Eliava Institute
Tbilisi, Republic of Georgia

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The Eliava Institute
 

In its heyday in the 1970s and 80s, nearly 800 people worked in the Industrial Branch of the Eliava Institute, using enormous vats, pill stampers and automatic bottling machines to pump out tons of phage products for military and civilian uses all over the Soviet Union.  Another 200 worked to analyze hundreds of thousands of bacterial samples that continuously poured in at the direction of the Soviet Ministry of Health, testing the phage cocktails for efficacy and constantly isolating new phage and making refinements.  They also fought infectious disease in other ways – vaccines, immune enhancers, probiotic bacterial cultures – but phage were their main focus.  By then, Institutes and factories in places like Gorki and Ufa were also producing these phage products for Soviet use, but Tbilisi phage were especially prized as far away as Lithuania even in 1990.  Guram Gvasalia, chief surgeon at the enormous State Hospital, has relied heavily on their phage preparations against purulent bacteria like Staphylococcus, Streptococcus and Pseudomonas to prevent and treat severe infections for over 25 years.   The complex “pyophage” mixtures he uses contain over 30 phages against 5 key bacteria, and are continually refined by his collaborators at the Bacteriophage Institute to control any bacterial strains currently prevalent in the hospital.  They are particularly important for such challenging cases as bone infections (osteomyelitis), diabetic foot ulcers and bed sores, where lack of circulation as well as bacterial resistance block antibiotic treatment.

International Grants: INTAS-Georgia (joint funding from EC and Georgia) - Bacteriophage - a new approach for combating of the nosocomial respiratory infection caused by Ps. aeruginosa, PI - Dr. Nina Chanishvili, Co-ordinator - Dr. Paul Barrow, UK, - 50.000,00 EURO;
CRDF Grant N 527 A new strategy for control of potato bacterial diseases based on application of specific phages, PI, Dr. Marina Tediashvili (IBMV, GE), 150 000 US dollars;
INTAS Open Call - An epidemiological study of outbreaks of B. anthracis in Georgia, PI- Professor Sergo Rigvava, Co-ordinator Professor Richard Sharp, CAMR, UK - 90 000 Euro;
CRDF - Regional Experimental Support Centers Program - Regional Experimental Center for Applied and Microbiology Research (RECAMBR), PI-Dr. Nina Chanishvili - 316 000 US dollars
 

Scientists from the Eliava Institute are also collaborators on other international grants where the PIs are from other Georgian institutions; CR: Eliava Institute lead collaborator
INTAS Grant N 1390 - The Biological Dispersion Phenomenon and the Energetic of Microplankton: A Search for the Regularities and the Relationship to Environmental Fluctuations, CR Marina Tediashvili, Co-ordinator Professor Richard Kemp University of Wales, UK, 150 000 Euro;
INTAS FOOD-2000, Prevention of food spoilage by suppression of phenoloxidase perioxidase and growth of pathogenic micro-flora by use of natural inhibitors of plant origin, CR - Dr. Marina Tediashvili, Co-ordinator , Dr. Jose Neptuno Rodrigues Lopes, University of Mursia, Spain- 120 000 Euro;
INTAS-Polluted Environments - Evaluation of coastal pollution status and bio-indicators for the Black Sea (BIOBS), CR - Dr. Marina Tediashvili,Co-ordinator Dr James Wilson, Center for the Environment Trinity College, Dublin, Ireland - 120 000 Euro;

Eliava Labs and People: August, 2002

Many people seem to be considering visits to Tbilisi or at least raising questions about the Eliava Institute - hopefully this introduction to the human and physical topology there will be some help.

