Want more cheese, insulin, vaccines and serum? No problem, just go for biotechnology

A man who's helping change the world. Prof. Ramareddy Guntaka from the
Department of Molecular Sciences, University of Tennessee Health Sciences
Centre, addressing the last meeting on 'Latest developments in
biotechnology and impact on health'

To the uninitiated, developments in the fields of biotechnology, molecular biology and other such subjects may sound like distant wonders being performed in some remote, rich pockets of the world.

But that.s not really the case. For, these modern tools of science are right now helping India produce cheap, effective vaccines against hepatitis; in the production of humungous quantities of insulin; and also in the manufacture of the cheese being used in the Pizza Hut round the corner.

Even a single nucleotide change can result in cancer, according to Prof. Ramareddy
Guntaka, who has been working in the field of DNA for the last forty years

In fact, according to the guest speaker at the last meeting, Prof. Ramareddy Guntaka, who is associated with the Department of Molecular Sciences, University of Tennessee Health Sciences Centre, this is just the beginning . biotechnology has the potential to revolutionise health care in India.

Addressing the "Latest developments in biotechnology and impact on healt", he said that his association with some Indian companies, especially Sudarshan Biotech Ltd., had enabled him to overcome some very difficult challenges, especially with regard to cheaper substitutes for prohibitively expensive imported drugs and medicines.

Thank you for an excellent presentation. President Dr. Rumi Jehangir presents a memento to
Prof. Ramareddy Guntaka, the guest speaker at the last meeting. In the second picture, the
good professor tells Dr. Vikram Lele that his area of work is not as difficult as
it sometimes seems

Dr. Vikram Lele, who introduced the guest speaker, said that Prof. Guntaka was born and brought up in Hyderabad and educated there (he completed his B.Sc. in Chemistry and Biology and M.Sc. in Microbiology). But he then went to the US where he did his Ph.D. in Microbiology at the Kansas State University.

Pradeep again. In the picture he is introducing Prof. Guntaka, the guest
speaker at the last meeting, to Dr. Rohini Chowgule.

He received innumerable awards and honours, including the Sir C.V. Raman Professorship, the Jawaharlal Nehru Professorship of the University of Hyderabad and so on. He had trained many students and several doctorates had been awarded under his guidance.

Associated with eight major discoveries, he held a patent in one of them. He was an important member of the group which sequenced the Indian strain of the hepatitis virus for the first time. He was also in the group that discovered proto-oncogenes, involved in the genesis of cancer.

Prof. Guntaka said he had been working in the field of DNA for the last 40 years and could throw some light on the use and applications of biotechnology in India.

His first effort at applying basic molecular biology started in the 1900's. Elected to the Indian Agricultural Research Institute, he helped conduct trials on the plant viruses that were devastating several crops in India. He also helped combat some of these viruses.

But "molecular biology is like a computer, you can apply it to any field". So he started spending three to four months every year in Hyderabad with Sudarshan Biotech, which wanted to apply basic molecular biology techniques for human health.

The vaccine for hepatitis-B was discovered in the 1980's and 1990's. But it cost Rs. 1,200 to Rs. 1,300 per dose. Since an individual required three doses, very few people were actually vaccinated. It was then that Mr. Varaprasad Reddy of Shanta Biotech asked him to help make a cheaper vaccine.

Prof. Guntaka said the first thing his team did was that "we took a piece of the DNA (from the deadly hepatitis- B virus) and we made it into a vaccine" by cloning. The resultant vaccine cost less than Rs. 50 per dose - and now, more than ten million people had already been vaccinated.

Another area where he took the help of DNA and cloning was with the cancer drug, interferon; he had helped clone the compound and it was now available for Rs. 200 to Rs. 300 as against the earlier cost of Rs. 1,000 per dose.

Turning to the discovery of protooncogenes, Prof. Guntaka said he was involved in one of the Nobel Prizewinning discoveries, viz., the discovery of cancer-causing genes, when it was shown in 1974 that the human body harboured about 100 genes whose mutations could result in cancer. These were called proto-oncogenes.

He was working on a virus that readily induced cancer in animals. From that he managed to isolate a single gene, a small piece of DNA material present in all humans - and in almost all the cells. It was a normal cellular gene which everybody inherited. But a simple mutation of that gene caused cancer.

Skirting the "controversy" regarding the Nobel Prize for this work in1989 (it was awarded to some of the team members), Prof. Guntaka explained the genesis of cancer.

Every human being.s genetic code was made up of DNA; DNA consisted of just four (basic) nucleotides which were repeated billions of times. But sometimes, one single gene changed its character and became aggressive, thus causing cancer.

"That is how important this is - even a single nucleotide change can result in cancer; and depending on the type of gene, a person can get liver cancer or leukaemia or one of the many other forms of cancer".

Giving another example of the use of DNA technology for the benefit of mankind, Prof. Guntaka talked about the vital protein, erythropoietin, manufactured in very small quantities in the human kidney. It required about 2,500 litres of urine to isolate a few micrograms of erythropoietin (used for treatment).

He developed a technique whereby just 100 litres of urine yielded the equivalent of a million doses of erythropoietin.

"We don't isolate anything from the body, rather, we. clone the genes in bacteria which actually live in the human intestines; that bacterium can be used to express this gene and we can get it from there".

But what actually was genetic engineering? Explaining this, Prof. Guntaka repeated the fact that DNA only had four nucleotides, like an alphabet, but these were repeated billions of times. The human genome thus had billions of nucleotides.

Today, it was easily possible to take the DNA and to change it or transcribe it into RNA; the RNA then went into the protein... and the end product of this was"the most functional molecule".

The genetic code for this and for other similar procedures was established way back in the 1960's by the Nobel Prize-winning Dr. Hargovind Khurana.

