early 1990s cancer researchers such as Bert Vogelstein began demonstrating the association of tumor-specific mutations in certain human cancers, such as RAS mutations in colorectal cancers.{{Cite journal|title=Prevalence of ras gene mutations in human colorectal cancers| volume=327|issue=6120|doi=10.1038/327293a0|pmid=3587348|journal=Nature|pages=293–297|date=May 1987|last1=Vogelstein|first1=Bert|last2=Eb|first2=Alex J. van der|last3=Boom|first3=Jacques H. van|last4=Vries|first4=Matty Verlaan-de|last5=Hamilton|first5=Stanley R.|last6=Fearon|first6=Eric R.|last7=Bos|first7=Johannes L.|bibcode=1987Natur.327..293B| s2cid=2595895}}{{Cite journal|url=http://www.cell.com/cell/abstract/0092-8674(88)90571-5|doi= 10.1016/0092-8674(88)90571-5|pmid= 2453289|title=Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes|access-date=2016-05-09|volume=53|issue= 4|journal=Cell|pages=549–554|date= 1988-05-20|last1= Perucho|first1= Manuel|last2= Arnheim|first2= Norman|last3= Martin|first3= John|last4= Forrester|first4= Kathleen|last5= Shibata|first5= Darryl|last6= Almoguera|first6= Concepcion|s2cid= 22457575}}Hirai H, Kobayashi Y, Mano H, Hagiwara K, Maru Y, Omine M, Mizoguchi H, Nishida J, Takaku F: A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome" Nature 327: 430–432, 1987 Stroun took notice and realized that newly available PCR technologies could be used to possibly detect such RAS mutations in circulation. In fact, his group was one of the first to demonstrate successful detection of such tumor-specific DNA in the circulation of cancer patients.Vasioukhin V, Stroun M, Maurice P, Lyautey J, Lederrey C, Anker P: K-Ras point mutations in the Blood plasma DNA of Patients with colorectal tumors. In: Verna R, Shamoo A (eds) Biotechnology Today, Challenges of Modern Medicine, Ares-Serono Symposia Publications, 1994, Vol 5, pp 141–150.{{cite journal|title=Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia|journal=British Journal of Haematology|doi=10.1111/j.1365-2141.1994.tb04828.x|pmid=7918071|volume=86|issue=4|pages=774–779|year = 1994|last1 = Vasioukhin|first1 = Valeri|last2=Anker|first2=Philippe|last3=Maurice|first3=Pierre|last4=Lyautey|first4=Jacqueline|last5=Lederrey|first5=Christine|last6=Stroun|first6=Maurice|s2cid=26365875}} Stroun was also the first to demonstrate the successful detection of alterations beyond point mutations in plasma, such as microsatellite alterations, gene expression changes and copy-number alterations.{{Cite journal|title=Microsatellite alterations in serum DNA of head and neck cancer patients|journal=Nature Medicine|volume=2|issue=9|pages=1035–1037|doi=10.1038/nm0996-1035|pmid=8782464|date=September 1996|last1=Sidransky|first1=David|last2=Stroun|first2=Maurice|last3=Anker|first3=Philippe|last4=Koch|first4=Wayne|last5=Nawroz|first5=Homaira|s2cid=11759121}}{{Cite journal|title=Microsatellite alterations in plasma DNA of small cell lung cancer patients.|pmid=8782463 | volume=2|issue=9 |year=1996|pages=1033–5 | last1 = Chen | first1 = XQ | last2 = Stroun | first2 = M | last3 = Magnenat | first3 = JL | last4 = Nicod | first4 = LP | last5 = Kurt | first5 = AM | last6 = Lyautey | first6 = J | last7 = Lederrey | first7 = C | last8 = Anker | first8 = P | journal=Nat. Med. | doi=10.1038/nm0996-1033|s2cid=31591119 }}{{Cite web|url=https://www.researchgate.net/publication/12275878|title=Chen, X. Q. et al. Telomerase RNA as a detection marker in the serum of breast cancer patients. Clin. Cancer Res. 6, 3823-3826|website=www.researchgate.net|access-date=2016-05-09}}