Lab Groups - these individuals also form the governing Institute Lab Council:
(A number are involved in the various grants and proposals - see International Support)
1. Director Teimuraz Chanishvili -- MD, PhD, DSc, Prof.
2. Molecular Biology in Phage Characterization and Application: Rezo Adamia - PhD, DSc, member of Parliament, just chosen Georgian ambassador to the United Nations --- (Staph,, Pseudomonas, Salmonella primarily) -- PhDs Nana Balarjishvili, Mzia Kutateladze and Leila Kvachadze.
3. Amiran Meipariani - MD, PhD, DSc -- Group Chief; Former head of the Industrial Production Facility
4. Physiology and Morphology of Phages -- PhD Zemphira Alavidze; PhD Marina Goderdzishvili -- isolating and characterizing new therapeutic phages (including all components of Pyophage and Intestiphage); phage preparation and stabilization techniques
5. Phage Selection and Taxonomy Liana Gachechiladze MD, PhD, DSc -- Pseudomonas, E. coli, Serratia. Enterobacter, Proteus -
6. Biochemistry: Tina Birkadze, PhD, DSc; PhD Manana Loladze - Enzymes such as Hyaluronidase for phage and other medicinal purposes
7. Storage and Collection of Bacteria and Phages PhD, Marina Darsavelidze -
8. Virology -- Prof. Inga Georgadze, MD, PhD, DSc, -- influenza, adenovirus, interferon; also clinical diagnostics; PhD, DSc Nana Tophria
9. Ira Chirakadze PhD, DSc Group Chief
10. Microbiology (d'Herelle's original lab)-- Tato Gabisonia - DVM, PhD, DSc Prof. -- various animal pathogens, especially staph; new human clinical cocktails of several sorts
11. anaerobic phages PhD Guliko Tskhvediani - Botulinus, Clostridium, etc.
12. Immunology PhD, DSC Sergei Rigvava - particularly anthrax
Two new groups have been elevated to independent laboratory status this year:
13. microorganism and bacteriophage genetics PhD Nino Chanishvili - Lactobacillus; recently some pseudomonas phage sensitivity studies
14. microbial ecology. PhD Marina Tediashvili - environmental monitoring, plant pathogens, food safety


A Physical Introduction to the Eliava Institute and its Groups

As one enters the spacious Eliava Institute compound, there is a small building on the right used as a clinic to see patients and then a larger building on the left which has the Administrative Offices and two meeting rooms, on the second floor. This is the domain of Academician Teimuraz Chanishvili - Director of the Institute since 1997. He has been at the Institute since 1949 and was Scientific Director from 1965 to 1997; before that, he had briefly directed the Production Facility. In the mid-1990's, there was a period of uncertainty in the Institute status after the USSR broke up and the Institute no longer was under the All-Union Ministry of Health. The Industrial Production part underwent privatization, with 8 small companies being formed and a general struggle for survival, individually and collectively. (It is unclear how the decisions were made as to where the line was drawn defining the Research parts of the Institute, which were unequivocally not to be privatized, or who got the various parts of the old Production portion.) By 1997, the Scientific part became the Institute of Bacteriophages, Microbiology and Virology of the Georgian Academy of Sciences.

Straight ahead is the H-shaped Main Building, with sweeping stairs leading up to the main entrance on the second floor. The ground gradually drops off toward the Mtkvari River, so that there are still two more floors above ground in the back section. The front section has a very long wing extending out to the right. Photograph

Second (main entrance) floor:
Left side: Front: small computer room, set up with internet access and security gates - but the Academy-supplied computer was recently taken back into the Director's building and labs without computers must now go to the few labs that have grants and access. General English lessons (supported by the PhageBiotics Foundation) are now held there.
Back: Rezo Adamia's main lab space - with a strong security gate and 5 lab/office spaces. Leads: Nana Balarjishvili, Mzia Kutateladze, Leila Kvachadze; Technicians: Rusiko Patazidze (background in physics and with Liana); Nanuka (makes media) Students: Sophi (ours; came as Master's student from the Technical University. Tamuna Abuladze, who was one of our first students for 1 year and then spent 2 years in Maryland w. Sandro, plans to return soon as a PhD student, as a grant-supported participant with Mzia.

Right wing, second floor is a very large privatized space: "Biochimpharm", under Alexandr Golejashvili (Aleko), who also is formally a member of Liana Gachechiladze's lab at the Institute; Biochimpharm and Liana together have just been awarded an ISTC grant to integrate research and production of new phage formulations against several gram-negative bacteria and are already refurbishing while negotiating the final work plan. Biochimpharm has licensure to make tablets against dysentary, etc. The area is in relatively good shape physically, with large old fermenters and stamping machines that could make 100,000 tablets per hour - far too much for Georgia, and they are looking into markets for their products.

