Scribd Logo
Upload

Welcome to Scribd!

  • Avra Interview

    Uploaded by

    Buddhi Dhamma
    5 views9 pages
    avra

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Report this Document
    avra

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    5 views9 pages

    Avra Interview

    Uploaded by

    Buddhi Dhamma
    avra

    Copyright:

    © All Rights Reserved
    Download as PDF or read online from Scribd
    Flag for inappropriate content
    of 9
    PRUE Sa ere icy” cia wk Nave, PUN eNAy cele caredteyt] ideas that are tough, relevant for the society and cammake Feb rebe ale for India’ outsourced research Is the buzzword, Dr AV Fama Rao ought to be icon. He runs india’s onty ‘Scientific research fab as a business venture. His company Avra Laboratories provides technical services, process technologies and synthesis of new chemical entities ior world's leading drug companies like GD Seatle, Piizer and Bristol-Myers Squibb. From extremely humble origins of rural Andhra Pradesh, Dr Rama Rao became an innovative scientist with National Chemical Laboratory in Pune and later turned the Indian Institute of Chemical Technology into a centre of excellence. His outstanding research work has fed to 30 patents, 50 drug technologies for the industry and 109 PhDs. While his outspoken and straightforward nature has upset a few mediocre people, Dr Rama Rao has had a fong triondship with Dr YK Hamiod of Cipla, synthesising the anti-AlDS drug that fetched global tame for Cipla and Dr Hamied. Excerpts trom ‘Dr Fama Fao's interview with MoneyLiFE editors Sucheta Delal and Debashis Basu at his lab in Hyderabad. ML: Can you tell us a little about your background and vour childhood? AVR: Ihave seen your other interviews whers everybody seems 10 be a ropper. Let me be very frank. I was never a copper in school, My father was a stare employee who got transferred Frequently. 1 a the fir child and used vo move around with may parents, Usaally by the time {finished half a year, my father was transferred and I often didn't go t0 school in the second half at all I was happy spenling most of my vime playing. ‘Then, I scraped through the sixth standard and gor into the high school Since my father ased to get transferred frequently, Loften stayed with my grandparents at Guntur. But when 1 was in my fourth standard, | had a friend who played cards Now, in Andhra Pradesh, everybody has thre laying cards, drinking and wemanising. We used to bbunk schoo! in the aftemeon and play cards behind a temple. I somehaw got through the exams because Thad a eecrifie memory. ML: When did you get serious about studies? AVR: The year I was supposed to appear for my SSC, 1 realiged what I was doing, By then, Iwas sent to live wich my aunt who was very poor. My father used to send Rs40/eveey month for my upkeep and they managed the house with that money. Ie made me tealise, for the first time, that if did not have proper have had it, We used to have just one meal id leftovers in the evening, ML: How did this ecalisation change you? AVR: I used to dominate everything that Hdl. L was nota igreat football player, but | was the team leader. I also realised, for the first rime during. my SSC exams, that scoring marks ie noe diffieule and L topped my school. At thac time, my father used to say that he Would get me a let's job when I pass my SSC. Because I dlidn't study regularly, I had become weak in mathematics and L opced for biology, physics and chemistry at the intermedkate level bur dida’t know that students with biology went on to do medicine. I cassally applied 1 « medical college in Gi the 50 seats were lor merit students, ranked 14¢h or 15th. My father could nor afford to send me onesie Gantur. So, alehough Vishakapatnam {medical college) hhad more seats, {could not go. I did’ feel bad, | had, by then, started liking chemistry, so I joined AC College in ntur for my BSe. Getting first class was a big thins those days and I was a topper. I was also the college student leader Our principal bebeved that student leaders are rogues and don't study, So whenever he got ‘complaints from che faculty, he always called for my marks. | used to get away with a warning, since I was a topper. One had to gp out of che seate for a Master's dlegrce those days and most people wene to the Benaras Hindu University. Since we were nine siblings, there was nno money for me to go, My father had asked me co apply for the post of a clerk and [get the job, but { yas reluetant to join, ‘ML: What did you wane to do? AVR: I