Another area where cloning and other biotechnological techniques were employed was the production of insulin. With the number of diabetic patients throughout the world, including India, galloping away, already about 10% to 15% of the world's population seemed to have become diabetic. Several drugs were available, but in the end everything boiled down to insulin, Prof. Guntaka pointed out.

In the 1970's and 1980's, insulin was isolated from pigs and used as a medicine in humans. It was established that there was very little difference in the genes of humans and pigs; and that human insulin and pig insulin were very similar.

As the requirement for insulin started rocketing, it became clear that about 90 million pigs would have to be killed for their insulin. This was almost impossible. Calves could be killed in place of pigs; but this, too, was an impossible task, given the sheer numbers.

In the 1980's, researchers at the American company Eli Lily took out a gene from human pancreatic RNA, converted it into DNA, cloned it and put it into the bacterium. With this commenced the production of human insulin.

Now, the whole world's demand was being met by this procedure. A single clone was enabling the production of humungous amounts of insulin. In other words, a single clone would be used for hundreds of years (with no fear of price increases). Several variations of insulin were now available, all genetically engineered.

Prof. Guntaka then turned to a tasty topic, cheese, and the application of biotechnology.

Thanks to the mushrooming of pizza parlours, the demand for cheese was astronomical. The manufacture of cheese required a milk-clotting enzyme which was extracted from the fourth stomach of calves. This meant the killing of calves.

"So at Sudarshan Biotech we took the gene only once - just once we took a very small sample, only a milligram, of a calf's stomach. we took out that gene and now the yeastwalla is making tonnes of cheese. I can give you just a drop of that and you can use it to convert a litre of milk into cheese".

A similar approach was used for the human serum albumin, a very big molecule and difficult to clone. It was made from human blood. But since nobody in India screened blood even for hepatitis-B or C, or for HIV or the AIDS virus, there was a high possibility of the albumin serum being contaminated.

Therefore, Prof. Guntaka said, Sudarshan Biotech applied the recombinant DNA technology in the manufacture of human serum albumin to prevent contamination. It thus became one of only two or three companies in the world to adopt this approach.

His team cloned the gene, put it in yeast and now, from one litre, it was able to extract one gram of human serum albumin normally made by the liver cells in the body.

Returning to hepatitis, Prof. Guntaka said that thanks to the absence of stringent blood tests, especially during transfusions, over 350 million people throughout the world were infected with the hepatitis-B and 250 million with the hepatitis-C virus.

"In the US, a single dose of hepatitis- B vaccine costs about $50. But in India it is available for Rs. 60 per dose because of the DNA technology which we started using in 1993; we released the first product in 1997".

Enthused by this success, he took a sabbatical in 1999-2000 and came to Hyderabad to work on the hepatitis-C virus.

It was a silent killer . at the time of contracting the infection there were hardly any symptoms. But after ten or 12 years, it struck with a vengeance - in the form of cirrhosis of the liver or liver cancer.

About 30% of the people infected ten to 12 years earlier showed these conditions. But nobody had done any work on hepatitis- C in India.

Working in association with Hyderabad 's Dr. Habibullah who gave him blood samples from 1999 on-wards, he cloned the whole genome and submitted the cloned Indian virus to the gene bank on Republic Day of 2001.

It was found that there was some (slight) difference from the American virus, as also the Japanese and the French virus. This meant that even if a vaccine had been developed for hepatitis-C, it would not have worked on Indian patients.

"Therefore, we had to develop a vaccine for the Indian virus. And that's exactly what we have been doing at Sudarshan Biotech. In 2005, we cloned from a second hepatitis-C infected patient and again we found differences between the first patient and the second.

"Finally, after screening several thousand people in India, in Delhi, Bombay and Hyderabad, we concluded that there were two main forms of hepatitis-C virus in India. Now, we are proceeding with the development of vaccines for these viruses".

Prof. Guntaka said that apart from making vaccines, simple enzymes used in the food industry and therapeutic molecules like human serums, he was also involved with interferon variants for multiple sclerosis.

These cost over Rs. 10,000 per dose and had to be taken once a week. Thus, the yearly cost was Rs. 5 lakhs. But once his product was commercialised, it would cost about Rs. 1,000 per dose.

What did he do when he was not busy with Sudarshan Biotech? In his laboratory in the US, Prof. Guntaka said, he was studying the hardening of the liver following infection by the hepatitis-B or hepatitis-C viruses.

He had found that such an infection caused hardening (sclerosis or fibrosis) of the liver. And that the process was triggered by the activation of a collagen molecule which caused hardening. There was just no treatment for this and the only way out was a liver transplant.

Now, Prof. Guntaka added, he was using a (patented) DNA-mediated drug to target the collagen gene. So far, the results were promising. Although the hardening of collagen had not been reversed so far, he was able to prevent the formation of fibrosis (and hence hardening).

In conclusion, he said,"I hope I have convinced you that you can apply the basic molecular biology tools for better human health. But not only human health, these tools can be used even in agriculture, for example, using alcohol and so on for making biodiesels.

"This technology has a lot of potential which can be applied and tapped for human use with minimal cost".

Burjor Poonawala, referring to the use of interferons for the treatment of multiple sclerosis, pointed out that interferon was mainly used for relapsing or remitting multiple sclerosis, not for progressive MS. He asked whether any progress had been made in the use of interferons for progressive MS.

Prof. Guntaka said that no one was doing any research on preventing further progress of MS. At present, interferon was mainly used to prevent progress in existing patients. Of the 50,000 MS patients in India, only 1,000 to 1,400 were using it because it was prohibitively expensive (only the American product was available here).

The vote of thanks was proposed by Sitaram Shah.