Third floor, front section, reached by a broad sweeping staircase:
Left lies the large library, the stacks of which house an amazing, extensive collection of early phage and microbiology work. However, the ceiling in the reading room is badly damaged and falling and they have few resources for repairs or current journals and books. At the T4 meeting, State Dept. representatives David Allen and Elizabeth Scharl suggested the possibility of getting a small grant for library infrastructure facilities through the ISTC - a proposal is needed here.

The center front of building contains a large old lecture hall.

Right: The first rooms on both sides of the hall, Nino Chanishvili's space, are being renovated with a mix of funds, to be shared between her group and the new CRDF-funded "Regional Experimental Center of Applied Microbiology and Bacteriophage Research" (RECAMBR), required to be open for users from throughout the region; this is discussed in detail elsewhere. There are then three rooms which will provide additional space for the Adamia group, to be renovated with money built into their upcoming ISTC grant.
The last 5 rooms before a set of double doors belong to Marina Tediashvili and the phage ecology lab; the renovation is complete, using funds from her CRDF/3M potato pathogen grant.

The space beyond the double doors, which also has its own stairway access, is being developed into a badly-needed joint therapeutic phage research-scale production facility. The attic area above will again become an animal quarters for product testing. The heads of the 4 labs carrying out such production and several others from the Institute have just formed a nonprofit foundation to raise money for this purpose, since the Institute has not been able to provide any funding for it since first committing the space several years ago. The project and its importance are discussed elsewhere.

Bottom floor, right front wing: The proximal portion houses the electron microscope center and a very large ultracentrifuge and storage room. It has no windows but has direct same-level outside access.
The outer, privatized part was rented by its owner, Lela **, to a German bakery! This is being fought by most at the Institute as illegal and a potential serious hazard in a building with this sort of biological pathogen work. Through some means Lela won the first round of the court battle and it was open for 1 ½ years but it is currently closed.

Back wing of the building: extends primarily to the left.
second floor right end Ketevan (Leana) Gachechiladze - Lab of phage taxonomy and selection -- 4 small rooms currently in use. [Note: she also has a pair of relatively unused rooms on the right along the corridor between the two buildings. She currently has only a small grant from Intralytix and a little help from us. She is included in various ways on several grant proposals from other groups, including being on the Adamia lab ISTC grant, and also works with the Clinic to test phage sensitivities, etc. - right now her lab is supported with that plus the small Intralytix grant.] She has one of our students, Marina Dzaliashvili, working on finishing degree; Tamula Meschi, Liana's age, excellent with isolating and preparing therapeutic phage; technicians Marica (about 30) and Dodo (about 50), who do such things as prepare media, and A. Golidjashvili, all of whom are half time on her official List. Until she gets significant funding, most of these are mainly supporting themselves by working elsewhere, such as with Inga's Diagnostic company. She also on paper has Teimuraz's nephew Sviadi Chanishvili, who was also one of the people getting space on privatization - 1 floor in big factory building, plus room next to Marina in lower back part. [He was the one Nino rented the space from for her venture with Caisey - rooms were then renovated, but he doesn't seem to have done much anywhere since.]

Then office of Amiran Meipariani - Chief over 3 neighboring labs

Lab of Zemphira Alavidze and of Marina Goderdzishvili (who is on maternity leave): Physiology and Morphology of phages - have quite a large lab (get names) and have made phage preparations for hospitals, military, phage bioderm - pyophage, intestiphage, staph, individual phages - renting some space/rights from the Institute for that part. (They have discussed this arrangement with the Vice-Director of the National Academy and have set this up similarly to commercial ventures tied to another Institute of the Academy, with things properly set up to pay taxes on any actual profits they generate.) For a couple of months when the power was shut off, Lado (see below) let them use some of his excess capacity and electricity free of charge, with them supplying all materials, to continue to make their preparations for the hospitals, etc. They make only about 30 liters/month currently.

End of hall, fairly isolated, with doors: Guliko Tskhvediani - phages of anaerobic bacteria
[These are among the most pathogenic bacteria at the institute.]