wanted to study more. But I knew the fail situation, so [decided to join AC College as a chemistry demonstrator for one or two years. Those days, post: ageadaaces applied for the demonstrator’: job, but sometimes they 100k graduares too, The evening before the interview, I went to meet the Head of the Department (HOD) hoping be would put in a good word for me, He neur where only 13 of did the opposite. He said, “You area student leader and don’t deserve 10 be a teacher”. Anyway, [got the job. A year later, [was selected as a chemist in the Agriculsaral College at Bapatia. Ie is there that [realised that a BSe was not enough and roll my father thae 1 wanted to study further. I saw an advertisement of the University Department of Chemica! Technology, Bombay. | applied aand gor through. [landed in Bombay on a rainy day like Sharma {Prof MM Sharma, see inteeview in Money IFE “th December issue}. I didn’t know the city and someone ‘op the train asked me to get off at Dadac. Look @ taxi, which took me to V{TTand dumped me there. | then walked in the rain to the hostel. That is how I stated, | wanted to do pure chemistry and not engineering. Those clays, Prof K Venkataraman was the best in organic ‘chemistry. He was at the National Cheraical Laboratories (NCLi, Pune. [applied to do my PRD under him, even though many students took 8-10 years to complete their PRD with him. 1 was abo gecting job offers from ‘companies ike Glaxo and Ptizer. Nobody other than me went for research from my hateh. ML: Did you know Prof Venkataraman eatlier? AVR: No, [din’t; but he was a former faculty member of 'DCT and had a soit spot for UDCT snidents. For the first three months, whea there was no fellowship, 1 had «| plead with my father for support and he sent me RS100 a ‘month for expenses, | completed my PhD in a record time oof three and a half years ond Prof Venkstaraman asked ‘me to stay on for post-doctoral work. After a year ‘wanted to leaye NCI for further studies, He insisted that 1 tack. [told him that he should atleast give mea During my high school, I was sent to live with my aunt who was very poor, My father used to send Rs40 every month for my upkeep and they managed the house with chat money. We used to have just one meal and leftovers in the evening, It made me realise, for the first time, that if I did not have proper education, Thave had ity regular position. | became a ‘Scientist BY at NCL in 1965. Until then, everyone was appointed to this post only on returning from abroad after higher studies. Has already married and had a child, A permanent government job seemed like a Gd-ziven gift. For the neve 10 years, [was focused on chemistry of natural prexlucts and isolated 100 ombay. H. YK Hamied, then R&D at Ciph bulk d took He was t he w. A few days ter, he came to NCL and paid a on fee of Rs30,000 to bus amazed yy new compounds from plants and insects, which led to 70 pablications in top international journals, ML: During 1965-1975, you also worked closely with industry, shifing from your desire o do only fundamencal research, the process, We AVR: | had the noxion that fundamental research was the pure ching and industrial research was mediocte. But NCL ‘was changing at that time, Director Dr BD Tilsk insisted fundamental cesearch had no relevance and the ganic chemisery di ‘nalustry. My first brush with industrial research was the cease of Poona Synthetics in 1970, The owner, Maharaj 1h, was the son-in-law of LK Jha (then Reserve Bank Governor) Jha had requested Venkactraman t0 help the sion had to find ways to serve ‘company solve a problem, But Venkataraman didn't know anything about it so he asked me to help, The company suecharine, and in the process i threw away a by-product called PTS-amide. Saccharine prices went down and Poona Synthetics was making heavy losses. [elt that the ing OTS-amide, a key intermediate for only way to revive the company was «9 add value co PTS: amide by converting i to an intermediate called turethan possible buyer, But Singh felt that Hlocchst would never for an anti-diabetic drug. Hoechst India was a accept a local product. He was right. ML: That was very surprising. Arrogance of MNCs? av ight. Hochst simply threw our the gers of Poona Synthetics. [bough a cicket to Bombay om my evn and went fo Hochst. I didn't even have a business card and wrote “from NCL’ an a piece of paper. The Hoechst manager was also a former scadene of Venkataenina id called me in, He knew my name and agreed to give me rial. He gave us an oder for Rs two lakh immediately. But