Circulating Nucleic Acids in Plasma and Serum Congress

The early work of Stroun and Anker spurred intense investigation into the relationship of circulating nucleic acids and human conditions, such as disease, trauma, and pregnancy. For example, Lo demonstrated that fetal-specific nucleic acids could be detected in maternal peripheral blood in the late 1990s.{{Cite journal|url=http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)02174-0/fulltext|title=Presence of fetal DNA in maternal plasma and serum|access-date=2016-05-09 | doi=10.1016/S0140-6736(97)02174-0|pmid=9274585|volume=350|issue=9076|journal=The Lancet|pages=485–487|date=1997-08-16|last1=Wainscoat|first1=James S.|last2=Redman|first2=Christopher WG|last3=Sargent|first3=Ian L.|last4=Rai|first4=Vik|last5=Chamberlain|first5=Paul F.|last6=Corbetta|first6=Noemi|last7=Lo|first7=Y. M. Dennis|s2cid=14234791}}{{Cite journal|url= |title=Quantitative Analysis of Fetal DNA in Maternal Plasma and Serum: Implications for Noninvasive Prenatal Diagnosis|doi= 10.1086/301800|pmid=9529358|pmc=1377040|volume=62|issue=4|journal=The American Journal of Human Genetics|pages=768–775|date=April 1998|last1=Hjelm|first1=N. Magnus|last2=Chang|first2=Allan M. Z.|last3=Johnson|first3=Philip J.|last4=Wainscoat|first4=James S.|last5=Poon|first5=Priscilla M. K.|last6=Leung|first6=Tse N.|last7=Haines|first7=Christopher J.|last8=Lau|first8=Tze K.|last9=Tein|first9=Mark S. C.|last10=Lo|first10=Y. M. Dennis}} As such, the pair organized the first global symposium dedicated to circulating nucleic acid research in 1999 held in Menthon, France. The conference was named CNAPS (Circulating Nucleic Acids in Plasma and Serum) and is held every other year to this day. In fact, the 2015 conference organizers’ welcome address begins, “When our forerunners and field-founders Philippe Anker and Maurice Stroun organized the first event in 1999 in Menthon, France, none of us attendees could have imagined that Circulating Nucleic Acids would be a game changer” {{Cite web|url=http://www.cnaps-congress.com/en/|title=Dear Colleagues|website=www.cnaps-congress.com|access-date=2015-05-09}}

Later years

In later years, Stroun promoted the development and validation through large clinical studies of cancer diagnostics based on circulating nucleic acid detection.{{cite journal|title=Circulating nucleic acids in plasma and serum as a noninvasive investigation for cancer: Time for large-scale clinical studies?|journal=International Journal of Cancer|doi=10.1002/ijc.10791|pmid=12455027|volume=103|issue=2|pages=149–152|year = 2003|last1 = Anker|first1 = Philippe|last2=Mulcahy|first2=Hugh|last3=Stroun|first3=Maurice|doi-access=}} Stroun and Anker would later set up a company, OncoXL, in Geneva to commercialize a cancer diagnostic test, or liquid biopsy, as it later become known, based on the fruits of their multiple decades of research into circulating nucleic acids. In 2005, Stroun’s semi-forgotten pioneering work in circulating nucleic acids was later acknowledged in a compilation of scientists that gave rise to various groundbreaking fields.{{Cite journal|url=https://www.academia.edu/7840979|title="THESE SCHOLARS WHO TALK TO THE WIND": INTRODUCTORY COMMENTS|website=www.academia.edu/|access-date=2016-05-09|last1=Mentré|first1=Pascale}} Maurice Stroun currently serves as an advisor to Guardant Health, a company that has commercialized a comprehensive liquid biopsy based on circulating DNA in peripheral blood.{{Cite web|url=http://www.guardanthealth.com/company/#advisors|title=Company - Guardant Health|website=guardanthealth.com|access-date=2016-05-09}}

Maurice Stroun died in August 2017, at the age of 90.{{cite web |title=Hommage à Maurice Stroun, agitateur et précurseur |url=https://www.unige.ch/lejournal/numeros/journal153/hommage-stroun/ |website=Université de Genève |access-date=13 October 2023}}

References

Category:1926 births

Category:2017 deaths

Category:Swiss biochemists

Category:Academic staff of the University of Geneva