Third floor: up a very narrow stair in Liana's area, the old low attic rooms of Nino Chanishvili and Marina Tediashvili

First floor, back wing -
Laboratory of Microbiology (Eliava's original lab) - Dr. Dr. Tato Gabisonia (also on the faculty of the vet school) - plus Dr. Dr. Ira Chirakadze and Lamara Chanishvili (who did excellent Shigella T-even pseudolysogeny work - both of these women have been at the Institute 50 years, and learned from people who worked closely with Eliava and d'Herelle!).
The lab studies both veterinary and human therapeutic applications - it is a large group, with 2 vet students and one of mine, and a wide range of collaborations inside and outside the Institute.
They have a BTEP grant involving Constantin Severinov as US partner and a mastitis grant submitted to Ukraine program, with Katsarava and me;
Their lab is also now preparing and selling 4 Institute-approved new human phage preps

Laboratory of Biochemistry - right end of floor - Tina Birkadze and Manana Loladze; Manana has focussed mainly on hyaluronidase and its applications for 20 years and is just finishing her Dr.Sci; she now is working more closely with Tato's group, bringing her cell-surface and hyaluronidase expertise to bear in both infection-process and therapeutic cocktail work.)

Ground floor, left at back under Tato, with outside entrances to each suite-
Storage and Collection of Bacteria and Phages - Marina Darsavelidze -- a small lab focussing particularly now on Pseudomonas from throughout Georgia and also making some new commercial phage cocktails.

Virology -- Inga Georgadze, daughter of a former long-time Institute director, is actively involved in providing therapy in a small clinic at the entrance to the grounds where patients are regularly treated for various kinds of problems and various phage preparations, supplements and immunological reagents are sold. She also has a rented space in a separate building that she renovated and uses for the diagnostic work of her company "Diagnos 90", discussed under companies.

Immunology: Sergei Rigvava: -- in a separate very high-containment building nearby, focussing particularly on serological aspects of Anthrax of veterinary origin, now supported with a substantial grant and expanding their work with Anthrax phages

Other significant players:
Lado Gulisashvili and Lela Kalandarishvili: Have most of original big main production plant - for BioPharm company, making vitamins, various biological reagents, probiotics and currently also about 20 liters a month of phages - continuing those being produced number of years early, without research or upgrading. Now working at about 40% of capacity - did much to obtain all sorts of equipment, from bankrupt companies, including in Moscow.
Lela, a biophysicist and the main person involved with phages, was once with Rezo working on basic problems in DNA packaging. There are some disputes currently involving some spaces in the main building that she claims or also owns.
Sviadi Chanishvili - nephew of Teimuraz; has some space next to Marina Darsavelidze and one floor in Lado's building, the old factory. This latter is the area that Caisey Harlingten supported and Nino Chanishvili refurbished for their rather short-lived 1997 joint venture (depicted extensively in the BBC program The Virus that Cures) before Caisey's company became Phage Therapeutics in Bothel, Washington. He had his own generators then that were later stolen.

Ramaz Katsarava - developer, with Zemphira Alavidze, of Phage Bioderm -head of the Research Center for Medical Polymers and Biomaterials (RCMPB), Georgian Technical University. Originally he had a joint appointment at the Biophysics Institute across the street from the Eliava, where Tsotne Dzhavakishvili, Nino Mzhavia and Nino Trapaidze (all of whom spent multiple years at Evergreen a decade ago) studied under Rezo Vashakidze.

Guram Gvasalia - Chief Surgeon, main Regional Hospital; he als headed the military medical support during fighting in Abkasian (where all soldiers were supplied with little Piophage spray bottles); has worked extensively with phage for over 25 years and virtually always uses it as part of his surgical practice.

David Gamrekeli - biophysicist, Moscow State University - long-time friend of people at the Institute who volunteers to teach the twice-weekly student English classes and is now working with Zemphira Alavidze, Liana Gachechiladze, Gvasalia and several advanced medical students on a project exploring antibiotic/phage interactions and looking carefully at Gvasia's clinical data from recent years. They are designing clinical trials tied to several supurative types of infections such as diabetic foot infections.

Georgian CDC: collaborations with Sandro Sulakvelidze of Intralytix and with Nino Trapaidze on BTEP grants related to various microbial problems - they are interested in developing phage collaborations and will soon have a DNA sequencer and pulse-gel electrophoresis system that will be excellent resources.

Georgian ISTC office: Prof. Irina Khomeriki, PhD - khomeriki@istc.ru; ikhomeriki@hotmail.com;
http://www.istc.ru
(The ISTC and Partner grants listed here were taken from the list she supplied us with that apparently includes current and approved pending grants.)

For more information contact Dr. Elizabeth Kutter at t4phage@evergreen.edu

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