the company had no money to execute it, So, l approached Stare Bank of India which asked me for a technical guarantee. The manager said: “I will give money only-on your werd". I took an NCL lettechesd, wrote that the product w ull work and signed it Lates, 1 to know that we are not supposed to do such things. Tused to do some daring things bur only with good ML: You were involved in supervising the production too, AVR: [had co design the plant needed to produce urethane and f was also spending Saturdays and Sundays 10k avway supervisin from Pune, Within one year, the company’ w: rel In fact, Hound g the produce batches in the factory 28 out of ther application for PTS-anide Aluoresweat pigments which were being imported. ML: Alter that, you got involved with the drag industry AVR: Around 1972, | was ke synthetic drugs. Indian patent lays had be allow Incian versions of foreign drugs andl pesticides. 1 selected the product diazepam but Regional Research Laboratory (RRL), Hyderabad, was already doing it for Ranbaxy. cold Dr Tilak that my approach would be different and it would work out much cheaper, But we had problems getting the raw materials, which were imported, In carly 1972, Lyyent to meet a trader in Bombay, He took me to Dr YK Hamied, then the director ‘of R&D at Cipla, He was trying to set up a bulk deug He en ed about ony dmy Lexpl cular product. He wante to buy the know-how. A few days later, he came to NCL and paid a one-time fee of Rs30,00 10 buy the process approach co synthesising a pa ‘We were amazed. Later, we completed the synthesis of diazepam which was given to Centaur Chemical ML: What was your next career move? AVR the best organic labs. In 1975, I landed up at Harvard worlcing. with EJ Corey fa Nobel Laitreate). Somebody had iniially recom fele che ned to spend one o¢ two years at one of nded my name to Har Gobind Khorana, sho was ot MIT, But Khorana wes working more on biological chemistry eather than pure organic. So Lopted for Harvard, After two years, | was very Ieeen to come back because I was well established here and wanted t0 continue my fundamental and industrial research, (ML: Whar did you do alter you nesuened from Harvard in 1977? AVR: When Tretured, I was very ambitious and wanted to work on tough molecules, especially relating to cancer De Tilak cold me: “Don't think you alone have come from Harvard with an ambition. 110 have worked with Dr Woodward at Harvard, Forgot all your ambitions and sgoals and go back and work on natural products" But L ‘was adamant. He said: “In that case, you should get outside funds”. Then, J met Dr Hamied. He knew | had eally good potential, He olfered me a job, He said he ‘would build an R&D lab in Bangalore, He gave a blank cheque to siga for my salary. Isaid: "No, I did not go t0 Harvacd for nothing; Eyeanted to be in research”. He said. “1 will give you 10 research fellows to work with you" ssid: “Once ane enters the industry, research becomes secondary: For me, research is a primary commitment". He suggested that | become a consultant I have been a consultant ro every major pharnia company ~- Ranbaxy, Gopla, Lupin Dr Hamied was a regular He used 10 sponsar all kinds of projects, so money was never a problem later. ML: Around that ime, you made a major breakthrough AVR: While L was looking for outside sourees of maney, somebody told me very casually that the Maharashtra Government has a swall grant ia what they called a Science & Technology Gell and that they may provide funds for one of my projects. The head of the Cell was ‘one Dr Malshe. Unknown to me at that timey he was suffering from cancer and was reading a Jot on anti-cancer research and medicine. He wanted to work on anti-cancer medication and hed probably read about my work on vinblastine and vincristine at the Corey group far Harvard\. in che 1960s, Fl Lilly came to India and did research on some Indian plants haced on the ayurvedic system as part of the collaboration with NCL. for plant extraction, ‘They had picked up this plant hich is traditionally known to have medicinal properties. The plane grows anywhere. Ie doesn't need watering and strangely no animal tonches the plan, Fvon plane virus doesn’ affect it. The reason, a8 we now know, is thac it contains powerful alkaloids, which gjve out a pungent smell. Do you knew thar women do not offer this flower at some or time oF the other Bat he Vinca rosea 1» God? Nobody knows why, but nebody packs this ower, although it grows in the wild, The Malayalis make aa decoction by boiling dried leaves in water and drink i They believe it cures diabetes, On that basis, they were looking for an anci-diabetic medicine, bur it was not responding in animal tests. ML: How was it identified as a cure for cancer? AVR: Vinea rosea affected the bone marrow and the white blood corpuscles reduced, That indicated that an anti In. 1975, | went to Harvard to work 66 with EJ Corey (a Nobel Laureate). Somebody had fiest recommended my name to Har Gobind Khorana, who was at MIT, But Khorana was working more on biological chemistry rather than pare organic. So T opted for Harvard yy ‘cancer deug was a possiility. So vinblastine and vincristine, che rwo dimeric alkaloids widely used as ane ‘cance: agents were isolated and even today are the only means of cure for leakaemia among children, India was the only source of dried vinea leaves. “Tradecs were procuring it from eribals in Mahareshtra and exporting them to Fit Lilly, USA. But people became greedy and started adulterating the leaves. When Bi Lilly realised this, ie started cultivating the plant in che US sand Afri, In response, the Minisiry of Social Welare began co buy eaves from the tribals to support them. When exports dried up, huge stocks had piled up. They then approached the Science & ‘Technology Cell to see if anything could be lone with the leaves, That is how Dr Malshe wanted to ‘work with this plant. He wanted Pune or Boubay University to isolate vinblastine and vincristine, but neither of rhem came forward When I met him, [began co talk about the plant and gaye him more and mote details, He soon cealised that I knew more about ie than he did. He asked me “how do you know so nach about this plane”? I cold him I was working on anticancer drugs, told him about wanting to isolate vinblastine and vincristine, He asked me how: mich money L would need. [said Rs ewo lakh. He sanctioned it in 24 hours, Since NCL had cokl me there ‘was ne money for fundamental research, I went to the I got drams, boug! with my own money and welded it to the dcum. F packed 30kg of leaves in ‘ht solvent and that is how the drum; [be chnology of the anti-cancer drug was process Osmania Universiey o look for research students. I started work in 1978 to process 10 to 20 to pet a 0.00) extract of vinblastine. I gor druns, bought ‘of Vinea rosea leaves ‘cap with my owen money and welded ie to the drum. T packed kg of leaves in the druny; I bought solvent snd that is how the entire technology was developed, usin. a very simple process without chromatography: -ML: This is really a fascinating story AVR: Yes. [informed Dr Malshe that we were able to get vinblastine, He was very excited andl asked me abou my ‘other basic project for anthracyclines. asked him if he ‘would be willing to give money for that. His mandate was to fand stat niversties not central inefitutes, but he realised the importance of what we were doing. He said, “De Rama Rao, if you make vinblastine a success, then inoney is not a problem”, He later agreed to give ws another Rs three lakh, His entire budget was Rs eight lakh and he had given more than half of ie to us. 1 commercialised the vinblastine project and successfully completed the anthracycline programme ‘ML: Why dida’t anybody else think about this procedure, 1 simple solvent extracsion method? AVR: There are 95 alkuloids in Vinca rosea of which you have to pick one, Sciencists read the literature and make things complicated. They carry on with what was done before, Maybe today I will not be able to do what I dil before, Those days, I didn’t have the right facilites, Pushed to a corner, you are determined to find a way out. ven on anthsacyeline, when I published papers, all the MING read my papers, because the methods were so Simple, And Igor ivited by all the pharma companies to give lectures, All thote projects were relevant to them. Tram one chemist who has probably lectured at all the pharma companies and made more money from my lectures than coosultancy. Fused to pay more income tax than my salary. ‘ML: Vinblastin was an astounding breakthrough that combined both fundamental and industrial research and surely made waves at thar ime? AVR Ina coincidence, the very morving I gave the sample to Dr Malshe, he had me: Chief Minister AR Antulay who was under fite from the MLAs wanting the Science & Technology cell to be wound up. Anmulay was supposed to reply in the Assembly, He asked Dr Malshe “Will sou get any money from this esearch”? He said, “We will get royalty, but tiore chan that, it isa prodacs thar will pat India on the world map”. Now; [had not discovered the deug. Whar did was 1 iscover a new cechnology to lower the price of making the key intermediate. But Ancalay, being a politician, did rot understand the difference ancl went ahead and announced that an Indian scientist had discovered an anti cancer drug, It was reported on the front pages of all the newspapers the next day; but the text we had given him ML: What abour the next steps ~ establishing the efficacy and actual manufycturing of the drug? AVR: Our process of isolating vinblastine and vincristine 1i Lilly was doing, But who was ing to exploit it in India? Hindustan Antibioties was Supposed to make the praducr. Ie insisted on using vials to demonstrate the efficacy of the product, That is where Dr Hamied helped. He pur me in touch with Tata Cancer Hospital. There wa Dr Shetty who was the chemotherapy head. L spent my ‘own money visiting the Hospital, Hindusan Anubionies The authorities wanced bad a machine which was unused. I cleaned it up and used it to make vials for rests. We used the drug. on the, Tata Hospital pa and Dr Shetty concluded that the resis were identical to the Bl Lilly product. Bur HAL cefused to make chem. Tent to Dr Hamied and asked him ithe would manufacture the drug, Hie said, "No. Rama Rao, you are a ‘20d scientist, but you have to learn business from me’, ats, along with the El Lilly products Twas surprised. I thought I had done something fantastic He asked me what is the val sule of de drug in India? Ih was Rs25 lakh, He said, "My investment would be Re two erore plas two years of interest which would then have amounted to Re40 lakh”. [eanade no sense and Thad no teal answer for this ML: Was there an expart possibility? AVR: Those days, nobody thought about the world market. Ciplr’s exports were only Rs1.5 crore, $o | used to sit in the library, late into the night and wonder what is going wrong for this kind of inn discovered that the parent for the El Lily product was. due to expiee in 1985, I called Dr Hamied the next mo-ning and said, “Ieisa world market jon. Then, I suddenly the patent is going to expire in 1985 and we are already in L982 ‘We need two years to start production aud you need regulatory permissions”. He said, *My God, Rams Rao, T didn’t realise his”. Cipla’: Bangalore facility was ceeated. That was the beginning of exports by the Indian drug industey. Th Thecame well-known. Cipla signed the agreement for technology in 1983 and supplied the first 500 vials to 1983. Irsold ‘each vial of vineristine sulphate at Rs25 comparcd to the imported price of Rs80, ‘Through the entite process I learnt not only technology and formulation but dealing with che doctors, linial trials, dealing with FDA rules, good manufacturing practices (GMP) and exports. That's why my own venture Avra Laboratories has the Vinea rosea (the Periwinkle flower) as its logo. The whole thing opened up my mind, Even today, no scientist knows all these aspeccs from fundamental research ro commercialisation, You need ‘extreme commitment 10 get solutions. Today, there specialised people in industry to take care of different phases of the process; bur at shat rime, there was no one. MIL: You worked on other projects with Cipla and Lupin. ‘What was the next big piece of your work? AVR: Another area where | think I made some contribution co the coantry is in HIV/AIDS, Thave a knack for identifying the right products ~ it is a God! siven gift through mundane sourcss. There is another in asience, everybody becomes expert in one fs how Cipla also moves very fast and three major cancer hospitals in December In science, everybody be S Ger in one chosen ficld: they rarely change teack and do something different. But every five years I changed my area of work - from anti- cancer to cyclical peptides 10 AIDS yy ‘chosen field; they rarely ch different. Bor every five years, Lchanged my area of work, MI: Tell us about each of these phases. AVR: When I 16 cancer research, Then, in 1985, 1 decided I mast change track and was looking for new areas. MG Ramachanelran was the chief minister of Tamil Nadu and had undergone kidney transplant, One morning, while reading che newspaper, I noticed that the opposition parties were asking who had paid for it ~ the party or the state government. He aceded to take Cyclosporine A, which is nge track and do something wned from Harvard, I sas into anti 2 rug given to organ transplant patients and has to be taken lifelong, The cost was RSS0)000 per person per year I wondered why does this drug cost so mush and ‘why can’t it be mage here, Lrushed to the library and started looking up Cyclosporine A. | found ie was an immunosuppressant, Thad never worked on this. SoH went ro the laboratory and wrote on the board - immunosuppressant, This i the project we are going to work on. My researchers were very celuctant because they knew nothing about it, I said, wwe will read and learn. To work in this area, we had to do asymmetric synthesis. T ne forthe frst time in India. Then there isa compound which i 100 times more powerful than Cyclosporine, which is given today to heart transplant patients, We did the total symthesis forthe frst time outside the US, We worked on this tll 1990-91 = was d From 1980 t0 1995 was the period when I worked on my ‘own and the way T wanted 10. Since I had made a name in research, money Was pouring in from industry and Lutlised it for fandamemal research, Tused to have a large number of student groups. I had supervised 109 PhDs over LY years. 1 used to tell them to s20 and sit inthe library and ge ime some new ideas. The ideas should he for something that is tough, relevant to society and get us name and fame. These were the three ctieria. One day, { was looking at vancomycin which is used when all antibiotics fail Ie is very complex ipolecule, I is most fascinating structure-wise and activiy: wise. [knew that if we could do something. with it, we will be noriced. We worked on it from 1992.95, Guess who was our competitor? A Harvard professor He had 46 molecule. E knew that if we could do with it, we will be noticed. We worked on it from 1992-95. Guess who was our competitor? A Harvard professor. He had been working on it for 10 years, We beat him to it yy been working on ic for 10 years, Everyone sail he ie ‘working on it for a long time and coulen’s so why did we want to get into it ML: "the product was already there. You wanted to make a new analogue for better results? AVR: Yes. JC like, why did you elim the Everest? It is for the excitement, Here, there was not only excitement bout the work has relevance. Industry takes your work, makes a variety of analogues. Even for vincomycin, there et anywhere, are hundeeds of new analogues. It was 4 fermentation, product made by Fh Lilly. We were the frst ro synthesise it. We aimed to extend its knowledge and efficacy. We made it in rwo halves, Then a problem arase, How to, hook the two halves together. That was the problem the Harvard professor was strugging with. [go for morning walks and, at that time, I think abour all my problems One day, while walking, it suddenly oceutred to me that this may not be the way Nature has built it, So [came back and said, fer us reverse the sequ first to complete the synthesis, ML: You have also worked on ALDS medicine. AVR: In 1988-89, I read in a newspaper that a young man had come from the Gulf and died of AIDS because of blood transfusion, There was only one drug available for AIDS which had responded in animal testing. The USEDA had approved it withour any clinical trials, bypassing all the cules, [twas very expensive. [deeply felt cat every Indian must have access tn it. We came out with a new method of making the drag, Ie ise it in 1991, Usa, annount for the Indian market, otherwise our people will be deprived”. He was reluctant but agreed, At that time, Burroughs Wellcome had introduced the drug in India and wanted co block ur product. The Indian FDA wanted the drug tested on eight HIV patients, bu there ‘weren't that maay patienis in Indian hospitals. This meant that it was impossible 1o meet the requirement. One year passed and ic was no cleared, In 1992, D: Hamied said, “Ihave done what you wanted; it i not in my hands, nee; we were the rested Dr Hamied to commer Pleave make atleast a because this anf wot moving the file” I then picked up the phore and called the officer. I knew the person because he was on various government ‘committees that I headed. For the frst time in my life, I threatened someone. I said, “If you don’t clear the drug. within 24 hours, Iwill take up the issue with the prime minister, who is the president of CSIR. It was cleared in 24 hours. Cipla manufactured about L0 millon tablets of Zidovudine, but there were no patients. Dr he was willing 19 distribute it through the ICMR (Indian Council for Medical Research), but the director of ICMR. seid that was not his mandate. By 1995, however. AIDS had beceme widespread and the market for the deug jst ammied said took off ‘ML: Cipla has made such a global name by offering the

    You might also like